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Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.

No modern studies of the natural course of depression have been done since the nineteen fourties of the last century. A large number of depressive episodes spontaneously remit. Because of this, some psychiatrists call for more use of a therapeutic approach called watchful waiting, especially for milder forms of depression. At the Institute of mental health in Belgrade, from November 2019 until November 2021, a study in watchful waiting will be done. In this paper the methodology of the planned study is described.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Introduction: Media influence on suicide in the adolescent population is well known and explored in many researches. Unfortunately, despite great efforts to improve measures to protect the mental health of young people and the media - the last few years we have witnessed frequent abuse of suicidality and suicidal behavior among young people through news and social media in order to popularize media sources. The aim of study was to investigate the possible link of caracteristics using social networks by adolescents hospitalized in Day Hospital for Adolescents with suicide and self-harm behavior, as well as to explore whether different forms of risky behavior and satisfaction with peers are related to self-harm behavior. Methods: 80 hospitalized patients of Day Hospital for Adolescents filled in the questionnaire related to socio-demographic data with questionnaires on the use of social networks (Facebook and Instagram) and risky behaviors, made for the purposes of this study. Results: From the total sample 90% of the subjects where using social networks (Facebook or Instagram). The average number of friends / followers on social networks was 431.66 ± 648.11. The average number of hours per week spent on social networks amounted 7.20 ± 8.20. When it comes to the number of accounts on social networks, the average number of Instagram accounts was 1.96 ± 6.73, while the average number of Facebook accounts per person was 0.84 ± 0.78. Self-harm behavior was significantly correlated with time spent on social networks. Conclusion: Social networks have become a new training ground for social interaction for young people which raises the question of whether vulnerable categories more used social networks or social networks and inducing vulnerability.

Prompted by the need to measure the impact of the coronavirus disease 2019 on main areas of quality of life related to mental health (MH), the COV-19-impact on quality of life (COV19-QoL) scale has been developed recently. We measured how patients seeking face-to-face MH care perceived the coronavirus disease 2019 impact on QoL and how socio-demographic factors, stress, and personality contributed to QoL in this diagnostically diverse population.Patients aged 18 to 65 years (n = 251) who came for the first time to the outpatient units during the 6-week index-period (May 21-July 1, 2020) were included. The cross-sectional assessment involved sociodemographic variables, working diagnosis, personality traits (7-dimension model, including HEXACO and DELTA), stress (list of threatening experiences and proximity to virus), and COV19-QoL.The perceived impact of the pandemic on QoL was above the theoretical mean of a 5-point scale (COV19-Qol = 3.1 ±â€Š1.2). No association between total COV19-QoL score, sociodemographic parameters, and working diagnoses was found in the present sample. After testing whether positional (threatening experiences), or dispositional (personality) factors were predominant in the perceived impact of COV-19 on QoL, significant predictors of the outcome were personality traits Disintegration (B = 0.52; P 

Transforming growth factor beta (TGF-β), which has a role as a regulatory cytokine, has not been widely investigated in patients with major depressive disorder (MDD) who experienced childhood trauma. The aim of our study was to investigate the differences in circulating TGF-β levels between the patients with major depressive disorder (MDD) with and without child maltreatment (CM) history, and to compare them to the corresponding control subjects' groups (with or without CM). Blood samples were obtained from 55 patients, fulfilling DSM-IV-R criteria for a current MDD episode without psychotic symptoms, and 45 healthy controls, matched for age and gender. Participants were administered the Childhood Trauma Questionnaire (CTQ). Serum TGF-β concentration was determined by enzyme-linked immunosorbent assay. The concentration of TGF-β was significantly higher in patients with MDD with CM history, compared to MDD patients with no CM, as well as both control groups. Furthermore, we have shown that the combined effect of CM history and MDD affected TGF-β levels in adulthood, which was not observed in the control group with CM. These results indicate that MDD patients with the experience of CM have altered immune-regulatory response, and they may constitute a specific subtype within this heterogenic disorder (ecophenotype).

Background Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. Aim The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. Methods TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls. Results: The TCS detected BR abnormalities were significantly more frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5 out of 56; 9%). The prevalence of short allele (s) homozygocity in the length polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR) was significantly higher in MDD patients relative to those with normal BR echogenicity. A stepwise statistical discriminant analysis revealed statistically significant separation between MDD patients with and without BR abnormalities groups based on the four predictors combined: the Hamilton Anxiety Rating Scale item 5 („difficulty in concentration, poor memory“), presence of social phobia, s allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized anxiety disorder. Limitations Cross-sectional design and heterogenous treatment of depressed patients. Conclusions Reduced BR echogenicity in at least a subgroup of MDD patients may reflect a particular phenotype, characterized by more prevalent comorbid anxiety disorders, associated with particular genetic polymorphisms and neurotransmitter(s) deficits, most probably altered serotonergic mechanisms.

