[Show abstract][Hide abstract] ABSTRACT: Experiencing an adverse childhood and parental neglect is a risk factor for depression in the adult population. Patients with a history of traumatic childhood develop a subtype of depression that is characterized by earlier onset, poor treatment response and more severe symptoms. The long-lasting molecular mechanisms that are engaged during early traumatic events and determine the risk for depression are poorly understood. In this study, we altered adult depression-like behavior in mice by applying juvenile isolation stress. We found that this behavioral phenotype was associated with a reduction in the levels of the deacetylase sirtuin1 (SIRT1) in the brain and in peripheral blood mononuclear cells. Notably, peripheral blood mRNA expression of SIRT1 predicted the extent of behavioral despair only when depression-like behavior was induced by juvenile—but not adult—stress, implicating SIRT1 in the regulation of adult behavior at early ages. Consistent with this hypothesis, pharmacological modulation of SIRT1 during juvenile age altered the depression-like behavior in naive mice. We also performed a pilot study in humans, in which the blood levels of SIRT1 correlated significantly with the severity of symptoms in major depression patients, especially in those who received less parental care during childhood. On the basis of these novel findings, we propose the involvement of SIRT1 in the long-term consequences of adverse childhood experiences.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies indicate that separation anxiety disorder occurs more frequently in adults than children. It is unclear whether the presence of adult separation anxiety disorder (ASAD) is a manifestation of anxious attachment, or a form of agoraphobia, or a specific condition with clinically significant consequences. We conducted a study to examine these questions. A sample of 141 adult outpatients with panic disorder participated in the study. Participants completed standardized measures of separation anxiety, attachment style, agoraphobia, panic disorder severity and quality of life. Patients with ASAD (49.5% of our sample) had greater panic symptom severity and more impairment in quality of life than those without separation anxiety. We found a greater rate of symptoms suggestive of anxious attachment among panic patients with ASAD compared to those without ASAD. However, the relationship between ASAD and attachment style is not strong, and adult ASAD occurs in some patients who report secure attachment style. Similarly, there is little evidence for the idea that separation anxiety disorder is a form of agoraphobia. Factor analysis shows clear differentiation of agoraphobic and separation anxiety symptoms. Our data corroborate the notion that ASAD is a distinct condition associated with impairment in quality of life and needs to be better recognized and treated in patients with panic disorder.
[Show abstract][Hide abstract] ABSTRACT: In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.
World psychiatry: official journal of the World Psychiatric Association (WPA) 10/2014; 13(3). DOI:10.1002/wps.20167 · 14.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Indirect evidence suggests partially common pathogenetic mechanisms for Neurological Soft Signs (NSS), neurocognition, and social cognition in schizophrenia. However, the possible association between NSS and mentalizing impairments has not yet been examined. In the present study, we assessed the ability to attribute mental states to others in patients with schizophrenia and predicted that the presence of theory of mind deficits would be significantly related to NSS. Participants were 90 clinically stable patients with a DSM-IV diagnosis of schizophrenia. NSS were assessed using the Neurological Evaluation Scale (NES). Theory of mind deficits were assessed using short verbal stories designed to measure false belief understanding. The findings of the study confirmed our hypothesis. Impaired sequencing of complex motor acts was the only neurological abnormality correlated with theory of mind deficits. By contrast, sensory integration, motor coordination and the NES Others subscale had no association with patients׳ ability to pass first- or second-order false belief tasks. If confirmed by future studies, the current findings provide the first preliminary evidence for the claim that specific NSS and theory of mind deficits may reflect overlapping neural substrates.
