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MOTIVATION:Polygenic risk score (PRS) methods based on genome-wide association studies (GWAS) have a potential for predicting the risk of developing complex diseases and are expected to become more accurate with larger training datasets and innovative statistical methods. The area under the ROC curve (AUC) is often used to evaluate the performance of PRSs, which requires individual genotypic and phenotypic data in an independent GWAS validation dataset. We are motivated to develop methods for approximating AUC of PRSs based on the summary level data of the validation dataset, which will greatly facilitate the development of PRS models for complex diseases. RESULTS:We develop statistical methods and an R package SummaryAUC for approximating the AUC and its variance of a PRS when only the summary level data of the validation dataset are available. SummaryAUC can be applied to PRSs with SNPs either genotyped or imputed in the validation dataset. We examined the performance of SummaryAUC using a large-scale GWAS of schizophrenia. SummaryAUC provides accurate approximations to AUCs and their variances. The bias of AUC is typically

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.

Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five clusters of people with distinct profiles of character traits regardless of genotype. Third, we found 42 SNP sets that identified 727 gene loci and were significantly associated with one or more of the character profiles. Each character profile was related to different SNP sets with distinct molecular processes and neuronal functions. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of 95% of the 42 SNP sets in healthy Korean and German samples, as well as their associations with character. The identified SNPs explained nearly all the heritability expected for character in each sample (50 to 58%). We conclude that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes despite variable cultures and environments. These gene sets modulate specific molecular processes in brain for intentional goal-setting, self-reflection, empathy, and episodic learning and memory.

Schizophrenia has a heritability of 60-80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences., (© 2019. The Author(s).)

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by frustrating and rewarding interactions ("partial object relations"). Such affective dichotomization appears to be genetically hardwired the amygdala. Intrinsic propensity of mPFC to form schematic frameworks for episodic memories may pilot non-conscious integration of dichotomized mental representations in neonates and infants. With the emergence of working memory in toddlers, an activated self- and object-representation of a particular valence can be juxtaposed with its memorized opposites creating a balanced cognitive-affective frame (conscious "integration of object relations"). Specific events of object relations are forgotten but nevertheless profoundly influence the mental future of the individual, acting (i) as implicit schema-affect templates that regulate attentional priorities, relevance, and preferential assimilation of new information based on past experience, and (ii) as basic units of experience that are, under normal circumstances, integrated as attractors or "focal points" for interactive self-organization of functional brain networks that underlie the mind. A failure to achieve integrated object relations is predictive of poor adult emotional and social outcomes, including personality disorder. Cognitive, cellular-, and systems-neuroscience of episodic memory appear to support key postulates of object relations theory and help elucidate neural mechanisms of psychodynamic psychotherapy. Derived through the dual prism of psychoanalysis and neuroscience, the gained insights may offer new directions to enhance mental health and improve treatment of multiple forms of psychopathology., Competing Interests: CZ is on Scientific Advisory Board of Sage Therapeutics. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Svrakic and Zorumski.)

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10 -15 ), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10 -6 ). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10 -11 ) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10 -5 ). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

