Machine learning in small sample neuroimaging studies: Novel measures for schizophrenia analysis.

Novel features derived from imaging and artificial intelligence systems are commonly coupled to construct computer-aided diagnosis (CAD) systems that are intended as clinical support tools or for investigation of complex biological patterns. This study used sulcal patterns from structural images of the brain as the basis for classifying patients with schizophrenia from unaffected controls. Statistical, machine learning and deep learning techniques were sequentially applied as a demonstration of how a CAD system might be comprehensively evaluated in the absence of prior empirical work or extant literature to guide development, and the availability of only small sample datasets. Sulcal features of the entire cerebral cortex were derived from 58 schizophrenia patients and 56 healthy controls. No similar CAD systems has been reported that uses sulcal features from the entire cortex. We considered all the stages in a CAD system workflow: preprocessing, feature selection and extraction, and classification. The explainable AI techniques Local Interpretable Model-agnostic Explanations and SHapley Additive exPlanations were applied to detect the relevance of features to classification. At each stage, alternatives were compared in terms of their performance in the context of a small sample. Differentiating sulcal patterns were located in temporal and precentral areas, as well as the collateral fissure. We also verified the benefits of applying dimensionality reduction techniques and validation methods, such as resubstitution with upper bound correction, to optimize performance.

Dampened motivation in schizophrenia: evidence from a novel effort-based decision-making task in social scenarios.

Apathy represents a significant manifestation of negative symptoms within individuals diagnosed with schizophrenia (SCZ) and exerts a profound impact on their social relationships. However, the specific implications of this motivational deficit in social scenarios have yet to be fully elucidated. The present study aimed to examine effort-based decision-making in social scenarios and its relation to apathy symptoms in SCZ patients. We initially recruited a group of 50 healthy participants (16 males) to assess the validity of the paradigm. Subsequently, we recruited 45 individuals diagnosed with SCZ (24 males) and 49 demographically-matched healthy controls (HC, 25 males) for the main study. The Mock Job Interview Task was developed to measure effort-based decision-making in social scenarios. The proportion of hard-task choice and a range of subjective ratings were obtained to examine potential between-group differences. SCZ patients were less likely than HC to choose the hard task with strict interviewers, and this group difference was significant when the hard-task reward value was medium and high. More severe apathy symptoms were significantly correlated with an overall reduced likelihood of making a hard-task choice. When dividing the jobs into two categories based on the levels of social engagement needed, SCZ patients were less willing to expend effort to pursue a potential offer for jobs requiring higher social engagement. Our findings indicated impaired effort-based decision-making in SCZ can be generalized from the monetary/nonsocial to a more ecologically social dimension. Our findings affirm the critical role of aberrant effort allocation on negative symptoms, and may facilitate the development of targeted clinical interventions.

A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.

ARID4A plays an important role in regulating gene expression and cell proliferation. ARID4A belongs to the AT-rich interaction domain (ARID)-containing family, and a PWWP domain immediately precedes its ARID region. The molecular mechanism and structural basis of ARID4A are largely unknown. Whole-exome sequencing (WES) revealed that a novel heterozygous missense variant, ARID4A c.1231 C > G (p.His411Asp), was associated with schizophrenia (SCZ) in this study. We determined the crystal structure of the PWWP-ARID tandem at 2.05 Å, revealing an unexpected mode in which ARID4A assembles with its PWWP and ARID from a structural and functional supramodule. Our results further showed that compared with the wild type, the p.His411Asp ARID mutant protein adopts a less compact conformation and exhibits a weaker dsDNA-binding ability. The p.His411Asp mutation decreased the number of cells that were arrested in the G0-G1 phase and caused more cells to progress to the G2-M phase. In addition, the missense mutation promoted the proliferation of HEK293T cells. In conclusion, our data provide evidence that ARID4A p.His411Asp could cause a conformational change in the ARID4A ARID domain, influence the DNA binding function, and subsequently disturb the cell cycle arrest in the G1 phase. ARID4A is likely a susceptibility gene for SCZ; thus, these findings provide new insight into the role of ARID4A in psychiatric disorders.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Reduced learning bias towards the reward context in medication-naive first-episode schizophrenia patients.