[Show abstract][Hide abstract] ABSTRACT: Social anhedonia, or the diminished capacity to experience pleasure and reward from social affiliation, is a major symptom of different psychiatric disorders, including some forms of infantile autism and schizophrenia spectrum disorders. The brain opioid hypothesis of social attachment is a promising model for achieving insights into how neurobiological and developmental factors contribute to the regulation of social reward. In this study, genetic knocking-out and naltrexone (NTRX) treatment during the first 4 days of life were used to disrupt opioid neurotransmission in mouse pups and their attachment relationships with the mother. Both permanent (genetic) and transient (pharmacological) manipulations of opioid neurotransmission exerted long-term effects on social affiliation. When juveniles, both μ-opioid receptor knockout mice and NTRX-treated pups showed reduced interest in peers and no preference for socially rewarding environment. These results demonstrate that sociability in juvenile mice is highly dependent on the establishment during infancy of a positive affective relationship with their mothers and that opioid neurotransmission has a major role in the regulation of social hedonic capacity. If the validity of this animal model will be confirmed by future research, translational studies focusing on the interaction between early experience and opioid neurotransmission could provide useful insights for identifying endophenotypes of human psychiatric disorders associated with social anhedonia.
[Show abstract][Hide abstract] ABSTRACT: The "hijacking" and "drug instrumentalization" models of psychoactive drug use predict opposite outcomes in terms of adaptive behavior and fitness benefits. Which is the range of applicability of each model? To answer this question, we need more data than those reported by studies focusing on medical, psychiatric, and legal problems in addicted users. An evolutionary analysis requires a much wider focus.
[Show abstract][Hide abstract] ABSTRACT: There is evidence that both early experience and genetic variation play a role in influencing sensitivity to social rejection. In this study, we aimed at ascertaining if the A118G polymorphism of the μ-opioid receptor gene (OPRM1) moderates the impact of early maternal care on fearful attachment, a personality trait strongly related to rejection sensitivity. In 112 psychiatric patients, early maternal care and fearful attachment were measured using the Parental Bonding Inventory and the Relationship Questionnaire (RQ), respectively. The pattern emerging from the RQ data was a crossover interaction between genotype and maternal caregiving. Participants expressing the minor 118 G allele had similar and relatively high scores on fearful attachment regardless of the quality of maternal care. By contrast, early experience made a major difference for participants carrying the A/A genotype. Those who recalled higher levels of maternal care reported the lowest levels of fearful attachment whereas those who recalled lower levels of maternal care scored highest on fearful attachment. Our data fit well with the differential susceptibility model which stipulates that plasticity genes would make some individuals more responsive than others to the negative consequences of adversity and to the benefits of environmental support and enrichment.
Social Cognitive and Affective Neuroscience 07/2011; 7(5):542-7. DOI:10.1093/scan/nsr037 · 7.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A large body of evidence links altered opioid signaling with changes in social behavior in animals. However, few studies have attempted to determine whether similar links exist in humans. Here we investigate whether a common polymorphism (A118G) in the mu-opioid receptor gene (OPRM1) is associated with alterations in personality traits linked to affiliative behavior and attachment. In a mixed sample (N = 214) of adult healthy volunteers and psychiatric patients, we analyzed the association between the A118G polymorphism of the OPRM1 and two different psychological constructs reflecting individual differences in the capacity to experience social reward. Compared to individuals expressing only the major allele (A) of the A118G polymorphism, subjects expressing the minor allele (G) had an increased tendency to become engaged in affectionate relationships, as indicated by lower scores on a self-report measure of avoidant attachment, and experienced more pleasure in social situations, as indicated by lower scores on a self-report measure of social anhedonia. The OPRM1 variation accounted for about 3.5% of the variance in the two measures. The significant association between the A118G polymorphism and social hedonic capacity was independent of the participants' mental health status. The results reported here are in agreement with the brain opioid hypothesis of social attachment and the established role of opioid transmission in mediating affiliative behavior.
Social neuroscience 02/2011; 6(1):88-97. DOI:10.1080/17470919.2010.482786 · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with physical symptoms for which no organic cause can be found are distributed along a continuum of disease simulation that ranges from a sincere belief of having a serious disease to intentional presentation of false symptoms. The evolutionary hypothesis that self-deception improves the deception of others can explain such a combination of unconscious and intentional production of physical symptoms.
