Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain.

BACKGROUND: Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. METHODS: In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. RESULTS: In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. CONCLUSIONS: We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

Cluster analysis exploring the impact of childhood neglect on cognitive function in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported. METHODS: We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains. RESULTS: The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose. CONCLUSIONS: Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Salvage therapy for refractory sudden sensorineural hearing loss (RSSNHL): a systematic review and network meta-analysis.

OBJECTIVE: Approximately 30-50% of sudden sensorineural hearing loss (SSNHL) patients show poor response to systemic steroid therapy. Additionally, the most appropriate treatment for patients with refractory sudden sensorineural hearing loss (RSSNHL) is unknown. This study aimed to explore the best treatment for RSSNHL. DESIGN: Using a frequentist contrast-based model and PRISMA guidelines, this study compared five salvage regimes: intratympanic injection of steroids (ITS), hyperbaric oxygen (HBO) therapy, post auricle steroid injection (PSI), ITS combined with HBO therapy, and continued systemic steroids. STUDY SAMPLE: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomised controlled trials and cohort studies comparing treatment regimens for RSSNHL. RESULTS: Compared with the control group (no additional treatment), PSI and ITS demonstrated significant improvements. The mean hearing gain was greater after PSI (11.1 dB [95% CI, 4.4-17.9]) than after ITS (7.7 dB [95% CI, 4.8-10.7]). When a restricted definition of RSSNHL was used, the ITS + HBO therapy showed the largest difference in improvement for pure tone average compared with the control group (14.5 dB [95% CI, 4.2-25.0]). CONCLUSIONS: The administration of either PSI or ITS leads to the greatest therapeutic effect in patients with RSSNHL. However, a consensus on the definition of RSSNHL is needed.

Plant-based dietary patterns and risk of insomnia: a prospective study.

BACKGROUND: Accumulating evidence suggests that dietary factors may affect sleep, but the associations between dietary patterns and insomnia risk have been poorly explored. The aim of this study was to investigate if plant-based diets are associated with reduced insomnia risks in a cohort study design. METHODS: Tzu Chi Health Study participants (N = 5821) recruited from 2007 to 2009 without insomnia were followed until 2018. A traditional classification method (vegetarians vs. non-vegetarians) and a healthful plant-based index (hPDI) were used to define adherence to plant-based dietary patterns. Incident cases of insomnia were ascertained by linking with the National Health Insurance Research Database (NHIRD). Associations between plant-based diets and insomnia were estimated using Cox proportional hazard models. RESULTS: A total of 464 incident cases of insomnia were identified in the 55,562 person-years of follow up. Insomnia risk was lower in vegetarians when compared to non-vegetarians, hazard ratios (HR) 0.47 (95% CI: 0.27, 0.81) and 0.71 (95% CI: 0.55, 0.91) for males and females respectively. Male participants with the highest hPDI were associated with a significant lower risk of insomnia (HR 0.50 [95% CI: 0.30, 0.85]) when compared to those in the lowest quintile. No association between adherence to hPDI and insomnia in female participants was observed. CONCLUSIONS: Our study showed that vegetarians are associated with a lower risk of insomnia, but there may be sex-specific associations between adherence to hPDI and insomnia risk. These favorable associations are important when considering plant-based diets for their potential additional sleep benefits.

An evolutionary perspective on complex neuropsychiatric disease.

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere. Understanding the genetic causes of neuropsychiatric disease in the widest possible range of human populations thus yields the greatest possible range of insight into genes critical to human brain development. In this perspective, we explore some of the relationships between genes, adaptation, and history that can be illuminated by an evolutionary perspective on studies of complex neuropsychiatric disease in diverse populations.

Statin use reduces radiation-induced stroke risk in advanced nasopharyngeal carcinoma patients.

