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 < 0.001; right: d = -0.158, pFWE < 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.

The importance of social activity to risk of major depression in older adults.

BACKGROUND: Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifespan, we aimed to identify the SDoH that was most strongly related to newly diagnosed MDD in a cohort of older adults. METHODS: We used self-reported health-related survey data from 41 174 older adults (50-89 years, median age = 67 years) who participated in the Mayo Clinic Biobank, and linked ICD codes for MDD in the participants' electronic health records. Participants with a history of clinically documented or self-reported MDD prior to survey completion were excluded from analysis (N = 10 938, 27%). We used Cox proportional hazards models with a gradient boosting machine approach to quantify the RI of 30 pre-selected SDoH variables on the risk of future MDD diagnosis. RESULTS: Following biobank enrollment, 2073 older participants were diagnosed with MDD during the follow-up period (median duration = 6.7 years). The most influential SDoH was perceived level of social activity (RI = 0.17). Lower level of social activity was associated with a higher risk of MDD [hazard ratio = 2.27 (95% CI 2.00-2.50) for highest v. lowest level]. CONCLUSION: Across a range of SDoH variables, perceived level of social activity is most strongly related to MDD in older adults. Monitoring changes in the level of social activity may help identify older adults at an increased risk of MDD.

The effects of the pandemic on mental health in persons with and without a psychiatric history.

BACKGROUND: Prospective studies are needed to assess the influence of pre-pandemic risk factors on mental health outcomes following the COVID-19 pandemic. From direct interviews prior to (T1), and then in the same individuals after the pandemic onset (T2), we assessed the influence of personal psychiatric history on changes in symptoms and wellbeing. METHODS: Two hundred and four (19-69 years/117 female) individuals from a multigenerational family study were followed clinically up to T1. Psychiatric symptom changes (T1-to-T2), their association with lifetime psychiatric history (no, only-past, and recent psychiatric history), and pandemic-specific worries were investigated. RESULTS: At T2 relative to T1, participants with recent psychopathology (in the last 2 years) had significantly fewer depressive (mean, M = 41.7 v. 47.6) and traumatic symptoms (M = 6.6 v. 8.1, p < 0.001), while those with no and only-past psychiatric history had decreased wellbeing (M = 22.6 v. 25.0, p < 0.01). Three pandemic-related worry factors were identified: Illness/death, Financial, and Social isolation. Individuals with recent psychiatric history had greater Illness/death and Financial worries than the no/only-past groups, but these worries were unrelated to depression at T2. Among individuals with no/only-past history, Illness/death worries predicted increased T2 depression [B = 0.6(0.3), p < 0.05]. CONCLUSIONS: As recent psychiatric history was not associated with increased depression or anxiety during the pandemic, new groups of previously unaffected persons might contribute to the increased pandemic-related depression and anxiety rates reported. These individuals likely represent incident cases that are first detected in primary care and other non-specialty clinical settings. Such settings may be useful for monitoring future illness among newly at-risk individuals.

Inhibition Predicts the Course of Depression and Anxiety Symptoms Among Adolescents: The Moderating Role of Familial Risk.

ABSTRACT: Numerous theoretical models suggest that inhibition difficulties-the inability to moderate automatic responses-contribute to the onset and/or maintenance of internalizing symptoms. Inhibition deficits and internalizing disorders run in families and share overlapping genetic risk factors, suggesting that inhibition deficits may be particularly prognostic of internalizing symptoms in those with high familial risk. This study tested this hypothesis in a longitudinal sample during the transition from adolescence to early adulthood. As hypothesized, prospective associations between inhibition and anxiety and depressive symptoms 8 years later were moderated by familial risk for depression. Specifically, poorer inhibition prospectively predicted greater anxiety and depressive symptoms in those at high (but not low) familial risk for major depressive disorder. These findings provide preliminary support for impaired inhibition as an indicator of risk for later internalizing symptoms in those at high familial risk.

Major depression, temperament, and social support as psychosocial mechanisms of the intergenerational transmission of parenting styles.