[Show abstract][Hide abstract] ABSTRACT: This study examined the relationship between cholesterol levels and impulsivity in a large sample of patients with mood symptoms. Three hundred and one patients with mood, anxiety, and personality disorders completed a battery of psychometric scales including the Barratt Impulsiveness Scale-Version 11 (BIS-11) and the Profile of Mood States (POMS). On the same day of psychometric assessment, blood samples were analyzed for total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). Statistical analysis controlling for the confounding effects of age, gender, diagnosis, and current mood symptoms showed that lower TC levels were associated with increased attentional impulsivity. There was a weak linear correlation between TC and attentional impulsivity across the entire range of TC levels (110-295mg/dL) but a highly significant difference between participants with TC levels lower than 165mg/dL and the rest of the sample. The current study adds to the growing body of evidence pointing to the association between serum cholesterol and mental health. Considering that attentional impulsivity is a demonstrated risk factor for suicide, patients presenting with low cholesterol and mood symptoms may warrant increased clinical attention and surveillance.
Psychiatry Research 11/2010; 188(1):83-7. DOI:10.1016/j.psychres.2010.11.005 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies that have explored associations between attachment measures and interpersonal dispositions have found that people with avoidant attachment consistently express a preference for being alone rather than affiliating with others. These findings suggest that the lack of sociability of avoidant individuals reflects high levels of social anhedonia. We tested such a hypothesis by administering the Attachment Style Questionnaire (ASQ) and the social anhedonia subscale of the Snaith–Hamilton Pleasure Scale (SHAPS) to 163 healthy volunteers. Social anhedonia was not related to gender, age or current mood state, as measured by the Profile of Mood States (POMS). In a stepwise regression model, the confidence and the discomfort with closeness scales of the ASQ emerged as significant predictors of the SHAPS social score, indicating that higher levels of social anhedonia were associated with avoidant attachment but not with anxious attachment. These findings raise interesting questions about the causal link between avoidant attachment and social anhedonia. It is possible that the construct of avoidant attachment as measured by self-report measures includes a heterogeneous group of individuals and that some have a basic deficit in the capacity to experience social reward rather than a defensive deactivation of intimacy needs.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the frequency and clinical correlates of adult separation anxiety disorder in a large cohort of patients with mood and anxiety disorders.
Overall, 508 outpatients with anxiety and mood disorders were assessed by the structured clinical interview for diagnostic and statistical manual (IV edition) axis I disorders for principal diagnosis and comorbidity and by other appropriate instruments for separation anxiety into adulthood or childhood.
Overall, 105 subjects (20.7%) were assessed as having adult separation anxiety disorder without a history of childhood separation anxiety and 110 (21.7%) had adult separation anxiety disorder with a history of childhood separation anxiety. Adult separation anxiety was associated with severe role impairment in work and social relationships after controlling for potential confounding effect of anxiety comorbidity.
Adult separation anxiety disorder is likely to be much more common in adults than previously recognized. Research is needed to better understand the relationships of this condition with other co-occurring affective disorders.
[Show abstract][Hide abstract] ABSTRACT: Several studies have shown that physical and/or sexual abuse during childhood may lead to the development of obesity later in life. Despite these consistent findings, the mechanism for the increased risk of obesity following developmental trauma is unknown. It has been suggested that psychological dysfunction, including the presence of disordered eating behavior, may account for the added risk of adult obesity. To test this hypothesis, we analyzed the prevalence and severity of different types of early traumatic life events, assessed the presence of co-existing psychiatric disorders and measured adult attachment style in a sample of 200 subjects including non-obese healthy volunteers and obese participants undergoing a psychiatric assessment to determine suitability for bariatric surgery. Participants who scored higher on a scale measuring the severity of traumatic events experienced during the first 15years of their lives were more likely to be obese at the time of testing. The exclusion of the participants who experienced physical and/or sexual abuse did not change the results of statistical analysis. Severity of early trauma remained a significant predictor of adult obesity when the influence of psychiatric diagnosis and anxious attachment was taken into account. These findings suggest that: (1) not only sexual or physical abuse but also less severe forms of early-life stress are linked to the development of obesity later in life; and (2) psychological dysfunction is not the only mechanism mediating the elevated risk of obesity in persons exposed to early-life trauma.
