Familial risk factors in social anxiety disorder: calling for a family-oriented approach for targeted prevention and early intervention

Within the last decade, social anxiety disorder (SAD) has been identified as a highly prevalent and burdensome disorder. Both the characterization of its symptomatology and effective treatment options are widely documented. Studies particularly indicate that SAD aggregates in families and has its onset in early adolescence. Given the family as an important context for children’s cognitive, emotional and behavioural development, familial risk factors could be expected to significantly contribute to the reliable detection of populations at risk for SAD. Reviewing studies on familial risk factors for SAD argues for the importance of parental psychopathology and unfavourable family environment, but also denotes to several shortcomings such as cross-sectional designs, short follow-up periods, diverging methodologies and the focus on isolated factors. Using a prospective longitudinal study that covers the high-risk period for SAD, including a broader spectrum of putative risk factors may help to overcome many of the methodological limitations. This review sets out to develop a more family-oriented approach for predicting the onset and maintenance of SAD that may be fruitful to derive targeted prevention and early intervention in SAD

The Behavior and Mind Health (BeMIND) study: Methods, design and baseline sample characteristics of a cohort study among adolescents and young adults

Objectives: The Behavior and Mind Health (BeMIND) study is a population‐based cohort study of adolescents and young adults from Dresden, Germany. The aim is to investigate psychological and behavioral factors linked to a range of mental disorders and health behaviors and their interaction with social‐environmental and genetic/biologic factors. Methods: A random sample of 14–21 year olds was drawn from the population registry in 2015. The baseline investigation was completed 11/2015–12/2016 (N = 1,180). Assessments include standardized diagnostic interview, cognitive‐affective tasks, questionnaires, biosamples, and ecologic momentary assessment in real life with combined actigraphic/geographic monitoring. In the family study component, parents completed similar assessments and provided information on child's early development. Results: The participation rate (minimum response proportion) was 21.7%; the cooperation rate was 43.4%. Acceptance and completion of study components were high. General health data indicate that more than 80% reported no or only mild impairment due to mental or somatic health problems in the past year; about 20% ever sought treatment for mental health problems or chronic somatic illnesses, respectively. Conclusions: Data from BeMIND baseline and follow‐up investigations will provide novel insights into contributors to health and disease as adolescents grow into adulthood

Mental disorders and the risk for the subsequent first suicide attempt: results of a community study on adolescents and young adults

Adolescents and young adults represent the high-risk group for first onset of both DSM-IV mental disorders and lifetime suicide attempt (SA). Yet few studies have evaluated the temporal association of prior mental disorders and subsequent first SA in a young community sample. We examined (a) such associations using a broad range of specific DSM-IV mental disorders, (b) the risk of experiencing the outcome due to prior comorbidity, and (c) the proportion of SAs that could be attributed to prior disorders. During a 10-year prospective study, data were gathered from 3021 community subjects, 14-24 years of age at baseline. DSM-IV disorders and SA were assessed with the Munich-Composite International Diagnostic Interview. Cox models with time-dependent covariates were used to estimate the temporal associations of prior mental disorders with subsequent first SA. Most prior mental disorders showed elevated risk for subsequent first SA. Highest risks were associated with posttraumatic stress disorder (PTSD), dysthymia, and nicotine dependence. Comorbidity elevated the risk for subsequent first SA, and the more disorders a subject had, the higher the risk for first SA. More than 90% of SAs in the exposed group could be attributed to PTSD, and over 30% of SAs in the total sample could be attributed to specific phobia. Several DSM-IV disorders increase the risk for first SA in adolescents and young adults. Several promising early intervention targets were observed, e.g., specific phobia, nicotine dependence, dysthymia, and whether a young person is burdened with comorbid mental disorders

Specific Traumatic Events Elevate the Risk of a Suicide Attempt in a 10-year Longitudinal Community Study on Adolescents and Young Adults