In this three-generation longitudinal study of familial depression, we investigated the continuity of parenting styles, and major depressive disorder (MDD), temperament, and social support during childrearing as potential mechanisms. Each generation independently completed the Parental Bonding Instrument (PBI), measuring individuals' experiences of care and overprotection received from parents during childhood. MDD was assessed prospectively, up to 38 years, using the semi-structured Schedule for Affective Disorders and Schizophrenia (SADS). Social support and temperament were assessed using the Social Adjustment Scale - Self-Report (SAS-SR) and Dimensions of Temperament Scales - Revised, respectively. We first assessed transmission of parenting styles in the generation 1 to generation 2 cycle (G1→G2), including 133 G1 and their 229 G2 children (367 pairs), and found continuity of both care and overprotection. G1 MDD accounted for the association between G1→G2 experiences of care, and G1 social support and temperament moderated the transmission of overprotection. The findings were largely similar when examining these psychosocial mechanisms in 111 G2 and their spouses (G2+S) and their 136 children (G3) (a total of 223 pairs). Finally, in a subsample of families with three successive generations (G1→G2→G3), G2 experiences of overprotection accounted for the association between G1→G3 experiences of overprotection. The results of this study highlight the roles of MDD, temperament, and social support in the intergenerational continuity of parenting, which should be considered in interventions to "break the cycle" of poor parenting practices across generations.

Trajectories of childhood anxiety disorders in two generations at high risk.

BACKGROUND: The course of anxiety disorders during childhood is heterogeneous. In two generations at high or low risk, we described the course of childhood anxiety disorders and evaluated whether parent or grandparent major depressive disorder (MDD) predicted a persistent anxiety course. METHODS: We utilized a multigenerational study (1982-2015), following children (second generation, G2) and grandchildren (third generation, G3) of generation 1 (G1) with either moderate/severe MDD or no psychiatric illness. Psychiatric diagnoses were based on diagnostic interviews. Using group-based trajectory models, we identified clusters of children with similar anxiety disorder trajectories (age 0-17). RESULTS: We identified three primary trajectories in G2 (N = 275) and G3 (N = 118) cohorts: "no/low anxiety disorder" during childhood (G2 = 66%; G3 = 53%), "nonpersistent" with anxiety during part of childhood (G2 = 16%; G3 = 21%), and "persistent" (G2 = 18%; G3 = 25%). Childhood mood disorders and substance use disorders tended to be more prevalent in children in the persistent anxiety trajectory. In G2 children, parent MDD was associated with an increased likelihood of being in the persistent (84%) or nonpersistent trajectory (82%) versus no/low anxiety trajectory (62%). In G3 children, grandparent MDD, but not parent, was associated with an increased likelihood of being in the persistent (83%) versus nonpersistent (48%) and no/low anxiety (51%) trajectories. CONCLUSION: Anxiety trajectories move beyond what is captured under binary, single time-point measures. Parent or grandparent history of moderate/severe MDD may offer value in predicting child anxiety disorder course, which could help clinicians and caregivers identify children needing increased attention and screening for other psychiatric conditions.

Commentary: Studies of prenatal antidepressant exposures: what can you recommend? A reflection on Sujan et al. (2019).

The review by Sujan et al. asks a question of clinical and public health importance: are antidepressant medications safe to use during pregnancy from the perspective of their potential effects on the infant and growing child? They provide a thorough review of the animal and human literature to date, focusing primarily on offspring neurodevelopmental outcomes (autism spectrum disorder, ASD, and attention deficit hyperactivity disorder, ADHD). They conclude, based on their review, that antidepressant exposure in pregnancy does not substantially increase the risk of these outcomes, and that women should therefore be reassured about the safety of these medications when used in pregnancy. While their review should be of interest to clinicians and researchers, we would advocate a more conservative approach. Even if associations with ASD and ADHD are equivocal, there is still evidence that SSRI exposure may be associated with outcomes occurring at other developmental timepoints. Clinical recommendations should be based on a fuller picture of potential risks and benefits to both the mother and the fetus, in the context of the mother's underlying depression. In this commentary, we also suggest some approaches that future observational studies may adopt to help strengthen the interpretability of findings.

