The other face of depression, reduced positive affect: The role of catecholamines in causation and cure

Article · August 2007with70 Reads
DOI: 10.1177/0269881106069938 · Source: PubMed
Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.
    • Preliminary evidence from the secondary outcomes in a study byPeters et al. (2017)indicated that CBM may have some effects on anhedonia. Given that anhedonia is linked with poor treatment outcomes and is currently difficult to treat (Nutt et al., 2007;Vrieze et al., 2013), investigating the cognitive and neural mechanisms underlying the observed training and behavioral effects is important for developing an understanding of the etiology of these conditions and guiding the development of more targeted interventions. Understanding the therapeutic value of CBM would require research on its dose response (Cristea, Kok, & Cuijpers, 2015 ;Hallion & Ruscio, 2011) among people with mood disorders with different neuropathological origins and in real-life settings using meaningful outcome measures (e.g., functional outcomes, quality-of-life measures).
    [Show abstract] [Hide abstract] ABSTRACT: Our perception of emotion in the faces of others affects our own behavior and mood. Indeed, individuals with mood disorders such as depression and aggression often show biases in facial-emotion perception. Here, we review recent and ongoing research suggesting that biased emotion perception may be on the causal pathway of the onset and maintenance of mood disorders, and hence a potential target for intervention. Simple cognitive-bias modification tasks that change participants’ perception of facial expressions of emotion have shown some promise as a therapeutic technique. We outline further directions for continued research investigating the robustness and clinical impact of emotion-bias modification in real-world settings.
    Full-text · Article · Jun 2017
    • Depression and social anxiety are marked by high trait negative affect (ie, the propensity to experience distressing emotions) and low trait positive affect (ie, the propensity to not experience pleasurable emotions) [4]. Not surprisingly, individuals higher in trait negative affect and lower in trait positive affect tend to experience more negative and less positive emotional states (ie, transient fluctuations in mood), as found in past research on depression and social anxiety [5,6]. One key corollary of both trait and state affect is thought to be the degree to which someone seeks out or avoids social contact and engages in activities that provide reinforcement from the environment.
    [Show abstract] [Hide abstract] ABSTRACT: Background Research in psychology demonstrates a strong link between state affect (moment-to-moment experiences of positive or negative emotionality) and trait affect (eg, relatively enduring depression and social anxiety symptoms), and a tendency to withdraw (eg, spending time at home). However, existing work is based almost exclusively on static, self-reported descriptions of emotions and behavior that limit generalizability. Despite adoption of increasingly sophisticated research designs and technology (eg, mobile sensing using a global positioning system [GPS]), little research has integrated these seemingly disparate forms of data to improve understanding of how emotional experiences in everyday life are associated with time spent at home, and whether this is influenced by depression or social anxiety symptoms. Objective We hypothesized that more time spent at home would be associated with more negative and less positive affect. Methods We recruited 72 undergraduate participants from a southeast university in the United States. We assessed depression and social anxiety symptoms using self-report instruments at baseline. An app (Sensus) installed on participants? personal mobile phones repeatedly collected in situ self-reported state affect and GPS location data for up to 2 weeks. Time spent at home was a proxy for social isolation. Results We tested separate models examining the relations between state affect and time spent at home, with levels of depression and social anxiety as moderators. Models differed only in the temporal links examined. One model focused on associations between changes in affect and time spent at home within short, 4-hour time windows. The other 3 models focused on associations between mean-level affect within a day and time spent at home (1) the same day, (2) the following day, and (3) the previous day. Overall, we obtained many of the expected main effects (although there were some null effects), in which higher social anxiety was associated with more time or greater likelihood of spending time at home, and more negative or less positive affect was linked to longer homestay. Interactions indicated that, among individuals higher in social anxiety, higher negative affect and lower positive affect within a day was associated with greater likelihood of spending time at home the following day. Conclusions Results demonstrate the feasibility and utility of modeling the relationship between affect and homestay using fine-grained GPS data. Although these findings must be replicated in a larger study and with clinical samples, they suggest that integrating repeated state affect assessments in situ with continuous GPS data can increase understanding of how actual homestay is related to affect in everyday life and to symptoms of anxiety and depression.
    Full-text · Article · Mar 2017
    • Although previous research has shown the involvement of serotoninergic genes in well-being (Chen et al., 2013; De Neve, 2011), an important advance made by this study is that we identified COMT Val158Met, a common functional polymorphism that has no direct link to the serotoninergic system, as an additional genetic contributor to well-being. Indeed, the COMT gene encodes COMT enzyme that degrades catecholamines such as dopamine and norepinephrine, while previous studies have already demonstrated the importance of dopamine and norepinephrine functions in well-being (Nutt et al., 2007; Rutledge et al., 2015) and depression (Arango et al., 1993; Cohn et al., 1970). Thus, our results provide new genetic evidence indicating the fundamental roles of catecholamines (dopamine and norepinephrine) in human well-being.