Abstract: The purpose of this study was to evaluate emotion dysregulation and temperament-character traits in adolescents with functional neurological symptom disorder (FNSD). Forty adolescents with FNSD and 40 healthy adolescents were evaluated by a semiconstructed diagnosis interview, Temperament and Character Inventory (TCI), Difficulties in Emotion Regulation Scale (DERS), Regulation of Emotions Questionnaire (REQ), and Children's Somatization Inventory-24 (CSI-24). The external and internal dysfunctional emotion regulation scores of REQ, all subscales of DERS, except the awareness subscale, and CSI-24 scores were significantly higher in FNSD patients compared with healthy controls. There were significant differences between the groups in terms of harm avoidance and reward dependence subscale scores of TCI. Multiple logistic regression analysis showed that the external dysfunctional emotion regulation strategy, somatization, and reward dependence are significant predictors of FNSD. Our results provide evidence that adolescents with FNSD experience emotional dysregulation and that the differential value of some temperament-character traits in the diagnosis of FNSD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This is the first study exploring how temperament and character personality dimensions impact self-reported resilience in major depressive disorder (MDD) and bipolar disorder (BD). We included 130 euthymic patients with affective disorders (AFD; 66 MDD and 64 BD) and 134 healthy controls (HC). Connor and Davidson resilience scale and Temperament and Character Inventory (TCI-140) were administered. Multiple linear regressions and interaction analyses were performed. Mediation analyses examined if personality dimensions explained group differences in resilience. Resilience was lower in MDD and BD vs. HC and in MDD vs. BD, adjusting for sex, age and education. Higher resilience was predicted by lower harm avoidance (HA) and higher persistence (P) in AFD and MDD, lower HA in BD and higher P and self-directedness (SD) in HC. However, only HA and P had a group-specific effect on resilience in AFD vs. HC. In mediation analyses, specific TCI dimensions at least partially explained differences in resilience: HA, P and SD in AFD or MDD vs. HC; SD in BD vs. HC; P in BD vs. MDD. Concludingly, two temperament traits (HA, P) and a character trait (SD) predict resilience in AFD. Focusing on personality could identify sources of compromised resilience as potential treatment targets., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Clinically significant depression is present in one of every four people with type 2 diabetes mellitus (T2DM). Depression increases the risk of the development of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro- and macrovascular complications. Conversely, a diagnosis of T2DM increases the risk of incident depression and can contribute to a more severe course of depression. This linkage reflects a shared etiology consisting of complex bidirectional interactions among multiple variables, a process that may include autonomic and neurohormonal dysregulation, weight gain, inflammation, and hippocampal structural alterations. Two recent meta-analyses of randomized controlled depression treatment trials in patients with T2DM concluded that psychotherapy and antidepressant medication (ADM) were each moderately effective for depression and that cognitive behavior therapy (CBT) had beneficial effects on glycemic control. However, the number of studies (and patients exposed to randomized treatment) included in these analyses is extremely small and limits the certainty of conclusions that can be drawn from the data. Ultimately, there is no escaping the paucity of the evidence base and the need for additional controlled trials that specifically address depression management in T2DM. Future trials should determine both the effects of treatment and the change in depression during treatment on measures of mood, glycemic control, and medical outcome.

Background: Interpersonally synchronized behaviors play a fundamental role in social interactions. An important prereqvisite for behavioral synchronization is the mentalization ability of the individuals involved in the interaction. While the Reading the Mind in the Eyes Test (RMET) is widely applied to measure mentalization, most studies of RMET used single-subject designs, which lack ecological validity and have limited generalizability for real, on-going, reciprocal social interactions. Using a two-subject design, our objectives were to examine (i) the predictive validity of RMET for the synchronous behavior of two interacting individuals during a reaction time task; (ii) the association of age-related RMET performance with interpersonal coordination; and (iii) the influence of various potentially important covariates on the association, including psychological distress, basic personality domains such as impulsive responding, and lack of attention. Methods: We investigated 24 dyads, using 48 subjects (mean age 32.9 [SD = 12.8] years). Synchronous behavior was indexed by the correlation of participants' responses in terms of reaction times (RTs) to visual stimuli. We used the correct recognition rate from the RMET as a measure of mentalization ability. Results: Our results indicated that the synchronization of the behavioral responses (i.e., RTs) between the interacting pairs and their mentalization ability, as measured by the RMET, showed significant association. Specifically, with good performance (100% correct recognition), the behavioral response synchronization was significantly (F = 153.34, p < 0.0001) higher (Pearson correlation, r = 0.41) than with poor performance (50% correct recognition, r = 0.25). Higher age was inversely related to behavioral synchronization, with no interaction (p > 0.1) with RMET performance). The inclusion of additional covariates (e.g., measures for psychological distress and basic personality domains) in the analyses did not alter the significance of the association between RMET performance and behavioral synchronization (p < 0.05, after adjustment). Conclusions: Our results confirm the utility of RMET, as a measure of mentalization, to predict participants' ability to achieve behavioral synchronization during cooperative interaction. These results may facilitate research into mental disorders, where problems with social interactions play a role in symptom presentation. For this purpose, future studies with larger sample size should examine whether our findings can be dimensionally extrapolated to patients with such disorders. [ABSTRACT FROM AUTHOR]