In major depressive disorder (MDD), the need to study multiple-gene effect on brain structure is emerging. Our aim was to assess the effect of accumulation of specific SERT, BDNF and COMT gene functional polymorphisms on brain structure in MDD patients. Seventy-seven MDD patients and 66 controls underwent a clinical assessment, genetic testing and MRI scan. Compared with controls, patients were more BDNF-Val homozygotes, COMT-Met carriers and SERT-L' carriers. Thus, subjects were split into three groups: 1. High-frequency susceptibility polymorphism group (hfSP, subjects with all three SPs); 2. Intermediate-frequency SP group (ifSP, two SPs); and 3. Low-frequency SP group (lfSP, one/none SP). Cortical thickness, volumetry of hippocampus, amygdala and subcortical structures, and white matter (WM) tract integrity were assessed. Compared to controls, hfSP patients showed thinning of the middle frontal cortex bilaterally, left frontal pole, and right lateral occipital cortex, and smaller hippocampal volume bilaterally; and both hfSP and lfSP patient groups showed thinning of the left inferior parietal cortex and reduced WM integrity of the corpus callosum. Compared to patients, hfSP controls showed greater integrity of the fronto-occipital cortices and corpus callosum. We showed that cortical prefrontal and occipital damage of MDD patients is modulated by the SP accumulation, while damage to the parietal cortex and corpus callosum seem to be independent of genetic accumulation. HfSP controls may experience protective mechanisms leading to a preserved integrity of critical cortical and WM regions. Investigating the effect of multiple genes is promising to understand the pathological mechanisms underlying MDD. Hum Brain Mapp 37:2173-2184, 2016. © 2016 Wiley Periodicals, Inc.

To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (SFE, n = 19), patients in relapse (SR, n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between SFE, SR and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in SFE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the SFE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS.

Our study was intended to test whether there are any differences in the way defense mechanisms are used by patients suffering from pure anxiety and those with pure depressive disorders. The sample size was as follows: depressive disorders without psychotic symptoms 30, anxiety disorders 30, and the healthy control group 30. The assessment of defense mechanisms was made using the DSQ-40 questionnaire. Our findings show that "pure" anxiety disorders differ from "pure" depressive disorders only in the use of immature defense mechanisms. The group with depressive disorders was significantly more prone to use immature defense mechanisms than the group with anxiety disorders (p = 0.005), primarily projection (p = 0.001) and devaluation (p = 0.003). These defense mechanisms may therefore be used both to differentiate between anxiety and depressive disorders and also to determine which symptoms (anxiety or depressive disorders) are dominant at any given stage of treatment.

Introduction. The two types of stigmatization are social stigma, which includes discrimination, underestimation and distance in various social circumstances and personal stigma, which includes private relation i.e. a contact in person with stigmatized subject. Majority of recent publications has shown gender asymmetry in stigmatization (mostly indicating male predominance in stigmatizing processes), whereas the opposite data can be also found in some publications. The present study was aimed at exploring the relation of students' gender with their tendency to stigmatize subjects visiting a psychiatrist and at analyzing whether the gender influences the process of stigmatization. Material and methods. The survey included 523 students (227 on the second and 296 on the sixth year of School of Medicine, University of Belgrade). The instrument consisted of a vignette with questionnaire (14 items). Four versions of vignette were distributed: with/without 'label' and male/female subject in the vignette. Results. A more personal stigmatization was evident in the female students (p0.05). The stigmatization positively correlated with the intimacy of student's relation with the subject going to a psychiatrist. A higher rate of stigmatization was evident if the vignette was showing a person of the opposite gender. Discussion and conclusion. This is a unique study which analyzes separately the gender of a stigmatizing subject versus the subject being stigmatized and types of stigmatization. The data obtained should contribute to recognizing, understanding and controlling the widespread problem of stigma.

An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits.

Kelleher et al ’s study is very interesting and raises some important questions,[1][1] but we think that it also has some confounding factors that need to be addressed before conclusions are made. In addition, there are some methodological issues which we would like to be clarified. The response