When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population.

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two-fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders - a prospective pilot study.

BACKGROUND: Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18-49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022. METHODS: Employing a standardized strength circuit consisting of computerized strength training devices, we measured the maximal muscle strength (Fmax) using three repetitions maximum across four muscle regions (abdomen, arm, back, leg) at three time points (t1-t3) over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood lipid profiling in a clinical setting. For analysis of psychopharmacotherapy, medication was split into activating (AM) and inhibiting (IM) medication and dosages were normalized by the respective WHO defined daily dose. RESULTS: While we observed a significant decrease of the MADRS score and increase of the relative total Fmax (rTFmax) in the first two weeks (t1-t2) but not later (both p < .001), we did not reveal a significant bivariate correlation between disease severity (MADRS) and muscle strength (rTFmax) at any of the timepoints. Individuals with longer disease history displayed reduced rTFmax (p = .048). IM was significantly associated with decreased rTFmax (p = .032). Regression models provide a more substantial effect of gender, age, and IM on muscle strength than the depressive episode itself (p < .001). CONCLUSIONS: The results of the study indicate that disease severity and muscle strength are not associated in young to middle-aged inpatients with affective disorders using a strength circuit as observational measurement. Future research will be needed to differentiate the effect of medication, gender, and age on muscle strength and to develop interventions for prevention of muscle weakness, especially in younger patients with chronic affective illnesses.

The combination of olfactory dysfunction and depression increases the risk of incident dementia in older adults.

OBJECTIVES: Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk. DESIGN: Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up. PARTICIPANTS: Participants were 780 older adults (aged 70-90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline. RESULTS: Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = -.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185-2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789-.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model. CONCLUSIONS: Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

Making meaning of multimorbidity and severe mental illness: A viewpoint.

People living with severe mental illness, such as schizophrenia and bipolar affective disorder, frequently experience poorer physical health compared to those without mental illness. This issue has hitherto been approached through the disease-centred construct of comorbidity, where subsequent conditions are viewed as secondary to an 'index condition'. In contrast, this Viewpoint sets out to explain why multimorbidity, a patient-centred concept that instead refers to the coexistence of multiple chronic illnesses, is a more versatile and robust framework for tackling the issue of poor physical health in people with severe mental illness. In establishing this argument, this Viewpoint has sought to address three key areas. First, this article will discuss the epidemiology of both physical and psychiatric multimorbidity, with respect to how they manifest at greater frequency and at younger ages in people with severe mental illness. Second, the profound consequences of this multimorbidity burden will be explored, with respect to the 'three D's' of death (premature mortality), disability (functional impacts) and deficit (health-economic impacts). Finally, the utility of multimorbidity as a framework will be illustrated through a proposal for a three-dimensional multimorbidity construct composed of (1) quantity, (2) severity and (3) duration of an individual's chronic illnesses. Consequently, this Viewpoint aims to capture why it is necessary for modern psychiatry to grasp the concept of multimorbidity to facilitate holistic healthcare for people living with severe mental illness.

Peripheral Upregulation of Parkinson's Disease-Associated Genes Encoding α-Synuclein, ß-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression.

Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme ß-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.

A case-control study to differentiate parents' personality traits on anorexia nervosa and affective disorders.

Eating disorders (ED) and affective disorders (AD) in adolescent population and several investigations have pointed out that specific family dynamics play a major role in the onset, course, and maintenance of both disorders. The aim of this study was to extend the literature of this topic by exploring differences between parents' personality traits, coping strategies, and expressed emotion comparing groups of adolescents with different mental conditions (anorexia nervosa vs. affective disorder vs. control group) with a case-control study design. A total of 50 mothers and 50 fathers of 50 girls with anorexia nervosa (AN), 40 mothers and 40 fathers of 40 girls with affective disorder (AD), and 50 mothers and 50 fathers of 50 girls with no pathology that conformed the control group (CG) were measured with the Temperament and Character Inventory (TCI), the COPE Inventory, the Family Questionnaire (FQ), and psychopathology variables, anxiety, and depression. Both parents of girls with AN showed a significant difference in personality, coping strategies, and expressed emotion compared to both parents in the CG, while they presented more similarities to parents of girls in the AD group. Identifying personality traits, expressed emotion, coping strategies, and psychopathology of parents and their daughters will allow improvements in the interventions with the adolescents, parents, and families.

