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COMT Val108/158Met polymorphism effects on emotional brain function and negativity bias
Abstract
Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders.
... So kommt bspw. bei Bar-Haim et al. (2007); Compton et al. (2003); Isenberg et al. (1999); Whalen et al. (1998) Zudem lassen sich auch Studien aufführen, die eine positive Korrelation zwischen der Anzahl an Met-Allelen und präfrontaler Hyperaktivierung nachweisen (Drabant et al. 2006;Mier et al. 2010;Smolka et al. 2005;Williams et al. 2010). Die ...
... Autoren solcher Studien sehen im Gegensatz zu Bishop et al. (2006) den Nachteil in der Hyperaktivierung, welche die Met-Träger in der Verarbeitung emotionaler Stimuli benachteiligen würde. Sie blieben aufgrund einer gewissen Inflexibilität geradezu auf negativen Reizen haften (Drabant et al. 2006) und würden eine negativity bias zeigen (Williams et al. 2010). Unterstützt werden diese Ergebnisse durch Studien, die bei depressiven Patienten höhere basale Katecholamin-Spiegel als bei gesunden Kontrollen fanden (Wyatt et al. 1971), durch Studien, die eine höhere Angstbereitschaft bei Met-Homozygoten zeigen (Enoch et al. 2003), durch solche, die bei weiblichen COMT Knockout-Mäusen ein gesteigertes ängstliches Verhalten nachweisen (Gogos et al. 1998), oder auch durch Studien, die eine verminderte Selbstkontrolle bei den Met-Trägern zeigen (Williams et al. 2010) sowie durch bereits einleitend zitierte Studien, die das Met-Allel mit Krankheiten aus dem psychischen Formenkreis assoziiert sehen (Ohara et al. 1998b;Woo et al. 2004 (Drabant et al. 2006;Smolka et al. 2005), sodass dadurch die neural gemessene emotionale Verarbeitung verändert werden könnte (Lange et al. 2003;Taylor et al. 2003 (Compton et al. 2003). ...
... Sie blieben aufgrund einer gewissen Inflexibilität geradezu auf negativen Reizen haften (Drabant et al. 2006) und würden eine negativity bias zeigen (Williams et al. 2010). Unterstützt werden diese Ergebnisse durch Studien, die bei depressiven Patienten höhere basale Katecholamin-Spiegel als bei gesunden Kontrollen fanden (Wyatt et al. 1971), durch Studien, die eine höhere Angstbereitschaft bei Met-Homozygoten zeigen (Enoch et al. 2003), durch solche, die bei weiblichen COMT Knockout-Mäusen ein gesteigertes ängstliches Verhalten nachweisen (Gogos et al. 1998), oder auch durch Studien, die eine verminderte Selbstkontrolle bei den Met-Trägern zeigen (Williams et al. 2010) sowie durch bereits einleitend zitierte Studien, die das Met-Allel mit Krankheiten aus dem psychischen Formenkreis assoziiert sehen (Ohara et al. 1998b;Woo et al. 2004 (Drabant et al. 2006;Smolka et al. 2005), sodass dadurch die neural gemessene emotionale Verarbeitung verändert werden könnte (Lange et al. 2003;Taylor et al. 2003 (Compton et al. 2003). ...
Hintergrund: Das Catechol-O-Methyltransferase-Gen (COMT) ist ein vielversprechendes Kandidatengen zur Untersuchung kognitiver und emotionaler Funktionen sowie deren pathologischer Veränderungen. Ein einzelner Basenaustausch in diesem Gen führt zu einer 3-4fach höheren COMT-Aktivität der Val Variante. Ein dadurch vermitteltes dopaminerges Defizit wird als relevanter Faktor für eine veränderte Hirnfunktion angenommen. Mit dem kognitiven Stroop-Paradigma wurden kognitive Verarbeitungsprozesse bisher gut erforscht. Zur Erfassung emotionaler Verarbeitungsprozesse wurde eine emotionale Variante entwickelt, deren neurale Grundlagen bislang weniger gut bekannt sind. Ziel: Unsere imaging genetics-Arbeit untersucht den Einfluss genetischer Varianten auf die neurale Funktion. Ziel dieser experimentellen Arbeit war es, den Einfluss des COMT-Polymorphismus (COMT-PM) auf die Frontalkortex-Funktion in ausgewählten Regionen von Interesse (ROI) zu erfassen und der Frage nachzugehen, ob das Val-Allel als Risiko-Allel zur Pathogenese einer Angststörung (AS) beitragen könnte. Zudem sollte die Tauglichkeit des emotionalen Stroop- Paradigmas als angstsensibles Messinstrument zur Untersuchung dieser Fragestellung geprüft werden. Demgegenüber steht die Annahme, das emotionale Stroop-Paradigma könnte lediglich eine Arbeitsgedächtnis (AG)-Aufgabe darstellen. Methoden: Mittels funktioneller Nahinfrarotspektroskopie (fNIRS) und ereigniskorrelierter Potentiale untersuchten wir 121 gesunde nach dem COMT- Val158Met-PM stratifizierte Probanden während eines kombiniert emotional- kognitiven Stroop-Paradigmas. Als neurale Korrelate von Exekutivfunktionen und AG-Aufgaben waren die ROI dabei der laterale präfrontale und inferiore Kortex, die auch mit emotionaler Regulation in Verbindung gebracht werden. Als Parameter der Reaktion des autonomen Nervensystems (ANS) diente die Erfassung der elektrodermalen Aktivität sowie die kontinuierliche Messung von Blutdruck, Herzfrequenz und Herzratenvariabilität. Ergebnisse: Bei allen drei COMT Varianten zeigte sich ein kognitiver Stroop-Effekt mit verlängerter Reaktionszeit und erhöhter Fehleranzahl während der Präsentation inkongruenter Farbworte. Als Reaktion des ANS stellte sich eine erhöhte elektrodermale Aktivität bei inkongruenten Farbworten dar. Die funktionelle Bildgebung ließ in den analysierten Regionen eine erhöhte präfrontale Aktivierung während der Verarbeitung inkongruenter Farbworte nachweisen. Es fanden sich keine Gruppenunterschiede im kognitiven Stroop-Paradigma. Der einzige emotionale Stroop-Effekt zeigte sich in der P300. Der einzig nachweisbare Gruppeneffekt stellte sich im emotionalen Stroop-Paradigma als höhere Fehleranzahl bei Met-Homozygoten verglichen mit Heterozygoten dar. Schlussfolgerung: Genetische Information und funktionelle Bildgebung kombiniert sollten ermöglichen, neurale Mechanismen zu definieren, die mit genetischen Varianten verlinkt sind. Die Ergebnisse bezogen auf die analysierten Regionen liefern keinen Hinweis auf ein Val-Allel assoziiertes Risiko für die Entwicklung einer AS. Damit gelingt es nicht, bisher gewonnene Ergebnisse zum Einfluss des COMT-PM auf die präfrontale Funktion zu replizieren. Fraglich ist jedoch, ob sich das emotionale Stroop-Paradigma zur Untersuchung dieser Frage eignet, da weder in den fNIRS-, noch in den autonomen oder Verhaltensdaten ein emotionaler Stroop-Effekt nachgewiesen werden konnte.
... The COMT gene codes for the COMT enzyme, a protein that degrades catecholamine neurotransmitters and modulates dopamine metabolisms 20 . Among the COMT polymorphisms, Val158Met (rs4680) has been most reported to play a role in face processing [15][16][17][18][19][20][21][22][23][24] . For example, individuals with the Met/Met (rs4680) genotype are more sensitive to configural changes in faces than those with other genotypes 15 . ...
... For example, individuals with the Met/Met (rs4680) genotype are more sensitive to configural changes in faces than those with other genotypes 15 . Healthy homozygous subjects with the Met allele of rs4680 are better at recognizing facial emotions 16 and show a stronger bias to perceive neutral faces as expressions of anger 21 than those with other genotypes. Previous studies also investigated the impact of the COMT gene on the brain activity during face emotional processing [22][23][24][25] and demonstrated that the COMT Met allele seems to contribute to neural substrates of negativity biases [22][23][24] , and the COMT Val allele is associated with increased amygdala activity in response to fearful/angry facial expressions 25 . ...
... This is consistent with previous studies demonstrating associations between dopamine hyper-or hypo-function in cortical or subcortical regions and cognitive dysfunctions [54][55][56] . Therefore, it would be interesting to examine the level of dopamine in the FFA in individuals with developmental prosopagnosia 10,57-59 , who show specific deficits in face recognition with unclear genetic basis 60 and those with mental disorders who might have disturbances in COMT modulation of face processing 16,18,21,23 . ...
Previous studies have shown that face-specific recognition ability (FRA) is heritable; however, the neural basis of this heritability is unclear. Candidate gene studies have suggested that the catechol-O-methyltransferase (COMT) rs4680 polymorphism is related to face perception. Here, using a partial least squares (PLS) method, we examined the multivariate association between 12 genotypes of 4 COMT polymorphisms (rs6269-rs4633-rs4818-rs4680) and multimodal MRI phenotypes in the human fusiform face area (FFA), which selectively responds to face stimuli, in 338 Han Chinese adults (mean age 20.45 years; 135 males). The MRI phenotypes included gray matter volume (GMV), resting-state fractional amplitude of low-frequency fluctuations (fALFF), and face-selective blood-oxygen-level-dependent (BOLD) responses (FS). We found that the first COMT-variant component (PLS1) was positively associated with the FS but negatively associated with the fALFF in the FFA. Moreover, participants with the COMT heterozygous-HEA-haplotype showed higher PLS1 FFA-MRI scores, which were positively associated with the FRA in an old/new face recognition task, than those with the COMT homozygous HEA haplotype and HEA non-carriers, suggesting that individuals with an appropriate (intermediate) level of dopamine activity in the FFA might have better FRA. In summary, our study provides empirical evidence for the genetic and neural basis for the heritability of face recognition and informs the formation of neural module functional specificity.
... A single nucleotide polymorphism predicts the substitution of amino acid methionine (Met) for valine (Val) at codon 158 (VAL158MET), which results in a threefold to fourfold reduction of catecholamine degradation in Met as compared to Val carriers (Lachman et al., 1996). The associated differences in extracellular catecholamine levels appear to account for neural differences in face processing as suggested by imaging studies revealing increased amygdala activity (Williams et al., 2010;Lonsdorf et al., 2011) and increased amygdala-prefrontal connectivity (Surguladze et al., 2012) in response to negative expressions in Met carriers. Met carriers, thus, show an enhanced processing of negative expressions, indicating a negativity bias during face processing. ...
... Two studies failed to find robust differences in emotion recognition between Met and Val carriers (Weiss et al., 2007;Defrancesco et al., 2011), whereas a third study revealed that Met carriers misperceived neutral expressions as negative ones (Gohier et al., 2014). Met carriers may, thus, not only show an enhanced processing of negative expressions as suggested by the imaging studies (Williams et al., 2010;Lonsdorf et al., 2011;Surguladze et al., 2012) but also a negatively tuned processing of neutral expression as suggested by one of the behavioral studies (Gohier et al., 2014). In this respect, it is important to note that this behavioral study (Gohier et al., 2014) differed markedly from the other two behavioral studies (Weiss et al., 2007;Defrancesco et al., 2011) in terms of sample size (e.g., inclusion of more than 100 participants), genotype frequencies (e.g., consideration of COMT and 5-HTTLPR polymorphisms), task design (e.g., presentation of expressions with varying emotional intensity) and data analysis (e.g., control of multiple comparisons). ...
... These analyses were based on an a priori power analysis and corrected for multiple comparisons to guard of false positive or false negative findings, indicating that our analyses were liberal and conservative enough to detect meaningful differences in face processing. As the aforementioned studies suggest that the negativity bias in face processing is more pronounced in Met than Val carriers (Williams et al., 2010;Lonsdorf et al., 2011;Surguladze et al., 2012;Gohier et al., 2014), we expected Met carriers to recognize more negative expressions than Val carriers. ...
