Psychiatry and Clinical Neurosciences最新文献

Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.

This article relates to Comment on: is clozapine use a risk of hematological malignancies? Insights from a meta-analysis "Clozapine and Malignancy Risk".

Aim: Cognitive impairment in schizophrenia shows limited improvement with pharmacotherapy, indicating a need for effective treatment. The frontoparietal network supports working memory, and a biomarker has successfully predicted performance in patients, with the left frontoparietal network contributing the most to working memory. We hypothesized that enhancing functional connectivity in this network through real-time neurofeedback (NF) will improve working memory in patients with schizophrenia.

Methods: We conducted a two-arm, nonrandomized pilot study in patients with schizophrenia, with a NF group (N = 11) and a control N-back training group (N = 11). The NF training lasted 5 days (one session per day). The first session included baseline measurements, while the next four sessions involved training. The participants completed cognitive and clinical assessments and resting-state scans preintervention and postintervention. Our primary neural outcome was increased functional connectivity during NF, and the behavioral outcome was improvement in working memory, as indicated by scores on the digit-span backward task and working memory capability measured by the N-back task.

Results: The NF group showed increased functional connectivity within the left frontoparietal network during the final session. A significant correlation existed between functional connectivity and the improvement in the mean N-back level, indicating that enhancing this network can boost working memory. A group-by-time interaction effect improved postintervention task score on the digit-span backward task in the NF group. In addition, post-NF scans indicated an enhanced resting-state functional connectivity within the left frontoparietal network.

Conclusion: These results highlight the potential of functional connectivity-informed NF as a novel therapeutic approach for improving working memory in schizophrenia.

Clinical trial registration: Japan Registry of Clinical Trials (UMIN000024831, jRCTs052180168, jRCTs032190244).

Aim: Telepsychiatry is increasingly integral to psychiatric practice. However, few reviews have examined the concordance between assessments conducted in telepsychiatric and face-to-face settings. This systematic review and meta-analysis evaluated the agreement between telepsychiatric and face-to-face settings in the diagnosis and symptom assessment of various psychiatric disorders.

Methods: A literature search was conducted using MEDLINE/PubMed, Cochrane Library, Scopus, EMBASE, CINAHL, and PsycINFO. Studies evaluating the concordance between telepsychiatric and face-to-face settings in the diagnosis and symptom assessment of various psychiatric disorders were included and analyzed.

Results: Of the 6875 studies in the initial search, 22 studies that met the inclusion criteria were included in the analyses. The diagnostic concordance for 16 psychiatric disorders was "almost perfect" between the two settings (N = 16, n = 848, Cohen's κ = 0.824, confidence interval [CI] = 0.466 to 0.950, P < 0.001). Additionally, the concordance for the symptom rating scales between the two settings ranged from "substantial" in the Brief Psychiatric Rating Scale (N = 1, n = 533, Cohen's κ = 0.789, CI = 0.699 to 0.855, P < 0.001) to "almost perfect" in the Autism Diagnostic Observation Schedule (N = 1, n = 92, intraclass correlation coefficients = 0.943, CI = 0.798 to 0.985, P < 0.001).

Conclusions: Telepsychiatry is highly concordant with face-to-face settings regarding psychiatric diagnoses and symptom assessment. In contrast, the present results also suggest that the suitability of telepsychiatry varies across disease types, specific symptoms, and assessment modalities. Although the present results must be interpreted with caution owing to the small number of studies for each assessment and disease, our findings suggest that telepsychiatry may have greater utility in psychiatric diagnostic assessment settings.

Aim: A GGC repeat expansion in the 5' untranslated region of NOTCH2NLC is a genetic cause of Neuronal Intranuclear Inclusion Disease (NIID) that exhibits cognitive, motor, and autonomic dysfunction. Our objective is to determine whether there are undiagnosed NIID cases in a psychiatry-based dementia-enriched cohort and to identify their clinical characteristics.