Hemodynamics and arrhythmia disorder caused by lithium poisoning: A case report. / 锂中毒导致心律失常、血流动力学障碍1例.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography.

BACKGROUND: Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. METHODS: Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females). RESULTS: No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT. CONCLUSIONS: In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. CLINICALTRIALS.GOV IDENTIFIER: NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).

Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

BACKGROUND: Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. METHODS: Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. RESULTS: In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). CONCLUSION: Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Light Therapy for Adolescent Depression: A Scoping Review.

PURPOSE: Depressive disorders in adolescents are a major health concern associated with developmental, social, and educational impairment. Bright Light Therapy (BLT) is a feasible and effective treatment for depressive disorders in adults, but few controlled trials have been conducted with children or adolescents. This scoping review focuses on the current state of knowledge for BLT in the treatment of adolescent depression. We reviewed the literature for novel data and methodologic approaches using BLT and pediatric and young adult populations. RECENT FINDINGS: BLT is a tolerable treatment with few side effects. However, there is a marked lack of well-powered studies to support BLT as a treatment for depressive disorders in adolescent populations. Given evidence of tolerability and positive treatment effect on depression in the adult literature, research is needed to establish the efficacy, feasibility, and acceptability of BLT in adolescents.

Absconding among admitted patients with bipolar affective disorder diagnosis in Uganda.

BACKGROUND: Hospitalization is often necessary for individuals with Bipolar affective Disorder (BAD) during severe manic or depressive episodes, as well as for stabilizing treatment regimens. However, a significant proportion of patients admitted for treatment of BAD abscond or leave the hospital without permission during their stay. In addition, patients managed for BAD may have unique characteristics that might force them into absconding. For example, the high prevalence of co-morbid substance use disorder - craving to use substances, suicidal behaviors - attempts to die by suicide, and cluster B personality disorders - characterized by impulsive acts. It is, therefore, essential to understand the factors contributing to absconding among patients with BAD, to facilitate designing strategies for preventing and managing this behavior. METHOD: This study was based on a retrospective chart review of the inpatients diagnosed with BAD at a tertiary psychiatry facility in Uganda from January 2018 to December 2021. RESULTS: Approximately 7.8% of those with BAD absconded from the hospital. The likelihood of absconding among those with BAD increased with the use of cannabis [adjusted odds ratio (aOR) = 4.00, 95% confidence interval (CI) = 1.22-13.09, p-value = 0.022] and having mood lability [aOR = 2.15, 95% CI = 1.10-4.21, p-value = 0.025]. However, receiving psychotherapy during the admission (aOR = 0.44, 95 CI = 0.26-0.74, p-value = 0.002) and treatment with haloperidol (aOR = 0.39, 95% CI = 0.18-0.83, p-value = 0.014) reduced the likelihood of absconding. CONCLUSION: Absconding among patients with BAD is common in Uganda. Those with symptoms of affective lability and those with comorbid cannabis use tend to abscond more, while those who receive haloperidol and psychotherapy are less likely to abscond.

Readmission and associated clinical factors among individuals admitted with bipolar affective disorder at a psychiatry facility in Uganda.