OBJECTIVE: This cohort study aimed to evaluate the impact of statin use on ischemic stroke risk in patients with advanced nasopharyngeal carcinoma (NPC) undergoing standard concurrent chemoradiotherapy (CCRT). METHODS: Using data from the Taiwan Cancer Registry Database, we conducted an inverse probability of treatment-weighted Cox regression analysis to examine the association between statin use during CCRT and ischemic stroke risk. RESULTS: The adjusted hazard ratio (aHR) for ischemic stroke in the statin group compared to the non-statin group was 0.70 (95 % CI: 0.54-0.92; P < 0.0107). This protective effect was observed across different statin classes, with hydrophilic statins such as pravastatin showing an aHR of 0.37 (95 % CI: 0.17-0.85) and lipophilic statins including atorvastatin displaying an aHR of 0.32 (95 % CI: 0.21-0.50) compared to non-statin use. Analysis of cumulative defined daily doses (cDDD) revealed a dose-response relationship, with lower stroke risk observed in higher quartiles of cDDD. Additionally, patients with a daily defined dose (DDD) > 1 had a reduced risk of stroke with an aHR of 0.49 (95 % CI: 0.31-0.63), while those with DDD ≤ 1 showed an aHR of 0.59 (95 % CI: 0.40-0.84). CONCLUSIONS: Our study provides evidence supporting the beneficial effects of statin use during the CCRT period in reducing radiation-induced stroke risk among patients with advanced NPC undergoing definitive CCRT. Notably, pravastatin and atorvastatin demonstrated significant reductions in stroke occurrence. Furthermore, the findings suggest a dose-response relationship, where higher cumulative doses and greater daily dose intensity of statin use were associated with a lower risk of stroke.

Classifying Alzheimer's disease and normal subjects using machine learning techniques and genetic-environmental features.

BACKGROUND: Alzheimer's disease (AD) is complicated by multiple environmental and polygenetic factors. The accuracy of artificial neural networks (ANNs) incorporating the common factors for identifying AD has not been evaluated. METHODS: A total of 184 probable AD patients and 3773 healthy individuals aged 65 and over were enrolled. AD-related genes (51 SNPs) and 8 environmental factors were selected as features for multilayer ANN modeling. Random Forest (RF) and Support Vector Machine with RBF kernel (SVM) were also employed for comparison. Model results were verified using traditional statistics. RESULTS: The ANN achieved high accuracy (0.98), sensitivity (0.95), and specificity (0.96) in the intrinsic test for AD classification. Excluding age and genetic data still yielded favorable results (accuracy: 0.97, sensitivity: 0.94, specificity: 0.96). The assigned weights to ANN features highlighted the importance of mental evaluation, years of education, and specific genetic variations (CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650) for AD classification. Receiver operating characteristic analysis revealed AUC values of 0.99 (intrinsic test), 0.60 (TWB-GWA), and 0.72 (CG-WGS), with slightly lower AUC values (0.96, 0.80, 0.52) when excluding age in ANN. The performance of the ANN model in AD classification was comparable to RF, SVM (linear kernel), and SVM (RBF kernel). CONCLUSIONS: The ANN model demonstrated good sensitivity, specificity, and accuracy in AD classification. The top-weighted SNPs for AD prediction were CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650. The ANN model performed similarly to RF and SVM, indicating its capability to handle the complexity of AD as a disease entity.

Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits.

Genome-wide association studies (GWASs) have identified tens of thousands of genetic loci associated with human complex traits. However, the majority of GWASs were conducted in individuals of European ancestries. Failure to capture global genetic diversity has limited genomic discovery and has impeded equitable delivery of genomic knowledge to diverse populations. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia. We identified 968 novel genetic loci, pinpointed novel causal variants through statistical fine-mapping, compared the genetic architecture across TWB, Biobank Japan, and UK Biobank, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores in disease risk prediction. These results demonstrated the potential to advance discovery through diversifying GWAS populations and provided insights into the common genetic basis of human complex traits in East Asia.

Functional connectivity analysis on electroencephalography signals reveals potential biomarkers for treatment response in major depression.