[Show abstract][Hide abstract] ABSTRACT: Medication overuse headache (MOH) can be considered a clinical condition at the boundaries between drug addiction and chronic pain disorder. The common 196G > A single-nucleotide polymorphism of BDNF gene, resulting in a valine 66 to methionine (Val66Met), is related with behaviour disorders and substance abuse. With the aim of identifying a worsening factor in MOH, rather than the detection of a specific risk factor for the development of the disease, we investigated whether the presence of a functional BDNF polymorphism might determine clinical differences within a group of 90 MOH patients, particularly in monthly drug consumption, that is the hallmark of disease. Directly comparing MOH patients homozygous for G allele (G/G) with carriers of A allele (non-G/G), we have observed 47 G/G genotypes and 60 non-G/G genotypes. Non-G/G had a higher consumption of monthly drug number (Cohen's d = 0.76) than G/G patients. At multiple regression analysis, the Val66Met BDNF polymorphism emerged as a significant independent predictor of analgesic drug consumption (Beta = 0.33, Cohen's f(2) = 0.134). These findings showed an influence of examined BDNF polymorphism in the MOH clinical features, supporting the idea that MOH is a substance abuse disorder.
The Journal of Headache and Pain 06/2009; 10(5):349-55. DOI:10.1007/s10194-009-0136-0 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this article is to review the studies that have linked low cholesterol levels with psychiatric symptoms or behavioral disorders in order to clarify which cholesterol fractions may influence psychological well being and mental health. The distinction between “bad” (i.e., pro-atherogenic) and “good” (i.e., anti-atherogenic) cholesterol is crucial to decide if the clinical benefits of low cholesterol levels for cardiovascular health might turn into a risk factor for psychiatric morbidity. Although the data from studies linking low cholesterol to aggression, suicide and self-harm, impulsivity, negative mood, postnatal depression, and cognitive dysfunction are far from unequivocal, the balance of evidence from new randomized controlled trials is reassuring. However, there are some subgroups of vulnerable individuals who, unlike the majority of persons in the general population, are susceptible to the psychological and behavioral adverse outcomes associated with low cholesterol levels. Because in some cases pro-atherogenic lipid and lipoprotein fractions are involved in this vulnerability, reaching the double goal of promoting both cardiovascular and mental health may be problematic for some individuals. A major task of future research is to identify these vulnerable individuals.
[Show abstract][Hide abstract] ABSTRACT: Social cognition is a broad term, incorporating all aspects of social functioning from perceiving emotional stimuli to attributional style and theory of mind. Not distinguishing between these different capacities may confound the interpretation of the data deriving from studies of the relationship between psychiatric disorders and the social brain. The distinction between cognitive and affective components of social cognition is clearly exemplified by the abnormalities observed in psychopathy and Williams syndrome.
[Show abstract][Hide abstract] ABSTRACT: Several studies have consistently shown that patients with schizophrenia or schizophrenia spectrum disorders (SSD) can be distinguished from normal controls on the basis of their nonverbal behavior during standardized interviews, with considerable interactions between negative symptoms and poor facial expressivity. However, most studies have examined unmedicated patients, and gender of both interviewer and interviewee has not been taken into account. In this study we assessed the nonverbal behavior of male and female patients with SSD who were receiving second-generation antipsychotic medication (SGA) using the Ethological Coding System for Interviews (Troisi, 1998). In addition, we used a novel 5-factor model of the Positive and Negative Symptom Scale (PANSS, van der Gaag et al., 2006) to correlate nonverbal behavior with standard psychopathology ratings. Our findings strongly resembled results of previous studies into nonverbal behavior of patients with SSD, despite differences in cultural backgrounds and gender of the interviewer. Negative symptoms were inversely correlated with several of the nonverbal behavioral dimensions. Medication dose did not correlate with any one of the behavioral or psychopathological measures. Patients with SSD make less use of their nonverbal behavioral repertoire compared with controls, independent of antipsychotic treatment. Culture-specific nonverbal expressivity seems to play an additional (minor) role in distinguishing patients from healthy controls.
The Journal of nervous and mental disease 05/2008; 196(4):282-8. DOI:10.1097/NMD.0b013e31816a4922 · 1.69 Impact Factor