The catechol-o-methyltransferase (COMT) gene has repeatedly been shown to change amygdala activity and amygdala-prefrontal connectivity during face processing. Although the COMT gene appears to induce a negativity bias during the neural processing of faces, it is currently unclear whether a similar negativity bias emerges during the behavioral processing of faces. To address this issue, we investigated differences in complex emotion recognition between participants (n = 181) that had been a priori genotyped for functional polymorphisms of the COMT (Val158Met) and serotonin transporter (5-HTTLPR) gene. We were, thus, able to analyze differences in face processing on basis of participants’ COMT genotype while controlling for participants’ 5-HTTLPR genotype. Variations of participants’ COMT but not 5-HTTLPR genotype accounted for differences in participants’ emotion recognition performance: Met/Met carriers and Met/Val carriers were more accurate in the recognition of negative, but not neutral or positive, expressions than Val/Val carriers. We, therefore, revealed a similar negativity bias during the behavioral processing of faces that has already been demonstrated during the neural processing of faces, indicating that genotype-dependent changes in catecholamine metabolism may affect face processing on the behavioral and neural level.
... A single nucleotide polymorphism predicts the substitution of amino acid methionine (Met) for valine (Val) at codon 158 (VAL158MET), which results in a threefold to fourfold reduction of catecholamine degradation in Met as compared to Val carriers (Lachman et al., 1996). The associated differences in extracellular catecholamine levels appear to account for neural differences in face processing as suggested by imaging studies revealing increased amygdala activity (Williams et al., 2010;Lonsdorf et al., 2011) and increased amygdala-prefrontal connectivity (Surguladze et al., 2012) in response to negative expressions in Met carriers. Met carriers, thus, show an enhanced processing of negative expressions, indicating a negativity bias during face processing. ...
... Two studies failed to find robust differences in emotion recognition between Met and Val carriers (Weiss et al., 2007;Defrancesco et al., 2011), whereas a third study revealed that Met carriers misperceived neutral expressions as negative ones (Gohier et al., 2014). Met carriers may, thus, not only show an enhanced processing of negative expressions as suggested by the imaging studies (Williams et al., 2010;Lonsdorf et al., 2011;Surguladze et al., 2012) but also a negatively tuned processing of neutral expression as suggested by one of the behavioral studies (Gohier et al., 2014). In this respect, it is important to note that this behavioral study (Gohier et al., 2014) differed markedly from the other two behavioral studies (Weiss et al., 2007;Defrancesco et al., 2011) in terms of sample size (e.g., inclusion of more than 100 participants), genotype frequencies (e.g., consideration of COMT and 5-HTTLPR polymorphisms), task design (e.g., presentation of expressions with varying emotional intensity) and data analysis (e.g., control of multiple comparisons). ...
... These analyses were based on an a priori power analysis and corrected for multiple comparisons to guard of false positive or false negative findings, indicating that our analyses were liberal and conservative enough to detect meaningful differences in face processing. As the aforementioned studies suggest that the negativity bias in face processing is more pronounced in Met than Val carriers (Williams et al., 2010;Lonsdorf et al., 2011;Surguladze et al., 2012;Gohier et al., 2014), we expected Met carriers to recognize more negative expressions than Val carriers. ...
The catechol-o-methyltransferase (COMT) gene has repeatedly been shown to change amygdala activity and amygdala-prefrontal connectivity during face processing. Although the COMT gene appears to induce a negativity bias during the neural processing of faces, it is currently unclear whether a similar negativity bias emerges during the behavioral processing of faces. To address this issue, we investigated differences in complex emotion recognition between participants (n = 181) that had been a priori genotyped for functional polymorphisms of the COMT (Val158Met) and serotonin transporter (5-HTTLPR) gene. We were, thus, able to analyze differences in face processing on basis of participants’ COMT genotype while controlling for participants’ 5-HTTLPR genotype. Variations of participants’ COMT but not 5-HTTLPR genotype accounted for differences in participants’ emotion recognition performance: Met/Met carriers and Met/Val carriers were more accurate in the recognition of negative, but not neutral or positive, expressions than Val/Val carriers. We, therefore, revealed a similar negativity bias during the behavioral processing of faces that has already been demonstrated during the neural processing of faces, indicating that genotype-dependent changes in catecholamine metabolism may affect face processing on the behavioral and neural level.
... Other studies, however, did not find a link between the COMT gene and the experience of positive affects (Bakker et al., 2014;Desmeules et al., 2012;Wacker et al., 2012) or anticipation of positive affects (Katz et al., 2015). Indeed, more studies showed an opposite pattern with increased negativity bias in affective processing for the Met allele (Gao et al., 2016;Kia-Keating et al., 2007;Ohara et al., 1998;Smolka et al., 2005;Williams et al., 2010). For example, clinical research demonstrated that the susceptibilities to depression and suicidal behavior were increased in the Met allele carriers (Kia-Keating et al., 2007;Ohara et al., 1998); neuroimaging studies also showed that the Met allele was associated with increased neural responses to negative emotional stimuli (Smolka et al., 2005) and decreased neural responses to positive facial expressions (Williams et al., 2010). ...
... Indeed, more studies showed an opposite pattern with increased negativity bias in affective processing for the Met allele (Gao et al., 2016;Kia-Keating et al., 2007;Ohara et al., 1998;Smolka et al., 2005;Williams et al., 2010). For example, clinical research demonstrated that the susceptibilities to depression and suicidal behavior were increased in the Met allele carriers (Kia-Keating et al., 2007;Ohara et al., 1998); neuroimaging studies also showed that the Met allele was associated with increased neural responses to negative emotional stimuli (Smolka et al., 2005) and decreased neural responses to positive facial expressions (Williams et al., 2010). ...
... Our study demonstrated that the increased number of the Met alleles was associated with increased depressive symptoms and decreased well-being. These findings, together with previous studies showing the increased negativity bias of the Met alleles in affective processing (Gao et al., 2016;Kia-Keating et al., 2007;Ohara et al., 1998;Smolka et al., 2005;Williams et al., 2010), highlight the involvement of the COMT gene in the susceptibility to depression. Our findings suggest a shared genetic basis of depressive symptoms and well-being, which is consistent with the high genetic overlap between depressive symptoms and well-being (Okbay et al., 2016). ...
Backround:
Previous studies have demonstrated the contributions of genetic variants and positive psychological traits (e.g. gratitude and forgiveness) to well-being. However, little is known about how genes interact with positive traits to affect well-being.
Methods:
To investigate to what extent the COMT Val158Met polymorphism modulates well-being and to what extent dispositional gratitude and forgiveness mediate the individual differences in well-being, 445 participants were recruited and required to complete a battery of questionnaires.
Results:
We found that individuals with a smaller number of the Met alleles reported greater well-being, less depressive symptoms, and greater tendencies for gratitude and forgiveness. Moreover, dispositional gratitude and forgiveness mediated the genotype effects on well-being and depressive symptoms. These results remained significant after controlling for non-genetic factors (socioeconomic status, religious beliefs, romantic relationship status, parenting style).
Limitation:
The sample size limits the generalizability of results.
Conclusion:
This study demonstrates the contribution of the COMT Val158Met polymorphism to individual differences in well-being and suggests a potential psychobiological pathway from dopaminergic and noradrenergic systems to happiness.
... The majority of studies have reported that the Met-allele is less advantageous than the Val-allele in emotion processing (Drabant et al., 2006;Swart et al., 2011;Williams et al., 2010). However, some studies are contradictory. ...
... However, some studies are contradictory. Williams et al. (2010) reported that the Met-allele is associated with sensitivity to negative emotional expressions, so that in a fearful face condition a greater number of COMT Val158Met Metalleles predicted increased activation in the brainstem. In contrast, Domschke et al. (2008) reported that a greater number of Val-alleles in panic disorder patients was associated with higher sensitivity (such as amygdala activation) while viewing fearful faces. ...
... The ADRA2A gene has the C-1291G polymorphism, which is a marker for the noradrenergic activity. The G-allele of that genetic variant has been associated with inattention (Domschke et al., 2008;Roman et al., 2006;Williams et al., 2010), impulsive personality traits (Comings et al., 2000;Mäestu et al., 2008), and with ADHD (Cummins et al., 2014;Kiive et al., 2010;Roman et al., 2006). Thus, in this study we expected the G-allele to predict slower response times in emotion detection (due to inattention during the task), and also affect emotion perception in interaction with COMT Val158Met. ...
Emotional facial stimuli are important social signals that are essential to be perceived and recognized in order to make appropriate decisions and responses in everyday communication. The ability to voluntarily guide attention to perceive and recognize emotions, and react to them varies largely across individuals, and has a strong genetic component (Friedman et al., 2008). Two key genetic variants of the catecholamine system that have been related to emotion perception and attention are the catechol-O-methyl transferase genetic variant (COMT Val158Met) and the α2A-receptor gene promoter polymorphism (ADRA2A C-1291G) accordingly. So far, the interaction of the two with sex in emotion perception has not been studied. Multilevel modeling method was applied to study how COMT Val158Met, ADRA2A C-1291G and sex are associated with measures of emotion perception in a large sample of young adults. Participants (n=506) completed emotion recognition and behavioral emotion detection tasks. It was found that COMT Val158Met genotype in combination with the ADRA2A C-1291G and sex predicts emotion detection, and perception of valence and arousal. In simple visual detection, the ADRA2A C-1291G G-allele leads to slower detection of a highly arousing face (scheming), which is modulated by each additional COMT Val158Met Met-allele and male sex predicting faster responses. The combination of G-allele, Met-allele and male sex also predicts higher perceived negativity in sad faces. No effects of C-1291G, Val158Met, and sex were found on verbal emotion recognition. Applying the findings to study the interplay between catecholamine-O-methyl transferase activity and α2A-receptors in emotion perception disorders (such as ADHD, autism and schizophrenia) in men and women would be the next step towards understanding individual differences in emotion perception.
Copyright © 2015. Published by Elsevier Inc.
... Starting with risk aversion and its relationship with dopaminergic pathways, we found the involved polymorphisms DRD4, MAOA, MAOA LPR, DAT1 and COMT Val 158 Met. All of them affect the level of dopamine that is available or the degree to which this neurotransmitter is able to act on the synaptic connections of the dopaminergic pathways, and especially on the striatum and the prefrontal cortex [55,59,60]. According to the results, many indicated that those alleles of the different polymorphisms whose presence translates into a lower level of dopamine or its decreased effectiveness of binding with receptors are associated with the lowest level of risk aversion. ...
... Again, this would make sense if we consider that serotonin is a key neurotransmitter in the regulation of emotional processes [33] and that risk aversion seems to be closely related to, or at least influenced by, the emotions [9]. In fact, positive correlations have been found between negative emotions such as fear, anger or sadness and the level of risk aversion [60,77]. In addition, ACC, one of the neural bases of risk aversion [17], has been highlighted as an important region in emotional processing [78,79], which can modulate amygdala activity [80] and serve as a connection between the limbic system and the prefrontal cortex [81]. ...
Risk and loss aversion are phenomena with an important influence on decision-making, especially in economic contexts. At present, it remains unclear whether both are related, as well as whether they could have an emotional origin. The objective of this review, following the PRISMA statements, is to find consistencies in the genetic bases of risk and loss aversion with the aim of understanding their nature and shedding light on the above issues. A total of 23 empirical research met the inclusion criteria and were included from PubMed and ScienceDirect. All of them reported genetic measures from human samples and studied risk and loss aversion within an economic framework. The results for risk aversion, although with many limitations, attributed mainly to their heterogeneity and the lack of control in the studies, point to the implication of multiple polymorphisms related to the regulation of the serotonergic and dopaminergic pathways. In general, studies found the highest levels of risk aversion were associated with alleles that are linked to lower (higher) sensitivity or levels of dopamine (serotonin). For loss aversion, the scarcity of results prevents us from drawing clear conclusions, although the limited evidence seems to point in the same direction as for risk aversion. Therefore, it seems that risk aversion could have a stable genetical base which, in turn, is closely linked to emotions, but more research is needed to answer whether this phenomenon is related to loss aversion, as well as if the latter could also have an emotional origin. We also provide recommendations for future studies on genetics and economic behavior.