Background: Self-care, a process of maintaining health through health-promoting practices and managing illness, is pivotal for the management of type 2 diabetes. This study aimed to explore the self-care level and investigate its socio-demographic and clinical determinants among Chinese adults with type 2 diabetes. Methods: In this multicenter cross-sectional study, we enrolled 495 Chinese adults with type 2 diabetes from the outpatient departments of three tertiary hospitals in Zhejiang province, China. The Self-Care of Diabetes Inventory (SCODI) was used to measure self-care maintenance, self-care monitoring, and self-care management as three critical components of the dynamic self-care process. Self-care self-efficacy is a critical factor affecting the self-care process, which was measured by the SCODI. Multiple quantile regression models were employed to identify the determinants of each self-care component and self-care self-efficacy. Results: Participants had a median age of 62 years, of whom 55.4% were male. The median scores for self-care maintenance, self-care monitoring, and self-care management were 66.67 (50.00-85.42), 47.06 (32.35–58.82), and 53.13 (34.38–68.75), respectively, whereas the median score for self-care self-efficacy was 70.45 (52.27–84.09). Living in the southwest of Zhejiang province and having lower self-care self-efficacy were associated with lower self-care maintenance. Female gender, belonging to minorities, having complications, not attending diabetes self-management education in the last year, living in the southwest of Zhejiang province, and having lower self-care self-efficacy were associated with lower self-care monitoring. Having complications, using insulin, living in the southwest of Zhejiang province, and having lower self-care self-efficacy were associated with a lower level of self-care management. Living in the southwest of Zhejiang province was associated with lower self-care self-efficacy. Conclusions/interpretation: The findings of this study provide invaluable insights into the factors affecting self-care among Chinese adults with type 2 diabetes. By enhancing self-care self-efficacy and participating in diabetes self-management education, healthcare providers can develop tailored self-care interventions to improve diabetes care, particularly for adults with type 2 diabetes who are female, belong to minority groups, have complications, use insulin, or reside in the southwest of Zhejiang province. [ABSTRACT FROM AUTHOR]

Background : Physical exercise is crucial in type 2 diabetes management (T2D), and training in the aquatic environment seems to be a promising alternative due to its physical properties and metabolic, functional, cardiovascular, and neuromuscular benefits. Research on combined training in aquatic and dry-land training environments is scarce, especially in long-term interventions. Thus, this study aims to investigate the effects of combined training in both environments on health outcomes related to the management of T2D patients. Methods: This is a randomized, unicentric, single-blinded, comparator clinical trial with two parallel arms. Participants with T2D, of both sexes, aged at 45 to 80 years old, will be randomized into two groups (aquatic combined training (AQUA) and dry-land combined training (LAND)), both performing combined aerobic and resistance training three times a week on alternate days for 24 weeks. Aerobic training will be performed using continuous and pyramidal methods, with linear exercise intensity and duration progression. Intensity will be prescribed by rated effort perception (Borg scale 6 to 20). Resistance training will be performed using exercise for the trunk, upper and lower limbs maximum speed, and target repetition zone in aquatic and dry-land environments, respectively, using multiple sets in a linear dosage progression. Before, at 12 weeks, and after the 24 weeks of training, biochemical analyses, functional capacity, maximum muscle strength, body composition assessments, cardiovascular measures, and the administration of questionnaires to assess mental, cognitive, sleep quality, and quality of life will be conducted. Throughout the 24 weeks, the training load date and acute capillary glucose and blood pressure measurements will also be conducted. The data will be analyzed using the SPSS (29.0) statistical package, using a significance level of 0.05. For intra- and inter-group comparisons, generalized estimating equations will be applied and analyzed by intention-to-treat and per-protocol adopting the Bonferroni post hoc test. Discussion: The obtained results may provide insights to enhance understanding of the benefits of the aquatic and dry-land environment on various health outcomes, as well as acute aspects and safety considerations of the training. Moreover, this could support the development of intervention strategies to optimize the T2D management. Trial registration: Brazilian Clinical Trial Registry (ReBEC) RBR-10fwqmfy. Registered on April 16, 2024. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS causes many changes in the lives of its patients, forcing them to renegotiate their lives. Part of these changes are related to patients' self- and others- mental representations. Despite the importance of mental representations in changes caused by or adaptation to MS, limited research has been conducted to examine the mental representations of people with MS. Methods: This study examines the mental representations that Healthy Controls (HC) and people with MS (PWMS) have of themselves and others, including childhood and current self-images, as well as those of their mothers, love partners, and close friends. In both groups (HC (n = 82) and PWMS (n = 82)), participants completed demographic variables as well as a modified version of the comfortable interpersonal distance (CID) task in both passive (when protagonists approached them) and active modes (when participants approach protagonists). Participants estimated the point at which they felt discomforted. Results: The PWMS group preferred a significantly larger interpersonal distance than the HC group for both current self-image and love partner. There is no difference between the two groups in preferring interpersonal distance from their childhood self-image, mother, and friends. Conclusions: Based on the research results, it seems that PWMS experience a kind of alienation at the level of self-mental representations. This research can be helpful in modifying MS interventions and increasing the engagement of support systems. [ABSTRACT FROM AUTHOR]