Traumatic events (TEs) have been associated with suicide attempts (SAs). However, the empirical status of some TEs is inconclusive. This also concerns community adolescents and young adults, known to be a high-risk group for SAs. We examined associations between (a) a range of prior TEs (physical attack, rape/sexual abuse, serious accident, and witnessing somebody else experiencing a TE) and a subsequent SA, and (b) the number of prior TEs and an SA, and (c) we estimated attributable proportions of SAs, in relation to each TE. Over a 10-year period, the Early Developmental Stages of Psychopathology (EDSP) study prospectively assessed community members, aged 14-24 years at baseline. Starting with 3021 subjects, each individual was assessed up to four times. Assessment was based on the Munich-Composite International Diagnostic Interview. Temporal associations were estimated using the Cox model with time-dependent covariates. Attributable proportions were based on the results of the Cox models. All four TEs elevated the risk for a subsequent SA, adjusting for confounders. Highest risk was found for the combined TE rape/sexual abuse. Results showed that 56-90% of SAs could be attributed to TEs in the exposed group; on the population level, attributable proportions ranged between 6.9% and 23.5%. Different TEs have been shown to elevate the risk of an SA in a young community sample. Our results suggest that both health professionals and health policy decision-makers consider specific TEs and the number of prior TEs as risk factors for SAs

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response

Common and specific amygdala-function perturbations in 2 depressed versus anxious adolescents

Context: Few studies directly compare amygdala function in depressive and anxiety disorders. 43 Data from longitudinal research emphasize the need for such studies in adolescents. 44 Objective: To compare amygdala response to varying attention and emotion conditions among 45 adolescents with Major Depressive Disorder (MDD) or anxiety disorders, relative to adolescents 46 with no psychopathology. 47 Design: Case-Control-Study. 48 Setting: Government Clinical Research Institute. 49 Participants: Eighty-seven adolescents matched on age, gender, intelligence, and social class: 26 50 with Major Depressive Disorder (MDD; 14 with and 12 without anxiety disorders), 16 with 51 anxiety disorders but no depression, and 45 with no psychopathology. 52 Main Outcome Measures: Blood oxygenated level dependent signal in the amygdala, measured 53 using event-related functional magnetic resonance imaging. During imaging, participants viewed 54 facial expressions (neutral, fearful, angry, happy) while attention was constrained (afraid, 55 hostility, nose width ratings) or unconstrained (passive-viewing). 56 Results: Left and right amygdala activation differed as a function of diagnosis, facial expression, 57 and attention-condition both when comorbid MDD/anxiety patients were included and excluded 58 (group-by-emotion-by-attention interactions: p-values≤.03). Focusing on fearful-face-viewing 59 events, anxiety and MDD patients both differed in amygdala responses from healthy participants 60 and from each other during passive-viewing. However, both MDD and anxiety patients, relative 61 to healthy participants, exhibited similar signs of amygdala hyper-activation to fearful faces when 62 rating subjectively experienced fear. 63 Conclusions: Adolescent MDD and anxiety disorders exhibit common and distinct functional 64 neural correlates during face processing. Attention modulates the degree to which common or 65 distinct amygdala perturbations manifest in these patient groups, relative to healthy peers

Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder?

We examined parental psychopathology and family environment in subthreshold and DSM-IV threshold conditions of social anxiety disorder (SAD) in a representative cohort sample of 1,395 adolescents. Offspring and parental psychopathology was assessed using the DIA-X/M-CIDI; recalled parental rearing and family functioning via questionnaire. Diagnostic interviews in parents were supplemented by family history reports from offspring. The cumulative lifetime incidence was 23.07% for symptomatic SAD, and 18.38 and 7.41% for subthreshold and threshold SAD, respectively. The specific parent-to-offspring association for SAD occurred for threshold SAD only. For subthreshold and threshold SAD similar associations were found with other parental anxiety disorders, depression and substance use disorders. Parental rearing behaviour, but not family functioning, was associated with offspring threshold SAD, and although less strong and less consistent, also with subthreshold SAD. Results suggest a continued graded relationship between familial risk factors and offspring SAD. Parental psychopathology and negative parental styles may be used defining high-risk groups to assign individuals with already subthreshold conditions of SAD to early intervention programs

Volume of subcortical brain regions in social anxiety disorder:mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE &lt; 0.001; right: d = −0.158, pFWE &lt; 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.</p

Volume of subcortical brain regions in social anxiety disorder:mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE &lt; 0.001; right: d = −0.158, pFWE &lt; 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.</p