High intensity transcranial altering current stimulation for cognitive dysfunction in schizophrenia: A pilot trial.

Lack of insight is frequent in schizophrenia and usually influences negatively both patient's treatment and prognosis. This study aimed to investigate the relationship between insight, symptomatology and cognitive dysfunctions in schizophrenia using the PANSS five-factor model (modified from Gaag et al. in Schizophr Res 85:280-287, 2006). Forty patients diagnosed with chronic schizophrenia (DSM-IV) were evaluated with the scale to assess unawareness of mental disorder (SUMD), the PANSS and a neuropsychological battery. Spearman correlation and linear regression analyses were performed to investigate the relationship between clinical, neurocognitive and insight measures. The SUMD current and past awareness of symptoms score showed a correlation with WCST indices (correct answers and non-persevering errors). The negative and disorganization factor of the PANSS showed a positive correlation with current and past awareness of symptoms. However, when submitted to a linear regression model only the disorganization factor emerged as significant contributor for insight. Considering that the core items of the "disorganization factor" of the PANSS are related to cognition (e.g., poor attention, difficult in abstract thinking), insight is associated cognitive symptoms although no direct relationship between insight and neuropsychological tests was observed.

Schizophrenia is a chronic psychiatric disorder characterized by positive, negative, and cognitive symptoms that impair daily functioning. Among these, cognitive dysfunction, affecting memory, attention, and executive function, is a core feature that lacks effective treatment. The clinical diagnosis of schizophrenia is contingent upon the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is based on symptom assessment. However, DSM-5 criteria are subjective and lack biological specificity, leading to diagnostic delays and heterogeneity in patient classification. Emerging evidence implies that microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are integral to the molecular pathways contributing to cognitive dysfunction in schizophrenia. Dysregulated miRNAs impact neurodevelopment, synaptic plasticity, and neurotransmitter signaling, key processes implicated in cognitive impairment. Notably, miRNAs can be found in peripheral biofluids, making them promising non-invasive biomarkers for schizophrenia. Their potential diagnostic utility could enhance early detection and classification, overcoming the limitations of symptom-based clinical assessment. This review discusses the function of dysregulated miRNAs in schizophrenia-associated cognitive deficits, their molecular mechanisms, and their implications as biomarkers. Understanding miRNA-mediated regulation of cognitive function could open the door for innovative diagnostic tools and personalized interventions, ultimately improving patient outcomes.

Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, 'accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30-1.97). Both YT and PE improved attention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

45-1 - Cognitive dysfunction in schizophrenia — Neuropathological origins and prospects for treatment

Integrative Brain Network and Salience Models of Psychopathology and Cognitive Dysfunction in Schizophrenia

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs.Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: “repetitive transcranial magnetic stimulation” or “Rtms,” “SZ,” or “schizophrenia,” and “neuro-cognition” or “neurocognitive performance” or “cognitive effects” or “cognitive” or “cognition” or “working memory” or “executive function” or “language function” or “processing speed,” After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA).Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs.Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time.

Background. The significance of cognitive dysfunction in schizophrenia is the subject of modern psychiatric and cognitive research. In particular, some authors propose to consider cognitive impairments as “core” symptoms of schizophrenia. The cognitive status affects the functional outcome and the level of social readaptation. The investigation of changes in the cognitive status of patients with schizophrenia at various stages of the disease, as well as the prognostic and differential role of cognitive diagnostics of patients, remains an urgent task. Objective. The aim is to structure information on the current state of cognitive impairment at various stages of schizophrenia. Methods. The research presents a literature review of studies on cognitive functions and their impairments at various stages of schizophrenia (premorbid, prodrome with high risk for psychosis, the first episode of schizophrenia). Publications were selected from the Russian Science Citation Index (RSCI), Web of Science, and PubMed databases according to the PRISMA-ScR guidelines, using the following keywords: cognitive dysfunction in schizophrenia, cognitive impairment in schizophrenia, the first episode, attenuated psychotic symptoms, ultra-high risk for psychosis. The review included articles on empirical research, metaanalytic studies, and systematic reviews. Results. The obtained research data indicate that cognitive dysfunction manifests itself in the premorbid period, long before the manifestation of the disease. Patients with an extremely high risk of psychosis demonstrate a significant severity of cognitive deficit associated with the severity of erased psychotic symptoms. Cognitive deficit is not a consequence of past psychotic episodes and does not depend on the duration of an untreated psychosis. Conclusions. The level of cognitive functioning in patients at the pre-psychotic states of schizophrenia development has an important prognostic significance along with the criteria of extremely high risk and familial risk. Cognitive deficit is a separate,“core” group of symptoms for schizophrenia, not secondary to productive symptoms.

