Risk Of Psychiatric Disorders Research Articles

Cardiomyopathies and Psychiatric Disorders: An Overview and General Clinical Recommendations.

The association between cardiomyopathies (CMPs) and psychiatric disorders is a complex and bidirectional phenomenon that involves multiple mechanisms and factors. CMPs may raise the risk of psychiatric disorders due to the psychological stress, physical limitations, social isolation, or poor prognosis associated with the underlying disease. Psychiatric disorders, on the other hand, can increase the possibility of developing or worsening CMPs due to the behavioral, neuroendocrine, inflammatory, or pharmacological effects of mental illness or its treatment. Moreover, some common genetic or environmental factors may have a relevant influence on both conditions. With this comprehensive review, we sought to provide an overview of the current evidence on the strict and intriguing interconnection between CMPs and psychiatric disorders, focusing on the epidemiology, pathophysiology, clinical implications, and management strategies.

Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study

BackgroundHearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time.MethodsThis was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders.ResultsA total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723–3.346, p < 0.001).ConclusionOur findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients’ psychological status.Trial registration TSGHIRB No. E202216036.

Genetic predisposition for negative affect predicts mental health burden during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic was accompanied by an increase in mental health challenges including depression, stress, loneliness, and anxiety. Common genetic variants can contribute to the risk for psychiatric disorders and may present a risk factor in times of crises. However, it is unclear to what extent polygenic risk played a role in the mental health response to the COVID-19 pandemic. In this study, we investigate whether polygenic scores (PGSs) for mental health-related traits can distinguish between four resilience-vulnerability trajectories identified during the COVID-19 pandemic and associated lockdowns in 2020/21. We used multinomial regression in a genotyped subsample (n = 1316) of the CovSocial project. The most resilient trajectory characterized by the lowest mental health burden and the highest recovery rates served as the reference group. Compared to this most resilient trajectory, a higher value on the PGS for the well-being spectrum decreased the odds for individuals to be in one of the more vulnerable trajectories (adjusted R-square = 0.3%). Conversely, a higher value on the PGS for neuroticism increased the odds for individuals to be in one of the more vulnerable trajectories (adjusted R-square = 0.2%). Latent change in mental health burden extracted from the resilience-vulnerability trajectories was not associated with any PGS. Although our findings support an influence of PGS on mental health during COVID-19, the small added explained variance suggests limited utility of such genetic markers for the identification of vulnerable individuals in the general population.

Susceptibility to Treatment-Resistant Depression Within Families

Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes. To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data. This cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26 554 001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34 467). A 1:4 comparison group (n = 137 868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship. Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality. This study included 172 335 participants (88 330 male and 84 005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings. To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.

Dispositional Mindfulness and Neural Activity in Youth: A Systematic Review

Abstract Objectives Dispositional mindfulness has been associated with improved emotional regulation, reduced stress, and increased well-being. Interventions aiming at developing dispositional mindfulness are thus promising non-invasive, early interventions for youth at risk for psychiatric disorders. However, little is known about the neural correlates of dispositional mindfulness in adolescents although this could inform response to preventive interventions in youth. This systematic review identified and synthesized existing literature on the functional MRI correlates of dispositional mindfulness in adolescents, to guide and pave the way for interventional studies. Method This systematic review included observational studies investigating resting-state or task-based fMRI correlates of mindfulness traits in participants aged between 6 and 25 years, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched up to October 2023, and narrative synthesis of the extracted results was conducted. Results The 7 included studies (out of the 2348 screened) had one task-based and six resting state analyses. We focused on reporting resting state studies, where neural correlates of dispositional mindfulness were found in various brain regions, including the frontal cortex, the insula, the thalamus. It was also related to transitions between brain states. These findings suggest that dispositional mindfulness may be associated to underlying processes such as attention, emotion regulation and mind wandering. Conclusions Due to the low number of papers, it is difficult to reach a conclusion. Given the need to further investigate the neural correlates of dispositional mindfulness in adolescents to understand the positive behavioral outcomes that are associated with mindfulness, we suggest caveats and perspectives for future studies. Preregistration This systematic review is not preregistered.

Assessment of mental health and quality of life among children with congenital heart disease.

The current study aimed to determine the prevalence of specific psychiatric disorders, identify predictors associated with these disorders, and assess the quality of life (QoL) among children with congenital heart disease. This comparative cross-sectional study was conducted in the National Heart Institute outpatient clinics. It included 204 children with structural congenital heart defects (CHD). In addition to assessing QoL with the Pediatric Quality of Life Inventory scale, the Mini-International Neuropsychiatric Interview for Children and Adolescents was utilized to identify psychiatric disorders in the children studied. Children with CHD were at increased risk for mood and anxiety disorders. They were also more susceptible to obsessive-compulsive disorder than the comprative healthy group. In children with CHD, the cyanotic group demonstrated a greater decrease in QoL than the acyanotic group. Children with CHD have an increased risk of psychiatric disorders and a lower overall QoL score.