... The enzyme catechol-O-methyltransferase (COMT) catabolizes dopamine (DA) and is located mostly in the prefrontal cortex (PFC) and temporal brain areas. The most investigated COMT polymorphism is Val108/158Met, which has been found to alter prefrontal cortex (PFC) activity during both emotion processing and executive tasks [25]. The COMT gene is a promising candidate for explaining age-related changes within the control-based theory of the positive effect in memory. ...
... For example, COMT Met allele carriers exhibit greater activity in the amygdala and prefrontal areas when presented with negative stimuli [26]. A meta-analysis [25] found that COMT had a strong influence on prefrontal activity, with Val carriers doing worse in cognition tasks and Met carriers performing worse in emotion-related tasks. COMT could have a pleiotropic effect on motivated cognition (more sensitive to cognitive-based vs. emotionbased motivational goals). ...
Fighting stress-related effects during spaceflight is crucial for a successful mission. Emotional, motivational, and cognitive mechanisms have already been shown to be involved in the decrease of negative emotions. However, emerging evidence is pointing to a neurogenetic profile that may render some individuals more prone than others to focusing on positive information in memory and increasing affective health. The relevance for adaptation to the space environment and the interaction with other stressors such as ionizing radiations is discussed. In particular, to clarify this approach better, we will draw from the psychology and aging literature data. Subsequently, we report on studies on candidate genes for sensitivity to positive memories. We review work on the following candidate genes that may be crucial in adaptation mechanisms: ADRA2B, COMT, 5HTTLPR, CB1, and TOMM40. The final aim is to show how the study of genetics and cell biology of positive memory can help us to reveal the underlying bottom-up pathways to also increasing positive effects during a space mission.
... The COMT enzyme is involved in the metabolic degradation of the dopamine neurotransmitter in brain regions such as the prefrontal cortex, amygdala and striatum. Research have shown that the Val158Met polymorphism of COMT gene is associated with the activity of the brain stem, amygdala, basal ganglia and prefrontal regions, and also is involved in the modulation of neural substrate structures responsible for processing negative and positive emotions (Williams et al., 2010), motivation (Åberg et al., 2011), recognition of negative emotions (Gohier et al., 2014), and is associated with aggressiveness (van Dongen et al., 2018). There is a connection between Val158Met polymorphism of COMT gene and the thickness of the cerebral cortex in associative areas of the brain (prefrontal, parietal, and cingulate), in which dopamine content is typically high (Williams et al., 2010). ...
... Research have shown that the Val158Met polymorphism of COMT gene is associated with the activity of the brain stem, amygdala, basal ganglia and prefrontal regions, and also is involved in the modulation of neural substrate structures responsible for processing negative and positive emotions (Williams et al., 2010), motivation (Åberg et al., 2011), recognition of negative emotions (Gohier et al., 2014), and is associated with aggressiveness (van Dongen et al., 2018). There is a connection between Val158Met polymorphism of COMT gene and the thickness of the cerebral cortex in associative areas of the brain (prefrontal, parietal, and cingulate), in which dopamine content is typically high (Williams et al., 2010). As a result, carriers of the Met allele of Val158Met polymorphism of COMT gene have a thicker cortical layer in these particular areas (Miranda et al., 2019). ...
Background: This study aimed to discover the association between parameters of event-related potentials (ERPs) and categorization of images of visual scenes, both emotionally-charged and neutral, in carriers of different genotypes of the COMT, HTR2A, BDNF genes.
Methods: Electroencephalogram (EEG) and ERPs were recorded at 128 leads, with two ear referents. Images of different visual scenes were presented to the study participants sequentially on a monitor screen. The participants’ task was to examine these images and indicate what emotions (negative, neutral or positive) they elicit. Comparison of event-related potentials was carried out using unpaired Student t-test in EEGLAB toolbox.
Results: COMT. A stronger reaction, as reflected in the amplitude of the ERPs, in participants with the recessive homozygous Met/Met genotype was observed on latency around 200 ms to the stimuli, assessed as positive. Carriers of dominant homozygous Val/Val genotype had higher amplitude of 200 ms peak when assessed scene images as either neutral or negative in comparison to other genotypes. Participant with the Val/Met heterozygous genotype had higher amplitude of ERP that Met/Met group on same latency when assessed stimuli as negative.
HTR2A . Significant increase in negativity in the parietal-occipital regions revealed in the range of 350-420 ms in participants with the recessive homozygous A/A genotype when choosing any type of assessment, compared to carriers of the heterozygous genotype A/G and the dominant homozygous G/G genotype.
BDNF. Participants with Val/Val genotype categorized the visual images more thoroughly, as reflected in greater activation of the parietal-occipital zones and higher amplitude on ERP peak on 190 ms (negative assessment) and 160 ms (neutral assessment) then Val/Met carriers.
Conclusions: The COMT, HTR2A, BDNF gene different genotypes are associated with the process of categorizing emotionally charged and neutral visual scenes, and this relationship is reflected in the ERP parameters.
... The COMT enzyme is involved in the metabolic degradation of the dopamine neurotransmitter in brain regions such as the prefrontal cortex, amygdala and striatum. Research have shown that the COMT gene is associated with the activity of the brain stem, amygdala, basal ganglia and prefrontal regions, and also is involved in the modulation of neural substrate structures responsible for processing negative and positive emotions (Williams et al., 2010), motivation (Åberg et al., 2011), recognition of negative emotions (Gohier et al., 2014), and is associated with aggressiveness (van Dongen et al., 2018). There is a connection between COMT gene and the thickness of the cerebral cortex in associative areas of the brain (prefrontal, parietal, and cingulate), in which dopamine content is typically high (Williams et al., 2010). ...
... Research have shown that the COMT gene is associated with the activity of the brain stem, amygdala, basal ganglia and prefrontal regions, and also is involved in the modulation of neural substrate structures responsible for processing negative and positive emotions (Williams et al., 2010), motivation (Åberg et al., 2011), recognition of negative emotions (Gohier et al., 2014), and is associated with aggressiveness (van Dongen et al., 2018). There is a connection between COMT gene and the thickness of the cerebral cortex in associative areas of the brain (prefrontal, parietal, and cingulate), in which dopamine content is typically high (Williams et al., 2010). As a result, carriers of the Met allele have a thicker cortical layer in these particular areas (Miranda et al., 2019). ...
Background: This study aimed to discover the association between parameters of event-related potentials (ERPs) and categorization of images of visual scenes, both emotionally-charged and neutral, in carriers of polymorphisms of the COMT, HTR2A, BDNF genes.
Methods: Electroencephalogram (EEG) and ERPs were recorded at 128 leads, with two ear referents. Images of different visual scenes were presented to the study participants sequentially on a monitor screen. The participants’ task was to examine these images and indicate what emotions (negative, neutral or positive) they elicit. Comparison of event-related potentials was carried out using unpaired Student t-test in EEGLAB toolbox.
Results: COMT. A stronger reaction, as reflected in the amplitude of the ERPs, in participants with the recessive homozygous Met/Met genotype was observed on latency around 200 ms to the stimuli, assessed as positive. Carriers of dominant homozygous Val/Val genotype had higher amplitude of 200 ms peak when assessed scene images as either neutral or negative in comparison to other genotypes. Participant with the Val/Met heterozygous genotype had higher amplitude of ERP that Met/Met group on same latency when assessed stimuli as negative.
HTR2A. Significant increase in negativity in the parietal-occipital regions revealed in the range of 350-420 ms in participants with the recessive homozygous A/A genotype when choosing any type of assessment, compared to carriers of the heterozygous genotype A/G and the dominant homozygous G/G genotype.
BDNF. Participants with Val/Val genotype categorized the visual images more thoroughly, as reflected in greater activation of the parietal-occipital zones and higher amplitude on ERP peak on 190 ms (negative assessment) and 160 ms (neutral assessment) then Val/Met carriers.
Conclusions: The COMT, HTR2A, BDNF gene polymorphisms are associated with the process of categorizing emotionally charged and neutral visual scenes, and this relationship is reflected in the ERP parameters.
... Functional magnetic resonance imaging meta-analytic data (d = 0.73) suggest that Met allele carriers tend to exhibit significant advantages in cognitive-related tasks but are disadvantaged in their performance under emotional challenge, whereas Val allele carriers show emotional resilience but are disadvantaged in cognitive tasks (19). Additionally, the Met allele has been associated with enhanced startle responses (20) and increased limbic and prefrontal activation while viewing negative emotion faces (21). In a sample of 8-to 12-year-old children, Met allele carriers were also shown to have a higher cortisol response after an acute social stressor compared with Val homozygotes, suggesting inadequacies in the stress response (22). ...
... In these exploratory analyses, however, the interactions between child genotype and parenting, child genotype and weight status and the higher order interaction predicting subsequent restrictive feeding were significant and consistent with our hypothesis regarding Met carriers. The role of the COMT gene in emotion and cognition has been well characterized (18), and previous studies have shown that the Met allele confers risk for emotional reactivity and difficulties regulating negative affect because of higher levels of dopamine in limbic and prefrontal brain regions (20)(21)(22)31). To our knowledge, these are the first data to connect individual variations in COMT genotypes in children with caregiver emotion regulation and restrictive feeding practices, but future studies that include behavioural assessments of child emotionality are needed to draw additional conclusions. ...
Background:
Restrictive feeding is implicated in pediatric obesity, and caregivers increase controlling feeding practices on the basis of higher child weight status. However, few studies have examined how child genetic and parenting characteristics together impact restrictive feeding.
Objectives:
We examined whether child body mass index (BMI) status predicts caregiver use of restrictive feeding and if this association is moderated by (i) caregiver strategies to manage their children's distress and (ii) child variations in the catechol-O-methyltransferase (COMT) gene (Val(158) Met, rs4680).
Methods:
Participants included 126 Caucasian children (50% girls) and their caregivers who were participating in a larger study in the USA. Caregivers reported on their feeding practices and responses to child distress when children were 2.5-3.5 years of age. Child anthropometric measurements were also obtained. Restrictive feeding was assessed again 1-1.5 years later. Genomic DNA was obtained from saliva samples, and COMT-rs4680 was genotyped using TaqMan® methodology.
Results:
Child BMI percentile predicted subsequent caregiver restrictive feeding for children who were Met/Met and who had caregivers reporting higher use of negative responses to child distress. For Val carriers, BMI percentile predicted restrictive feeding when caregivers were below the mean on these responses.
Conclusions:
Caregivers are at risk for use of restrictive feeding practices when their children are at higher BMI percentiles, and this association increases when caregivers use more ineffective stress regulation practices and their children are homozygous for the Met allele. Prevention programmes might focus on parenting behaviours that foster emotion regulation and consider variation in child responses to parenting.
... Importantly, these studies used tasks with negative emotional components. When positive stimuli were presented, no increase in other limbic and prefrontal activation (69) or a difference in hippocampal activation (67) was observed. It is therefore important to note that our responseinhibition task involved neutral stimuli. ...
... It is therefore important to note that our responseinhibition task involved neutral stimuli. It has been proposed that increased extracellular DA levels in Met carriers may result in enhanced neural sensitivity to negative cues (69). In line with this, several behavioral studies reported an association between mood and anxiety disorders with the Met allele (70)(71)(72)(73). ...
Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.