BACKGROUND: Reinforcement learning has been proposed to contribute to the development of amotivation in individuals with schizophrenia (SZ). Accumulating evidence suggests dysfunctional learning in individuals with SZ in Go/NoGo learning and expected value representation. However, previous findings might have been confounded by the effects of antipsychotic exposure. Moreover, reinforcement learning also rely on the learning context. Few studies have examined the learning performance in reward and loss-avoidance context separately in medication-naïve individuals with first-episode SZ. This study aimed to explore the behaviour profile of reinforcement learning performance in medication-naïve individuals with first-episode SZ, including the contextual performance, the Go/NoGo learning and the expected value representation performance. METHODS: Twenty-nine medication-naïve individuals with first-episode SZ and 40 healthy controls (HCs) who have no significant difference in age and gender, completed the Gain and Loss Avoidance Task, a reinforcement learning task involving stimulus pairs presented in both the reward and loss-avoidance context. We assessed the group difference in accuracy in the reward and loss-avoidance context, the Go/NoGo learning and the expected value representation. The correlations between learning performance and the negative symptom severity were examined. RESULTS: Individuals with SZ showed significantly lower accuracy when learning under the reward than the loss-avoidance context as compared to HCs. The accuracies under the reward context (90%win- 10%win) in the Acquisition phase was significantly and negatively correlated with the Scale for the Assessment of Negative Symptoms (SANS) avolition scores in individuals with SZ. On the other hand, individuals with SZ showed spared ability of Go/NoGo learning and expected value representation. CONCLUSIONS: Despite our small sample size and relatively modest findings, our results suggest possible reduced learning bias towards reward context among medication-naïve individuals with first-episode SZ. The reward learning performance was correlated with amotivation symptoms. This finding may facilitate our understanding of the underlying mechanism of negative symptoms. Reinforcement learning performance under the reward context may be important to better predict and prevent the development of schizophrenia patients' negative symptom, especially amotivation.

Negative belief-updating bias for positive daily life events in individuals with schizophrenia and social anhedonia.

INTRODUCTION: Low-pleasure beliefs are found in both patients with schizophrenia (SZ) and individuals with high social anhedonia (SocAnh), and are associated with anhedonia. However, little is known about the development and maintenance of these low-pleasure beliefs in the clinical and subclinical populations. We investigated whether patients with SZ and individuals with high SocAnh have deficits in updating their beliefs, which may contribute to the understanding of the formation and maintenance of low-pleasure beliefs. METHODS: The Modified Belief Updating Task was administered to assess belief-updating patterns in a clinical sample (36 SZ patients and 30 matched controls) and a subclinical sample (27 individuals with high SocAnh and 30 matched controls). RESULTS: We found that compared with controls, SZ patients updated their beliefs to a greater extent and more frequently when receiving bad news for positive life events, but not for negative life events. Moreover, individuals with high SocAnh also exhibited similar patterns in updating their beliefs for positive life events after controlling depressive symptoms. CONCLUSIONS: Our findings suggest that negative belief-updating patterns for positive events may play an important role in the formation and maintenance of low-pleasure beliefs in patients with SZ and individuals with high SocAnh.

Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia.

BACKGROUND: Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. METHODS: A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. RESULTS: A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, pBonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, pBonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = - 0.07, p = 0.02). CONCLUSION: Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients. METHODS: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted. RESULTS: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05). CONCLUSIONS: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

The remediation effects of working memory training in schizophrenia patients with prominent negative symptoms.

