At present, no well-established biomarkers were ever found to distinguish unipolar depression and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and ...major depressive disorder. Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. UA could distinguish BD and UD significantly both in acute and remission stage. The study suggests patients with BD had a higher level of UA than UD, especially in mania episode. UA may be a potential biomarker to distinguish BD from UD.
Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we ...sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1.1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L. We identify novel DN LGD recurrences (GIGYF2, MYT1L, CUL3, DOCK8 and ZNF292) and DN mutations in previous ASD candidates (ARHGAP32, NCOR1, PHIP, STXBP1, CDKL5 and SHANK1). Phenotypic follow-up confirms potential subtypes and highlights how large global cohorts might be leveraged to prove the pathogenic significance of individually rare mutations.
Recent studies show that oxidative stress is associated with the pathogenesis of schizophrenia. There are two major types of antioxidant systems in vivo, namely enzymatic antioxidants and ...non-enzymatic antioxidants. This study investigated differences of non-enzymatic antioxidants between schizophrenia patients and healthy controls.
Peripheral UA, ALB, and TBIL of 107 schizophrenic patients in the acute stage and 101 in the remission stage were measured respectively, so were 273 healthy controls.
The levels of UA (P = 0.020) and TBIL (P < 0.001) of schizophrenic patients in the acute stage were higher than those of healthy controls, while the level of ALB (P < 0.001) was lower. Similar results were detected form schizophrenic patients in the remission stage. Schizophrenic patients in the acute stage were divided into antipsychotics-use subgroup (n = 56) and antipsychotics-naïve/free subgroup (n = 51). The level of UA (P = 0.001) in the antipsychotics-use subgroup was higher than that in the antipsychotics-naïve/free subgroup, while the level of TBIL (P = 0.002) was lower than that in the antipsychotics-naïve/free subgroup. Seventy-seven schizophrenic patients in the acute stage were followed up, and there was no significant difference in the level of UA before and after treatment, but levels of ALB (P < 0.001) and TBIL (P < 0.001) decreased significantly after the treatment.
This study demonstrated that the dysfunction of the peripheral non-enzymatic anti-oxidation system might be involved in the pathogenesis of schizophrenia.
Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a ...significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms.
We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms.
This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.
Much evidence shows that some
, fifth edition (DSM-5)-defined unipolar depression (UD) with bipolarity manifests bipolar diathesis. Little is known about the cognitive profiles of patients with ...depression with bipolarity (DWB). The study aimed to investigate the differences in cognitive profiles among patients with bipolar depression (BD), major depressive disorder (namely, UD), and DWB. Drug-naïve patients with BD, UD, and DWB and healthy controls (HC) were recruited (30 cases in each group). Cognitive function was evaluated by THINC-it (THINC-intelligent tool), Wisconsin Card Sorting Test (WCST), and continuous performance test (CPT). For THINC-it, no significant differences of the Z-scores in both objective and subjective factors were found between the DWB group and BD group, but the Z-scores in the BD group were significantly lower than those in the UD group. For WCST, significant differences were found between the BD group and DWB group in the number of responses, categories completed, trails to completed first category, perseverative responses, and perseverative errors. All the indices of WCST in the DWB group were significantly worse than those in the UD group except for trails to completed first category and total number of response correct. For CPT, only scores of leakage responses and false responses in the four-digit number in the BD group and DWB group were significantly higher than those in the UD group; no significant difference was found between the BD group and DWB group. The results indicated that patients with DWB might perform differently from those with UD but similarly to those with BD with cognition impairment.
The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes ...in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI).
A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls.
Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p<0.005, corrected for multiple comparisons).
These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.
► Cohe-ReHo method detects different brain activity between patients with LLD and HC. ► Patients with LLD have widespread Cohe-ReHo alterations. ► The Cohe-ReHo method may be a tool for understanding the pathophysiology of LLD.
The genotype‐first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive ...genetic heterogeneity. We investigate the alternate possibility of whether phenotype‐specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype‐to‐genotype approach, we performed whole‐exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head‐size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype‐phenotype correlations for head‐size‐associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype‐to‐genotype strategy would accelerate the elucidation of genotype‐phenotype relationships for ASD by using phenotype‐restricted cohorts.
The current study explored how and to what extent sleep problems in children with autism spectrum disorder (ASD) impacted their parents’ quality of life (QOL). A total of 440 ASD children and 344 ...age-matched typically developing (TD) children were included in the case–control designed study. In the TD group, a linear regression model showed that the Children’s Sleep Habits Questionnaire (CSHQ) total scores were negatively associated with maternal mental health summary (MCS) scores in the SF-36v2 (β = − 2.831), while in the ASD group, the CSHQ total scores were negatively associated with the parental physical health summary (PCS) scores (β = − 3.030 for mothers, β = − 3.651 for fathers). Path analysis showed that sleep problems in ASD children had both direct and indirect effects on maternal PCS scores. The results indicated that sleep problems in children with ASD might affect parental QOL differently from TD children, and act as independent impact factors on parental physical health.
The use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these ...risk factors to predict autism.
A stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort.
Five factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism.
This risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.
We previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort ...of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype-phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent.
We sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes. We tested the inheritance of potentially pathogenic mutations, performed a meta-analysis of phase I and phase II data and combined our results with existing exome sequence data to investigate the phenotypes of carrier parents and patients with multiple hits in different autism risk genes.
We validated recurrent, LGD, de novo mutations (DNMs) in 13 genes. We identified a potential novel risk gene (
), one novel gene with recurrent LGD DNMs (
), as well as genes associated with macrocephaly (
and
). We identified the transmission of private LGD mutations in genes predominantly associated with DNMs and showed that parental carriers tended to share milder autism-related phenotypes. Patients that carried DNMs in two or more candidate genes show more severe phenotypes.
We identify new risk genes and transmission of deleterious mutations in genes primarily associated with DNMs. The fact that parental carriers show milder phenotypes and patients with multiple hits are more severe supports a multifactorial model of risk.
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