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.

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.

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.

Religiosity and longitudinal change in psychosocial functioning in adult offspring of depressed parents at high risk for major depression.

BACKGROUND: Recent findings suggest that beliefs about religious or spiritual importance or attending religious/spiritual services may protect high-risk offspring against depression. This research has not extended to examining religiosity in relation to psychosocial functioning in high-risk offspring. METHODS: Offspring selected for having a depressed parent and offspring of nondepressed parents were evaluated for lifetime major depressive disorder (MDD) in childhood and adolescence, and at 10-year (T10) and 20-year (T20) follow-ups. Relations between self-reported religiosity at T10 and longitudinal change in psychosocial function from T10 to T20 (assessed by clinical ratings on Global Assessment Scale [GAS]) were examined separately in 109 daughters and 76 sons by risk status. RESULTS: Lifetime MDD was diagnosed in 57.8% of daughters and 40.8% of sons by T20. Among daughters, only those with lifetime MDD showed improved psychosocial functioning in relation to higher level of service attendance at T10, their mean GAS score improving by 3.5 points (P = .018) over the next decade. For daughters with and without lifetime MDD, relations between higher levels of religiosity and improved psychosocial function were of greater magnitude in those with a depressed parent. Among sons, only those with lifetime MDD showed improved psychosocial function in relation to higher level of religious/spiritual importance, their mean GAS score improving by 4.6 points (P < .0001) over the next decade; that relation was of greater magnitude in sons with both lifetime MDD and a depressed parent. CONCLUSIONS: Greater improvement in psychosocial functioning in relation to religious involvement in more vulnerable offspring supports religiosity as a resilience factor.

Feedback negativity and feedback-related P3 in individuals at risk for depression: Comparing surface potentials and current source densities.

Blunted responses to reward feedback have been linked to major depressive disorder (MDD) and depression risk. Using a monetary incentive delay task (win, loss, break-even), we investigated the impact of family risk for depression and lifetime history of MDD and anxiety disorder with 72-channel electroencephalograms (EEG) recorded from 29 high-risk and 32 low-risk individuals (15-58 years, 30 male). Linked-mastoid surface potentials (ERPs) and their corresponding reference-free current source densities (CSDs) were quantified by temporal principal components analysis (PCA). Each PCA solution revealed a midfrontal feedback negativity (FN; peak around 310 ms) and a posterior feedback-P3 (fb-P3; 380 ms) as two distinct reward processing stages. Unbiased permutation tests and multilevel modeling of component scores revealed greater FN to loss than win and neutral for all stratification groups, confirming FN sensitivity to valence. Likewise, all groups had greater fb-P3 to win and loss than neutral, confirming that fb-P3 indexes motivational salience and allocation of attention. By contrast, group effects were subtle, dependent on data transformation (ERP, CSD), and did not confirm reduced FN or fb-P3 for at-risk individuals. Instead, CSD-based fb-P3 was overall reduced in individuals with than without MDD history, whereas ERP-based fb-P3 was greater for high-risk individuals than for low-risk individuals for monetary, but not neutral outcomes. While the present findings do not support blunted reward processing in depression and depression risk, our side-by-side comparison underscores how the EEG reference choice affects the characterization of subtle group differences, strongly advocating the use of reference-free techniques.

Subcortical volumes in offspring with a multigenerational family history of depression - A study across two cohorts.

BACKGROUND: Having multiple previous generations with depression in the family increases offspring risk for psychopathology. Parental depression has been associated with smaller subcortical brain volumes in their children, but whether two prior generations with depression is associated with further decreases is unclear. METHODS: Using two independent cohorts, 1) a Three-Generation Study (TGS, N = 65) with direct clinical interviews of adults and children across all three generations, and 2) the Adolescent Brain Cognitive Development Study (ABCD, N = 10,626) of 9-10 year-old children with family history assessed by a caregiver, we tested whether having more generations of depression in the family was associated with smaller subcortical volumes (using structural MRI). RESULTS: In TGS, caudate, pallidum and putamen showed decreasing volumes with higher familial risk for depression. Having a parent and a grandparent with depression was associated with decreased volume compared to having no familial depression in these regions. Putamen volume was associated with depression at eight-year follow-up. In ABCD, smaller pallidum and putamen were associated with family history, which was driven by parental depression, regardless of grandparental depression. LIMITATIONS: Discrepancies between cohorts could be due to interview type (clinical or self-report) and informant (individual or common informant), sample size or age. Future analyses of follow-up ABCD waves will be able to assess whether effects of grandparental depression on brain markers become more apparent as the children enter young adulthood. CONCLUSIONS: Basal ganglia regional volumes are significantly smaller in offspring with a family history of depression in two independent cohorts.

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.

Mental and physical health consequences of the September 11, 2001 (9/11) attacks in primary care: a longitudinal study.