Introduction: Negative symptoms, particularly amotivation and anhedonia, are important predictors of poor functional outcome in patients with schizophrenia. There has been interest in the efficacy and mechanism of non-pharmacological interventions to alleviate these symptoms. The present study aimed to examine the remediation effect of working memory (WM) training in patients with schizophrenia with prominent negative symptoms.Methods: Thirty-one schizophrenia patients with prominent negative symptoms were recruited and assigned to either a WM training group or a treatment-as-usual (TAU) control group. The WM training group underwent 20 sessions of training using the dual n-back task over one month. A functional neuroimaging paradigm of the Affective Incentive Delay (AID) task was administered before and after the training intervention to evaluate the remediation effect of the intervention.Results: Our results showed that the WM training group demonstrated significant improvement in the WM training task and inattention symptoms. Compared with the TAU group, increased brain activations were observed at the right insula and the right frontal sub-gyral after WM training in the training group.Conclusions: These findings support the efficacy of WM training in ameliorating hedonic dysfunction in schizophrenia patients with prominent negative symptoms.

Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients.

PURPOSE: The neurotrophin brain-derived neurotrophic factor (BDNF) has been found to be associated with both the pathophysiology of depression and antidepressants response. Gene expression differences were partly mediated by SNP, which might be identified as a predictor of antidepressant response. In the present study, we attempt to identify whether DNA methylation, another factor known to affect gene transcription, might also predict antidepressant response. METHODS: A total of 85 depressed Chinese Han patients were followed-up 8 weeks after initiating escitalopram treatment. Treatment response was assessed by changes in the Hamilton Depression Rating Scale-17 (HAMD-17) score. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) were utilized as the assessment of previous life stress. The bisulfate sequencing was used to assess DNA methylation. Four single nucleotide polymorphisms (SNPs) in the BDNF gene were genotyped using PCR-RFLP or PCR sequencing. RESULTS: We identified a DNA methylation predictor (P = 0.006-0.036) and a DNA methylation by LES interaction predictor (OR = 1.442 [1.057-1.968], P = 0.021) of general antidepressant treatment response. Lower mean BDNF DNA methylation was associated with impaired antidepressant response. Furthermore, the present data indicated that age, life stress, and SNPs genotype might be likely related to DNA methylation status. Average DNA methylation of BDNF at baseline was significantly lower than that at endpoint after 8 weeks of escitalopram treatment, which was based only on a subset of cases (n = 44). CONCLUSIONS: Our results suggest that BDNF DNA hypomethylation and its interaction with lower LES score might result in impaired antidepressant treatment response. The pharmacoepigenetic study could eventually help in finding epigenetic biomarkers of antidepressant response.

Faux pas recognition performance in a help-seeking population at clinical high risk of psychosis.

There is a growing body of evidence suggesting that patients with psychosis show impaired theory of mind (ToM). However, much remains to be understood as to whether ToM deficits occur in the premorbid or post-onset period of psychosis. Our primary aim was to examine empirically impairment on ToM tasks in a group of individuals with clinical high risk (CHR) of psychosis. Fifty CHR participants identified through the Structured Interview for Prodromal Syndromes and 52 age-/education-matched controls were assessed with a complete standard neuropsychological battery (the MCCB, MATRICS Consensus Cognitive Battery) and a social cognition assessment (Faux Pas Test, FPT). We then examined the association of baseline FPT performance with conversion to psychosis at 12-month follow-up. Compared with controls, the CHR group showed significantly poorer performances on the FPT and most MCCB domains. Significant positive correlations were found between faux pas detection and the MCCB domains of Attention/Vigilance and Working Memory in CHR participants when controlling for age and years of education. Mean scores on the FPT in 14 converters who were diagnosed with full-blown psychosis within 12 months were significantly lower than they were for non-converters. Impairments in ToM ability are acquired earlier in the prodromal stage of psychosis, along with general cognition (such as memory function) deficits. Declines in ToM ability may overlap with the progress of psychosis (the gradual loss insight), sharing similar neural substrates, and reflected by impairments in basic cognitive function.

