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Background: Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods: GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results: Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions: This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants. [ABSTRACT FROM AUTHOR]

Metabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of peripheral insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of neuronal insulin signaling in DNFES. To gain insight into neuronal insulin-signaling in vivo , we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting. Upstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3β, mTOR, p70S6K) revealed lower phosphorylated/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3β (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends. These findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores. [ABSTRACT FROM AUTHOR]

Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables. [ABSTRACT FROM PUBLISHER]

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight. [ABSTRACT FROM AUTHOR]

Abstract: Background: Differences in personality traits have long been acknowledged as potential risk factors in developing psychiatric disorders. Lately, several susceptibility genes of different psychiatric disorders have been linked to personality traits. This has not been done for schizophrenia yet. Neuregulin1 has been repeatedly shown to be associated with schizophrenia and is involved in numerous neurodevelopmental functions such as neuronal migration and myelination. The impact of this gene might also modulate personality traits in healthy subjects. Methods: The NRG1 status of 523 healthy subjects was determined with a single nucleotide polymorphism (SNP8NRG221533) which has been described as a tagging marker being part of the core at-risk haplotype for schizophrenia. Genotype was correlated with personality traits using the NEO-FFI questionnaire. Results: Subjects with the NRG1 risk allele scored higher on neuroticism (p <.05) and lower on conscientiousness (p <.05). Further, interactions of genotype by gender for extraversion (p <.05), openness (p <.05) and conscientiousness (p <.05) were found with men carrying the risk allele scoring the lowest. Conclusions: The data indicate that the NRG1 gene which has found to be associated with schizophrenia may also influence personality differences in healthy subjects. [Copyright &y& Elsevier]

Abstract: Background: To date, nearly all research of subtype differences in ADHD has been performed in children and only two studies, with conflicting results, have covered this subject in adults with ADHD. Objective: This study examined subtype differences in the clinical presentation of ADHD-symptoms, related psychopathological features, psychosocial functioning and comorbid psychiatric disorders in adults with ADHD. Method: One hundred and eighteen adults with ADHD, diagnosed according to DSM-IV criteria, and a population based control group underwent diagnostic evaluations with clinical interviews for ADHD, DSM-IV disorders and demographic features. Comparisons were made between ADHD combined type (n =64), predominantly inattentive type (n =30) and predominantly inattentive type, anamnestically combined type (n =24), relative to each other and to a community control group (n =70). Results: The four groups did not differ in age and gender composition. All ADHD groups had significantly less education, were significantly more often unemployed and reported significantly more lifetime psychiatric comorbidity than controls. In comparison to each other, the three ADHD groups differed mainly in core symptoms and the pattern of comorbid psychiatric disorders, whereas no prominent differences in associated psychopathological features and most of the assessed psychosocial functions could be found. Patients with ADHD combined type and inattentive, anamnestically combined type both presented with significantly more hyperactive symptoms and also showed more impulsive symptoms than those with the predominantly inattentive type. With a similar overall lifetime psychiatric comorbidity in the three groups, patients with ADHD combined type and inattentive, anamnestically combined type suffered significantly more from lifetime substance use disorders than patients with predominantly inattentive type. Conclusion: Our results clearly show impaired psychosocial adjustment and elevated risk for additional psychiatric disorders in adults with all subtypes of ADHD, compared to healthy controls. They provide preliminary evidence that in adult ADHD there might be a subgroup of patients, which is classified as predominantly inattentive subtype according to current diagnostic criteria, but which in its clinical presentation is in between ADHD combined and inattentive type. Further studies are needed to evaluate this finding and to gain a clear picture of its validity. [Copyright &y& Elsevier]

Abstract: Demographical and clinical characteristics have been reported to modulate the risk for suicide. This study analysed demographical and clinical characteristics with respect to lifetime suicide attempts in 500 individuals affected with schizophrenic or affective disorders. Suicide attempts were associated with poor premorbid social adjustment, low age at onset, low scores on the “Global Assessment Scale” and childlessness in females. [Copyright &y& Elsevier]