The magnitude of the September 11, 2001 (9/11) attacks was without precedent in the United States, but long-term longitudinal research on its health consequences for primary care patients is limited. We assessed the prevalence and exposure-related determinants of mental disorders, functioning, general medical conditions, and service utilization, 1 and 4 years after the 9/11 attacks, in an urban primary care cohort (N = 444) in Manhattan. Although the prevalence of posttraumatic stress disorder (PTSD) and levels of functional impairment declined over time, a substantial increase in suicidal ideation and missed work was observed. Most medical outcomes and service utilization indicators demonstrated a short-term increase after the 9/11 attacks (mean change of +20.3%), followed by a minor decrease in the subsequent year (mean change of -3.2%). Loss of a close person was associated with the highest risk for poor mental health and functional status over time. These findings highlight the importance of longitudinal assessments of mental, functional, and medical outcomes in urban populations exposed to mass trauma and terrorism.

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.

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.

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.

Cognitive Function in People With Familial Risk of Depression.

Importance: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span. Objective: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Design, Setting, and Participants: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022. Exposures: Family history (across 1 or 2 prior generations) and polygenic risk of depression. Main Outcomes and Measures: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons. Results: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were -0.55 (95% CI, -1.49 to 0.38) in TGS, -0.09 (95% CI, -0.15 to -0.03) in ABCD, -0.16 (95% CI, -0.31 to -0.01) in Add Health, and -0.10 (95% CI, -0.13 to -0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models. Conclusions and Relevance: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span.

Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets.

Organization of the social cognition network predicts future depression and interpersonal impairment: a prospective family-based study.

Deficits in social cognition and functioning are common in major depressive disorder (MDD). Still, no study into the pathophysiology of MDD has examined the social cognition-related neural pathways through which familial risk for MDD leads to depression and interpersonal impairments. Using resting-state fMRI, we applied a graph theoretical analysis to quantify the influence of nodes within the fronto-temporo-parietal cortical social cognition network in 108 generation 2 and generation 3 offspring at high and low-risk for MDD, defined by the presence or absence, respectively, of moderate to severe MDD in generation 1. New MDD episodes, future depressive symptoms, and interpersonal impairments were tested for associations with social cognition nodal influence, using regression analyses applied in a generalized estimating equations approach. Increased familial risk was associated with reduced nodal influence within the network, and this predicted new depressive episodes, worsening depressive symptomatology, and interpersonal impairments, 5-8 years later. Findings remained significant after controlling for current depressive/anxiety symptoms and current/lifetime MDD and anxiety disorders. Path-analysis models indicate that increased familial risk impacted offspring's brain function in two ways. First, high familial risk was indirectly associated with future depression, both new MDD episodes and symptomatology, via reduced nodal influence of the right posterior superior temporal gyrus (pSTG). Second, high familial risk was indirectly associated with future interpersonal impairments via reduced nodal influence of right inferior frontal gyrus (IFG). Finally, reduced nodal influence was associated with high familial risk in (1) those who had never had MDD at the time of scanning and (2) a subsample (n = 52) rescanned 8 years later. Together, findings reveal a potential pathway for the intergenerational transmission of vulnerability via the aberrant social cognition network organization and suggest using the connectome of neural network related to social cognition to identify intervention and prevention targets for those particularly at risk.

Prospectively Predicting Adult Depressive Symptoms from Adolescent Peer Dysfunction: a Sibling Comparison Study.

Previous studies have shown that peer dysfunction in adolescence predicts depression in adulthood, even when controlling for certain individual- and/or family-level characteristics. However, these studies have not controlled for numerous potential familial confounders, precluding causal inferences. The present study therefore used a sibling comparison design (i.e., comparing siblings within families) to test whether peer dysfunction (e.g., lack of friendships, victimization) in adolescence continues to predict depression in adulthood after accounting for unmeasured familial confounds and individual characteristics in adolescence. Participants' (N = 85) dysfunction with peers was assessed in adolescence (Mage = 13.21, SD = 3.47) by self- and parent-report, and adult depressive symptoms were assessed up to five times, up to 38 years later. Multilevel modeling was used to examine the effect of adolescent peer dysfunction on adult depressive symptoms after adjusting for familial confounds and/or individual characteristics in adolescence (e.g., baseline depressive symptoms, dysfunctional relations with siblings/parents). Both self-reported (b = 1.28, p < 0.001) and parent-reported (b = 0.56, p = 0.032) adolescent peer dysfunction were associated with greater depressive symptom severity in adulthood in unadjusted models. Self-reported (but not parent-reported) adolescent peer dysfunction continued to predict adult depressive symptoms after controlling for familial confounding and measured covariates such as adolescent depressive symptoms and relations with siblings and parents (b = 1.06, p = 0.035). Although confidence intervals were wide and the potentially confounding effects of numerous individual-level factors were not ruled out, these findings provide preliminary evidence that perceived peer dysfunction in adolescence may be an unconfounded risk factor for depressive symptoms in adulthood.

Functional impairment in adults with past posttraumatic stress disorder: findings from primary care.