BACKGROUND: Bipolar affective disorder (BAD) is a common severe mental health condition with a relapsing course that may include periods of hospital re-admissions. With recurrent relapses and admissions, the course, prognosis, and patient's overall quality of life can be affected negatively. This study aims to explore the rates and clinical factors associated with re-admission among individuals with BAD. METHOD: This study used data from a retrospective chart review of all records of patients with BAD admitted in 2018 and followed up their hospital records for four years till 2021 at a large psychiatric unit in Uganda. Cox regression analysis was used to determine the clinical characteristics associated with readmission among patients diagnosed with BAD. RESULTS: A total of 206 patients living with BAD were admitted in 2018 and followed up for four years. The average number of months to readmission was 9.4 (standard deviation = 8.6). The incidence of readmission was 23.8% (n = 49/206). Of those readmitted during the study period, 46.9% (n = 23/49) and 28.6% (n = 14/49) individuals were readmitted twice and three times or more, respectively. The readmission rate in the first 12 months following discharge was 69.4% (n = 34/49) at first readmission, 78.3% (n = 18/23) at second readmission, and 87.5% (n = 12/14) at third or more times. For the next 12 months, the readmission rate was 22.5% (n = 11/49) for the first, 21.7% (n = 5/23) for the second, and 7.1% (n = 1/14) for more than two readmissions. Between 25 and 36 months, the readmission rate was 4.1% (n = 2/49) for the first readmission and 7.1% (n = 1/14) for the third or more times. Between 37 and 48 months, the readmission rate was 4.1% (n = 2/49) for those readmitted the first time. Patients who presented with poor appetite and undressed in public before admission were at increased risk of being readmitted with time. However, the following symptoms/clinical presentations, were protective against having a readmission with time, increased number of days with symptoms before admission, mood lability, and high energy levels. CONCLUSION: The incidence of readmission among individuals living with BAD is high, and readmission was associated with patients' symptoms presentation on previous admission. Future studies looking at BAD using a prospective design, standardized scales, and robust explanatory model are warranted to understand causal factors for hospital re-admission and inform management strategies.

Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior.

Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.

Homicide as the first conviction: A retrospective cohort study.

The association between previous convictions and perpetrating homicide has been previously described but little is known about the characteristics of homicide offenders without previous convictions. By utilizing the unique database on homicide offenders held by the National Confidential Inquiry into Suicide and Safety in Mental Health, this study aimed to describe the sample of homicide perpetrators in England and Wales who have committed homicide as their first offense based on their sociodemographic and clinical characteristics. Compared with those with previous convictions, homicide offenders without previous convictions were more likely to be female and a member of an ethnic minority group. More of those without previous convictions belonged to the youngest (<25) and oldest (>55) age groups and were more likely to kill somebody family member or a spouse. Schizophrenia and other delusional disorders as well as affective disorders were more prevalent in those without previous convictions as were mental illness/insanity as a circumstance in homicide, but those without previous convictions were less likely to have been in previous contact with mental health services. There are clear sociodemographic and clinical differences between homicide perpetrators with and without previous convictions. Implications of these findings are discussed.

DETERMINING THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS DIAGNOSED WITH SCHIZOPHRENIA AND BIPOLAR AFFECTIVE DISORDER.

BACKGROUND: In Schizophrenia (SCZ) and Bipolar Affective Disorder (BAD) patients using the Framingham Heart Risk Scoring (FHRS), we aimed to investigate the possible cardiac arrhythmia risk by calculating electrocardiogram (ECG) parameters (QT, QTc, Tpe, and TPE/QTc ratios), which are ventricular repolarization markers. SUBJECTS AND METHODS: A total of 140 BAD and 253 SCZ patients were included in the study. Age, blood test results (fasting blood glucose, LDL-HDL-TC levels, hemogram values), blood pressure and heart rate, smoking status, antihypertensive drug use, and FHRS were calculated from the patient files, and sociodemographic information was recorded. In addition, ECG calculations were performed, and QT, QTc, TPe, TPe/QTc ratios and heart rate were measured. RESULTS: When we evaluated the cardiac risk indexes of SCZ and BAD patients, we detected that FHRS was higher in smokers, female patients, and those with other medical diseases such as diabetes mellitus (DM) (p<0.05). In addition, we found that QTc rates, markers of ventricular repolarization, were associated with FHRS, the number of antipsychotics used, patient age, disease duration, and the number of hospitalizations. TPe and QT rates were found to increase in parallel with FHRS. In addition, a positive correlation was found between QTc rates in females, patients with DM, and those using additional medical drugs. (p<0.05) CONCLUSIONS: In BAD and SCZ patients, diabetes diagnosis, other medical drug use, a high Framingham heart score, the number of antipsychotics, the disease duration, the patient's age, and an increased number of hospitalizations may increase the risk of cardiac arrhythmia. Therefore, possible cardiac risk should be considered in patients with chronic drug use, such as BAD and SCZ. Regulating the treatment and follow-up of this group of patients against possible cardiac risks will reduce cardiac mortality and morbidity