Decades of research on personality identified dissociable psychological temperaments. Cloninger's temperament and character theory used a psychobiological approach to differentiate three major dimensions of personality: harm avoidance, novelty seeking, and reward dependence. Previous studies, heretofore, did not examine the correspondence between Cloninger's psychological temperaments and statistically independent data-driven components and how that could enhance the clinical utility of personality temperaments. In this study, we validated an Arabic version of the tri-dimensional personality questionnaire (TPQ) to construct data-driven personality temperaments using independent component analysis (ICA). Using SVM, we contrasted the clinical utility of data-driven personality vs. Cloninger's psychological temperaments in differentiating medication-naïve patients with major depressive disorder (N=244) and healthy subjects (N=1109). Data-driven personality components based on ICA showed very little overlap with Cloninger's original temperaments. Both Cloninger's temperaments and data-driven components revealed low internal consistency (for subscales) but high test-retest reliability. Cloninger's temperaments, however, showed a poor goodness-of-fit for the structure of the TPQ. Data-driven components significantly outperformed psychological TPQ temperaments with higher accuracy and recall but not precision. To our knowledge, this is the first study to examine the clinical utility of data-driven vs. psychological personality metrics using a sizeable sample of patients and healthy individuals. Our results could have wide implications for reexamining psychometric data to extract data-driven latent structures that can improve replicability, clinical utility, and cross-disciplinary inference. [ABSTRACT FROM AUTHOR]

An association between the MAGI2 (S-SCAM) intron variant rs521851 and depression symptoms, as measured by the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), has been recently reported. The role of MAGI2 in depression has been linked to disruptions in the gut–brain axis. In this study, we investigated the association between rs521851 and HADS-D scores in an independent cohort of 380 individuals, consisting of 238 patients with an ICD-10 diagnosis of depression and 142 healthy controls. The original association was replicated in the patient cohort but not in the control group. Further analysis revealed that the effect size of rs521851 on HADS-D scores was moderated by Eating Attitudes Test 26 (EAT-26) scores. In participants with an EAT-26 score of ≥20, the effect size of rs521851 on HADS-D was more than 20 times greater compared to those with an EAT-26 score of <20. These findings successfully replicate the original association signal for MAGI2 and HADS-D, and highlight the role of MAGI2 in gut–brain interactions. [ABSTRACT FROM AUTHOR]