Eating Disorders and Suicidal Ideation in Morbid and Non-morbid Type 2 Diabetes Mellitus: A Cross-sectional Study

Background: Patients with chronic illnesses like type 2 diabetes mellitus (T2DM) are at a higher risk of depression and psychiatric disorders, potentially leading to adverse outcomes. Eating disorders appear to be one of the factors contributing to T2DM and resulting in poor glycemic control and complications. Objectives: This study aimed to compare the prevalence of eating disorders and suicidal ideation between morbid and non-morbid T2DM patients. Methods: A cross-sectional questionnaire was conducted at the Yazd Diabetes Research Center from August 2021 to March 2022. A total of 232 T2DM patients aged between 30 and 65 were included in the study. Through convenience sampling, data were collected using structured questionnaires to assess eating disorders, suicidal ideation, and demographic information. Statistical analyses were performed to evaluate the associations between variables. Results: The study revealed that there was no statistically significant difference in the prevalence of eating disorders between the two groups of T2DM patients (P = 0.083). However, upon considering age as a contributing factor, it was observed that younger patients afflicted with morbid T2DM exhibited a markedly higher incidence of eating disorders when compared to their non-morbid counterparts (P = 0.019). In contrast, a significant distinction emerged in terms of suicidal ideation between the two groups (P = 0.015), with patients suffering from morbid T2DM reporting elevated rates of contemplating suicide. Subgroup analyses further underscored a heightened prevalence of suicidal ideation among female patients and those aged 30 - 59 who were afflicted with morbid T2DM. Conclusions: This study highlights the importance of mental health assessment in T2DM patients, particularly those with morbid disease, younger age, higher Body Mass Index (BMI), and poor glycemic control. Early detection and intervention for eating disorders and suicidal ideation could significantly improve the overall well-being and outcomes of T2DM patients.

Alcohol drinking, DNA methylation and psychiatric disorders: A multi-omics Mendelian randomization study to investigate causal pathways.

Whether alcohol-related DNA methylation has a causal effect on psychiatric disorders has not been investigated. Furthermore, a comprehensive investigation into the causal relationship and underlying mechanisms linking alcohol consumption and psychiatric disorders has been lacking. This study aimed to evaluate the causal effect of general alcohol intake and pathological drinking behaviors on psychiatric disorders, alcohol-associated DNA methylation on gene expression and psychiatric disorders, and gene expression on psychiatric disorders. Two-sample design Mendelian randomization (MR) analysis. Various sensitivity and validation analyses, including colocalization analysis, were conducted to test the robustness of the results. Genome-wide association study (GWAS) data mainly from GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), Genetics of DNA Methylation Consortium (GoDMC) and Psychiatric Genomics Consortium (PGC) with European ancestry. The GWAS summary data on general alcohol intake (drinks per week, n = 941 280), pathological drinking behaviors (including alcohol use disorder [AUD, n = 313 959] and problematic alcohol use [PAU, n = 435 563]) and psychiatric disorders (including schizophrenia, major depressive disorder and bipolar disorder, n = 51 710-500 199) were included. Alcohol-related DNA methylation CpG sites (n = 9643) and mQTL data from blood (n = 27 750) and brain (n = 1160), BrainMeta v2 and GTEx V8 eQTL summary data (n = 73-2865) were also included. Genetic variants were selected as instrumental variables for exposures, including drinks per week, AUD, PAU, alcohol-related DNA methylation CpG sites (mQTL) and genes selected (eQTL). Pathological drinking behaviors were associated with an increased risk of psychiatric disorders after removing outliers or controlling for alcohol consumption. MR analysis identified 10 alcohol-related CpG sites with colocalization evidence that were causally associated with psychiatric disorders (P = 1.65 × 10-4-7.52 × 10-22). Furthermore, the expression of genes (RERE, PTK6, GATAD2B, COG8, PDF and GAS5) mapped to these CpG sites in the brain, led by the cortex, were significantly associated with psychiatric disorders (P = 1.19 × 10-2-3.51 × 10-7). Pathological drinking behavior and alcohol-related DNA methylation appear to have a causal effect on psychiatric disorders. The expression of genes regulated by the alcohol-related DNA methylation sites may underpin this association.

Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population.

Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n = 26,101), contemporary control with no evidence of infection (n = 380,337) and historical control predating the pandemic (n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42-1.67; P = 1.70 × 10-24; difference in incidence rate: 27.36, 95% CI 21.16-34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70-2.78; P = 5.80 × 10-10) than those not hospitalized (1.41, 1.30-1.53; P = 1.46 × 10-16), and were reduced in fully vaccinated people (0.97, 0.80-1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49-1.79; P = 4.95 × 10-26). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78-1.07; P = 0.278) but increased prescription risk (1.42, 1.00-2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.

Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice.

Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.

Relationship between Iron Saturation Indices and Psychiatric Disorders among Persons Seeking Care at Selected Psychiatry Health Facilities in Ghana

Aim: This study investigated the relationship between iron metabolism and psychiatric disorder and whether iron saturation indices could predict disease severity.&#x0D; Study Design: The study was a case-control study.&#x0D; Place and Duration of Study: The study was conducted between December 2020 to March 2022 in some selected psychiatric facilities in Ghana.&#x0D; Methodology: Venous blood was collected and serum iron, TIBC, ferritin, transferrin and full blood count were quantified to calculate intraindividual variation and to assess the relationships of these iron saturation indices to severity of psychiatric disorders.&#x0D; Results: Serum iron (38.98±14.55 µmol/L), ferritin (100.23±84.98 ng/mL) and transferrin saturation (44.35±14.6%) were significantly (p&lt;0.05) higher in group with psychiatric disorders compared with the controls (29.25±8.0 µmol/L; 75.25±42.71 ng/mL and 28.66±7.1%). However, total iron binding capacity (TIBC) (102.47±15.01 µmol/L), UIBC (73.22±13.12 µmol/L) and transferrin (4.08±0.6 g/L) concentrations were considerably greater in control group than in the case subjects (88.95±19.73 µmol/L; 49.97±18.32 µmol/L and 3.54±0.79 g/L). One unit increase in BMI is associated with 1.27 (aOR=1.27, p&lt;0.001) times risk of psychiatric disorders and males are 6 (aOR=5.87, p&lt;0.005) times at risk of disorders. At a cut off of ≤65.79 µmol/L, UIBC can distinguish psychiatric disorders from controls.&#x0D; Conclusion: Serum iron and transferrin saturation appears to be good prognostic markers of diseases severity but serum iron at cut off of &gt;35.23 µmol/L better classified individuals of severe form of psychiatric disorder.

The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders

The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders

Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

Childhood adversity modulates structural brain changes in borderline personality but not in major depression disorder

Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.

Causal links between sedentary behavior, physical activity, and psychiatric disorders: a Mendelian randomization study

BackgroundStudies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach.MethodsPotential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran’s Q test, the MR–Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis.ResultsAccording to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001–1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914–0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010–0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567–0.912; P = 0.006).ConclusionThe study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Pattern of Risks for Psychiatric and Substance Use Disorders in the Offspring of Parents With Alcohol Use Disorder.

The authors sought to clarify the components of the familial liability to alcohol use disorder (AUD) by examining parent-offspring transmission in a large Swedish population sample. To this end, 1,244,516 offspring in intact families with a mean age at follow-up of 37.7 years (SD=6.8) were examined. Hazard ratios for offspring of parents with AUD were calculated using Cox models for risk of five disorders assessed from Swedish medical and criminal registries: AUD, drug use disorders, attention deficit hyperactivity disorder, major depression, and anxiety disorders. The hazard ratio for the offspring was highest for AUD (hazard ratio=2.36), followed by drug use disorder (hazard ratio=2.04), attention deficit hyperactivity disorder (hazard ratio=1.82), major depression (hazard ratio=1.43), and anxiety disorder (hazard ratio=1.43). The risks for AUD were statistically indistinguishable between the children having mothers with AUD compared with those having fathers with AUD and between sons and daughters of a parent with AUD. All risks for offspring having two parents with AUD were higher than those having one parent with AUD, but the increase with two parents with AUD was greatest for AUD, followed by drug use disorder and attention deficit hyperactivity disorder. Age at AUD onset of the parents predicted risk among the offspring more strongly for AUD and drug use disorder, followed by attention deficit hyperactivity disorder, and then major depression and anxiety disorders. Number of recurrences of the parents with AUD predicted risks for all disorders equally. The risk pattern of disorders for the offspring of not-lived-with fathers with AUD was similar to that in the main analysis of intact families. No evidence was found for sex-specific transmission of AUD or a familial female protective effect. Familial and likely genetic liability to AUD has three components: a nonspecific risk of common internalizing and externalizing disorders, a moderately specific risk of externalizing disorders, and a highly specific risk of AUD.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Maternal experienced bereavement and offspring mental health in early adulthood: the role of modifiable parental factors.