Effects of Serotonin Transporter Gene Variation on Impulsivity Mediated by Default Mode Network: A Family Study of Depression.

Serotonergic neurotransmission, potentially through effects on the brain's default mode network (DMN), may regulate aspects of attention including impulse control. Indeed, genetic variants of the serotonin transporter (5-HTT) have been implicated in impulsivity and related psychopathology. Yet it remains unclear the mechanism by which the 5-HTT genetic variants contribute to individual variability in impulse control. Here, we tested whether DMN connectivity mediates an association between the 5-HTT genetic variants and impulsivity. Participants (N = 92) were from a family cohort study of depression in which we have previously shown a broad distribution of 5-HTT variants. We genotyped for 5-HTTLPR and rs25531 (stratified by transcriptional efficiency: 8 low/low, 53 low/high, and 31 high/high), estimated DMN structural connectivity using diffusion probabilistic tractography, and assessed behavioral measures of impulsivity (from 12 low/low, 48 low/high, and 31 high/high) using the Continuous Performance Task. We found that low transcriptional efficiency genotypes were associated with decreased connection strength between the posterior DMN and the superior frontal gyrus (SFG). Path modeling demonstrated that decreased DMN-SFG connectivity mediated the association between low-efficiency genotypes and increased impulsivity. Taken together, this study suggests a gene-brain-behavior pathway that perhaps underlies the role of the serotonergic neuromodulation in impulse control.

Dimensions and subtypes of oppositionality and their relation to comorbidity and psychosocial characteristics.

The symptoms of oppositional defiant disorder (ODD), or oppositionality, seem to constitute a three-dimensional structure of angry/irritable, vindictiveness and argumentative behavior dimensions. Also, subjects with oppositionality are characterized by different comorbidity and longitudinal trajectories, suggesting that they could be divided into subtypes. This study is the first to examine the dimensions and subtypes of oppositionality in Nordic children. Study participants included 3435 children aged 7-10 years from the Danish National Birth Cohort. Information was collected using the Development and Well-Being Assessment (DAWBA) online version. A three-factor ODD model was identified. The angry/irritable dimension was associated with emotional problems and disorders, fewer social skills and fewer personal positive attributes. The argumentative behavior dimension was associated with hyperactivity/conduct problems, reduced social skills and positive attributes. The vindictiveness dimension was associated with externalizing, internalizing and prosocial problems. Four ODD subtypes were identified. The subtypes with many or mainly angry/irritable symptoms were characterized by comorbid psychopathology, increased functional impairment and psychosocial problems. Children with ODD had fewer positive attributes, more friendship/school problems and higher functional impairment than children with emotional disorders and control group children. Oppositionality consists of three dimensions differently associated with comorbidity and psychosocial characteristics, and the same pattern is seen for the four ODD subtypes identified in this study. Children with ODD experience more adversities and functional impairment than children with emotional disorders. Our results indicate that treatment of children with ODD would improve from extended knowledge on individual ODD dimensions and subtypes and the related child psychosocial characteristics.

Prenatal smoking exposure and neuropsychiatric comorbidity of ADHD: a finnish nationwide population-based cohort study.