Depression or Anxiety According to Management Modalities in Patients With Unruptured Intracranial Aneurysms.

BACKGROUND: In the treatment of unruptured intracranial aneurysms, the risk was usually estimated by objective neurological sequelae. However, their effects on depression and anxiety are rare and remain controversial. We aimed to evaluate the risk of depression and anxiety in patients with unruptured intracranial aneurysm stratified by management strategies in a population-based, longitudinal cohort study. METHODS: Using the Korean National Health Insurance Research Database, 71 750 patients with unruptured intracranial aneurysms between 2008 and 2011 were identified and followed up until the end of 2020. The risk of depression and anxiety was compared among management strategies with respect to age, sex, and medical comorbidities. RESULTS: The Kaplan-Meier survival curves indicated that the treatment (clipping and endovascular treatment) group developed depression more frequently than the observation group (P<0.001). The adjusted hazard ratio was 1.11 (95% CI, 1.07-1.15) in the treatment group. According to the management modality, the Kaplan-Meier survival curves indicated that clipping and endovascular treatment groups developed depression more frequently than the observation group (P<0.0001). The adjusted hazard ratio was 1.15 (95% CI, 1.10-1.21) for clipping and 1.07 (95% CI, 1.02-1.12) for endovascular treatment. The depression risk was higher with advanced age (hazard ratio for 45-64 years, 1.37 [95% CI, 1.29-1.45] and hazard ratio for ≥65 years, 2.04 [95% CI, 1.92-2.17]). The risk for anxiety did not differ among the management modalities. CONCLUSIONS: In this study, the risk of depression was slightly greater after clipping surgery than endovascular treatment. Data on treatment-related, long-term psychological outcomes, such as depression, may aid decision-making for preventive treatment of asymptomatic unruptured intracranial aneurysm patients.

Mental health and periodontal and peri-implant diseases.

Mental health disorders, particularly depression and anxiety, affect a significant number of the global population. Several pathophysiological pathways for these disorders have been identified, including the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and the immune system. In addition, life events, environmental factors, and lifestyle affect the onset, progression, and recurrence of mental health disorders. These may all overlap with periodontal and/or peri-implant disease. Mental health disorders are associated with more severe periodontal disease and, in some cases, poorer healing outcomes to nonsurgical periodontal therapy. They can result in behavior modification, such as poor oral hygiene practices, tobacco smoking, and alcohol abuse, which are also risk factors for periodontal disease and, therefore, may have a contributory effect. Stress has immunomodulatory effects regulating immune cell numbers and function, as well as proinflammatory cytokine production. Stress markers such as cortisol and catecholamines may modulate periodontal bacterial growth and the expression of virulence factors. Stress and some mental health disorders are accompanied by a low-grade chronic inflammation that may be involved in their relationship with periodontal disease and vice versa. Although the gut microbiome interacting with the central nervous system (gut-brain axis) is thought to play a significant role in mental illness, less is understood about the role of the oral microbiome. The evidence for mental health disorders on implant outcomes is lacking, but may mainly be through behaviourial changes. Through lack of compliance withoral hygiene and maintenance visits, peri-implant health can be affected. Increased smoking and risk of periodontal disease may also affect implant outcomes. Selective serotonin reuptake inhibitors have been linked with higher implant failure. They have an anabolic effect on bone, reducing turnover, which could account for the increased loss.

