World Journal of Biological Psychiatry最新文献

Objectives: This study aimed at identifying reliable differentially expressed miRNAs (DEMs) for schizophrenia in blood via meta-analyses combined with deep learning methods.

Methods: First, we meta-analysed published DEMs. Then, we enriched the pool of schizophrenia-associated miRNAs by applying two computational learning methods to identify candidate biomarkers and verified the results in external datasets.

Results: In total, 27 DEMs were found to be statistically significant (p < .05). Ten candidate schizophrenia-associated miRNAs were identified through computational learning methods. The diagnostic efficiency was verified on a blood-miRNA dataset (GSE54578) with a random forest (RF) model and achieved an area under the curve (AUC) of 0.83 ± 0.14. Moreover, 855 experimentally validated target genes for these candidate miRNAs were retrieved, and 11 hub genes were identified. Enrichment analysis revealed that the main functions in which the target genes were enriched were those related to cell signalling, prenatal infections, cancers, cell deaths, oxidative stress, endocrine disorders, transcription regulation, and kinase activities. The diagnostic ability of the hub genes was reflected in a comparably good average AUC of 0.77 ± 0.09 for an external dataset (GSE38484).

Conclusions: A meta-analysis that combines computational and mathematical methods provides a reliable tool for identifying candidate biomarkers of schizophrenia.

Background: Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED). This review aims to synthesise the current evidence on the role of adrenergic dysregulation in the pathogenesis and management of FED.

Methods: A systematic review was conducted in MEDLINE, Cochrane Library, and Clinicaltrials.gov. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was adopted. Preclinical, clinical, and pharmacological studies assessing the adrenergic system in FED were included.

Results: Thirty-one out of 1415 recognised studies were included. Preclinically, studies on adrenaline's anorectic impact, receptor subtypes, and effects on hepatic function in rats show that catecholamine anorexia is primarily alpha-adrenergic, whereas beta-adrenergic anorexia can be obtained only after puberty, implying an impact of sexual hormones. Clinically, catecholamine levels may be higher in FED patients than in healthy controls (HC). Individuals with anorexia nervosa (AN) may show higher epinephrine-induced platelet aggregability response than HC. Pharmacological trials suggest that the alpha-2-adrenergic medication clonidine may not lower AN symptoms, but agents regulating the adrenaline-noradrenaline neurotransmission (bupropion, reboxetine, duloxetine, sibutramine) have been found to improve binge eating symptoms.

Conclusion: Adrenergic dysregulation may be involved in the pathophysiology of FED. More research is needed to comprehend underlying mechanisms and treatment implications.

Background: Obsessive-compulsive disorder (OCD) and eating disorders (EDs) share similarities in terms of clinical characteristics and deficits in inhibitory control.

Objective: To investigate whether inhibitory control could serve as a common behavioural phenotype between OCD and EDs and whether it might be underpinned by shared and/or distinct neural signatures.

Method: We performed a quantitative meta-analysis of brain function abnormalities during the inhibitory control task-based functional Magnetic Resonance Imaging (fMRI) scan across patients with OCD and EDs using seed-based d mapping (SDM).

Results: The meta-analysis included sixteen OCD fMRI studies and ten EDs fMRI studies. And findings revealed that patients with OCD showed hypoactivation relative to healthy controls and patients with EDs in the anterior cingulate cortex, while compared to healthy controls and patients with OCD, patients with EDs showed hypoactivation in the right insula.

Conclusions: Patients with OCD and EDs are inclined to exhibit impaired inhibitory control, which may be attributed to different abnormal patterns of neural activation.

Background: In mammals, circadian rhythms control metabolism, immunological response and reproductive processes. Bmal1 (brain and muscle Arnt-like protein-1) is a key element in the regulation of circadian rhythms.

Methods: This investigation explores the pathophysiological effects of sleep deprivation in a mouse model as well as the potential underlying mechanisms. A mouse sleep deprivation model was constructed using a modified multi-platform water environment method. The anxiety-like behaviours of mice were assessed by the open field test and elevated plus maze, and the cognitive function of mice was tested by the nest-building test. The expression levels of targeted genes were determined by Western blotting assay and RT-qPCR assay.

Results: We found that sleep deprivation profoundly enhanced anxiety levels and impaired cognitive function in mice. Sleep deprivation also reduced the expression levels of Bmal1 and BDNF (brain-derived neurotrophic factor) and increased oxidative stress in the hippocampus of mice. The intraperitoneal injection of human recombinant rhBmal1 protein alleviated sleep deprivation-induced anxiety and cognitive impairment, restored Bmal1 and BDNF levels, and reduced oxidative stress in the hippocampus of mice.

Conclusions: rhBmal1 treatment might serve as a potential therapy for mitigating sleep deprivation-related unfavourable symptoms.

Objectives: To assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) with an H1 coil as a treatment for hopelessness in patients with major depressive disorder (MDD).

Methods: We conducted a randomised controlled trial in a tertiary psychiatric institution in Croatia, including patients diagnosed with MDD without psychotic symptoms and with clinically relevant hopelessness. High-frequency (18 Hz) rTMS with an H1 coil was administered over four weeks on the left dorsolateral prefrontal cortex. We examined changes in the Beck Hopelessness Scale (BHS) scores.