BACKGROUND: The treatment efficacy varies across individual patients with major depressive disorder (MDD). It lacks robust electroencephalography (EEG) markers for an antidepressant-responsive phenotype. METHOD: This is an observational study enrolling 28 patients with MDD and 33 healthy controls (mean age of 40.7 years, and 71.4% were women). Patients underwent EEG exams at baseline (week0) and week1, while controls' EEG recordings were acquired only at week0. A resting eye-closing EEG segment was analyzed for functional connectivity (FC). Four parameters were used in FC analysis: (1) node strength (NS), (2) global efficiency (GE), (3) clustering coefficient (CC), and (4) betweenness centrality (BC). RESULTS: We found that controls had higher values in delta wave in the indices of NS, GE, BC, and CC than MDD patients at baseline. After treatment with antidepressants, patients' FC indices improved significantly, including GE, mean CC, and mean NS in the delta wave. The FC in the alpha and beta bands of the responders were higher than those of the non-responders. CONCLUSIONS: The FC of the MDD patients at baseline without treatment was worse than that of controls. After treatment, the FC improved and was close to the values of controls. Responders showed better FC in the high-frequency bands than non-responders, and this feature exists in both pre-treatment and post-treatment EEG.

The cysteine-altering p.R544C variant in the NOTCH3 gene is a probable candidate for blood pressure and relevant traits in the Taiwan Biobank.

BACKGROUND: The cysteine-altering variants in NOTCH3 have been suggested to be associated with stroke, dementia, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), where aberrant blood pressure levels represent the characteristics of these diseases. We aimed to assess whether the cysteine-altering p.Arg544Cys (p.R544C; rs201118034) variant and common single nucleotide variants (SNVs) in NOTCH3 could contribute to systolic and diastolic blood pressure and related phenotypes in the Taiwan Biobank. METHODS: We employed a discovery sample of 68,925 individuals, an independent replication sample of 45,676 individuals, and a combined/total sample of 114,601 individuals; all from the Taiwan Biobank. Blood pressure, such as systolic and diastolic blood pressure, was measured for all participants. Association was evaluated using a general linear model, where results were considered statistically significant if the P value < 0.05 divided by the number of independent tests per model. RESULTS: From our analysis, we identified and replicated three novel candidates for blood pressure that have not previously been reported: the cysteine-altering p.R544C variant for systolic blood pressure, the common SNV rs11669950 for diastolic blood pressure, and the common SNV rs4808235 for diastolic blood pressure. We also generalized two previously identified SNVs (i.e., rs10418305 and rs7408868) in NOTCH3 for blood pressure in European and non-Taiwanese East Asian populations to the Taiwanese population. Moreover, the participants with NOTCH3 p.R544C had an increased stroke frequency (P < 1.0 × 10-5) and a higher dementia frequency (P = 2.0 × 10-4) compared with the whole Taiwan Biobank population in the combined/total sample. CONCLUSION: NOTCH3 is a strong candidate for a role in stroke, dementia, and CADASIL, which has previously been linked to blood pressure changes. While our preliminary study suggests that NOTCH3 p.R544C may influence blood pressure, stroke, and dementia in the Taiwan Biobank, replication in a well-powered external sample is required. This study also underlines considerable prospects of detecting novel genetic biomarkers in underrepresented worldwide populations.

Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

The associations between working conditions and subjective sleep quality among female migrant care workers.

Background: Subjective sleep quality may reflect the mental well-being of migrant care workers; however, the related occupational factors remain unclear. This study examines the association between the characteristics of care labor and the subjective sleep quality of female migrants. Methods: In this cross-sectional study, Southeast Asian migrant care workers in Taiwan were recruited using convenience sampling. Data on working conditions, including workplace setting, wage, working hours, psychiatric symptoms of care recipients, and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI), were collected through computer-assisted personal interviews. Multiple linear regression analyses were performed to determine the independent relationship between working conditions and the PSQI global score. Results: There were 220 institution-(47.7%) and home-based (52.3%) care workers, and 47.7% had a PSQI score higher than 5. After controlling for covariates, the lowest tertile of wages and daily working hours (> 8 h) were independently correlated with poor sleep quality. Moreover, in the stepwise regression model, wage and working hours remained the most explainable correlates of poor sleep quality. Conclusion: This study lent support to the notion that low wages and long working hours are significant occupational factors that negatively impact the subjective sleep quality of female Southeast Asian migrant care workers in Taiwan.

The mediating effects of personality traits on the relationship of youth conduct problems and mood disorders with adulthood suicidality.