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Introduction: Anorexia nervosa (AN) has one of the highest mortality rates of all mental illnesses. No approved pharmacological treatments exist for AN, but novel neurobiological targets show promise. Areas covered: Studies show that in individuals with AN, there are alterations in brain neurotransmitter signaling, alongside associated mental rigidity and comorbid anxiety and depression. Available and new therapies could be used to improve alterations in neurobiology and behavior. This narrative review serves as a review of previously published literature assessing the efficacy of traditional pharmacotherapy in treating AN while also exploring novel treatments, including dissociative anesthetics, psychedelics, cannabinoids, hormones, neurosteroids, and ketogenic nutrition. Expert opinion: If best practice psychotherapeutic interventions have failed, we recommend a neuroscience and brain research-based medication approach that targets dopamine neurotransmitter receptors to enhance cognitive flexibility and illness insight while reducing dread and avoidance toward food. It is furthermore essential to recognize and treat comorbid conditions such as anxiety, depression, or obsessive-compulsive disorder as they interfere with recovery, and typically do not resolve even with successful AN treatment. Novel strategies have the promise to show efficacy in improving mood and reducing specific AN psychopathology with hopes to be used in clinical practice soon. [ABSTRACT FROM AUTHOR]

The burden of depression in China is heavy, with inadequate treatment and prevention. Tobacco exposure is widely recognized as a risk factor for depression, but the impact of tobacco control policy interventions on depression has not been evaluated. In 2015, a comprehensive tobacco control package was implemented in Beijing, which was considered the strictest smoking-free ban in China to date, and achieved remarkable tobacco control effects. The objective is to evaluate the impact of the tobacco control policy package on hospital admissions for depression in a global city. An interrupted time series study was conducted to collect hospital admission information of 17.7 million residents covered by the Beijing Medical Claim Data for Employees from January 2013 to June 2017. Segmented Poisson regression models were used to estimate the average percentage change in admission rates and reductions in hospital admissions for depression. A total of 5,028,228 hospital admissions for depression were identified with a crude rate of 633.1 per 10,000 participants during the observational period. After the implementation of the policy, the hospital admission rate for depression did not decrease immediately (0.2%, 95% CI: −0.2 to 0.6%), but its secular trend decreased significantly, with an annual change of −13.8% (95% CI: −14.9 to −12.7%). The annual secular change was substantially smaller among participants aged 65 years or older than among those younger than 65 years of age (−3.1% vs. −17.2%). During the 25-month post-policy period, a total of 267,227 admissions for depression were averted, with an absolute reduction of 9.02% compared with no intervention. The proportion of reduction due to the policy intervention was slight among participants aged ≥65 years, with only 7.25%. After the implementation of Beijing's 2015 comprehensive tobacco control policy package, hospital admissions for depression decreased significantly, especially in the young people aged less than 65 years. The results support the public health benefits of WHO-recommended tobacco control measures on mental diseases. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes., Method: In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies., Results: The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%)., Conclusions: Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.

Objective: The goal of this study was to investigate psychometric properties and factorial structure of the Croatian adaptation of the Temperament and Character Inventory-Revised (TCI-R) in a sample of psychiatric outpatients (n=328)., Method: The participants filled out the TCI-R, as well as self-report measures of the Big-Five personality traits (IPIP-50), trait impulsivity (BIS-11), depression (BDI-II), suicidality (SBQ-R), and life satisfaction (SWLS). We explored the internal consistency of 7 domains and 29 subscales and compared it with the Croatian version of the original TCI used in prior studies. Principal component analysis with promax rotation was conducted on temperament and character subscales separately, while concurrent validity was examined through the TCI-R's relations with the abovementioned psychological measures., Results: The TCI-R scales showed adequate internal consistencies, with Cronbach's alpha values ranging from 0.77 to 0.93. The internal consistency showed to be higher in comparison with the Croatian version of the original TCI. The postulated four-factor structure of temperament and the three-factor structure of character were confirmed. The meaningful associations with other measures supported the concurrent validity of the TCI-R., Conclusion: The Croatian adaptation of the TCI-R exhibited satisfactory reliability and validity in a sample of psychiatric outpatients. These findings support the use of the TCI-R in Croatian clinical settings over its predecessor (TCI)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

More than 200 million prescriptions are written annually for opioid analgesics despite limited evidence of their long-term efficacy. These medications currently are prescribed to 10% - 15% of Americans with use of long-acting opioids projected to double in the next three to four years. Despite this widespread use, little is known about the risks of opioids, particularly with chronic use. New data from our research group published in the Journal of General Internal Medicine provides clear evidence that prescription opioid used for non-cancer, non-HIV pain increases significantly the risk of development of major depressive disorder in opioid naïve individuals with no recent history of depression and substance used disorders. The risk of depression increased as the dose and/or the duration of opioid use increased. The purpose of the present paper is to elucidate the details of this study, to examine potential neurobiological mechanisms responsible for the depressogenic effect of opioid analgesics, and to discuss management options that emphasize depression prophylaxis.