BACKGROUND: Prenatal smoking exposure has been associated with attention-deficit/hyperactivity disorder (ADHD). ADHD is commonly associated with a wide spectrum of psychiatric comorbidity. The association between smoking and neuropsychiatric comorbidity of ADHD has remained understudied. The aim of this study is to examine the association between prenatal exposure to maternal smoking and offspring ADHD, and test whether the smoking-ADHD associations are stronger when ADHD is accompanied by other lifetime neuropsychiatric comorbidities. METHODS: The study is based on a nested case-control design and includes all Finnish singletons born between 1991 and 2005 and diagnosed with ADHD by 2011 (n = 10,132), matched with four controls (n = 38,811) on date of birth, sex and residence in Finland. RESULTS: The risk for ADHD with or without comorbidity was significantly increased among offspring exposed to maternal smoking on adjusting for potential confounders (OR = 1.75, CI 95 % = 1.65-1.86). Compared to the only ADHD cases, subjects with comorbid conduct disorder or oppositional defiant disorder had a significantly stronger association with smoking exposure (OR = 1.80, CI 95 % = 1.55-2.11). CONCLUSIONS: Prenatal smoking represents an important risk factor for the ADHD comorbid with CD/ODD. Further research on the association between prenatal smoking exposure and neuropsychiatric comorbidity of ADHD is needed considering the increased risk among these subjects of an overall poor health outcome as compared to only ADHD. In particular, studies utilizing biomarkers or including subjects with neuropsychiatric conditions with and without comorbid ADHD are needed.

Heritability of major depressive and comorbid anxiety disorders in multi-generational families at high risk for depression.

Family studies have shown that MDD is highly transmittable but have not studied its heritability. Twin studies show heritability of about 40% and do not include anxiety disorders. We assessed heritability of MDD and comorbid anxiety disorders in a multigenerational study of family members at high risk for MDD. In addition, we tested the hypothesis that examined clinical subtypes of MDD defined by early and late age of onset would be under relatively stronger genetic control than broadly defined DSM-IV MDD. The first generation with moderate to severe MDD was recruited from an ambulatory psychiatric treatment setting, and their descendants in the second, third, and fourth generation, were interviewed by clinicians up to six times during a 30-year period. Lifetime rates of MDD and anxiety disorders were collected for 545 participants from 65 multigenerational families. The heritability (h2 ) of MDD in this high risk sample was estimated at 67%. Anxiety and sequential comorbidity of anxiety disorders and MDD revealed h2 of 49% and 53%, respectively, and strong positive genetic correlation (rhog = 0.92, P = 7.3 × 10-7 ). Early onset MDD did not appear to be under greater genetic control than broadly defined DSM-IV MDD. Individuals who are direct descendants of subjects ascertained for moderate to severe MDD have strong genetic vulnerability to develop anxiety or MDD. Our findings support family based studies as appropriate and useful design to understand the heritability of common disorders such as MDD. © 2016 Wiley Periodicals, Inc.

Associations Between Family History of Alcohol and/or Substance Use Problems and Frontal Cortical Development From 9 to 13 Years of Age: A Longitudinal Analysis of the ABCD Study.

Background: Previous investigations that have examined associations between family history (FH) of alcohol/substance use and adolescent brain development have been primarily cross-sectional. Here, leveraging a large population-based sample of youths, we characterized frontal cortical trajectories among 9- to 13-year-olds with (FH+) versus without (FH-) an FH and examined sex as a potential moderator. Methods: We used data from 9710 participants in the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0). FH+ was defined as having ≥1 biological parents and/or ≥2 biological grandparents with a history of alcohol/substance use problems (n = 2433). Our primary outcome was frontal cortical structural measures obtained at baseline (ages 9-11) and year 2 follow-up (ages 11-13). We used linear mixed-effects models to examine the extent to which FH status qualified frontal cortical development over the age span studied. Finally, we ran additional interactions with sex to test whether observed associations between FH and cortical development differed significantly between sexes. Results: For FH+ (vs. FH-) youths, we observed increased cortical thinning from 9 to 13 years across the frontal cortex as a whole. When we probed for sex differences, we observed significant declines in frontal cortical thickness among boys but not girls from ages 9 to 13 years. No associations were observed between FH and frontal cortical surface area or volume. Conclusions: Having a FH+ is associated with more rapid thinning of the frontal cortex across ages 9 to 13, with this effect driven primarily by male participants. Future studies will need to test whether the observed pattern of accelerated thinning predicts future substance use outcomes.

Dentate Gyrus Microstructure Is Associated With Resilience After Exposure to Maternal Stress Across Two Human Cohorts.