... More specifically, there is evidence that carriers with Met alleles of COMT gene show heightened activation in amygdala and medial prefrontal regions to negative emotional and social cues (e.g., fearful faces) (Drabant et al. 2006;Smolka et al. 2005). These dysfunctions would render such individuals more susceptible to low levels of positive parenting, resulting in hyperactive impulsivity and deleterious hostile attribution bias (Buckholtz and Meyer-Lindenberg 2008;Williams et al. 2010) that are characteristics of reactive aggression. On the other hand, the Met allele carriers also exhibit diminished activation in amygdala and medial prefrontal regions to positively valenced emotional stimuli (e.g., happy faces) (Williams et al. 2010). ...
... These dysfunctions would render such individuals more susceptible to low levels of positive parenting, resulting in hyperactive impulsivity and deleterious hostile attribution bias (Buckholtz and Meyer-Lindenberg 2008;Williams et al. 2010) that are characteristics of reactive aggression. On the other hand, the Met allele carriers also exhibit diminished activation in amygdala and medial prefrontal regions to positively valenced emotional stimuli (e.g., happy faces) (Williams et al. 2010). Thus, these carriers could be more likely to be affected by high positive parenting and decrease the tendency to experience anger and frustration; therefore, exhibiting low levels of reactive aggression. ...
To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a “for better and for worse” manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M
age
= 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.
... Although the studies reviewed differ in the samples, genetic variants, and paradigms examined, they are united by the common goal of identifying the biological intermediates that translate genetic risk into behavior. [Pezawas et al., 2005;Smolka et al., 2007;Williams et al., 2009;Thomason et al., 2010;Drabant et al., 2012;Hermann et al., 2012;Klucken et al., 2013Klucken et al., , 2014Murphy et al., 2013;Klumpers et al., 2014;Lueken et al., 2015] 15 Murphy et al., 2013] 19 13 [Garpenstrand et al., 2001;Brocke et al., 2006;Armbruster et al., 2009;Crisan et al., 2009;Lonsdorf et al., 2009Williams et al., 2009;Agren et al., 2012;Hermann et al., 2012;Klumpers et al., 2012Klumpers et al., , 2014Glotzbach-Schoon et al., 2013;Wendt et al., 2014] 6 Larson et al., 2010;Pauli et al., 2010;Hartley et al., 2012;Heitland et al., 2013;Klucken et al., 2014] STPP [Smolka et al., , 2007Drabant et al., 2006;Domschke et al., 2008;Kempton et al., 2008;Williams et al., 2010; 0 8 7 [Montag et al., 2008;Lonsdorf et al., 2009Agren et al., 2012;Klauke et al., 2012;Norrholm et al., 2013;Wendt et al., 2014] 1 [Pauli et al., 2010] DAT1 (SLC6A3) Lau et al., 2010;Soliman et al., 2010;Lonsdorf et al., 2014] 0 8 6 Hajcak et al., 2009;Lonsdorf et al., 2010;Soliman et al., 2010;M€ uhlberger et al., 2014] 2 [Torrents-Rodas et al., 2012;Lonsdorf et al., 2014] CNR1 (CB1, CNR) Initially believed to be located in DRD2, the Taq1A restriction fragment length polymorphism has since been located in ANKK1. ...
... Several studies have examined patterns of acute threat-related neural activation that are associated with a functional A/G SNP in COMT (rs4680) that results in the substitution of valine (Val) by methionine (Met) at codon 158 (the Val158Met polymorphism). Compared to the Val allele, the Met allele is associated with lower enzymatic activity and, consequently, higher dopamine levels [Mannisto and Kaakkola, 1999], and it has been characterized by greater activation in frontolimbic regions (e.g., the amygdala, hippocampus, cingulate gyrus, and dorsal and ventrolateral PFC) in response to aversive stimuli Drabant et al., 2006;Smolka et al., 2007;Williams et al., 2010;. There is also initial evidence of increased functional coupling between limbic and prefrontal regions in Met allele homozygotes [Drabant et al., 2006]. ...
The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35–50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. © 2015 Wiley Periodicals, Inc.
... Lower rates of PFC DA catabolisis following neurotransmitter release, due to a lower COMT activity, increases the overflow of synaptic DA into the extrasynaptic space where it can stimulate extrasynaptic D1-receptors, thereby stabilizing cognitive performance (Garris et al., 1993;Tunbridge et al., 2004;Winterer and Weinberger, 2004;Lapish et al., 2009). In addition, as discussed, this increase in tonic PFC activity may also dynamically increase tonic DA output in the amygdala, which in turn sensitizes emotional processing (Smolka et al., 2005;Drabant et al., 2006;Heinz and Smolka, 2006;Hashimoto et al., 2007;Smolka et al., 2007;Williams et al., 2010). ...
... For example, Met-homozygosity has been associated with an increased distractibility and reduced efficiency of task performance when a peripheral aversive stimulus is presented, demonstrating a greater attentional breadth and sensitivity to peripheral and/or subthreshold stimuli (Bishop et al., 2006). Met-homozygosity was also related to increased PFC-toamygdalar coupling, increased activation in the amygdala towards consciously processed conditioned (i.e., unmasked unpleasant pictures) and unconditioned threatening stimuli (i.e., unmasked facial expression of fear), tendency to focus on aversive stimuli (i.e., negativity bias), heightened harm avoidance, and lower novelty seeking Hashimoto et al., 2007;Heinz and Smolka, 2006;Smolka et al., 2005Smolka et al., , 2007Williams et al., 2010). This COMT-mediated sensitization of the mPFC-amygdala circuitry in response to reinforcing cues and events is also apparent in psychophysiological findings. ...
... The catechol-O-methyltransferase (COMT) gene has the SNP rs4680 which involves a valine to methionine substitution at position 158 [61]. A higher number of Met alleles has been associated with reduced dopamine catabolism and thus higher dopamine levels and increased activation reward processing regions like the basal ganglia [61,68,69]. ...
Background
Coffee and tea consumption account for most caffeine intake and 2–3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem.
Objectives
To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake.
Methodology
We conducted PubMed and Embase searches using the terms “caffeine”, “reward”, “gene”, “polymorphism”, “addiction”, “dependence” and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included.
Results
A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2–5% effect size difference in number of cups of caffeinated drink for each allele per day.
Conclusion
Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine.
... Consequently, individuals with the Met allele have shown greater prefrontal activation and activation in certain regions of the amygdala [76,77]. Williams et al. [78] found that this increased activation may be specific to negative stimuli, suggesting that individuals with the Met allele may have less resilience to negative emotional states and lower emotional control. Furthermore, the brain regions influenced by the Met allele during the processing of these unpleasant stimuli have been found to be involved in aggression [79]. ...
The aim of the study was to explore the possible vulnerability (diathesis-stress), susceptibility (differential susceptibility), or vantage (vantage sensitivity) properties of COMT gen Val158Met polymorphism to adverse and favorable parenting styles from both parents in relation to children’s reactive and proactive aggressive behavior. Within 279 eight-year-old children (125 girls and 154 boys) from Spain, reactive and proactive aggressive behavior was measured through the “Reactive and Proactive Questionnaire” (RPQ). Saliva samples were collected to genotype for the COMT Val158Met polymorphism via real-time PCR. Finally, parenting styles were assessed using the “Parenting Styles and Dimensions Questionnaire” (PSDQ). The results revealed that for boys, the Met allele was a vulnerability factor for proactive aggression in response to low-authoritative parenting from the father. For girls, it was the Val allele, the vulnerability variable to the high authoritarian style of the father, and the susceptibility factor to the authoritative style of the mother over proactive aggression. The results are discussed, considering possible sex differences. Our results indicate that the COMT Val158Met polymorphism is a biological variable that confers greater sensitivity to the environment.
... 13 In the early stages after a TBI, the expression of catecholamines (and therefore dopamine concentration) in the pre-frontal cortex often decreases, likely attributable to damage in regions of the brain that modulate and transport dopamine. 14 The pre-frontal cortex plays a critical role in the regulation of emotions, by exerting top-down control of chemical signaling and connectivity in subcortical regions such as the striatum (reward processing), amygdala (emotional processing), and cingulate cortex (emotional and behavioral processing). 15 Psychiatric disorders, such as anxiety and depression, are commonly linked to dysregulated or decreased dopamine concentrations in the pre-frontal cortex. ...
Emotional distress is a common, but poorly addressed, feature of moderate-severe traumatic brain injury (TBI). Previously identified sociodemographic, psychological, and injury-related factors account for only a small proportion of the variability in emotional distress post-TBI. Genetic factors may help to further understand emotional distress in this population. The catechol-O-methyltransferase (COMT) Val158 and brain-derived neurotrophic factor (BDNF) 66Met single-nucleotide polymorphisms (SNPs) have been identified as possible contributory factors to outcomes after TBI. We investigated whether the COMT Val158 and BDNF 66Met SNPs were associated with emotional distress 1 year after moderate-severe TBI, and whether these associations were moderated by age, sex, and TBI severity (as measured by the duration of post-traumatic amnesia [PTA]). Moderate-severe TBI survivors (COMT, n = 391; BDNF, n = 311) provided saliva samples after admission to a TBI rehabilitation hospital. At a follow-up interview ∼1 year after injury, participants completed a self-report measure of emotional distress (Hospital Anxiety and Depression Scale; HADS). Multiple linear regression models were constructed for each SNP to predict total scores on the HADS. Neither COMT Val158 nor BDNF 66Met carriage status (carrier vs. non-carrier) significantly predicted emotional distress (COMT, p = 0.49; BDNF, p = 0.66). Interactions of SNP × age (COMT, p = 0.90; BDNF, p = 0.93), SNP × sex (COMT, p = 0.09; BDNF, p = 0.60), SNP × injury severity (COMT, p = 0.53; BDNF, p = 0.87), and SNP × sex × age (COMT, p = 0.08; BDNF, p = 0.76) were also non-significant. Our null findings suggest that COMT Val158 and BDNF 66Met SNPs do not aid the prediction of emotional distress 1 year after moderate-severe TBI, neither in isolation nor in interaction with age, sex and injury severity. The reporting of null findings such as ours is important to avoid publication bias and prompt researchers to consider the challenges of single-gene candidate studies in understanding post-TBI outcomes. Analyses in larger samples that incorporate multiple genetic factors and their relevant moderating factors may provide a greater understanding of the role of genetics in post-TBI emotional distress.
... Evidence from both human and animal studies demonstrates that COMT genotype influences aspects of emotional processing. Neuroimaging studies demonstrate consistent associations between the COMT Val 158 Met polymorphism and brain activation (determined using fMRI) during emotional processing: the Met 158 allele is associated with greater limbic brain activation (including hippocampus, amygdala and PFC) in response to negatively valanced stimuli (Drabant et al., 2006;Mier et al., 2010;Rasch et al., 2010;Smolka, 2005;Smolka et al., 2007;Williams et al., 2010; although see Kempton et al., 2009, who found greater limbic activation in Val 158 vs Met 158 homozygotes). Caution should be exercised when extrapolating simple differences in fMRI signal to underlying psychological processes; nevertheless, these findings are broadly consistent with a model in which the Met 158 allele confers greater attention and/or sensitivity to negative emotional information, compared to the Val 158 allele. ...
Background:
Catechol-O-methyltransferase (COMT) regulates cortical dopaminergic transmission and prefrontal-dependent cognitive function. However, its role in other cognitive processes, including emotional processing, is relatively unexplored. We therefore investigated the separate and interactive influences of COMT inhibition and Val158Met (rs4680) genotype on performance on an emotional test battery.
Methods:
We recruited 74 healthy men homozygous for the functional COMT Val158Met polymorphism. Volunteers were administered either a single 200 mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a double-blind, randomised manner. Emotional processing was assessed using the emotional test battery, and mood was rated using visual analogue scales and the Profile of Mood States (POMS) questionnaire across the test day.