Common variants of the PINK1 and PARL genes do not confer genetic susceptibility to schizophrenia in Han Chinese.

Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.

TCMID: Traditional Chinese Medicine integrative database for herb molecular mechanism analysis.

As an alternative to modern western medicine, Traditional Chinese Medicine (TCM) is receiving increasingly attention worldwide. Great efforts have been paid to TCM's modernization, which tries to bridge the gap between TCM and modern western medicine. As TCM and modern western medicine share a common aspect at molecular level that the compound(s) perturb human's dysfunction network and restore human normal physiological condition, the relationship between compounds (in herb, refer to ingredients) and their targets (proteins) should be the key factor to connect TCM and modern medicine. Accordingly, we construct this Traditional Chinese Medicine Integrated Database (TCMID, http://www.megabionet.org/tcmid/), which records TCM-related information collected from different resources and through text-mining method. To enlarge the scope of the TCMID, the data have been linked to common drug and disease databases, including Drugbank, OMIM and PubChem. Currently, our TCMID contains ∼47 000 prescriptions, 8159 herbs, 25 210 compounds, 6828 drugs, 3791 diseases and 17 521 related targets, which is the largest data set for related field. Our web-based software displays a network for integrative relationships between herbs and their treated diseases, the active ingredients and their targets, which will facilitate the study of combination therapy and understanding of the underlying mechanisms for TCM at molecular level.

Brain-derived neurotrophic factor levels and bipolar disorder in patients in their first depressive episode: 3-year prospective longitudinal study.

BACKGROUND: Early identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode. AIMS: To explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode. METHOD: A total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode. RESULTS: At baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (P<0.001 and P = 0.02 respectively) and plasma levels (P = 0.002 and P = 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree). CONCLUSIONS: Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.

Pharmacotherapy for acute mania and disconcordance with treatment guidelines: bipolar mania pathway survey (BIPAS) in mainland China.

BACKGROUND: With the recent attention to evidence-based medicine in psychiatry, a number of treatment guidelines for bipolar disorders have been published. This survey investigated prescribing patterns and predictors for guideline disconcordance in the acute treatment of a manic and mixed episode across mainland China. METHODS: The pharmacological treatments of 2828 patients with a recent hypomanic/manic episode or mixed state were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. RESULTS: The most common pattern of pharmacological treatments for an acute manic or mixed episode was a mood stabilizer plus an atypical antipsychotic (n = 1345, 47.6%), and the rate of guideline-disconcordant treatments was 11.1%. The patients who were treated in general hospitals were more likely to receive guideline-disconcordant treatments than those who were treated in psychiatric hospitals, with an OR of 1.84 (95% CI 1.44-2.36). Similarly, the patients with a mixed episode at study entry were more likely to receive guideline-disconcordant treatments than those with a manic episode, with an OR of 1.69 (95% CI 1.22-2.35). In contrast, the patients with a longer duration of disease (>5 years) were less likely to receive guideline-disconcordant treatments than those with a short duration, with an OR of 0.47 (95% CI 0.36-0.60). CONCLUSIONS: In mainland China, the disconcordance with treatment guidelines for a most recent acute manic or mixed episode was modest under naturalistic conditions. The higher risk for disconcordance in general hospitals than in psychiatric hospitals suggests that special education based on treatment guidelines to practitioners in general hospitals is necessary in order to reduce the risk for disconcordant treatments.

Association study of common variants within the G protein-coupled receptor kinase 6 gene and schizophrenia susceptibility in Han Chinese.

In this study, we examined whether common variants in the G protein-coupled receptor kinase 6 gene (GRK6) confers susceptibility to schizophrenia in Chinese. We genotyped two common variants in 697 schizophrenia patients and 563 healthy control subjects. No significant difference in either allele or genotype comparisons between the case and control groups was found. Our results imply that GRK6 may not play a role in the pathophysiology of schizophrenia among Han Chinese.

