Possible association of elevated CSF IL-6 levels with anxiety and frustration in psychiatric disorders.

AIM: Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders. METHODS: We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging. RESULTS: Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients. CONCLUSION: Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.

Association between overweight and central interleukin-6 in a nonclinical adult population.

AIM: Overweight is associated with low-grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan. METHODS: CSF and plasma levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasma levels of C-reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants. RESULTS: The BMI significantly correlated with CSF levels of IL-6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL-1ß (rs = 0.29, p = 0.019), IL-6 (rs = 0.25, p = 0.042), TNF-α (rs = 0.43, p < 0.001), and leptin (rs = 0.72, p < 0.001). Overweight participants (BMI ≧ 25) had significantly higher CSF levels of IL-6 (p < 0.001), plasma levels of IL-1ß (p = 0.023), TNF-α (p < 0.001), and leptin (p < 0.001) than the nonoverweight participants. CONCLUSION: Overweight is associated with central IL-6, a marker for neuroinflammation, as well as systemic inflammation markers, even in a nonclinical population.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls.

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.

Correlation between myelin basic protein levels in cerebrospinal fluid and motor speed in patients with schizophrenia.

Alterations in the white matter have been implicated in schizophrenia. Myelin basic protein (MBP), a component of the myelin sheath, in the cerebrospinal fluid (CSF) has been suggested as a biomarker for white matter damage in demyelinating diseases. This prompted us to examine the CSF-MBP levels in patients with schizophrenia. We analyzed the CSF-MBP levels in 152 patients with schizophrenia and 117 age- and sex-matched controls. A significant positive correlation between age and CSF-MBP levels was observed both in the patients (p < 0.001) and controls (p = 0.014). No significant difference was observed in the CSF-MBP levels between the two groups. However, among a subsample of the patients (N = 32), a significantly negative correlation was observed between CSF-MBP and age-adjusted motor speed score of the brief assessment of cognition in schizophrenia (ρ = -0.59, p < 0.001). Further, among patients who underwent diffusional magnetic resonance imaging of the brain (N = 27), the CSF-MBP levels showed a significantly negative correlation with the mean kurtosis value in the right temporo-parietal region (p < 0.001). Our results suggest that the CSF-MBP level has limited utility as a diagnostic marker; however, higher CSF-MBP levels are associated with poorer motor speed, which may be associated with regional white matter damage in the brain in patients with schizophrenia.

Assessing attribution in the criminal behavior of mentally disordered offenders: Developing a Japanese version of the Gudjonsson Blame Attribution Inventory-Revised.

Aim: Treating individuals with a mental disorder and a history of criminal behavior (mentally disordered offenders [MDOs]) aims to enable patients to maintain their health and facilitate social rehabilitation while preventing adverse outcomes, such as violent recidivism or suicide. Understanding and responding to their own insight on their criminal behavior is crucial to achieving this goal. This article aims to develop a Japanese version of the Gudjonsson Blame Attribution Inventory-Revised (GBAI-R) and investigate the reliability and validity of the scale for MDOs in Japan. Methods: In addition to developing the Japanese version of GBAI-R (GBAI-RJ), psychological data relevant to the Japanese study were collected and analyzed. Factor analysis was employed. Results: Seventy-seven Japanese native participants were recruited from forensic psychiatric inpatients, outpatients, and medical prison inmates between 2020 and 2022. The results demonstrated that the dimensions on the GBAI-RJ had a similar factor structure to those reported in previous studies. The GBAI-RJ has both test/retest reliability and internal consistency. Conclusion: The three dimensions Guilt Factor, External Factor, and Mental Element Factor from the original version in English are applicable to the Japanese version for assessing attribution and comparing the findings with those of the previous studies.

Electroconvulsive Therapy on Treatment-resistant Mania in Bipolar Disorder with No Concurrent Antipsychotics: A Case Report.

Pharmacotherapy is generally the first choice for the treatment of acute mania in bipolar disorder. Electroconvulsive therapy (ECT) is reported to be an effective treatment modality for mania; however, it is usually used as the "last resort." Herein, we report a case of a patient with treatment-resistant severe mania in bipolar disorder who recovered with ECT without concurrent antipsychotics and mood stabilizers. Our case report showed that ECT monotherapy can be an effective treatment modality for manic state in bipolar disorder, which may lead to a shorter hospital stay and better social outcomes.

Pathologic and Neuropathologic Study of a Case of COVID-19.

A 68-year-old woman with a history of schizophrenia developed coronavirus disease (COVID)-19 and was transferred to our hospital. Despite treatment, she died of respiratory failure 16 days after the onset. At the time of autopsy, polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA using swabs from the nasopharynx and the lung was positive; however, the cerebrospinal fluid was negative. An autopsy showed diffuse alveolar damage and recent multiple cerebral infarcts. Acute splenitis was observed with thrombi adhering to the vascular endothelium in areas of severe neutrophilic infiltration. Immunohistochemistry using an antibody against the SARS-CoV-2 nucleocapsid showed immunoreactivity along the hyaline membrane of the lung; however, the antibody showed no immunoreactivity in the medulla, the thalamus, the frontal lobe, and the pituitary. Future pathologic studies should clarify the mechanisms involved in a variety of clinical and pathological changes related to COVID-19.

Infectious Aneurysm Caused by Citrobacter koseri in an Immunocompetent Patient.

Citrobacter species can cause severe infection in immunocompetent patients. A 78-year-old man visited our hospital because he had had a fever lasting one day each month for the past 3 months. Antibiotics were initiated for suspected bronchial pneumonia, but the C-reactive protein level remained high. Contrast-enhanced computed tomography revealed saccular brachiocephalic artery aneurysm. Citrobacter koseri was isolated from a blood culture, and he was diagnosed with infectious brachiocephalic artery aneurysm. He underwent endovascular aneurysm repair after one month of intravenous cefepime and metronidazole. We herein report for the first time an immunocompetent patient with infectious aneurysm caused by C. koseri periodontal infection.