Results:
There were no main or interactive effects of Val158Met genotype or tolcapone on any of the emotional processing measures or mood ratings.
Conclusions:
Our findings suggest that, at least in healthy adult men, COMT has little or no effect on emotional processing or mood. These findings contrast with several neuroimaging studies that suggest that COMT modulates neural activity during emotional processing. Thus, further studies are required to understand how COMT impacts on the relationship between behavioural output and neural activity during emotional processing. Nevertheless, our data suggest that novel COMT inhibitors under development for treating cognitive dysfunction are unlikely to have acute off target effects on emotional behaviours.
... This was partially in line with previous work that has demonstrated that the low-activity Met alleles of COMT gene were more susceptible to the adverse or supportive environments (Laucht et al., 2012;Thompson et al., 2012;Zhang et al., 2016). Evidence has been provided that Met carriers showed more engagement bias (Gong et al., 2013) and increased activation in the amygdala as well as medial prefrontal regions to negative emotional stimuli (Drabant et al., 2006;Williams et al., 2010); these predispositions to emotional dysregulation would cause Met carriers more likely to be influenced by social exclusion and then exhibit high levels of aggression. This is consistent with the notion of the "aggression cascade" model, which indicates that the occurrence of aggression is associated with gene, environment, and epigenetic interaction involved with induced neuronal deficit and fluctuant neurotransmission (see Cupaioli et al., 2020 for a review). ...
Accumulating research has identified the interactive effects of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who (Val vs. Met carriers) are more affected by environmental conditions and has been challenged for the low power of analyses on gene–environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism (between-group variable) impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions (exclusion vs. inclusion, within-group variable) in a sample of 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene–environment interaction using a mixed design.
... Moreover, Val homozygotes were more altruistic, empathetic, and cooperative than Met homozygotes (146). On the other hand, regarding SC, it has been suggested that Met allele confers more intensive emotional processing, with more anxiety and sensitive behavior in response to aversive stimuli, as well as habitually experienced more negative affect and negative attentional bias (146)(147)(148)(149). However, to date the effect of the COMT gene on SC has not been sufficiently investigated in SSD and in ASD. ...
Schizophrenia and autism spectra disorders are currently conceptualized as distinct clinical categories. However, the relationship between these two nosological entities has been revisited in recent years due to the evidence that they share some important clinical and neurobiological features, putting into question the nature and the extent of their commonalities and differences. In this respect, some core symptoms that are present in both disorders, such as social cognitive deficits, could be a primary target of investigation. This review briefly summarizes the commonalities and overlapping features between schizophrenia and autism spectra disorders in social cognitive functions, considering this construct in a Research Domain Criteria perspective. The clinical manifestation of deficits in social cognition are similar in schizophrenia spectrum disorders and autism spectrum disorders, and brain areas that appear to be altered in relation to these impairments are largely shared; however, the results of various studies suggest that, in some cases, the qualitative nature of these alterations may be different in the two spectra. Moreover, relevant differences could be present at the level of brain networks and connections. More research is required in this field, regarding molecular and genetic aspects of both spectra, to better define the neurobiological mechanisms involved in social cognition deficits, with the objective of developing specific and targeted treatments.
... The catechol-o-methyltransferase gene COMT is associated with the activity of the striopallid system and prefrontal areas [10] at the functional level, with aggressiveness [11], motivation [12], the success of the recognition of negative emotions [13] -on the psychological level. ...
This article is a review of modern research on the relationship of genes of neurotransmitter, hormonal and neurotrophic systems of the brain with the work of perceptual and emotional systems of a person. The role of the BDNF, COMT, DRD2, HTR2A and other genes in the processes of visual recognition of words, virtual navigation, social perception, as well as in the implementation of other cognitive, emotional processes and executive functions, is discussed. The prospects of using the accumulated scientific data to study the characteristics of the visual perception of emotionally charged Internet-content with various informational orientations are discussed.
... The impact of COMT Val158Met on amygdalar reactivity has been less studied and has produced conflicting results. An increased amygdalar reactivity has been described for ValVal homozygotes (Domschke et al., 2012), as well as for MetMet homozygotes (Lonsdorf et al., 2011;Surguladze et al., 2012;Williams et al., 2010). Overall, S allele carrier and MetMet genotypes have been proposed to be more sensitive to biologically and socially significant information, which is critical for social interaction and emotional functioning (Lonsdorf et al., 2011). ...
Facial emotion recognition (FER) has been described to be impaired in borderline personality disorder (BPD), especially for neutral faces. Genetic modulation of FER has been studied in healthy individuals and some psychiatric conditions, but no genetic association studies have been conducted in BPD hitherto. The main objective of our study was to explore the influence of the serotonin-transporter-linked promoter region (5HTTLPR) and catechol-o-methyltransferase (COMT) Val158Met on facial emotion processing among BPD patients. To that end, seventy-six BPD outpatients were asked to complete a computer-based facial affect recognition task, representing four emotions (neutral, happy, fearful or angry). Accuracy of FER and perceptual biases were calculated. The 5HTTLPR and COMT Val158Met polymorphisms were genotyped using saliva samples. Individuals with the high-activity serotonin-transporter genotype and those with the low-activity COMT genotype had significantly more difficulties identifying neutral faces; the former showed stronger bias to perceive neutral faces as happy, and the latter, neutral faces as fearful. Interestingly, the perceptual biases observed in our patients are similar to previous reports in healthy individuals. The authors propose that the ability to accurately recognize neutral faces might be a possible endophenotype of BPD. Sex-genotype interactions were also observed in relation to angry faces and 5HTTLPR, and neutral faces and COMT Val158Met polymorphisms, in line with sex-related differences previously described for both polymorphisms in relation to FER and other cognitive and behavioral outcomes. The impact of inaccurate FER on psychosocial functioning and potential interventions are also discussed.
... Moreover, the PO and NB findings were not significantly different between the MS and NMO groups. Although NB is associated with depression, anxiety, and stress, [47] the measure did not differ between the MS and NMO groups despite significant differences in the levels of depression and anxiety. These findings suggest that although the objective measures of psychiatric disturbances are similar in patients with MS and NMO, those with MS report more subjective distress. ...
Although both multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases, their psychiatric disturbances may differ given differences in the neurological manifestations. We used subjective and objective measurements to compare the psychiatric disturbances in patients with MS and NMO.
Psychiatric disturbances were assessed in 24 MS and 35 NMO patients using the Beck Hopelessness Scale, Symptom Checklist-95 and the brief version of World Health Organization Quality of Life. Personality was assessed using the Big Five Inventory-10. Disease-related function was assessed using the Fatigue Severity Scale, Short-Form McGill Pain Questionnaire, and the Global Assessment of Function. Positivity offset (PO) and negativity bias (NB) and heart rate variability (HRV) were measured using a modified implicit affect test and photoplethysmograph, respectively. Data were analyzed using analysis of covariance with age and sex as covariates.
MS patients had higher levels of depression, anxiety, panic attacks, obsessive–compulsiveness, aggression, paranoia, interpersonal sensitivity, self-regulation problems, stress vulnerability, and lower psychological quality of life (QOL) compared with NMO patients. The PO and NB and HRV values were not significantly different between groups. However, NMO patients had lower QOL, and higher levels of hopelessness, suicidality, and fatigue than the normal range. Disease duration was associated with hopelessness in NMO patients and with several psychiatric disturbances, but not hopelessness, in MS patients.
Subjective psychiatric disturbances were more severe in patients with MS than in those with NMO, whereas PO and NB and HRV in patients with NMO were comparable with those of MS patients. Our findings highlight the need for different clinical approaches to assess and treat psychiatric disturbances in patients with MS and NMO.
... In the work of Williams and co-workers (Williams et al., 2010) the effect of the polymorphism Valte8/158 Met of catecholo-methyltransferase of the COMT gene (that is involved in dopamine and norepi-nephrine catabolism) on the emotional function of the brain and on the predisposition to recognise negative emotions in the expressions of happiness and fear. According to fMRI data, the presence of Met allele of COMT gene is associated with an increased activation of the brain stem, amygdala, basal ganglia and medial prefrontal areas during recognition of fear and with a reduced activation of these areas during recognition of happiness. ...
The article is an overview of modern studies of brain organization and genetic correlates of emotional intelligence. Emotional intelligence is becoming the subject of more and more attentive study of psychologists due to the fact that it influences the mental development of humans, plays an important role in many professions, and its impairment is a marker of some disorders. Nevertheless, the brain organization and genetic correlates of emotional intelligence have not been studied enough – first studies appeared only in the early 2000s. A review of the literature on the enceph-alographic showed that in rest, people with higher emotional intelligence show greater excitation of the left anterior regions of the brain. When per-ceiving affective stimuli, participants with high emotional intelligence show stronger synchronization of some EEG rhythms. Brain mapping technique made it possible to identify the areas of the brain involved in activities related to emotional intelligence. In regard to genetic correlates of emotional intelligence, some genes of neurotransmitter systems have been associated to this trait: the catechol-O-methyltransferase gene COMT, the dopamine DRD2 receptor gene, the serotonin receptor gene HTR2A, and the BDNF brain neurotrophic factor gene.
... Chen et al., 2004;Lachman et al., 1996). So far, studies indicated that the two functional polymorphisms are related to emotional processing ( Fisher et al., 2015;Montag et al., 2008;Viddal et al., 2017;Williams et al., 2010) and depressive symptoms ( Karg et al., 2011). Therefore, we examined the associations of 5-HTTLPR and COMT Val158Met polymorphisms with alexithymia. ...
... 18 Importantly, neuroimaging studies in adults show that these behavioral patterns relate to alterations in underlying emotional brain systems. 19 The amygdala is central to emotion-processing neural circuitry and is considered to be critical for detecting ambiguity and emotional salience of cues. 20,21 Disruptions in amygdala structure and function play a central role in PTSD and other emotion-related disorders. ...
1 Background
Pediatric cancer is a life‐changing, stressful experience for children and their families. Although most children adjust well, psychologically, a significant subset report posttraumatic stress symptoms (PTSS), with nearly 75% reexperiencing traumatic parts of cancer and/or its treatment. However, little research has examined the effects of pediatric cancer and related PTSS on emotional processing, and on functional properties of key emotional centers in the brain (e.g., amygdala).
2 Procedure
We examined cancer‐related PTSS, behavioral responses during an emotion‐processing task, and resting‐state functional connectivity of the amygdala in 17 pediatric cancer survivors (ages 6–11) and 17 age‐ and sex‐matched controls.
3 Results
Cancer survivors, relative to controls, were more likely to rate ambiguous (i.e., neutral) faces as negative (i.e., “negativity bias”). Higher reexperiencing PTSS was associated with faster responses to neutral faces. Although there were no group differences in amygdala centrality, within survivors, both higher reexperiencing PTSS and faster reaction times were associated with increased centrality of the amygdala—a functional property associated with hubs of information processing in the brain. In an exploratory mediation analysis, we found that amygdala centrality mediated the link between reaction time and PTSS, suggesting that changes in the brain may be a proximal marker of the expression of emotion‐related symptomology.
4 Conclusions
Negativity bias in cancer survivors may reflect their stressful experiences with cancer and/or its treatment. This negativity bias may represent a susceptibility to changes in emotion‐related brain functioning, which may, in turn, lead to PTSS.
... For example, the Met allele of the COMT gene is associated with the negative bias in affective processing, including decreased resilience in response to negative mood states and increased anxiety levels and limbic reactivity (e.g. amygdala) in response to unpleasant stimuli (Ohara et al., 1998;Enoch et al., 2003;Schupp et al., 2003;McGrath et al., 2004;Smolka et al., 2005;Drabant et al., 2006;Kia-Keating et al., 2007;Olsson et al., 2007;Montag et al., 2008;Williams et al., 2010; for a review, see Heinz and Smolka, 2006). Similarly, genetic variations of the monoamine oxidase gene (MAOA and MAOB) are key candidates in studies concerning the mechanisms of negative emotionality (Dlugos et al., 2009) and psychiatric disorders [e.g. ...