Background: Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations., Objective: The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression., Design: Retrospective cohort study, new user design., Patients: Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000., Main Measures: Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007., Key Results: Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90-180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05-1.46 for 90-180 days, and HR = 1.51; 95 % CI:1.31-1.74 for > 180 days)., Conclusions: In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.

Background and Objectives: Clinics licensed to provide pharmacotherapy for opiate dependence disorder are required to perform random urine drug screen (RUDS) tests. The results provide the empirical basis of individual treatment and programmatic effectiveness, and public health policy. Patients consent to witnessed testing but most tests are unwitnessed. The purpose of the present study was to compare treatment effectiveness estimates derived from witnessed versus unwitnessed urine samples., Methods: We adopted a policy requiring visually witnessed urine drug screens (WUDS) and studied its impact (a single group, pretest-posttest design) on the RUDS test results in 115 male veterans enrolled in the St. Louis VA Opioid Treatment Program., Results: The percentage of opioid-positive urine samples increased significantly following implementation of WUDS (25% vs. 41%, χ(2) = 66.5, p < .001)., Conclusions and Scientific Significance: Results of this preliminary study suggest that random testing alone does not ensure the integrity of UDS testing. Outcome calculations based on random unwitnessed tests may overestimate the effectiveness of opioid dependence disorder treatment., (Copyright © American Academy of Addiction Psychiatry.)

Whether and how the co-occurrence of depression and diabetes in pregnancy may worsen infant development has not been reported. Pregnant women with diabetes and with (n = 34) or without (n = 34) major depressive disorder (MDD) were followed during pregnancy and 6-months postpartum. The MDD subset received randomly assigned treatment with cognitive behavior therapy (CBT) or supportive counseling (SC). Depression severity was measured with the Beck Depression Inventory (BDI); infant developmental outcomes were measured with the Bayley Scales of Infant Development (BSID) and its Behavior Rating Scale (BRS). Infants of women with MDD had lower BRS scores (p = .02). Reduction in depression scores was associated with better infant outcomes on the BSID and BRS (p values <.03). These preliminary findings suggest depression occurring in pregnant women with diabetes is associated with poorer infant development and improvement in prepartum depression is associated with improvement in measures of infant development.

Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction., Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls., Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals., Conclusions: Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction., (Copyright © American Academy of Addiction Psychiatry.)

Empirical and clinical studies clearly demonstrate significant adverse effects of cannabis smoking on physical and mental health as well as its interference with social and occupational functioning. These negative data far outweigh a few documented benefits for a limited set of medical indications, for which safe and effective alternative treatments are readily available. If there is any medical role for cannabinoid drugs, it lies with chemically defined compounds, not with unprocessed cannabis plant. Legalization or medical use of smoked cannabis is likely to impose significant public health risks, including an increased risk of schizophrenia, psychosis, and other forms of substance use disorders.

Schizophrenia (SZ) is a highly heritable disorder, with about 80% of the variance attributable to genetic factors. There is accumulating evidence that both common genetic variants with small effects and rare genetic lesions with large effects determine risk of SZ. As recently shown, thousands of common single nucleotide polymorphisms (SNPs), each with small effect, cumulatively could explain about 30% of the underlying genetic risk of SZ. On the other hand, rare and large copy number variants (CNVs) with high but incomplete penetrance, variable in different individual, could explain about additional 30% of SZ cases. Although these rare CNVs frequently develop de novo, it is not clear whether they affect risk independently or via interaction with a polygenic liability in the background. Finally, the role of environmental risk factors has been well established in SZ. Environmental factors are rarely sufficient to cause SZ independently, but act in parallel or in synergy with the underlying genetic liability. Epigenetic misregulation of the genome and direct CNS injury are probably the main mechanism to mediate prenatal environmental effects (e.g., viruses, ethanol, or nutritional deficiency) whereas postnatal risk factors (e.g., stress, urbanicity, cannabis use) may also affect risk via use-based potentiation of vulnerable CNS pathways implicated in SZ. In this review, we outline a general theoretical background of epigenetic mechanisms involved in GxE interactions, and then discuss epigenetic and neurodevelopmental features of SZ based on available information from genetics, epigenetics, epidemiology, neuroscience, and clinical research. We argue that epigenetic model of SZ provides a framework to integrate a variety of diverse empirical data into a powerful etiopathogenetic synthesis. The promising future of this model is the possibility to develop truly specific prevention and treatment strategies for SZ.