BACKGROUND: Although many patients with posttraumatic stress disorder (PTSD) experience a reduction in posttraumatic symptoms over time, little is currently known about the extent of their residual functional impairment. This study examines functional impairment in primary care patients with a history of PTSD as compared to patients with current PTSD, and those who never developed PTSD following exposure to trauma. METHODS: The sample consisted of 321 trauma-exposed low-income, predominantly Hispanic adults attending a large urban primary care practice. PTSD was assessed with the Lifetime Composite International Diagnostic Interview and other psychiatric disorders with the SCID-I. Physical and mental health-related quality of life was assessed with the Medical Outcome Health Survey (SF-12), and functional impairment with items from the Sheehan Disability Scale and Social Adjustment Scale Self-Report. RESULTS: Logistic regression analyses controlling for gender, psychiatric comorbidity, and interpersonal traumas showed that although patients with past PTSD function significantly better than patients with current PTSD, they experience persisting deficits in mental health-related quality of life compared to trauma-exposed patients who never developed PTSD. Overall, results revealed a continuum of severity in psychiatric comorbidity, functioning, and quality of life, with current PTSD associated with the most impairment, never having met criteria for PTSD with the least impairment, and history of PTSD falling in between. CONCLUSIONS: In this primary care sample, adults with a history of past PTSD but no current PTSD continued to report enduring functional deficits, suggesting a need for ongoing clinical attention.

Enduring problems in the offspring of depressed parents followed up to 38 years.

BACKGROUND: while the increased risk of major depressive disorder (MDD) in offspring of depressed parents is one of the best-replicated findings in psychiatry, their long-term outcomes are less well known. The clinical outcomes of biological offspring of depressed (high-risk) and not depressed (low-risk) parents who have been directly interviewed over the years are presented. METHODS: a longitudinal retrospective cohort study began in 1982, and 276 biological offspring of moderately-to-severely depressed or non-depressed parents from the same community were followed up to 38 years. Rates of psychiatric disorders for offspring were collected by clinically trained interviewers. Final diagnoses were made by M.D. or Ph.D. clinicians. Mortality and cause of death were obtained from relatives and registries. FINDINGS: high- compared to low-risk offspring continue to have about a three-fold increased risk of MDD, increased rates of anxiety disorder, substance dependence, and poorer functioning over the life course. Adolescence and early adulthood remain prime age of first onsets. Within high-risk group only, the death rate due to unnatural causes, suicides and overdose was 4·97/100 in the offspring and 5·36/100 in their parents. This subsample of White, lower-educated, often unemployed persons, who died by unnatural causes are similar demographically to those described as having a recent increase in 'deaths of despair'. INTERPRETATION: family history of MDD continues to be a powerful predictor of clinical course and mortality and should be probed in clinical visits, especially in youth when depression usually first appears.

Altered Dentate Gyrus Microstructure in Individuals at High Familial Risk for Depression Predicts Future Symptoms.

BACKGROUND: Offspring of individuals with major depressive disorder (MDD) are at increased risk for developing MDD themselves. Altered hippocampal, and specifically dentate gyrus (DG), structure and function may be involved in depression development. However, hippocampal abnormalities could also be a consequence of the disease. For the first time, we tested whether abnormal DG micro- and macrostructure were present in offspring of individuals with MDD and whether these abnormalities predicted future symptomatology. METHODS: We measured the mean diffusivity of gray matter, a measure of microstructure, via diffusion tensor imaging and volume of the DG via structural magnetic resonance imaging in 102 generation 2 and generation 3 offspring at high and low risk for depression, defined by the presence or absence, respectively, of moderate to severe MDD in generation 1. Prior, current, and future depressive symptoms were tested for association with hippocampal structure. RESULTS: DG mean diffusivity was higher in individuals at high risk for depression, regardless of a lifetime history of MDD. While DG mean diffusivity was not associated with past or current depressive symptoms, higher mean diffusivity predicted higher symptom scores 8 years later. DG microstructure partially mediated the association between risk and future symptoms. DG volume was smaller in high-risk generation 2 but not in high-risk generation 3. CONCLUSIONS: Together, these findings suggest that the DG has a role in the development of depression. Furthermore, DG microstructure, more than macrostructure, is a sensitive risk marker for depression and partially mediates future depressive symptoms.

Dissociating disorders of depression, anxiety, and their comorbidity with measures of emotional processing: A joint analysis of visual brain potentials and auditory perceptual asymmetries.

In a multigenerational study of families at risk for depression, individuals with a lifetime history of depression had: 1) abnormal perceptual asymmetry (PA; smaller left ear/right hemisphere [RH] advantage) in a dichotic emotion recognition task, and 2) reduced RH late positive potential (P3RH) during an emotional hemifield task. We used standardized difference scores for processing auditory (PA sad-neutral) and visual (P3RH negative-neutral) stimuli for 112 participants (52 men) in a logistic regression to predict history of depression, anxiety or comorbidity of both. Whereas comorbidity was separately predicted by reduced PA (OR = 0.527, p = .042) or P3RH (OR = 0.457, p = .013) alone, an interaction between PA and P3RH (OR = 2.499, p = .011) predicted depressive disorder. Follow-up analyses revealed increased probability of depression at low (lack of emotional differentiation) and high (heightened reactivity to negative stimuli) levels of both predictors. Findings suggest that reduced or heightened right-lateralized emotional responsivity to negative stimuli may be uniquely associated with depression.