    [Show abstract] [Hide abstract] ABSTRACT: 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.
    Full-text · Article · Mar 2017
    • The application of GPC analysis to functional responses to emotional and neutral conditions provided accuracy in the range 63,5%–92%. These results are especially important if we believe that the neurobiological signature related to appetitive stimuli is related to the clinical symptom of anhedonia in depression [62,63] and that the neurobiological signature of aversion processing is related to the clinical symptom of low mood and enhanced negative information processing in depression [64]. Thus where univariate fMRI analysis has failed to decipher these signatures [29] multivariate GPC can provide more biologically meaningful descriptors which in turn may be used help classify, with a brain based approach, depression and its subtypes.
    [Show abstract] [Hide abstract] ABSTRACT: Background Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. Method 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. Results The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Conclusions Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder.
    Full-text · Article · Nov 2016
    • These results indicate that treatment of anxiety symptoms in patients with MDD may be complex, and more research may be needed to better understand how levomilnacipran ER and other medications work to alleviate these symptoms. Since NA-related symptoms (eg, retardation, lassitude, concentration difficulties) and anxiety-related symptoms (eg, tension, agitation) may negatively affect psychosocial functioning (Lin et al., 2014;Nutt et al., 2007;Stahl, 2002), analyses were conducted in 3 mutually exclusive subgroups of patients who had moderate-to-severe NA symptoms, anxiety symptoms, or both. In these subgroups, which represented approximately one-half of the pooled ITT population, the LSM differences between treatment groups and Cohen's effect sizes for SDS total and subscale score changes were larger than the results found in the overall population.
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To evaluate the effects of levomilnacipran extended-release (LVM-ER; 40-120mg/day) on noradrenergic (NA) and anxiety-related symptoms in adults with major depressive disorder (MDD) and explore the relationship between these symptoms and functional impairment. Methods: Data were pooled from 5 randomized, double-blind, placebo-controlled trials (N=2598). Anxiety and NA Cluster scores were developed by adding selected item scores from the Montgomery-Åsberg Depression Rating Scale (MADRS) and 17-item Hamilton Depression Rating Scale (HAMD17). A path analysis was conducted to estimate the direct effects of LVM-ER on functional impairment (Sheehan Disability Scale [SDS] total score) and the indirect effects through changes in NA and Anxiety Cluster scores. Results: Mean improvements from baseline in NA and Anxiety Cluster scores were significantly greater with LVM-ER versus placebo (both P<0.001), as were the response rates (≥50% score improvement): NA Cluster (44% vs 34%; odds ratio=1.56; P<0.0001); Anxiety Cluster (39% vs 36%; odds ratio=1.19; P=0.041). Mean improvement in SDS total score was also significantly greater with LVM-ER versus placebo (-7.3 vs -5.6; P<0.0001). LVM-ER had an indirect effect on change in SDS total score that was mediated more strongly through NA Cluster score change (86%) than Anxiety Cluster score change (18%); the direct effect was negligible. Limitations: NA and Anxiety Cluster scores, developed based on the face validity of individual MADRS and HAMD17 items, were not predefined as efficacy outcomes in any of the studies. Conclusion: In adults with MDD, LVM-ER indirectly improved functional impairment mainly through improvements in NA symptoms and less so via anxiety symptoms.
    Article · Nov 2016
    • That is, their guilt was ''felt in and lived through [their] bodies on a daily basis'' (295). Psychopharmacology research has linked guilt feelings with depression (Nutt et al. 2007; Torrente et al. 2012) and refers to guilt as ''introspective hostility'' (British Association for Psychopharmacology 1990, 306), thus giving a clue to its potential accumulating influence on a person's psychophysiology . Ultimately, as Sara Ahmed (2004) says, ''emotions do things'' (119; emphasis in the original), and therefore, rather than simply viewing emotions and feelings as psychological inclinations, ''we need to consider how they work, in concrete and particular ways, to mediate the relationship between the psychic and the social, and between the individual and the collective'' (119).
    [Show abstract] [Hide abstract] ABSTRACT: In this article, I discuss the presence and power of guilt in health and fitness discourses. As an intangible force, guilt has material-often negative-effects on women's lives; it is an active ingredient in gendered societal messages celebrating and moralizing an idealized fit feminine body. I invoke "the imperative pathway" to illustrate how discourses around women's exercise, health, and bodies create an impasse fraught with guilt feelings: complex social forces impose a nexus of competing responsibilities and expectations, even while bodies impose physical limitations. Ultimately, I question the ethical sensitivity of health and fitness promoters who induce guilt feelings.
    Full-text · Article · Sep 2016 · Journal of Affective Disorders
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