The genetic contribution to the comorbidity of depression and anxiety: a multi-site electronic health records study of almost 178 000 people.

BACKGROUND: Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation. METHODS: Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry. RESULTS: In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18-1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05-1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06-1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11-1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02-1.09), showing a genetic risk gradient across the conditions and the comorbidity. CONCLUSIONS: This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

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.

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.

Association of maternal exposure to Superstorm Sandy and maternal cannabis use with development of psychopathology among offspring: the Stress in Pregnancy Study.

BACKGROUND: Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied. AIMS: To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology. METHOD: The study included 163 children (53.4% girls), longitudinally tracked (ages 2-5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed. RESULTS: A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support. CONCLUSIONS: Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.

Comorbidity and healthcare utilization in patients with treatment resistant depression: A large-scale retrospective cohort analysis using electronic health records.

BACKGROUND: Medical comorbidity and healthcare utilization in patients with treatment resistant depression (TRD) is usually reported in convenience samples, making estimates unreliable. There is only limited large-scale clinical research on comorbidities and healthcare utilization in TRD patients. METHODS: Electronic Health Record data from over 3.3 million patients from the INSIGHT Clinical Research Network in New York City was used to define TRD as initiation of a third antidepressant regimen in a 12-month period among patients diagnosed with major depressive disorder (MDD). Age and sex matched TRD and non-TRD MDD patients were compared for anxiety disorder, 27 comorbid medical conditions, and healthcare utilization. RESULTS: Out of 30,218 individuals diagnosed with MDD, 15.2 % of patients met the criteria for TRD (n = 4605). Compared to MDD patients without TRD, the TRD patients had higher rates of anxiety disorder and physical comorbidities. They also had higher odds of ischemic heart disease (OR = 1.38), stroke/transient ischemic attack (OR = 1.57), chronic kidney diseases (OR = 1.53), arthritis (OR = 1.52), hip/pelvic fractures (OR = 2.14), and cancers (OR = 1.41). As compared to non-TRD MDD, TRD patients had higher rates of emergency room visits, and inpatient stays. In relation to patients without MDD, both TRD and non-TRD MDD patients had significantly higher levels of anxiety disorder and physical comorbidities. LIMITATIONS: The INSIGHT-CRN data lack information on depression severity and medication adherence. CONCLUSIONS: TRD patients compared to non-TRD MDD patients have a substantially higher prevalence of various psychiatric and medical comorbidities and higher health care utilization. These findings highlight the challenges of developing interventions and care coordination strategies to meet the complex clinical needs of TRD patients.

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.

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.

Social connectedness as a determinant of mental health: A scoping review.

Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from research examining social connectedness as a determinant of mental health. The goal of this review was to evaluate recent longitudinal research probing the effects of social connectedness on depression and anxiety symptoms and diagnoses in the general population. A scoping review was performed of PubMed and PsychInfo databases from January 2015 to December 2021 following PRISMA-ScR guidelines using a defined search strategy. The search yielded 66 unique studies. In research with other than pregnant women, 83% (19 of 23) studies reported that social support benefited symptoms of depression with the remaining 17% (5 of 23) reporting minimal or no evidence that lower levels of social support predict depression at follow-up. In research with pregnant women, 83% (24 of 29 studies) found that low social support increased postpartum depressive symptoms. Among 8 of 9 studies that focused on loneliness, feeling lonely at baseline was related to adverse outcomes at follow-up including higher risks of major depressive disorder, depressive symptom severity, generalized anxiety disorder, and lower levels of physical activity. In 5 of 8 reports, smaller social network size predicted depressive symptoms or disorder at follow-up. In summary, most recent relevant longitudinal studies have demonstrated that social connectedness protects adults in the general population from depressive symptoms and disorders. The results, which were largely consistent across settings, exposure measures, and populations, support efforts to improve clinical detection of high-risk patients, including adults with low social support and elevated loneliness.

Putamen Structure and Function in Familial Risk for Depression: A Multimodal Imaging Study.

BACKGROUND: The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression. METHODS: The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively. RESULTS: After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, ß-left = -0.17, ß-right = -0.15, ps = .002), N-acetylaspartate/creatine ratio (ß-left= -0.40, ß-right= -0.37, ps < .0001), and activation modulated by valence (ß-left = -0.22, ß-right = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (ß-left = -0.72, p = .013; ß-right = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33). CONCLUSIONS: Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them.