It is estimated that 78% of children experience the death of a close friend or family member by 16 years of age, yet longitudinal research examining the mental health outcomes of wider experiences of bereavement is scarce. We conducted a longitudinal investigation of the association between maternal experienced bereavement before the age of 11 years and offspring depressive and anxiety disorders at age 18 and examined moderation of this association by modifiable parental factors. We analysed data from the Avon Longitudinal Study of Parents and Children, a UK-based birth cohort, including 9,088 child participants with data available on bereavement. Bereavement was measured via maternal report at eight timepoints until children were 11 years. Offspring depressive and anxiety-related disorders were self-reported at 18 years old using the Clinical Interview Schedule-Revised (CIS-R). The potential moderating roles of maternal anxiety, maternal depression, parental monitoring, positive parenting and negative parenting practices were examined. Maternal experienced bereavement was not associated with depression or anxiety-related disorders in early adulthood among offspring. In addition, no support was found for negative parenting practices, parental monitoring or maternal anxiety and depression as moderators of the relationship between maternal experienced bereavement and offspring mental health problems at 18 years old. Findings in relation to the moderating role of positive parenting practices were inconsistent. Findings suggest that a large number of children are exposed to maternal experienced bereavement. We found no evidence that maternal experienced bereavement during childhood increases the risk for offspring psychiatric disorders in early adulthood. Several methodological considerations prudent to bereavement research are discussed.

Estimating the direct effects of the genetic liabilities to bipolar disorder, schizophrenia, and behavioral traits on suicide attempt using a multivariable Mendelian randomization approach.

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data from the Psychiatric Genomics Consortium (PGC) and the UK Biobank (UKB), we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the putative causal effect of BD (41,917 cases, 371,549 controls) and SZ (53,386 cases, 77,258 controls) on SA (26,590 cases, 492,022 controls). Then, we assessed the putative causal effect of BD and SZ on behavioral traits, socioeconomic factors, and substance use disorders. Considering the associations identified, we evaluated the direct causal effect of behavioral traits, socioeconomic factors, and substance use disorders on SA using a multivariable MR approach. The genetic liabilities to BD and SZ were associated with higher odds of SA (BD odds ratio (OR) = 1.24, p = 3.88 × 10-12; SZ OR = 1.09, p = 2.44 × 10-20). However, while the effect of mental distress (OR = 1.17, p = 1.02 × 10-4) and risk-taking (OR = 1.52, p = 0.028) on SA was independent of SZ genetic liability, the BD-SA relationship appeared to account for the effect of these risk factors. Similarly, the association with loneliness on SA was null after accounting for the effect of SZ genetic liability. These findings highlight the complex interplay between genetic risk of psychiatric disorders and behavioral traits in the context of SA, suggesting the need for a comprehensive mental health assessment for high-risk individuals.

SARS-CoV-2 Infection and Risk of Postacute Psychiatric and Neurologic Diagnoses: A Nationwide Danish Cohort Study.

The extent and burden of postacute psychiatric and neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not yet fully understood. To evaluate the association between SARS-CoV-2 infection and postacute manifestations of psychiatric and neurologic disorders, we conducted a nationwide cohort study including the entire Danish population aged 12 years or older on March 1, 2020. Individuals were followed up for SARS-CoV-2 infection and diagnosis of subsequent psychiatric and neurologic disorders from March 1, 2020, to January 31, 2023, using the Danish nationwide coronavirus disease 2019 (COVID-19) test surveillance database and the Danish National Patient Registry. The main period of interest was 1-12 months after infection. Incidence rate ratios (IRRs) of new onset of 11 psychiatric and 30 neurologic disorders were calculated by comparing incidence rates of disorders between SARS-CoV-2-positive individuals and individuals without a positive test (nonpositive individuals). Stratified analyses were conducted according to COVID-19 vaccination status, variant period, age, sex, and severity of infection. Overall, 1,775,639 individuals in the study cohort (n = 3,239,008) were tested SARS-CoV-2 positive during follow-up. SARS-CoV-2-positive individuals compared with nonpositive individuals were at 24% reduced risk of any psychiatric disease (IRR 0.76, 95% CI 0.74-0.78) in the postacute period. The risk of any neurologic disorder was slightly higher among SARS-CoV-2-positive individuals than among those without a positive test (IRR 1.05, 95% CI 1.04-1.07). IRRs for specific disorders varied considerably from a 3.9-fold increased risk of change in sense of smell or taste (IRR 3.91, 95% CI 2.77-5.53) to a 29% reduced risk of dementia (IRR 0.71, 95% CI 0.65-0.78). The severity of infection and vaccination status, more so than age, sex, and variant, were found to significantly influence the stratified IRRs. Compared with nonpositive individuals, hospitalized patients with COVID-19 were at a 2.1-fold (IRR 2.05, 95% CI 1.78-2.37) increased risk of psychiatric disorders and at a 2.4-fold increased risk of neurologic disorders (IRR 2.44, 95% CI 2.29-2.60). Our study does not support previous findings of substantial postacute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals, but does corroborate an elevated risk among the most severe cases with COVID-19.