Cognition in Schizophrenia: Impairments, Determinants, and Functional Importance

BackgroundThe expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.MethodsWe conducted a case–control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.ResultsOf four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR = 0.46, 95% CI: 0.357-0.59, P < 0.01) and 0.7-fold risk (OR = 0.707, 95% CI: 0.534-0.937, P = 0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR = 0.309, 95% CI: 0.218-0.439 for G allele, P < 0.01), and rs2075572 only in females (OR = 0.399, 95% CI: 0.246-0.648 for G allele, P < 0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR = 0.086, 95% CI: 0.048-0.151, P = 0.01; OR = 0.083, 95% CI: 0.045-0.153, P < 0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR = 0.468, 95% CI: 0.309-0.71, P < 0.01; OR = 0.34, 95% CI: 0.195-0.593, P < 0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P < 0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P < 0.01).ConclusionsThe present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

Objective To explore the characteristics and influencing factors of cognitive impairment in adult moyamoya disease (MMD). Methods A total of 466 adult patients with MMD (case group) admitted to Department of Neurosurgery, Huashan Hospital, Fudan University from June 2013 to December 2017 were retrospectively enrolled. The neuropsychological scale evaluation results were summarized. A matched group of 50 healthy adults were enrolled as the healthy control group. The characteristics of cognitive dysfunction were analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors of cognitive impairment in patients with MMD. Results Overall cognitive function, long-term memory, attention and executive function in the case group were significantly lower than those in the control group (all P 0.05). Conclusions According to the single-center experience of Huashan Hospital, Fudan University, cognitive dysfunction in adults with MMD involves specific cognitive domains and is affected by risk factors such as age, years of education and complications, while no significant difference in cognitive function has been found among different disease subtypes. Key words: Moyamoya disease; Adult; Cognition disorders; Factor analysis, statistical

DNA methylation regulates CHRNA7 transcription and can be modulated by valproate

British Journal of Medical PsychologyVolume 36, Issue 3 p. 253-260 An approach to the psychotherapy of cognitive dysfunction in schizophrenia JAMES CHAPMAN, JAMES CHAPMAN Senior Registrar Dundee Royal Mental Hospital.Search for more papers by this authorANDREW McGHIE, ANDREW McGHIE Principal Psychologist and Lecturer Clinical Psychology, Dundee Royal Mental Hospital.Search for more papers by this author JAMES CHAPMAN, JAMES CHAPMAN Senior Registrar Dundee Royal Mental Hospital.Search for more papers by this authorANDREW McGHIE, ANDREW McGHIE Principal Psychologist and Lecturer Clinical Psychology, Dundee Royal Mental Hospital.Search for more papers by this author First published: September 1963 https://doi.org/10.1111/j.2044-8341.1963.tb01286.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume36, Issue3September 1963Pages 253-260 RelatedInformation

Role of PI3K/Akt axis in cognitive impact of lumateperone in schizophrenia rat model induced by ketamine.

The role of glutamate and GABA in cognitive dysfunction in schizophrenia and mood disorders – A systematic review of magnetic resonance spectroscopy studies

IntroductionTreatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis.MethodsIn line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants.ResultsHere, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives.DiscussionThe identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.