Methods: A retrospective clinical cohort study was conducted in an inpatient and outpatient psychiatric clinic in a University Hospital in Osaka, Japan. Genomic DNA and clinical information were collected with written informed consent. Nine hundred fifty-eight cases were clinically classified according to the International Classification of Diseases (ICD)-10 system. Genetic analysis with Repeat-Primed PCR and Amplicon-Length PCRs were performed.

Results: Of the 958 cases, three were confirmed to have an aberrant GGC repeat expansion in NOTCH2NLC. Cases 1 and 2 had preceding anxiety and depressive episodes, and one of these cases also had a mild cognitive impairment. Case 3 met the diagnostic criteria for progressive supranuclear palsy. All three cases lacked hyperintensity at the corticomedullary border on diffusion-weighted MRI, which is known as a characteristic for NIID. Interestingly, one case exhibited the corticomedullary hyperintensity later in the disease course with apparent neurocognitive decline. All three cases exhibited a mix of slow waves in electroencephalogram and elevated total protein level in cerebrospinal fluid.

Conclusions: NIID is a rare cause of cognitive dysfunction in a psychiatry-based dementia-enriched cohort in Japan. Our data implicates psychiatric symptoms can be prodromal or early manifestation of a subset of NIID cases, thereby extending its phenotypic spectrum.

Next-generation sequencing has identified risk genes with large effect sizes for autism spectrum disorders (ASD). Although functional analysis of individual risk genes has progressed, the overall picture of ASD pathogenesis is unclear. Therefore, there is a need for morphological profiling of variants in these genes to fully comprehend their pathomechanism in cultured cells. High-content analysis (HCA) is a powerful approach to thoroughly analyze cellular alterations following genetic modifications in many disorders, including ASD. We begin this review with the latest phenotypic descriptions of ASD risk variants and different ASD cell models, which provide a basis to select features for extraction in image-based analysis to best capture ASD mechanisms. We then describe recent genetic and pharmacological screening campaigns for ASD using HCA systems. Generally, HCA enables imaging of ASD-derived cell models using measurements such as cell proliferation, differentiation, process growth, synapse numbers, and other morphological changes to neurons, astrocytes, and microglia. Advances in machine learning are reducing bias in feature identification and extraction. These data can be transformed for downstream analyses and visualization, such as clustering using heatmaps for morphological profiling. This provides image-based profiling data that can be used to determine the mechanisms of action of genetic modifications. Additionally, comprehensive methods, such as mixture-based and common structure ranking approaches, which can systematically examine the effects of millions of compounds, could identify compounds that might ameliorate the effects of ASD risk gene mutations using morphological profiling.

Aim: To test the hypothesis that neuromarker alternations associated with diagnosis, symptoms, or psychotropic medication use can be found in schizophrenia, we measured cerebrospinal fluid (CSF) neuromarkers in patients with schizophrenia and healthy controls.

Methods: This cross-sectional study comprised 148 patients with schizophrenia (39.0 ± 11.0 years; 88 men and 60 women) and 220 healthy controls (44.6 ± 14.8 years; 135 men and 85 women), all of Japanese ethnicity. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity in patients with schizophrenia. The levels of eight of the 18 CSF neuromarker were successfully measured using a multiplex immunoassay. Trait and state markers were identified by patient and control groups comparison and symptom-correlation analyses, respectively.

Results: CSF glial fibrillary acidic protein levels were significantly higher in patients with schizophrenia than in healthy controls. CSF neurogranin, total tau, and YKL-40 levels were significantly lower in patients with schizophrenia than in healthy controls. Particularly, in patients with schizophrenia, CSF neurogranin, total tau, and YKL-40 levels were lower in the psychotropic-medicated group than in the psychotropic-medication-free group. CSF amyloid beta _1-42 levels were significantly and negatively correlated with PANSS negative scores. CSF macrophage migration inhibitory factor levels were significantly and positively correlated with PANSS positive, general psychopathology, and total scores. CSF neural cell adhesion molecule-1 and S100 calcium-binding protein B levels were significantly and positively correlated with PANSS positive scores.

Conclusion: Our findings suggest trait and state neuromarkers and antidementia-like effects of psychotropics on the pathology of schizophrenia.