Morphological Biomarkers in the Amygdala and Hippocampus of Children and Adults at High Familial Risk for Depression.

Major Depressive Disorder (MDD) is highly familial, and the hippocampus and amygdala are important in the pathophysiology of MDD. Whether morphological markers of risk for familial depression are present in the hippocampus or amygdala is unknown. We imaged the brains of 148 individuals, aged 6 to 54 years, who were members of a three-generation family cohort study and who were at either high or low familial risk for MDD. We compared surface morphological features of the hippocampus and amygdala across risk groups and assessed their associations with depression severity. High- compared with low-risk individuals had inward deformations of the head of both hippocampi and the medial surface of the left amygdala. The hippocampus findings persisted in analyses that included only those participants who had never had MDD, suggesting that these are true endophenotypic biomarkers for familial MDD. Posterior extension of the inward deformations was associated with more severe depressive symptoms, suggesting that a greater spatial extent of this biomarker may contribute to the transition from risk to the overt expression of symptoms. Significant associations of these biomarkers with corresponding biomarkers for cortical thickness suggest that these markers are components of a distributed cortico-limbic network of familial vulnerability to MDD.

Religiosity and Depression at Midlife: A Prospective Study.

OBJECTIVES: Previously, authors found high personal importance of religion/spirituality (R/S) in early adulthood to predict a 75% decreased risk of recurrence of major depression in middle adulthood. Here, the authors follow up the original study sample to examine the association between R/S and major depression from middle adulthood into midlife. METHOD: Participants were 79 of 114 original adult offspring of depressed and non-depressed parents. Using logistic regression analysis, three measures of R/S from middle adulthood (personal importance, frequency of religious service attendance, and denomination) were used to predict Major Depressive Disorder (MDD) in midlife. RESULTS: High R/S importance in middle adulthood was prospectively associated with risk for an initial onset of depression during the period of midlife. Frequency of attendance in middle adulthood was associated with recurrence of depression at midlife in the high-risk group for depression, as compared to the low-risk group. CONCLUSION: Findings suggest that the relation between R/S and depression may vary across adult development, with risk for depression associated with R/S at midlife potentially revealing a developmental process.

Extracting social determinants of health from electronic health records using natural language processing: a systematic review.

OBJECTIVE: Social determinants of health (SDoH) are nonclinical dispositions that impact patient health risks and clinical outcomes. Leveraging SDoH in clinical decision-making can potentially improve diagnosis, treatment planning, and patient outcomes. Despite increased interest in capturing SDoH in electronic health records (EHRs), such information is typically locked in unstructured clinical notes. Natural language processing (NLP) is the key technology to extract SDoH information from clinical text and expand its utility in patient care and research. This article presents a systematic review of the state-of-the-art NLP approaches and tools that focus on identifying and extracting SDoH data from unstructured clinical text in EHRs. MATERIALS AND METHODS: A broad literature search was conducted in February 2021 using 3 scholarly databases (ACL Anthology, PubMed, and Scopus) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 6402 publications were initially identified, and after applying the study inclusion criteria, 82 publications were selected for the final review. RESULTS: Smoking status (n = 27), substance use (n = 21), homelessness (n = 20), and alcohol use (n = 15) are the most frequently studied SDoH categories. Homelessness (n = 7) and other less-studied SDoH (eg, education, financial problems, social isolation and support, family problems) are mostly identified using rule-based approaches. In contrast, machine learning approaches are popular for identifying smoking status (n = 13), substance use (n = 9), and alcohol use (n = 9). CONCLUSION: NLP offers significant potential to extract SDoH data from narrative clinical notes, which in turn can aid in the development of screening tools, risk prediction models, and clinical decision support systems.

Altruism and "love of neighbor" offer neuroanatomical protection against depression.

We prospectively investigate protective benefits against depression of cortical thickness across nine regions of a Ventral Frontotemporal Network (VFTN), previously associated with spiritual experience. Seventy-two participants at high and low risk for depression (Mean age 41 years; 22-63 years; 40 high risk, 32 low risk) were drawn from a three-generation, thirty-eight year study. FreeSurfer estimated cortical thickness over anatomical MRIs of the brain (Year 30) for each of the nine ROIs. Depression (MDD with SAD-L; symptoms with PHQ; Years 30 and 38) and spirituality (self-report on five phenotypes; Year 35), respectively, were associated with the weighted average of nine regions of interest. VFTN thickness was: 1) positively associated (p<0.01) with two of five spiritual phenotypes, altruism and love of neighbor, interconnectedness at a trend level, but neither commitment nor practice, 2) inversely associated with a diagnosis of MDD (SADS-L Year 30, for any MDD in the past ten years), and 3) prospectively neuroanatomically protective against depressive symptoms (PHQ-9 Year 38) for those at high familial risk.