Childhood trauma increases vulnerability to attempt suicide in adulthood through avoidant attachment.

BACKGROUND: Childhood trauma and affective disorders are known risk factors for adult suicidal behavior. Studies have shown a mediating effect of insecure attachment on the effect of childhood trauma and suicidal behavior but so far it is not clear whether this effect is related to an attachment dimension (anxiety, avoidance). AIM: The present study sought to examine the mediating effect of attachment anxiety and avoidance on suicidal behavior. METHODS: We analyzed data on childhood trauma, attachment style, depression severity, presence of prior suicide attempts and current suicide ideation from 96 patients diagnosed with an affective disorder. Two mediation analyses were conducted to assess the effect of childhood trauma on 1) prior suicide attempts and 2) current suicidal ideation through its effect on attachment. RESULTS: We found that childhood trauma had a complete mediated effect on the presence of prior suicide attempts through its effect on avoidant attachment (a1b1 = 0.0120, 95%-CI [0.0031, 0.0276]). However, only emotional abuse had a direct influence on suicidal ideation (c' = 0.0273, p < 0.01) without any indirect effect of anxious or avoidant attachment. LIMITATIONS: Variables were not assessed in a prospective way and sample size was small. CONCLUSIONS: Our findings suggest that individuals with avoidant attachment and childhood trauma are likely to present a high suicide risk. Since avoidant attachment is associated with altered perceptions and eventual rejection of social support, we recommend to screen for attachment early and to engage patients in therapeutical approaches focusing on the client-therapist alliance.

Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions. METHODS: We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range). RESULTS: Of 582 articles retrieved, we included nine RCTs (n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], -1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = -0.11; 95% CI, -2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated. CONCLUSIONS: The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.

Six-year prognosis of anxiety and depression caseness and their comorbidity in a prospective population-based adult sample.

BACKGROUND: Anxiety and depression are amongst the most prevalent mental health problems. Their pattern of comorbidity may inform about their etiology and effective treatment, but such research is sparse. Here, we document long-term prognosis of affective caseness (high probability of being a clinical case) of anxiety and depression, their comorbidity, and a no-caseness condition at three time-points across six years, and identify the most common prognoses of these four conditions. METHODS: Longitudinal population-based data were collected from 1,837 participants in 2010, 2013 and 2016. Based on the Hospital Anxiety and Depression Scale they formed the four groups of anxiety, depression and comorbidity caseness, and no caseness at baseline. RESULTS: The three-year associations show that it was most common to recover when being an anxiety, depression or comorbidity caseness (36.8 - 59.4%), and when not being a caseness to remain so (89.2%). It was also rather common to remain in the same caseness condition after three years (18.7 - 39.1%). In comorbidity it was more likely to recover from depression (21.1%) than from anxiety (5.4%), and being no caseness it was more likely to develop anxiety (5.9%) than depression (1.7%). The most common six-year prognoses were recovering from the affective caseness conditions at 3-year follow-up (YFU), and remain recovered at 6-YFU, and as no caseness to remain so across the six years. The second most common prognoses in the affective conditions were to remain as caseness at both 3-YFU and 6-YFU, and in no caseness to remain so at 3-YFU, but develop anxiety at 6-YFU. CONCLUSIONS: The results suggest that only 37 - 60% of individuals in the general population with high probability of being a clinical case with anxiety, depression, and their comorbidity will recover within a three-year period, and that it is rather common to remain with these affective conditions after 6 years. These poor prognoses, for comorbidity in particular, highlight the need for intensified alertness of their prevalence and enabling treatment in the general population.