Objective: In this work, we report data on construct validity and cross cultural applicability of the revised Temperament and Character Inventory (TCI R) (Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., & Wetzel, R.D. (1999). The Temperament and Character Inventory-revised, Washington University, St. Louis), a 5-point scale scoring formatrevision of the original, true-false version TCI (Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., & Wetzel, R.D. (1994). The Temperament and Character Inventory-A guide to its development and use, Washington University, St. Louis). Both versions are based on the seven factor Psychobiological Model of Personality (Cloninger CR, Svrakic, DM & Przybeck TR (1993). A Psychobiological Model of temperament and Character, Archives of General Psychiatry, 50, 975-990)., Methods: The sample consisted of 473 normal adult subjects representing a number of Serbian cities and towns, recruited consecutively while registering at the National Employment Center, located in Belgrade, Serbia. The sample was the designed to be highly representative of urban and suburban population in Serbia to match to TCI R sample in the US. The 240-item, 5-point scale scoring TCI R was used to assess temperament and character traits. In addition to a number of other revisions, the scoring format in the TCI R was changed into a 5-point Likert scale to increase its sensitivity to subtle variations in personality expression. The TCI R mean scores and standard deviations were compared between Serbian and US subjects, internal consistency of the TCI R scales was estimated using Cronbach's alpha coefficients, and principal component analysis was used separately for temperament and character (because of their non-linear relationship) to test the underlying factorial structure of the TCI R. Parallel analysis and randomized simulation data were used to determine the number of factors for temperament and character., Results: The results generally supported the construct validity and the cross cultural applicability of the TCI R in Serbia. With a few exceptions, the observed internal consistency for the TCI R scales was acceptable. For the most part, the US and Serbian subjects manifested comparable temperament traits, whereas US subjects had higher character scores. The observed differences are understood as partly reflective of local culture and partly of dramatic socio-economic change in Serbia over the last 20 years. Principal component analysis fully supported the four factor structure of temperament and the three factor structure of character, as postulated by theory. The inadequacy of using linear statistical methods in studying complex non-linear systems such as personality is discussed in some detail., (Published by Elsevier Inc.)

After 30 years of clinical work and research based on categorical criteria for personality disorders (Diagnostic and Statistical manual of Mental Disorders - DSM IV TR) and (International Classification of Diseases - ICD 10th revision), a solid conceptual understanding and treatment of these disorders have not been established. For the field to move forward, it is imperative that future classifications introduce major revisions of the concept, diagnosis, and classification of personality disorders. This paper proposes one such revision. Based on recent advances in molecular biology and epigenetics, we define personality disorders as maladaptive syndromes developed trough person-environment interaction. We conceptualize maladaptation as a failure of integrative functions of personality (i.e., those that carry out adaptive processes) caused by strong biogenetic dispositions or by pathological environmental effects, or both. Hence, accurate diagnosis of personality disorder depends upon neurobiological (innate) and adaptive (interactive) etiological factors. We propose a 2-step diagnostic algorithm for personality disorders: adaptive processes (i.e., character) are used to diagnose maladaptation, whereas biological aspects (i.e., temperament) are used to specify dominant clinical presentation and for differential diagnosis. We suggest that the term "Personality Disorder" be replaced by a more appropriate term "Adaptation Disorder" as the latter reflects more accurately the real nature of the disorder and distributes the causality of maladaptive syndromes more evenly, between the person and the environment. Diagnostic, research, and treatment advantages of the proposed solution are discussed in some detail.