World Journal of Biological Psychiatry最新文献

This study aimed to explore the relationship between alterations in plasma metabolites and treatment responses amongst antipsychotic-naïve female patients with schizophrenia. A total of 38 antipsychotic-naïve female schizophrenia patients (ANS) and 19 healthy female controls (HC) were recruited. Plasma samples were obtained from all participants, and targeted metabolomics were measured with FIA-MS/MS and LC-MS/MS. The positive and negative syndrome scale (PANSS) was used to assess the severity of psychotic symptoms before and after eight weeks of treatment. Receiver operator characteristics (ROC) curves were used to predict diagnostic and therapeutic responses. A total of 186 metabolites passed quality control procedures and were used in statistical analysis to identify potential biomarkers. Before treatment, the ANS patients had lower levels of γ -Aminobutyric Acid (GABA) and higher levels of Cholesteryl esters (CE) (20:3), Cholic Acid (CA) and Glycocholic Acid (GCA) compared to the HCs. These four differential metabonomic markers were synthesised into a combinatorial biomarker panel. This panel significantly distinguished ANS from HC. Moreover, this biomarker panel was able to effectively predict therapeutic responses. Our results suggest that plasma CE (20:3), CA, GCA, and GABA levels may be useful for diagnosing and predicting antipsychotic efficacy amongst female schizophrenia patients.

Objectives: Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) is the most common enzymopathy globally. Early studies suggested an association with severe psychotic illness; however, changes to laboratory testing and diagnostic classification renders the association unclear. This study aims to explore the interaction between G6PD deficiency and psychotic symptoms, in particular to identify specific patterns of presentation or impact on outcomes.

Methods: Pubmed, Embase, and PsycInfo databases were searched from inception to May 2023. Descriptive statistics and narrative review of were used to synthesise data on demographics, mental and physical health diagnoses, investigations, treatment, and outcomes.

Results: No clear link was found in published data (eight case reports, case series of n = 29) with a high rate (63%) of haemolytic crisis at the time of psychiatric presentation suggested delirium as an alternative diagnosis. Four case control studies found no significant difference in the prevalence of G6PD deficiency. However, catatonic presentation was reported in 40% of the case series and a higher prevalence of G6PD deficiency in catatonic schizophrenia was noted in case control studies.

Conclusions: Based on the information available there was no clear association between G6PD deficiency and psychotic illness or treatment resistance, although paucity of studies and risk of bias limit strong conclusions.

Objective: During hypnosis, significant changes in the BOLD signal associated with the anterior default mode network (DMN) and prefrontal attentional systems have been reported as evidence of dissociation defined since Charcot. However, it remains uncertain whether these changes are mainly attributable to the hypnotic state per se or to the target suggestions used to verify subject's state during neuroimaging studies. The aim of the present study is to evidence the brain in hypnosis, contrasting the common resting state versus neutral hypnosis (hypnosis in the absence of target suggestions).

Methods: Twenty-four healthy right-handed volunteers (age 28.3 y.o., 12 females) rated moderate hypnotic responsiveness underwent resting state fMRI at 3.0 T in two sessions, once in neutral hypnosis and the other in the common resting state. Each subject's functional data were analyzed for low-frequency BOLD signal correlations seed-to-voxel for the whole brain in the first-level analysis, and seed-to-voxel in a second-level analysis to estimate group results using seeds for five resting state networks: the default mode (DMN), the central executive (CEN), the salience (SaN), the dorso-lateral attention (DAN), and the sensorimotor (SMN) networks.

Results: In general, all network maps of the hypnotic condition presented higher connectivity than those of the resting condition. However, only contrasts for the DAN, SaN, and SMN were statistically significant, including correlated out-of-the-network regions.

Conclusion: Parietal and occipital regions displayed increased connectivity across networks, implying dissociation from the frontal cortices. This is the first fMRI intrinsic study of hypnosis without target suggestion.

Objectives: Schizophrenia is a psychiatric disorder affecting 1% of the population. Accumulating evidence indicates that neuroinflammation is involved in the pathology of these disorders by altering neurodevelopmental processes and specifically affecting glutamatergic signalling and astrocytic functioning. The aim of this study was to curate interactive biological pathways involved in schizophrenia for the identification of novel pharmacological targets implementing pathway, gene ontology, and network analysis.

Methods: Neuroinflammatory pathways were created using PathVisio and published in WikiPathways. A transcriptomics dataset, originally created by Narla et al. was selected for data visualisation and analysis. Transcriptomics data was visualised within pathways and networks, extended with transcription factors, pathways, and drugs. Network hubs were determined based on degrees of connectivity.

Results: Glutamatergic, immune, and astrocytic signalling as well as extracellular matrix reorganisation were altered in schizophrenia while we did not find an effect on the complement system. Pharmacological agents that target the glutamate receptor subunits, inflammatory mediators, and metabolic enzymes were identified.

Conclusions: New neuroinflammatory pathways incorporating the extracellular matrix, glutamatergic neurons, and astrocytes in the aetiology of schizophrenia were established. Transcriptomics based network analysis provided novel targets, including extra-synaptic glutamate receptors, glutamate transporters and extracellular matrix molecules that can be evaluated for therapeutic strategies.

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: 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: 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: 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: 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 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.