BACKGROUND: Maternal stress (MS) is a well-documented risk factor for impaired emotional development in offspring. Rodent models implicate the dentate gyrus (DG) of the hippocampus in the effects of MS on offspring depressive-like behaviors, but mechanisms in humans remain unclear. Here, we tested whether MS was associated with depressive symptoms and DG micro- and macrostructural alterations in offspring across 2 independent cohorts. METHODS: We analyzed DG diffusion tensor imaging-derived mean diffusivity (DG-MD) and volume in a three-generation family risk for depression study (TGS; n = 69, mean age = 35.0 years) and in the Adolescent Brain Cognitive Development (ABCD) Study (n = 5196, mean age = 9.9 years) using generalized estimating equation models and mediation analysis. MS was assessed by the Parenting Stress Index (TGS) and a measure compiled from the Adult Response Survey from the ABCD Study. The Patient Health Questionnaire-9 and rumination scales (TGS) and the Child Behavior Checklist (ABCD Study) measured offspring depressive symptoms at follow-up. The Schedule for Affective Disorders and Schizophrenia-Lifetime interview was used to assign depression diagnoses. RESULTS: Across cohorts, MS was associated with future symptoms and higher DG-MD (indicating disrupted microstructure) in offspring. Higher DG-MD was associated with higher symptom scores measured 5 years (in the TGS) and 1 year (in the ABCD Study) after magnetic resonance imaging. In the ABCD Study, DG-MD was increased in high-MS offspring who had depressive symptoms at follow-up, but not in offspring who remained resilient or whose mother had low MS. CONCLUSIONS: Converging results across 2 independent samples extend previous rodent studies and suggest a role for the DG in exposure to MS and offspring depression.

Decoding unattended fearful faces with whole-brain correlations: an approach to identify condition-dependent large-scale functional connectivity.

Processing of unattended threat-related stimuli, such as fearful faces, has been previously examined using group functional magnetic resonance (fMRI) approaches. However, the identification of features of brain activity containing sufficient information to decode, or "brain-read", unattended (implicit) fear perception remains an active research goal. Here we test the hypothesis that patterns of large-scale functional connectivity (FC) decode the emotional expression of implicitly perceived faces within single individuals using training data from separate subjects. fMRI and a blocked design were used to acquire BOLD signals during implicit (task-unrelated) presentation of fearful and neutral faces. A pattern classifier (linear kernel Support Vector Machine, or SVM) with linear filter feature selection used pair-wise FC as features to predict the emotional expression of implicitly presented faces. We plotted classification accuracy vs. number of top N selected features and observed that significantly higher than chance accuracies (between 90-100%) were achieved with 15-40 features. During fearful face presentation, the most informative and positively modulated FC was between angular gyrus and hippocampus, while the greatest overall contributing region was the thalamus, with positively modulated connections to bilateral middle temporal gyrus and insula. Other FCs that predicted fear included superior-occipital and parietal regions, cerebellum and prefrontal cortex. By comparison, patterns of spatial activity (as opposed to interactivity) were relatively uninformative in decoding implicit fear. These findings indicate that whole-brain patterns of interactivity are a sensitive and informative signature of unattended fearful emotion processing. At the same time, we demonstrate and propose a sensitive and exploratory approach for the identification of large-scale, condition-dependent FC. In contrast to model-based, group approaches, the current approach does not discount the multivariate, joint responses of multiple functional connections and is not hampered by signal loss and the need for multiple comparisons correction.

Maternal Mental Health and Offspring Brain Development: An Umbrella Review of Prenatal Interventions.