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association (GWA) data and the gene-based principal components regression (PCReg) method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making.
... The BRISC is also inversely correlated with physiological and brain imaging measures of negative emotionality (Williams et al., 2009). Negativity bias (20 items) is conceptualized as hypersensitivity to stress and the expectation of negative outcomes (Williams et al., 2009(Williams et al., , 2010. Emotional resilience (14 items) is defined as the capacity for self-efficacy that may offset risk for poor emotional health and facilitate good functioning. ...
Previous studies have established that personality traits related to emotionality are moderately heritable. However, the relative heritability of the strategies people use to regulate emotions is unknown. The present study compared the magnitude of additive genetic, shared environmental, and nonshared environmental influences on 2 commonly used emotion regulation strategies: cognitive reappraisal and expressive suppression. In 743 twin pairs (1,486 twins), we replicated previous estimates of heritability of neuroticism (a2 = .41). Furthermore, cognitive reappraisal was significantly less heritable and more influenced by nonshared environment (a2 = .20; e2 = .80) than either neuroticism or suppression (a2 = .35; e2 = .65), another emotion regulation strategy. Finally, Cholesky decomposition modeling suggested that while there were common genetic and environmental influences on neuroticism, reappraisal and suppression, there were also significant nonshared environmental influences common between reappraisal and adaptive emotional functioning after controlling for neuroticism and suppression. These findings highlight that different aspects of emotional processing, even the use of different emotion regulation strategies, are differentially heritable. The importance of the nonshared environmental influences specific to reappraisal and adaptive emotional functioning speaks to the potential impact of social context, social partners, and psychosocial interventions on reappraisal habits. (PsycINFO Database Record
... The Met/Met genotype is associated with a peak level of the Inverted-U-shape curve of dopamine transmission in the PFC. Considering human emotion processing, the Met allele promotes increased reactivity to negative stimulus in the PFC and limbic system (Drabant et al., 2006;Smolka et al., 2005;Williams et al., 2010), and foment stronger responses to losses in the ventral striatum (Schmack et al., 2008). The Met allele alters exploratory behavior, thereby making emotion-processing less flexible, which in turn incurs changes in sensitivity to rewards and punishments, and also in the learning process of outcomes probability altering the parameters of decisionmaking (Bilder et al., 2004). ...
The biological underpinnings of sex-related differences in decision-making are still under-explored. The COMT gene is related to sexual dimorphism and with different choices made under uncertainty, albeit no study has specifically investigated a moderation effect of sex on the association between the COMT gene and the performance on decision-making paradigms. In this study, we investigated the influence of the COMT Val¹⁵⁸Met polymorphism on Iowa Gambling Task (IGT) performance depending on sex in a healthy adult sample. Participants were 192 healthy adults (84 men and 108 women). The first 40 choices in the IGT were considered decisions under ambiguity and the last 60 choices decisions under risk. To test our moderation hypothesis we used a separate regressions approach. The results revealed a sex-dependent effect of COMT Val158Met polymorphism on decision-making as measured by the IGT. Val/Val women showed the best performance in the last trials of the IGT. Therefore, the COMT Val158Met polymorphism may be considered a genetic marker underlying sex differences in decision-making.
... Similar inconsistencies have been observed in the frontal cortices (Scharinger et al. 2010). COMT Met-allele carriers have shown decreased activity in the ACC relative to Val-allele homozygotes (Smolka et al. 2007;Williams et al. 2010); the reverse has also been found (Pomarol-Clotet et al. 2010). Moreover, Val-carrier status has been associated with both increased (Bishop, Cohen, Fossella, Casey, and Farah 2006;Pomarol-Clotet et al. 2010) and decreased OFC activity (Dreher, Kohn, Kolachana, Weinberger, and ...
Given evidence that major depressive disorder (MDD) is highly heritable, there has been considerable interest in examining potential associations between genotype and brain function and structure in this disorder. This chapter reviews the current state of neuroimaging genetics and depression, discussing findings concerning associations of single genes (the serotonin transporter gene [5-HTT], catechol-O-methyltransferase [COMT], and brain-derived neurotrophic factor [BDNF]), gene interactions (gene-gene and gene-environment), and polygenic burden with brain structure and function in MDD. Growing evidence indicates that specific gene-gene and gene-environment interactions may be associated with aberrant neural structure and function in MDD. In this context, investigators have begun to examine interactions between 5-HTT and COMT, 5-HTT and BDNF, 5-HTT and early life stress, and BDNF and early life stress, in addition to polygenic burden, typically assessed in genome-wide association studies. Analyses of these interactions suggest that they have the potential to yield critical insights into the pathophysiology of MDD.
... In particular, Met homozygotes show higher DA levels relative to Val homozygotes leading to poorer emotion regulation abilities (e.g., Mier et al., 2010). For instance, carriers of COMT Met allele show increased activity in the amygdala and prefrontal regions for negative stimuli alone (Williams et al., 2010). A meta-analysis by Mier et al. (2010) highlighted a robust effect of COMT on prefrontal activity, with Val carriers showing reduced performance on cognitive tasks, while Met carriers reduced performance on emotion tasks. ...
Better memory for positive information compared to negative and neutral information has been repeatedly associated with successful aging. The main psychological explanations for this so-called “positivity effect” in memory principally rely on emotional, motivational, and cognitive mechanisms that make older adults' cognition highly sensitive to positive information according to ultimate goals of well-being. However, emerging evidence also delineates a genetic profile for positivity effects in memory, which may render some older adults more prone than others to encoding and remembering positive memories. First, we present a brief overview of behavioral and neuroimaging studies about the positivity effect in aging. Subsequently, we report studies on candidate genes associated with positive memories. In particular, we review work to date on several candidate genes that are sensitive to stimulus valence such as ADRA2B, COMT, and 5HTTLPR. Finally, we propose that the future approach to the study of genetic correlates of positivity effects in memory should also include mitochondrial functioning (TOMM40). Altogether, the study of genetics and cell biology of positivity effects in memory can help us to reveal the underlying bottom-up pathways to positive affect in healthy aging.
... An event-related potential study (Herrmann et al., 2009) found that the Met/Met genotype manifests enhanced sensory encoding of affective stimuli, which is reflected by increased posterior negativity amplitudes (Schupp et al., 2003), during the processing of unpleasant stimuli. Neuroimaging studies demonstrated that the Met allele carriers have stronger reactivity to negative stimuli (pictures or facial expressions) in the prefrontal cortex and limbic system than the Val allele carriers (Drabant et al., 2006;Smolka et al., 2005;Williams et al., 2010); they also show stronger responses in the ventral striatum to losses, although not to gains, in a monetary incentive delay task (Schmack et al., 2008). ...
Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
... In summary, these findings imply that fronto-striatal regions may play a modulatory role in aversive learning, potentially reflected in learning-related changes of cognitive processes such as attention, anticipation, working memory. Previous work partly supports this notion: During viewing of aversive stimuli, as well as during emotional memory tasks, Met carriers tend to show heightened amygdala and hippocampal activation compared to Non-Met carriers (Drabant et al., 2006;Smolka et al., 2007;Smolka et al., 2005;Williams et al., 2010). In terms of autonomic engagement, Met carriers show enhanced startle potentiation during passive viewing of aversive stimuli (Montag et al., 2008). ...
The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (SNP) alters metabolic activity of the COMT enzyme regulating catecholamines, with the Val (valine) allele resulting in 40% greater enzymatic activity than the Met (methionine) allele. Previous research has identified systematic inter-individual differences in cognitive and behavioral phenotypes related to this polymorphism, often attributed to the fact that extracellular dopamine in the prefrontal cortex is strongly affected by the COMT enzyme. The neurophysiological mechanisms mediating these inter-individual differences in specific brain systems and task contexts remain to be established however. In the current study, we examined the extent to which physio-mechanistic differences by COMT genotype affect somato-visceral and visual cortical responses to learned threat cues. Classical aversive differential conditioning was implemented using rapidly phase-reversing grating stimuli, previously shown to engage retinotopic visual cortex. Differential response patterns in sensory and autonomic systems were elicited by pairing one grating (CS+, conditioned stimulus), but not the other (CS-), with a noxious stimulus. Dense-array electroencephalography and somato-visceral measures of defensive reactivity were recorded in addition to self-report data. Individuals of the Val/Val genotype, compared to Met allele carriers, reliably showed greater initial enhancement in their visuocortical response to the CS+, accompanied by stronger defensive engagement, indexed by heart rate acceleration and startle potentiation. The finding that COMT polymorphism status affects threat cue reactivity at the visuocortical level is consistent with the notion that sensory processing of threat is facilitated by strong re-entrant bias signals from anterior areas, including the prefrontal cortex.
... Biological correlates of negativity bias have been identified. Negativity bias is associated with greater autonomic reactivity and early neural excitation to signals of danger, heightened startle amplitude and heart rate responses to fear conditions (Gordon, Barnett, Cooper, Tran, & Williams, 2008;Williams et al., 2010;Williams et al., 2009). Correlates of negativity bias include high activation of brainstem, amygdala, ACC, and ventral and dorsal medial prefrontal cortex to conscious and nonconscious fear probes and differences in electrical brain measures of working memory and EEG theta power (Gordon et al., 2008;Williams et al., 2009). ...
The recent increase in the aging population, specifically in the United States, has raised concerns regarding treatment for mental illness among older adults. Late-life depression (LLD) is a complex condition that has become widespread among the aging population. Despite the availability of behavioral interventions and psychotherapies, few depressed older adults actually receive treatment. In this paper we review the research on refining treatments for LLD. We first identify evidence-based treatments (EBTs) for LLD and the problems associated with efficacy and dissemination, then review approaches to conceptualizing mental illness, specifically concepts related to brain plasticity and the Research Domain Criteria (RDoc). Finally, we introduce ENGAGE as a streamlined treatment for LLD and discuss implications for future research.
The objective of our study was to investigate the attributes of the cognitive, affective, and value-semantic domains, along with genetic predictors, that influence the digital behavior of young individuals. The study involved 91 people (33 males and 58 females) aged 18 to 25 years (Russian Federation). In order to measure digital behavior the questioner “Strategies of informational behavior” (SIP) was used. In order to study the cognitive, affective and value-semantic characteristics, the following tests were used: the Test of Life-Sense Orientations, the Buss-Durkee Hostility Inventory, the Gottschaldt Figures Test (a measure of embedded figures perception), and a method for assessing thinking style. Genotyping was use to examine polymorphisms of the COMT, DRD2, and BDNF genes. Our findings demonstrate statistically significant associations between constructive and destructive digital behaviors and specific facets of the participants’ cognitive, affective, and value-semantic domains, as well as distinct aspects of dopaminergic system functionality.
Previous studies have demonstrated that sleep deprivation results in a negativity bias, especially in the context of impaired response inhibition. In the present study we investigated spontaneous eye blink rate (EBR), a correlate of dopamine function, as a mediator of the relationship between subjective sleepiness and impulsivity toward negative stimuli on a Go/NoGo task. Participants rated their sleepiness on a number of measures including the Epworth Sleepiness Scale (ESS), the Karolinska Sleepiness Scale (KSS) and subscales of the Chronic Sleep Reduction Questionnaire (CSRQ). The findings revealed that EBR mediated the relationship between sleepiness as measured by the Karolinska Sleepiness Scale (KSS) and commission errors on negatively valanced stimuli. These findings suggest that reduced inhibition in responding to negative stimuli can be found as a function of subjective sleepiness and that changes in dopamine function may be one contributing factor explaining this relationship.