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.

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.

Differential Association of Spirituality and Religiosity With Rumination: Implications for the Treatment of Depression.

ABSTRACT: Recent studies have shown that religiosity (R) is associated with lower rates of depression, whereas spirituality (S) is associated with higher rates. Rumination has also been associated with higher rates of depression. Some have hypothesized that rumination mediates the differential association of religiosity and spirituality with depression. We empirically test this hypothesis in a longitudinal, multigenerational sample through associations between rumination and depression, R/S and depression, and R/S and rumination. Cross-sectionally, total rumination scores were predicted by spirituality (standardized ß = 0.13; 95% confidence interval [CI], 0.00-0.26), with subscale (reflection, depression, and brooding) standardized betas ranging from 0.11 to 0.15 (95% CI, -0.03 to -0.29). Cross-sectionally, rumination was not predicted by religiosity. Longitudinally, and consistent with previous findings, religiosity, but not spirituality, predicted reduced depressive symptoms (standardized ß = -0.3; 95% CI, -0.58 to -0.01). The association between spirituality and rumination was driven by millennials. Psychotherapies that target rumination for depression might therefore be especially effective in the millennial demographic.

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.

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.

Concordance in parent and offspring cortico-basal ganglia white matter connectivity varies by parental history of major depressive disorder and early parental care.

Social behavior is transmitted cross-generationally through coordinated behavior within attachment bonds. Parental depression and poor parental care are major risks for disruptions of such coordination and are associated with offspring's psychopathology and interpersonal dysfunction. Given the key role of the cortico-basal ganglia (CBG) circuits in social communication, we examined similarities (concordance) of parent-offspring CBG white matter (WM) connections and how parental history of major depressive disorder (MDD) and early parental care moderate these similarities. We imaged 44 parent-offspring dyads and investigated WM connections between basal-ganglia seeds and selected regions in temporal cortex using diffusion tensor imaging (DTI) tractography. We found significant concordance in parent-offspring strength of CBG WM connections, moderated by parental lifetime-MDD and care. The results showed diminished neural concordance among dyads with a depressed parent and that better parental care predicted greater concordance, which also provided a protective buffer against attenuated concordance among dyads with a depressed parent. Our findings provide the first neurobiological evidence of concordance between parents-offspring in WM tracts and that concordance is diminished in families where parents have lifetime-MDD. This disruption may be a risk factor for intergenerational transmission of psychopathology. Findings emphasize the long-term role of early caregiving in shaping the neural concordance among at-risk and affected dyads.

Predicting Depression Symptoms in Families at Risk for Depression: Interrelations of Posterior EEG Alpha and Religion/Spirituality.

BACKGROUND: Posterior EEG alpha has been identified as a putative biomarker of clinical outcomes in major depression (MDD). Separately, personal importance of religion and spirituality (R/S) has been shown to provide protective benefits for individuals at high familial risk for MDD. This study directly explored the joint value of posterior alpha and R/S on predicting clinical health outcomes of depression. METHODS: Using a mixed-effects model approach, we obtained virtual estimates of R/S at age 21 using longitudinal data collected at 5 timepoints spanning 25 years. Current source density and frequency principal component analysis was used to quantify posterior alpha in 72-channel resting EEG (eyes open/closed). Depression severity was measured between 5 and 10 years after EEG collection using PHQ-9 and IDAS-GD scales. RESULTS: Greater R/S (p = .008, η2p = 0.076) and higher alpha (p = .02, η2p = 0.056) were separately associated with fewer symptoms across scales. However, an interaction between alpha and R/S (p = .02, η2p = 0.062) was observed, where greater R/S predicted fewer symptoms with low alpha but high alpha predicted fewer symptoms with lower R/S. LIMITATIONS: Small-to-medium effect sizes and homogeneity of sample demographics caution overall interpretation and generalizability. CONCLUSIONS: Findings revealed a complementary role of R/S and alpha in that either variable exerted protective effects only if the other was present at low levels. These findings confirm the relevance of R/S importance and alpha oscillations as predictors of depression symptom severity. More research is needed on the neurobiological mechanism underlying the protective effects of R/S importance for MDD.