Range adaptive value representations in schizophrenia and major depression.

Anhedonia and amotivation are core symptoms of schizophrenia (SCZ) and major depressive disorder (MDD). Reward processing involves constructing and contrasting the representations for expected value (EV) and outcome value (OV) of a given stimulus, a phenomenon termed range adaptation. Impaired range adaptation can lead to anhedonia and amotivation. This study aimed to examine range adaptation in SCZ patients and MDD patients. Fifty SCZ, 46 MDD patients and 56 controls completed the Effort-based Pleasure Experience Task to measure EV and OV adaptation. SCZ and MDD patients showed altered range adaptation, albeit in different patterns. SCZ patients exhibited over-adaptation to OV and reduced adaptation to EV. By contrast, MDD patients exhibited diminished OV adaptation but intact EV adaptation. Both OV and EV adaptation were correlated with anhedonia and amotivation in SCZ and MDD. Taken together, our findings suggest that range adaptation is altered in both SCZ and MDD patients. Associations of OV and EV adaptation with anhedonia and amotivation were consistently found in SCZ and MDD patients. Impaired range adaptation in SCZ and MDD patients may be putative neural mechanisms and potential intervention targets for anhedonia and amotivation.

The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Sex differences in subjective cognitive impairment and clinical correlates in Chinese patients with subthreshold depression.

OBJECTIVE: Subthreshold depression (SD) is a global mental health problem given its high prevalence, comorbidity, functional impairment, and its association with increased service utilization. However, currently little is known about sex differences of SD in cognitive impairment with clinical correlates. This study aims to explore sex differences in subjective cognitive impairment and clinically associated risk factors in Chinese patients with subthreshold depression (SD). METHODS: A total of 126 patients with SD, 40 males and 86 females, aged 18-45 years, were included in this cross-sectional observational study. Their general information, psychological assessments, and psychiatric symptom assessments were collected online. The Patient Health Questionnaire depression-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Deficits Questionnaire-Depression (PDQ-D), and Toronto Alexithymia Scale (TAS-20) with 3 subdomains were used. The obtained scores were analyzed with partial correlation and multiple linear regression analysis models. RESULTS: Our results showed that females had significantly higher PDQ-D-20 total score than males. However, the differences in TAS-20 and subdomain score according to sex were not significant. Notably, TAS-20 and DDF (difficulty describing feelings) subdomain contributed to cognitive impairment in males, whereas both PHQ-9 total score and TAS-20 or DDF subdomain contributed to cognitive impairment in females. CONCLUSION: These findings revealed significant sex differences in cognitive impairment and clinical correlates in SD, which should be further followed-up in the future.

Personality traits as mediators in the association between SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students.

Background: Previous research has linked polymorphisms in the SIRT1 gene to depressive symptoms, particularly in Chinese individuals. However, it is not clear how personality traits may contribute to this association. Methods: To explore the potential mediating effect of personality traits, we utilized a mediation model to examine the relationship between the SIRT1 rs12415800 polymorphism and depressive symptoms in 787 Chinese college students. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, while personality traits were measured using the Big Five Inventory (BFI). Results: Our analysis indicated a significant association between the SIRT1 rs12415800 polymorphism and depressive symptoms, with this relationship partially mediated by the personality traits of neuroticism and conscientiousness. Specifically, individuals who were heterozygous for the rs12415800 polymorphism and had higher levels of conscientiousness were less likely to experience depressive symptoms. Conversely, those who were homozygous for the rs12415800 polymorphism and had higher levels of neuroticism were more likely to experience depressive symptoms. Conclusion: Our results suggest that personality traits, particularly neuroticism and conscientiousness, may play a critical role in the association between the SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students. These findings highlight the importance of considering both genetic factors and personality traits when exploring the etiology of depressive symptoms in this population.