Identifying the relevant factors for suicidality in individuals with conduct problems is a public health concern, especially if they were under the influence of mood disorders later in life. This study investigates the relationship between youth conduct problems and mood disorders and adulthood suicidality, and to further explore the mediating effects of personality on this relationship. A retrospective cohort study was administered to 308 individuals aged 20-65 years, with or without mood disorders diagnosed by psychiatrists. The Composite International Diagnosis Interview was used to evaluate conduct problems in youth and suicidality (i.e., suicide plan and suicide attempt) in the past year. Personality traits were assessed using Eysenck Personality Questionnaire-Revised for extraversion and neuroticism. Multiple-mediator analysis was used to investigate the mediation effects of personality traits on the relationship between conduct problems and suicidality. The average age of enrolled participants was 31.6 years, and 42.5% of them were female. 39.2% reported suicidality and 43.2% reported conduct problems in youth. Participants who were diagnosed with mood disorders (p < 0.001) and reported having conduct problems (p = 0.004) were associated with high suicidality. Multiple-mediator analysis showed that conduct problems in youth increased the risk of adulthood suicidality through the indirect effects of higher neuroticism (suicide plan: OR = 1.30, BCA 95% CI = 1.04-1.83; suicide attempt: OR = 1.27, BCA 95% CI = 1.05-1.66). Neuroticism mediates the association between youth conduct problems and adulthood suicidality. This finding raises our attention to assess personality traits in individuals with youth conduct problems for designing proper intervention strategies to reduce the risk of suicide.

Co-exposure to toxic metals and phthalates in pregnant women and their children's mental health problems aged four years - Taiwan Maternal and Infant Cohort Study (TMICS).

BACKGROUND: Childhood and adolescent mental health problems may increase the global burden of disease. Neurotoxic metals are associated with inflammation and cytotoxicity in the brain. In addition, prenatal phthalate ester (PAE) exposure is associated with cognitive function deficits. However, the effect of co-exposure to toxic metals, PAEs, and their association with child behavior is less well studied. Hence, we aimed to investigate prenatal co-exposure to the metals and PAEs and the consequent behavioral outcomes in early childhood. METHODS: We followed pregnant women and their newborns from the Taiwan Maternal and Infant Cohort Study between 2015 and 2017, with a focus on women from the central, southern, and eastern areas of Taiwan. We quantified maternal urinary concentrations of metals and metabolites of PAEs as surrogates of prenatal exposure. We recorded the Child Behavior Checklist scores according to caregiver reports at 4 years of age, and identified Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-oriented problems. RESULTS: Ultimately, 408 children were included in the statistical analysis. Maternal urinary copper levels were significantly associated with depressive problems (odds ratio [OR] = 2.13) in children. Maternal urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) were also significantly associated with depressive symptoms (odds ratio [OR] = 1.51 and 1.53, respectively). Further analysis considering prenatal co-exposure to metals and PAEs showed that co-exposure to these materials was significantly associated with autism spectrum problems (OR = 3.11). CONCLUSIONS: We observed that prenatal single exposure or co-exposure to metals and PAEs may play a role in some DSM-5-oriented problems in children at 4 years of age. Reduction of exposure to toxic metals and PAEs in pregnancy is suggested to prevent increased mental health problems in children.

Investigating genetic variants for treatment response to selective serotonin reuptake inhibitors in syndromal factors and side effects among patients with depression in Taiwanese Han population.

Major depressive disorder (MDD) is associated with high heterogeneity in clinical presentation. In addition, response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably among patients. Therefore, identifying genetic variants that may contribute to SSRI treatment responses in MDD is essential. In this study, we analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. Treatment response was defined for all syndromal factors and total scores. In addition, a genome-wide association study was performed to investigate the treatment outcomes at week 4 and repeatedly assess all visits during follow-up by using mixed models adjusted for age, gender, and population substructure. Moreover, the role of genetic variants in suicidal and sexual side effects was explored, and five syndromal factors for depression were derived: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. Subsequently, several known genes were mapped to suggestive signals for treatment outcomes, including single-nucleotide polymorphisms (SNPs) in PRF1, UTP20, MGAM, and ENSG00000286536 for psychomotor-insight and in C4orf51 for anorexia. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (ß = -0.638, p = 1.8 × 10-4) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (ß = 0.089, p = 2.0 × 10-6) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10-8). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, we identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation.

Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes.