Results: We randomly assigned 51 participants to the intervention group (rTMS plus standard therapy) and 52 to the control group (standard therapy). The mean (SD) ages were 50 (12.3) and 50 (10.4) years, and 47% and 52% of the participants were females in the intervention and control groups, respectively. Following treatment, the BHS scores decreased (unadjusted bivariate analysis, p = 0.043; false discovery rate (FDR) >5%). Multivariate analysis revealed that the BHS score was reduced by 10.8% (95% confidence interval (CI: -17.8% to -3.9%) in the rTMS group and 0.7% (95% CI: 7.5% -6.1%) in the control group (p = 0.037; FDR < 5%).

Conclusions: rTMS with an H1 coil improved the symptoms of hopelessness in patients with MDD.

Objectives: We have postulated that common changes in gene expression after treatment with different therapeutic classes of psychotropic drugs contribute to their common therapeutic mechanisms of action.

Methods: To test this hypothesis, we measured levels of cortical coding and non-coding RNA using GeneChip^® Rat Exon 1.0 ST Array after treatment with vehicle (chow only), chow containing 1.8 g lithium carbonate/kg (n = 10) or chow containing 12 g sodium valproate/kg (n = 10) for 28 days. Differences in levels of RNA were identified using JMP Genomics 13 and the Panther Gene Ontology Classification System was used to identify potential consequences of RNA.

Results: Compared to vehicle treatment, levels of cortical RNA for 543 and 583 coding and non-coding RNAs were different after treatment with valproate and lithium, respectively. Moreover, levels of 323 coding and non-coding RNAs were altered in a highly correlated way by treatment with valproate and lithium, changes that would impact on cholinergic, glutamatergic, serotonergic and dopaminergic neurotransmission as well as on voltage gated ion channels.

Conclusions: Our study suggests that treating with mood stabilisers cause many common changes in levels of RNA which will impact on CNS function, particularly affecting post-synaptic muscarinic receptor functioning and the release of multiple neurotransmitters.

Objectives: To describe the cognitive test battery of the German National Cohort (NAKO), a population-based mega cohort of 205,000 randomly selected participants, and to examine associations with demographic variables and selected psychiatric and neurological conditions.

Methods: Initial data from 96,401 participants providing data on the cognitive performance measured by a brief cognitive test battery (12-word list recall task, semantic fluency, Stroop test, digit span backwards) was examined. Test results were summarised in cognitive domain scores using exploratory and confirmatory factor analyses. Associations with sociodemographic and psychiatric factors were analysed using linear regression and generalised additive models.

Results: Cognitive test results were best represented by two domain scores reflecting memory and executive functions. Lower cognitive functions were associated with increasing age and male sex. Higher education and absence of childhood trauma were associated with better cognitive function. Moderate to severe levels of anxiety and depression, and a history of stroke, were related to lower cognitive function with a stronger effect on executive function as compared to memory. Some associations with cognition differed by German language proficiency.

Conclusions: The NAKO cognitive test battery and the derived cognitive domain scores for memory and executive function are sensitive measures of cognition.

Objectives: The present study introduces the assessment of depression and depressive symptoms in the German National Cohort (NAKO), a population-based mega cohort. Distribution of core measures, and associations with sociodemographic factors are examined.

Methods: The current analysis includes data from the first 101,667 participants (NAKO data freeze 100,000). Depression and depressive symptoms were assessed using a modified version of the depression section of the Mini-International Neuropsychiatric Interview (MINI), self-reported physician's diagnosis of depression, and the depression scale of the Patient Health Questionnaire (PHQ-9).

Results: A lifetime physician's diagnosis of depression was reported by 15.0% of participants. Of those, 47.6% reported having received treatment for depression within the last 12 months. Of the subset of 26,342 participants undergoing the full depression section of the modified MINI, 15.9% were classified by the MINI with a lifetime depressive episode. Based on the PHQ-9, 5.8% of the participants were classified as currently having a major or other depression by the diagnostic algorithm, and 7.8% according to the dimensional assessment (score ≥ 10). Increased frequency of depression measures and higher depression scores were observed in women and participants with lower education level or a family history of depression.

Conclusions: The observed distributions of all depression measures and their associations with sociodemographic variables are consistent with the literature on depression. The NAKO represents a valuable epidemiologic resource to investigate depression, and the range of measures for lifetime and current depression allows users to select the most suitable instrument for their specific research question.

Objectives. Evaluate the block-adaptive number series task of reasoning, as a time-efficient proxy of general cognitive ability in the Level-2 sample of the German National Cohort (NAKO), a population-based mega cohort.Methods. The number series task consisted of two blocks of three items each, administered as part of the touchscreen-based assessment. Based on performance on the first three items, a second block of appropriate difficulty was automatically administered. Scoring of performance was based on the Rasch model. Relations of performance scores to age, sex, education, study centre, language proficiency, and scores on other cognitive tasks were examined.Results. Except for one very difficult item, the data of the remaining 14 items showed sufficient fit to the Rasch model (Infit: 0.89-1.04; Outfit: 0.80-1.08). The resulting performance scores (N = 21,056) had a distribution that was truncated at very high levels of ability. The reliability of the performance estimates was satisfactory. Relations to age, sex, education, and the executive function factor of the other cognitive tasks in the NAKO supported the validity.Conclusions. The number series task provides a valid proxy of general cognitive ability for the Level-2 sample of the NAKO, based on a highly time-efficient assessment procedure.