The idea that risk for psychiatric disorders may be transmitted intergenerationally via prenatal programming places interest in the prenatal period as a critical moment during which intervention efforts may have a strong impact, yet studies testing whether prenatal interventions also protect offspring are limited. The present umbrella review of systematic reviews and meta-analyses (SRMAs) of randomized controlled trials aimed to synthesize the available evidence and highlight promising avenues for intervention. Overall, the literature provides mixed and limited evidence in support of prenatal interventions. Thirty SRMAs were included. Of the 23 SRMAs that reported on prenatal depression interventions, 16 found a significant effect (average standard mean difference = -0.45, SD = 0.25). Similarly, 13 of the 20 SRMAs that reported on anxiety outcomes documented significant reductions (average standard mean difference = -0.76, SD = 0.95 or -0.53/0.53 excluding one outlier). Only 4 SRMAs reported child outcomes, and only 2 (of 10) analyses showed significant effects of prenatal interventions (massage and telephone support on neonatal resuscitation [relative risk = 0.43] and neonatal intensive care unit admissions [relative risk = 0.91]). Notably missing, perhaps due to our strict inclusion criteria (inclusion of randomized controlled trials only), were interventions focusing on key facets of prenatal health (e.g., whole diet, sleep). Structural interventions (housing, access to health care, economic security) were not included, although initial success has been documented in non-SRMAs. Most notably, none of the SRMAs focused on offspring mental health or neurodevelopmental outcomes. Given the possibility that interventions deployed in this period will positively impact the next generation, randomized trials that focus on offspring outcomes are urgently needed.

Helpful activities during the COVID-19 pandemic: Perceived benefits and actual association with psychiatric symptoms and psychological wellbeing.

BACKGROUND: Few studies have rigorously examined the effectiveness of commonly reported coping activities during the COVID-19 pandemic. This study was designed to assess perceived helpful activities during the pandemic and to investigate the extent to which these activities were associated with psychological outcomes. METHOD: Adults living in the US (N = 204), who were part of a longitudinal family study of depression responded to an online survey. They reported on their perceived helpful activities during the pandemic. General linear regression models (GLM) were used to evaluate the association between perceived helpful activities and current psychiatric symptoms, controlling for demographic factors, and pre-pandemic psychiatric history and symptoms. RESULTS: The top perceived helpful activity during COVID-19 was communicating with friends/family via telephone text or video (75.5 %). However, of the top five activities endorsed, cooking/baking was associated with the most clinical outcomes, including lower anxiety/depression and greater psychological wellbeing (all ps < 0.05). These relationships were most prominent among younger individuals < age 40 years, females, and those with recent psychiatric history, although they extended to younger males, and individuals at high or low depression risk. LIMITATIONS: Close ended items limited variability in coping activities reported. The study lacked data on substance use. The sample was racially and ethnically homogenous. CONCLUSIONS: These findings move beyond anecdotal evidence that cooking/baking as a coping activity yields protection against psychopathology. Its ready accessibility and ability to confer benefits across a range of individual characteristics, make it a useful adjunct in therapeutic interventions for people confined to their homes.

Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22. METHODS: We prospectively followed 1,094,202 single-birth Danish children born 1997-2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997-2003) to further quantify potential residual confounding by subclinical factors. RESULTS: The final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7-13] years) versus unexposed (12 [IQR:12-17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes. CONCLUSIONS: While SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.

Pre- and Post-Pandemic Religiosity and Mental Health Outcomes: A Prospective Study.

Relatively few studies have prospectively examined the effects of known protective factors, such as religion, on pandemic-related outcomes. The aim of this study was to evaluate the pre- and post-pandemic trajectories and psychological effects of religious beliefs and religious attendance. Male and female adults (N = 189) reported their beliefs in religious importance (RI) and their religious attendance (RA) both before (T1) and after (T2) the pandemic's onset. Descriptive and regression analyses were used to track RI and RA from T1 to T2 and to test their effects on psychological outcomes at T1 and T2. The participants who reported a decrease in religious importance and attendance were greater in number than those who reported an increase, with RI (36.5% vs. 5.3%) and RA (34.4% vs. 4.8%). The individuals with decreased RI were less likely to know someone who had died from COVID-19 (O.R. =0.4, p = 0.027). The T1 RI predicted overall social adjustment (p < 0.05) and lower suicidal ideation (p = 0.05). The T2 RI was associated with lower suicidal ideation (p < 0.05). The online RA (T2) was associated with lower depression (p < 0.05) and lower anxiety (p < 0.05). Further research is needed to evaluate the mechanisms driving decreases in religiosity during pandemics. Religious beliefs and online religious attendance were beneficial during the pandemic, which bodes well for the use of telemedicine in therapeutic approaches.