BACKGROUNDS: A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups. METHODS: This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups. RESULTS: The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups. CONCLUSIONS: Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

Social Support Reduces the Risk of Unfavorable Parenting Styles for Suicidal Behaviors in Early Adolescents.

OBJECTIVE: Depression and perceived stress are important risk factors for suicidal behaviors among adolescents. The current study examined the joint effects of parenting styles on suicidal ideation (SI) and attempt (SA) in early adolescents while considering relevant individual factors, and evaluated whether social support can offset the risk. METHODS: The present study was part of a large cohort study aiming at tracing the mental health and risk behaviors in adolescents, and we utilized baseline data collected from 645 4th grade students with complete assessment of suicidal behaviors, social support, parental bonding, depression, and perceived stress. Participants' mean age was 9.97 years (SD = 0.38) with 53.02% boys. Logistic regression was performed to analyze the associations between independent variables and youth suicidal behaviors. RESULTS: 16.28% students reported to have SI and 4.96% had SA. Depression (SI: OR = 3.66-3.89; SA: OR = 3.98-4.50), father's low care and high authoritarian (LCHA) (SI: OR = 3.04; SA: OR = 2.43), and low acceptance and high authoritarian (LAHA) (SI: OR = 3.58; SA: OR = 4.77) parenting styles were strong risk factors, while overall social support (SI: OR = 0.98; SA: OR = 0.97) was a protective factor of SI and SA for early adolescents. Perceived stress (OR = 1.07-1.08) and mother's LCHA parenting style (OR = 2.03) were risk factors of SI. Overall, a family with LCHA parenting (OR = 2.82) or LAHA parenting (OR = 3.35-3.72) regardless parental gender had increased risk for SI and SA. CONCLUSION: Family and social factors are important to consider in suicidal prevention and interventions among early adolescents, in addition to assessing individual risk factors. HighlightsSuicidal ideations (16.28%) and attempts (4.96%) were prevalent in early adolescents at elementary schools. Depression status remains a significant risk factor for both SI and SA in early adolescents.Unfavorable parenting styles (LCHA or LAHA) increased the risk of SI and SA, especially received from father.Overall social support had independent protective effect on suicidal behaviors, when taking aforementioned individual and family risk factors into account.

Exploration of the relationship between gut microbiota and fecal microRNAs in patients with major depressive disorder.

Microbiota-gut-brain axis signaling plays a pivotal role in mood disorders. The communication between the host and the gut microbiota may involve complex regulatory networks. Previous evidence showed that host-fecal microRNAs (miRNAs) interactions partly shaped gut microbiota composition. We hypothesized that some miRNAs are correlated with specific bacteria in the fecal samples in patients with major depressive disorder (MDD), and these miRNAs would show enrichment in pathways associated with MDD. MDD patients and healthy controls were recruited to collect fecal samples. We performed 16S ribosome RNA sequence using the Illumina MiSeq sequencers and analysis of 798 fecal miRNAs using the nCounter Human-v2 miRNA Panel in 20 subjects. We calculated the Spearman correlation coefficient for bacteria abundance and miRNA expressions, and analyzed the predicted miRNA pathways by enrichment analysis with false-discovery correction (FDR). A total of 270 genera and 798 miRNAs were detected in the fecal samples. Seven genera (Anaerostipes, Bacteroides, Bifidobacterium, Clostridium, Collinsella, Dialister, and Roseburia) had fold changes greater than one and were present in over 90% of all fecal samples. In particular, Bacteroides and Dialister significantly differed between the MDD and control groups (p-value < 0.05). The correlation coefficients between the seven genera and miRNAs in patients with MDD showed 48 pairs of positive correlations and 36 negative correlations (p-value < 0.01). For miRNA predicted functions, there were 57 predicted pathways with a p-value < 0.001, including MDD-associated pathways, axon guidance, circadian rhythm, dopaminergic synapse, focal adhesion, long-term potentiation, and neurotrophin signaling pathway. In the current pilot study, our findings suggest specific genera highly correlated with the predicted miRNA functions, which might provide clues for the interaction between host factors and gut microbiota via the microbiota-gut-brain axis. Follow-up studies with larger sample sizes and refined experimental design are essential to dissect the roles between gut microbiota and miRNAs for depression.