The aim of this systematic review was to qualitatively synthesise the available research that investigated the influence of COMT genotype at SNP rs4680 on both task‐based and resting‐state connectivity in healthy adults. Thirty‐five studies were identified that met inclusion criteria. Of the included studies, 20 studies reported resting‐state findings and 16 studies reported task‐based findings (emotion processing, memory, working memory, reward‐based learning, and executive function). Studies were highly heterogeneous but an overall trend towards an association of the Val allele with greater resting‐state connectivity and the Met allele with greater task‐based connectivity is reported. A possible interpretation of current findings is discussed, whereby the Val allele is associated with improved cognitive flexibility allowing integration of novel relevant stimuli, and the Met allele allows improved sustained attention and targeted neural processing, particularly between limbic regions and prefrontal cortex. The most promising brain regions implicated in a COMT genotype influence on functional connectivity include prefrontal regions, amygdala and hippocampus.
Resilience refers to the process of adaptive recovery following adversity or trauma. It is likely to include an intertwined series of dynamic interactions between neural, developmental, environmental, genetic, and epigenetic factors over time. Neuroscientific research suggests the potential role of the brain’s threat and reward systems, as well as executive control networks. Developmental research provides insight into how the environment may affect these neural systems across the lifespan towards greater risk or resilience to stress. Genetic work has revealed numerous targets that alter key neurochemical systems in the brain to influence mental health. Current challenges include ambiguities in the definition and measurement of resilience and a simplified focus on resilience as the absence of psychopathology, irrespective of levels of positive mental functioning. Greater emphasis on understanding the protective aspects of resilience and related well-being outcomes are important to delineate the unique neurobiological factors that underpin this process, so that effective interventions can be developed to assist vulnerable populations and resilience promotion.
Association between COMT Val158Met polymorphism and depression
LIU Didi; WANG Meiping; CHEN Pian; ZHANG Wenxin
( School of Psychology, Shandong Normal University, Jinan 250014, China )
Abstract: The development of depression has important genetic underpinnings. COMT (catechol-O-
methyltransferase) Val158Met polymorphism is an important candidate gene locus for depression. At
present, the studies associated with the relationship between COMT Val158Met polymorphism and
depression mainly adopt single gene design, single gene-environment design and multiple gene-environment
design. The researches have demonstrated that negativity bias and its related brain mechanism may play an
intermediary role between COMT Val158Met polymorphism and depression. However, the mechanism
underlying is still not clear and need to be explored. Future research should focus on issues as the
moderation effect of participants’ ethnicity, gender and age on the association between COMT Val158Met
polymorphism and depression, and further investigate the role of negativity bias and the neuralbiological
mechanisms between COMT Val158Met polymorphism and depression by using multiple gene-environment
design and comprehensively using positive and negative environmental factors.
Key words: COMT gene; depression; negativity bias; brain mechanism; Val158Met polymorphism
Mood disorders are a group of diagnoses in which there is a disturbance in an individual’s mood and include major depressive disorder and bipolar disorder. Individuals who serve in the military may be prone to depression and other mood disorders, at least partially as a result of exposure to combat, separation from family during deployment or training, and other traumatic factors. Veterans are more likely to develop a mood disorder than their civilian counterparts, despite having several protective factors associated with military service. Special considerations are warranted for subpopulations of veterans, such as veteran women and older adult veterans. This chapter highlights the prevalence of mood disorders in veterans, common symptoms and specific diagnostic criteria related to each disorder, history of mood disorders within military and veteran cultures and care systems, etiologies of mood disorders, treatment options found within military and Veterans Administration health-care systems, and cutting-edge advancements in mood disorders research.
Although the genetic risk component for major depressive disorder (MDD) is considered to be substantial, genes do not directly encode for psychiatric symptoms. Therefore, intermediate phenotypes of neuroanatomical nature in MDD have been detected by imaging techniques. In order to evaluate the impact of genetic variation on behavior-related psychiatric symptoms, imaging genetics has been applied in various psychiatric disorders. Numerous studies have used magnetic resonance imaging to measure gray matter (GM) structure, white matter (WM) integrity and density, and functional metabolic activity patterns. This paper provides a comprehensive review of currently existing imaging genetics studies on MDD susceptibility gene polymorphisms (BDNF rs6265 (Val66Met), COMT rs4680 (Val158Met), MAOA-uVNTR, HTR1A rs6295 C(–1019)G, 5-HTTLPR, TPH2 rs4570625 (G-703T)), which have measured changes in GM structure, WM integrity, and functional abolic activity patterns of the brain.
The Val158Met catechol‐O‐methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia.
Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. The Schedule for the Assessment of Negative Symptoms, Schedule for the Assessment of Positive Symptoms, and Beck Depression Inventory were used to rate of patient symptoms.
There were 100 patients with the following genotypes: Val/Val (21), Met/Met (30), and Val/Met (49). The genotype distribution of polymorphism of Val158Met COMT did not differ between the patient and control groups. Schizophrenia carriers of the Val/Val genotype performed worse in social cognitive measures, in comparison with the other groups. No statistically significant correlations were recorded between age at schizophrenia onset and polymorphism of Val158Met COMT. There was an influence of genotype in the control group: the Met homozygotes performing better.
Schizophrenia patients homozygous for the Val allele showed significant disadvantages over patients homozygous or heterozygous for the Met allele in social cognitive processes. The COMT genotype may not, however, contribute to the age of onset of schizophrenia.
Catechol-O-methyltransferase (COMT) inactivates catecholamines, Val/Val genotype was associated to an increased amygdala (Amy) response to negative stimuli and can influence the symptoms severity and the outcome of bipolar disorder, probably mediated by the COMT polymorphism (rs4680) interaction between cortical and subcortical dopaminergic neurotransmission. The aim of this study is to explore how rs4680 and implicit emotional processing of negative emotional stimuli could interact in affecting the Amy connectivity in bipolar depression. Forty-five BD patients (34 Met carriers vs. 11 Val/Val) underwent fMRI scanning during implicit processing of fearful and angry faces. We explore the effect of rs4680 on the strength of functional connectivity from the amygdalae to whole brain. Val/Val and Met carriers significantly differed for the connectivity between Amy and dorsolateral prefrontal cortex (DLPFC) and supramarginal gyrus. Val/Val patients showed a significant positive connectivity for all of these areas, where Met carriers presented a significant negative one for the connection between DLPFC and Amy. Our findings reveal a COMT genotype-dependent difference in corticolimbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of clinical and prognostic outcome of BD. Specifically, a worse antidepressant recovery and clinical outcome previously detected in Val/Val patients could be associated to a specific increased sensitivity to negative emotional stimuli.
Since its inception, the concept of ?secondary psychopathy? has been contrasted with primary psychopathy on the grounds of neuroticism, affect instability, and anxiety. Nonetheless, while the etiology of primary psychopathy, and its various possible expressions, has received ample attention, secondary psychopathy has been largely neglected and only discussed in cluster-analytic studies. This paper seeks to fill that caveat by delineating the continuum on which secondary psychopathic individuals may be set apart and exploring potential sources of within group homogeneity and heterogeneity. While secondary psychopathic individuals share a number of etiological antecedents (attachment problems, childhood maltreatment, neurobiological dysfunctions) they can vary on different temperamental predispositions and specific types of maltreatment experienced in childhood (neglect/abuse vs. trauma/abuse, low vs. high prefrontal catecholaminergic activity), thus creating the heterogeneity observed in this group. Secondary psychopathic individuals may be situated on a continuum that spans from attentional hyposensitivity and cognitive distractibility on the far left side, associated with deficient prefrontal catecholamine activity and childhood neglect/abuse, ultimately culminating in more detached expressions of secondary psychopathy (callousness, hedonism, and low worrying), to attentional hypersensitivity and cognitive rigidity on the far right side, associated with non-optimally high levels of catecholamine activity and childhood relational trauma/abuse leading to more unstable expressions of secondary psychopathy (hostility, neuroticism, instability, and worrying).
Objectives:
Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender.
Methods:
Out of 977 retrieved articles, 21 included case-control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender-subgroups.
Results:
In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs.
Conclusions:
The results imply a complex nature of the genotype × phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes.
Existing data point to a link, within the general population, between polymorphic variants of the serotonin transporter gene (5-HTTLPR SLC6A4) and catechol-O-methyltransferase on the one hand and the processing of information related to emotional facial expressions on the other. Schizophrenia patients are characterized by a deficit in the recognition of mimicked emotional expressions, which has adverse effects on their social adaptation. With the aim of seeking the molecular mechanisms of this deficit, we have assessed the main and epistatic effects of these polymorphisms on the recognition of emotions among schizophrenia patients (n = 299) and healthy control subjects (n = 232). The 5-HTTLPR polymorphism showed a significant relationship with the recognition of emotions by patients. Homozygotes for the long allele identified facial emotions significantly better than carriers of the short allele (F = 8.00, p = 0.005). Although the recognition of emotions in the patients group correlated with negative symptoms, verbal learning, and trait anxiety, these signs did not have significant modifying influences on the association detected here. COMT was found to have no effect on the recognition of emotions either in normal subjects or in schizophrenia patients.
The aim of the study was to evaluate the association of transmembrane protein 132D (TMEM132D), catechol-O-methyltransferase (COMT), and gamma-aminobutyric acid (GABA) receptor alpha 6 subunit (GABRA6) genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic disorder (PD) and major depressive disorder (MDD).
The single nucleotide polymorphisms (SNPs) in TMEM132D, COMT, and GABRA6 were examined in patients with MDD, PD, and healthy controls. Functional magnetic resonance imaging (fMRI) was performed in patients with MDD, PD, and healthy controls.
rs4680 in COMT and rs3219151 in GABRA6 showed positive associations with PD and MDD. A dynamic fearful face was shown to the participants during fMRI scanning. In PD patients, responses in the bilateral anterior cingulate were stronger in carriers of the AA genotype of SNP rs11060369 in TMEM132D compared with carriers of the AC + CC genotype, and stronger in CT + TT genotype carriers of SNP rs3219151 in GABRA6 compared with carriers of the CC genotype. The response in the medial orbital frontal cortex was stronger in carriers of the CT + TT genotypes of SNP rs3219151 in PD. In MDD patients, the response in the right parahippocampus of carriers of the GG genotype of rs4680 in COMT was stronger than that of carriers of the AA + AG genotype.
These results suggest that TMEM132D, GABRA6, and COMT variants may increase vulnerability to panic.
Anxious patients (n = 20) and normal controls (n = 20) carried out a modified Stroop color-naming task with anxiety- and depression-related words in supraliminal and subliminal exposure conditions. Within the anxious group, patients with generalized anxiety disorder (GAD) without concurrent depression (n = 11) showed more color-naming interference for anxiety words than neutral words in comparison with patients with a combined diagnosis of GAD and depression (n = 9). Compared with controls, the GAD subgroup without concurrent depression showed slower color naming for negative than neutral words, in both supraliminal and subliminal conditions, replicating K. Mogg, B. P. Bradley, R. Williams, and A. Mathews's (1993) results. These findings provide further evidence of an anxiety-related bias for negative information in preconscious processes and highlight the importance of assessing concurrent depression.