Differences in White Matter Structural Networks in Family Risk of Major Depressive Disorder and Suicidality: A Connectome Analysis.

Background: Depression and suicide are leading global causes of disability and death and are highly familial. Family and individual history of depression are associated with neurobiological differences including decreased white matter connectivity; however, this has only been shown for individual regions. We use graph theory models to account for the network structure of the brain with high levels of specialization and integration and examine whether they differ by family history of depression or of suicidality within a three-generation longitudinal family study with well-characterized clinical histories. Methods: Clinician interviews across three generations were used to classify family risk of depression and suicidality. Then, we created weighted network models using 108 cortical and subcortical regions of interest for 96 individuals using diffusion tensor imaging derived fiber tracts. Global and local summary measures (clustering coefficient, characteristic path length, and global and local efficiencies) and network-based statistics were utilized for group comparison of family history of depression and, separately, of suicidality, adjusted for personal psychopathology. Results: Clustering coefficient (connectivity between neighboring regions) was lower in individuals at high family risk of depression and was associated with concurrent clinical symptoms. Network-based statistics showed hypoconnected subnetworks in individuals with high family risk of depression and of suicidality, after controlling for personal psychopathology. These subnetworks highlighted cortical-subcortical connections including between the superior frontal cortex, thalamus, precuneus, and putamen. Conclusions: Family history of depression and of suicidality are associated with hypoconnectivity between subcortical and cortical regions, suggesting brain-wide impaired information processing, even in those personally unaffected.

Adverse Childhood Experiences and Risk Patterns of Alcohol and Cannabis Co-Use: A Longitudinal Study of Puerto Rican Youth.

PURPOSE: Adverse childhood experiences (ACEs) are common in Puerto Rican youths. Few large longitudinal studies of Latine youth examined what predicts co-use of alcohol and cannabis in late adolescence and young adulthood. We investigated the prospective association between ACEs with alcohol/cannabis co-use in Puerto Rican youth. METHODS: Participants from a longitudinal study of Puerto Rican youth (n = 2,004) were included. Using multinomial logistic regressions to test associations between prospectively reported ACEs (11 types, reported by parents and/or children, categorized as 0-1, 2-3, and 4+ ACEs) with young adult alcohol/cannabis use patterns in the past month (i.e., no lifetime use, low-risk [no binge drinking and cannabis use < 10], binge-drinking only, regular cannabis use only, and alcohol/cannabis co-use). Models were adjusted for sociodemographic variables. RESULTS: In this sample, 27.8% reported 4+ ACEs, 28.6% endorsed binge drinking, 4.9% regular cannabis use, and 5.5% alcohol/cannabis co-use. Compared to individuals with no lifetime use, those reporting 4+ (vs. 0-1) ACEs had greater odds of low-risk use (adjusted odds ratio [aOR] 1.60, 95% confidence interval [CI] = 1.04-2.45), regular cannabis use (aOR 3.13 95% CI = 1.44-6.77), and alcohol/cannabis co-use (aOR 3.57, 95% CI = 1.89-6.75). In relation to low-risk use, reporting 4+ ACEs (vs. 0-1) was associated with 1.96 odds (95% CI = 1.01-3.78) of regular cannabis use and 2.24 odds (95% CI = 1.29-3.89) of alcohol/cannabis co-use. DISCUSSION: Exposure to 4+ ACEs was associated with the occurrence of adolescent/young adulthood regular cannabis use and alcohol/cannabis co-use. Importantly, ACEs exposure differentiated young adults who were co-using compared to those engaged in low-risk use. Preventing ACE or interventions for Puerto Rican youth experiencing 4+ ACEs may mitigate negative consequences associated with alcohol/cannabis co-use.