Identifying genetic differences between bipolar disorder and major depression through multiple GWAS.

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

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.

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.

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.

Trends in Healthcare Service Disruptions and Associations with COVID-19 Outcomes among Patients with SMI vs. Non-SMI during COVID-19.

Objective: The study aims to quantify differential changes in outpatient mental health service utilization among 3,724,348 individuals, contrasting those with Severe Mental Illness (SMI) to those without, in the context of the COVID-19 pandemic. Design & Setting: A retrospective cohort study was conducted, utilizing data from Healthix, the second-largest health information exchange in the U.S. Participants: The study population included 3,134,959 Non-SMI patients (84.2%), 355,397 SMI patients (9.5%), and 149,345 Recurrent SMI Patients (4.0%). Exposures: The primary exposure was the COVID-19 pandemic, with a focus on its impact on outpatient mental health services. Main Outcomes and Measures: The primary outcome was the rate of utilization of outpatient mental health services. Secondary outcomes included COVID-19 infection rates and vaccination rates among the study cohorts. Results: Among the non-SMI patients, there was a 30% decline in emergency visits from 650,000 pre-COVID to 455,000 post-COVID (OR=0.70, p < 0.001), and outpatient visits decreased by 50% from 1.2 million to 600,000 (OR=0.50, p = 0.002). In contrast, the SMI group witnessed a 20% reduction in outpatient visits from 120,000 to 96,000 (OR=0.80, p = 0.015) and a 40% decrease in inpatient visits from 50,000 to 30,000 (OR=0.60, p = 0.008). Recurrent SMI patients exhibited a 25% decline in emergency visits from 32,000 to 24,000 (OR=0.75, p = 0.03) and a 35% drop in outpatient visits from 40,000 to 26,000 (OR=0.65, p = 0.009).The pandemic influenced the type of disorders diagnosed. Non-SMI patients experienced a 23% rise in anxiety-related disorders (n=80,000, OR=1.23, p = 0.01) and an 18% increase in stress-related disorders (n=70,000, OR=1.18, p = 0.04). SMI patients had a 15% surge in severe anxiety disorders (n=9,000, OR=1.15, p = 0.02) and a 12% uptick in substance-related disorders (n=7,200, OR=1.12, p = 0.05). Recurrent SMI patients showed a 20% increase in anxiety and adjustment disorders (n=6,400, OR=1.20, p = 0.03).SMI patients were more adversely affected by COVID-19, with a higher infection rate of 7.8% (n=45,972) compared to 4.2% (n=131,669) in non-SMI patients (OR=1.88, p < 0.001). Hospitalization rates also followed this trend, with 5.2% (n=30,648) of SMI patients being hospitalized compared to 3.7% (n=115,995) among non-SMI patients (OR=1.41, p = 0.007). Moreover, SMI patients had lower vaccination rates of 45.6% (n=268,888) versus 58.9% (n=1,844,261) among non-SMI patients (OR=0.77, p = 0.019). Conclusions: In conclusion, our findings reveal significant disparities in healthcare service utilization between individuals with Serious Mental Illness (SMI) and those without. Notably, the SMI cohort experienced greater disruptions in service continuity, with a more pronounced decline in both outpatient and inpatient visits. Furthermore, the types of disorders diagnosed among this group also saw a shift, emphasizing the need for specialized care and attention during times of crisis. The higher rates of COVID-19 infection and hospitalization among SMI patients compared to non-SMI patients underscore the urgency of targeted public health interventions for this vulnerable group. The lower vaccination rates in the SMI cohort highlight another layer of healthcare disparity that needs to be urgently addressed. These findings suggest that the pandemic has amplified pre-existing inequalities in healthcare access and outcomes for individuals with SMI, calling for immediate, evidence-based interventions to mitigate these effects and ensure equitable healthcare service provision.

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.

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.

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.

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.

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.

Alterations in resting-state functional activity and connectivity for major depressive disorder appetite and weight disturbance phenotypes.

BACKGROUND: Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing. METHODS: Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement. RESULTS: Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD. CONCLUSIONS: Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.

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.

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.

Trends in psychiatric diagnoses by COVID-19 infection and hospitalization among patients with and without recent clinical psychiatric diagnoses in New York city from March 2020 to August 2021.

Determining emerging trends of clinical psychiatric diagnoses among patients infected with the SARS-CoV-2 virus is important to understand post-acute sequelae of SARS-CoV-2 infection or long COVID. However, published reports accounting for pre-COVID psychiatric diagnoses have usually relied on self-report rather than clinical diagnoses. Using electronic health records (EHRs) among 2,358,318 patients from the New York City (NYC) metropolitan region, this time series study examined changes in clinical psychiatric diagnoses between March 2020 and August 2021 with month as the unit of analysis. We compared trends in patients with and without recent pre-COVID clinical psychiatric diagnoses noted in the EHRs up to 3 years before the first COVID-19 test. Patients with recent clinical psychiatric diagnoses, as compared to those without, had more subsequent anxiety disorders, mood disorders, and psychosis throughout the study period. Substance use disorders were greater between March and August 2020 among patients without any recent clinical psychiatric diagnoses than those with. COVID-19 positive patients (both hospitalized and non-hospitalized) had greater post-COVID psychiatric diagnoses than COVID-19 negative patients. Among patients with recent clinical psychiatric diagnoses, psychiatric diagnoses have decreased since January 2021, regardless of COVID-19 infection/hospitalization. However, among patients without recent clinical psychiatric diagnoses, new anxiety disorders, mood disorders, and psychosis diagnoses increased between February and August 2021 among all patients (COVID-19 positive and negative). The greatest increases were anxiety disorders (378.7%) and mood disorders (269.0%) among COVID-19 positive non-hospitalized patients. New clinical psychosis diagnoses increased by 242.5% among COVID-19 negative patients. This study is the first to delineate the impact of COVID-19 on different clinical psychiatric diagnoses by pre-COVID psychiatric diagnoses and COVID-19 infections and hospitalizations across NYC, one of the hardest-hit US cities in the early pandemic. Our findings suggest the need for tailoring treatment and policies to meet the needs of individuals with pre-COVID psychiatric diagnoses.

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.