Abnormalities of prefrontal cortical function are prominent
features of schizophrenia and have been associated with genetic risk,
suggesting that susceptibility genes for schizophrenia may impact on
the molecular mechanisms of prefrontal function. A potential
susceptibility mechanism involves regulation of prefrontal dopamine,
which modulates the response of prefrontal neurons during working
memory. We examined the relationship of a common functional
polymorphism (Val108/158 Met) in the
catechol-O-methyltransferase (COMT) gene, which accounts
for a 4-fold variation in enzyme activity and dopamine catabolism, with
both prefrontally mediated cognition and prefrontal cortical
physiology. In 175 patients with schizophrenia, 219 unaffected
siblings, and 55 controls, COMT genotype was related in allele dosage
fashion to performance on the Wisconsin Card Sorting Test of executive
cognition and explained 4% of variance (P = 0.001)
in frequency of perseverative errors. Consistent with other evidence
that dopamine enhances prefrontal neuronal function, the load of the
low-activity Met allele predicted enhanced cognitive performance. We
then examined the effect of COMT genotype on prefrontal physiology
during a working memory task in three separate subgroups
(n = 11–16) assayed with functional MRI. Met
allele load consistently predicted a more efficient physiological
response in prefrontal cortex. Finally, in a family-based association
analysis of 104 trios, we found a significant increase in transmission
of the Val allele to the schizophrenic offspring. These data suggest
that the COMT Val allele, because it increases prefrontal dopamine
catabolism, impairs prefrontal cognition and physiology, and by this
mechanism slightly increases risk for schizophrenia.
Personality psychologists from a variety of theoretical perspectives have recently concluded that personality traits can be summarized in terms of a 5-factor model. This article describes the NEO Personality Inventory (NEO–PI), a measure of these 5 factors and some of the traits that define them, and its use in clinical practice. Recent studies suggest that NEO–PI scales are reliable and valid in clinical samples as in normal samples. The use of self-report personality measures in clinical samples is discussed, and data from 117 "normal" adult men and women are presented to show links between the NEO–PI scales and psychopathology as measured by D. N. Jackson's (1989) Basic Personality Inventory and L. Morey's (1991) Personality Assessment Inventory. The authors argue that the NEO–PI may be useful to clinicians in understanding the patient, formulating a diagnosis, establishing rapport, developing insight, anticipating the course of therapy, and selecting the optimal form of treatment for the patient. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
This review evaluates evidence of attentional biases in generalized anxiety disorder (GAD) and depressive disorder from studies using modified Stroop and visual probe tasks. There appears to be fairly consistent evidence for an attentional bias for external negative cues in GAD, and for the involvement of non-conscious processes in this bias. By contrast, in clinical depression, the evidence for an attentional bias is less robust, despite depressive disorder being commonly associated with high levels of co-morbid anxiety. Where an attentional bias has been found in depressed patients, it seems to occur mainly for self-relevant negative information which is presented under conditions that allow or encourage elaborative processing. Possible explanations for this discrepant pattern of results, and their theoretical and clinical implications are discussed.
Processing affective facial expressions is an important component of interpersonal relationships. However, depressed patients show impairments in this system. The present study investigated the neural correlates of implicit processing of happy facial expressions in depression and identified regions affected by antidepressant therapy.
Two groups of subjects participated in a prospective study with functional magnetic resonance imaging (fMRI). The patients were 19 medication-free subjects (mean age, 43.2 years) with major depression, acute depressive episode, unipolar subtype. The comparison group contained 19 matched healthy volunteers (mean age, 42.8 years). Both groups underwent fMRI scans at baseline (week 0) and at 8 weeks. Following the baseline scan, the patients received treatment with fluoxetine, 20 mg daily. The fMRI task was implicit affect recognition with standard facial stimuli morphed to display varying intensities of happiness. The fMRI data were analyzed to estimate the average activation (overall capacity) and differential response to variable intensity (dynamic range) in brain systems involved in processing facial affect.
An attenuated dynamic range of response in limbic-subcortical and extrastriate visual regions was evident in the depressed patients, relative to the comparison subjects. The attenuated extrastriate cortical activation at baseline was increased following antidepressant treatment, and symptomatic improvement was associated with greater overall capacity in the hippocampal and extrastriate regions.
Impairments in the neural processing of happy facial expressions in depression were evident in the core regions of affective facial processing, which were reversed following treatment. These data complement the neural effects observed with negative affective stimuli.
Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene-environmental interactions is warranted.
The aim of the paper is to describe a standardized "Integrative Neuroscience" Platform that can be applied to elucidate brain-body mechanisms. This infrastructure includes a theoretical integration (the INTEGRATE Model). To demonstrate this infrastructure, hypotheses from the INTEGRATE Model are applied in an example investigation of the cognitive, brain and body markers of individual differences in the trait characteristic of Negativity Bias (the tendency to see oneself and one's world as negative). A sample of 270 healthy participants (18-65 years old) were grouped into equal sized matched subsets of high "Negativity Bias" and high "Positivity Bias" (n = 135 in each group). Participants were assessed using a standardized battery of psychological traits, cognition and brain and body (autonomic) activity. Greater "Negativity Bias" relative to "Positivity Bias" was characterized by greater autonomic reactivity and early neural excitation to signals of potential danger, at the timescale of Emotion (< 200 ms). Concomitantly, there was a relatively lower level of "Thinking", reflected in cognitive dimensions and associated electrical brain measures of working memory and EEG Theta power. By contrast, Negativity and Positivity Bias did not differ in levels of emotional resilience and social skills at the longer time scale of Self Regulation. This paper provides a demonstration of how an Integrative Neuroscience infrastructure can be used to elucidate the brain-body basis of trait characteristics, such as Negativity Bias, that are key indicators of risk for poor well-being and psychopathology.
One of the functions of automatic stimulus evaluation is to direct attention toward events that may have undesirable consequences for the perceiver's well-being. To test whether attentional resources are automatically directed away from an attended task to undesirable stimuli, Ss named the colors in which desirable and undesirable traits (e.g., honest, sadistic) appeared. Across 3 experiments, color-naming latencies were consistently longer for undesirable traits but did not differ within the desirable and undesirable categories. In Experiment 2, Ss also showed more incidental learning for undesirable traits, as predicted by the automatic vigilance (but not a perceptual defense) hypothesis. In Experiment 3, a diagnosticity (or base-rate) explanation of the vigilance effect was ruled out. The implications for deliberate processing in person perception and stereotyping are discussed.
Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces--suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.
MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.
In a community sample of 2,327 Caucasians, we tested the hypotheses that polymorphisms in the COMT and DRD3 genes are associated with personality traits conferring vulnerability to anxiety, depression, or alcohol misuse, or with current symptoms of these; and that the association is stronger in persons who also have been exposed to stressor experiences. To conserve resources and to allow replication, the genetic analysis was undertaken in two stages. For the COMT polymorphism, no statistically significant associations were found in the first sample of 862 persons. The remainder of the sample was therefore not analysed for that gene. For the DRD3 polymorphism, those in the first sample with at least one of the Ser⁹ alleles had significantly higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003). There was a trend, failing to meet the 1% significance criterion, for those with this genotype also to have higher depression and anxiety. The groups did not differ in alcohol use. In persons with the Ser⁹ allele who were also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reached statistical significance. We conclude that neither the COMT nor DRD3 polymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:102–107, 2000 © 2000 Wiley-Liss, Inc.
This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action ten- dencies triggered by signals that are significant due to their relevance to minimizing danger- maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a “paradox” of declining function in the “thinking” time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of “emotion” and “self regulation”. This paradox was paralleled by a greater loss of grey mat- ter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy func- tion and susceptibility to disorder (including the BDNFVal66Met, COMTVal158/108Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.
Objective:
While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity.
Measurements:
The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as "0" (not at all) to "3" (nearly every day). The PHQ-9 was completed by 6,000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients.
Results:
As PHQ-9 depression severity increased, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and health care utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-9 score > or =10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Results were similar in the primary care and obstetrics-gynecology samples.
Conclusion:
In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity. These characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.
Objective: Databases bring together diverse information in neuroimaging and psychiatry. They usually aim for both size and diversity of measures. The present article outlines the potential insights from the first entirely standardized and centralized International Brain Database.
Method: The database consists of data from over 1000 normal subjects (age range 6-70 years) and a growing number of age-matched patients with a psychiatric illness, acquired from seven laboratories (New York, Rhode Island, London, Holland, Adelaide, Melbourne and Sydney). It is an ‘integrative’ neuroimaging (electroencephalography (EEG), event-related potentials (ERP), structural and functional magnetic resonance imaging (sMRI, fMRI)), psychometric, demographic and genomic database.
Results: The most notable relationships in normal controls thus far include (i) an association between grey matter volume and EEG alpha frequency in frontal regions; (ii) a systematic reduction with age in cortical arousal (EEG power), speed of processing (ERP components) and most aspects of cognitive function, particularly for >50 years; (iii) a greater cortical arousal in female versus male subjects, but slower speed of processing; and (iv) a dissociation between speed (greater in male subjects) and accuracy/verbal processing (greater in female subjects) for psychological tasks. There is potential to explore the specificity of findings in psychiatric disorders in this international standardized database.
Conclusions: The size of this database has allowed for statistical tests of greater power than normal. The combination of size and diversity of measure has broader significance in providing a normative framework for evidence-based psychiatric research. It enables control for widespread individual differences, enhancing investigations of the sensitivity and specificity of brain findings, and the efficacy of medication in psychiatric disorders.
Traces the development of the cognitive approach to psychopathology and psy hotherapy from common-sense observations and folk wisdom, to a more sophisticated understanding of the emotional disorders, and finally to the application of rational techniques to correct the misconceptions and conceptual distortions that form the matrix of the neuroses. The importance of engaging the patient in exploration of his inner world and of obtaining a sharp delineation of specific thoughts and underlying assumptions is emphasized. (91/4 p ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Although 18% of Australians suffered a psychiatric disorder in the last 12 months, only 38% presented to health services. Of these, the vast majority (76%) consulted their general practitioner [1]. While two-thirds of those who present to primary care have significant psychological symptoms, at least 30% have psychological disorders that result in disability, long-term morbidity and/or mortality [2–4]. These disorders are often co-morbid with other medical disorders and/or substance abuse [1]. Despite the advances in pharmacological and non-pharmacological therapies available [5,6] less than half of the patients who present receive a psychiatric diagnosis and less than half of these receive any specific treatment [7]. Recommendations under the National Mental Health Strategy [8] recognise the urgent need for educational programs and practice support mechanisms to correct these major public health deficits.
OBJECTIVE: While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity.
MEASUREMENTS: The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as “0” (not at all) to “3” (nearly every day). The PHQ-9 was completed by 6,000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients.
RESULTS: As PHQ-9 depression severity increased, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and health care utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-9 score ≥10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Results were similar in the primary care and obstetrics-gynecology samples.
CONCLUSION: In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity. These characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.
There are several reported associations between depressive disorders, panic disorder, and obsessive–compulsive disorder (OCD) and a variety of polymorphisms in the monoamine oxidase A (MAOA) gene. Associations have also been reported between the catechol-O-methyltransferase (COMT) gene and both OCD and bipolar depression. However, the role of these markers has not been explored for the personality trait of neuroticism (N), a normally distributed quantitative trait, which is highly genetically correlated with anxiety and depression and may be a vulnerability to either type of disorder. We explored the possible role of MAOA, COMT, and their interaction on N using a selected extremes design. From a sample of 2,085 individuals, each assessed for N by two independent peers rather than using self-report questionnaires, we selected 57 individuals from the top 10% of scores, and 62 individuals from the bottom 10%. Using selected extreme low subjects as the controls, rather than an unselected control group gives roughly twice the power of a standard case-control design. We typed a functional variable number tandem repeat (VNTR) in the MAOA gene promoter, and a functional polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA VNTR were identified on the basis of their size, and their structure examined by sequencing analysis. We found weak evidence for association with COMT genotype, when the females and males were considered separately, and for MAOA genotype in males only. There was no significant interaction between COMT and MAOA. © 2003 Wiley-Liss, Inc.
At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.
Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression--probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.
The INTEGRATE Model draws on the framework of ‘integrative neuroscience’ to bring together brain-body and behavioral concepts of emotion, thinking and feeling and their regulation. The key organizing principle is the drive to ‘minimize danger and maximize reward’ that determines what is significant to us at each point in time. Traits of ‘negativity bias’ reflect the tendency to perceive danger rather than reward related information, and this bias influences emotion, thinking and feeling processes.