Neuropsychopharmacology Reports最新文献

Background: Residual fatigue is a common and debilitating symptom in patients with unipolar and bipolar depression, even after achieving partial or full remission. It significantly impacts patients' quality of life and increases the risk of relapse. This systematic review aims to evaluate the prevalence and effectiveness of therapeutic options for residual fatigue in individuals with unipolar major depressive disorder (MDD) and bipolar disorder (BD).

Methods: A comprehensive search was conducted in the PubMed, SCOPUS, and Web of Science databases up to September 2024. The protocol for this systematic review was registered in PROSPERO. The search strategy included terms related to depression and residual fatigue. Studies were included if they provided data on adult patients diagnosed with MDD or BD, and if they measured the prevalence or treatment of residual fatigue. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for non-randomized studies.

Results: Twenty studies were included in the review. The vast majority reported on MDD, and single papers investigated BD. Residual fatigue was reported by up to 83% of patients, and moderate to severe residual fatigue affected a smaller percentage. Pharmacological treatments, such as modafinil and to a lesser extent atomoxetine, demonstrated short-term reductions in residual fatigue.

Conclusion: Residual fatigue remains a significant challenge in the treatment of depression, persisting in a large portion of patients despite remission. Pharmacological interventions like modafinil appear promising, but more research is needed, especially in BD. Standardized assessment tools and longer-term studies are essential to better understand and treat residual fatigue.

Trial registration: PROSPERO identifier: CRD42024543087.

Aim: Constipation is one of the most common adverse effects in schizophrenia treatment, and it can sometimes cause severe gastrointestinal disease. However, the results of association studies between constipation and psychotropic medications in patients with schizophrenia are inconsistent. Therefore, we investigated the characteristics of psychotropic and laxative prescriptions at discharge in patients with schizophrenia to clarify the association between psychotropics and constipation.

Methods: We analyzed the data of 139 patients with schizophrenia with or without laxative prescriptions at discharge from eight institutions in 2020.

Results: Sixty-two patients were prescribed laxatives at discharge. The prescription of benzodiazepines in the laxative use group (66.1%) was significantly higher than that in the non-laxative use group (39.0%) (p = 1.4 × 10^-3), and the mean number of benzodiazepines in the laxative use group (1.2 ± 1.1/day) was significantly higher than that in the non-laxative use group (0.7 ± 0.9/day) (p = 2.6 × 10^-3). Multivariate logistic regression analyses revealed that benzodiazepine prescriptions were significantly associated with laxative usage (odds ratio, 3.059; 95% confidence interval, 1.523-6.144; p = 2.0 × 10^-3).

Conclusion: Benzodiazepines may be associated with constipation in patients with schizophrenia. Therefore, clinicians should be cautious when prescribing benzodiazepines for the treatment of schizophrenia.

One of the challenges in diagnosing psychiatric disorders is that the results of biological and neuroscience research are not reflected in the diagnostic criteria. Thus, data-driven analyses incorporating biological and cross-disease perspectives, regardless of the diagnostic category, have recently been proposed. A data-driven clustering study based on subcortical volumes in 5604 subjects classified into four brain biotypes associated with cognitive/social functioning. Among the four brain biotypes identified in controls and patients with schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and other psychiatric disorders, we further analyzed the brain biotype 1 subjects, those with an extremely small limbic region, for clinical utility. We found that the representative feature of brain biotype 1 is enlarged lateral ventricles. An enlarged ventricle, defined by an average z-score of left and right lateral ventricle volumes > 3, had a sensitivity of 99.1% and a specificity of 98.1% for discriminating brain biotype 1. However, the presence of an enlarged ventricle was not sufficient to classify patient subgroups, as 1% of the controls also had enlarged ventricles. Reclassification of patients with enlarged ventricles according to cognitive impairment resulted in a stratified subgroup that included patients with a high proportion of schizophrenia diagnoses, electroencephalography abnormalities, and rare pathological genetic copy number variations. Data-driven clustering analysis of neuroimaging data revealed subgroups with enlarged ventricles and cognitive impairment. This subgroup could be a new diagnostic candidate for psychiatric disorders. This concept and strategy may be useful for identifying biologically defined psychiatric disorders in the future.

Background: An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient-specific and evidence-based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real-world data collected by CMAS.

Methods: A sub-set of de-identified, patient-specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.

Results: Most patient-specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10-90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non-neuropathic pain, and insomnia. Comedications were most commonly non-opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta-9-tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD-only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.

Conclusion: The findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision-making about medical cannabis and can inform the development of clinical guidance resources.

Aim: Although numerous studies have reported that chronic alcohol consumption causes brain volume reduction and cerebrospinal fluid volume increase, few studies have examined the acute effects of alcohol on brain structure. This study aims to investigate the short-term brain volume changes following alcohol administration.

Methods: Moderate doses of alcohol were administered intravenously to 18 healthy volunteers for a total of 90 min to achieve a blood alcohol concentration of 0.5 mg/mL. An alcohol clamp method combined with physiologically based pharmacokinetic modeling was used to achieve fine control over blood alcohol concentration. T1 images with 3T MRI were scanned at three time points: baseline, 0 min, and 90 min after the end of alcohol administration. Cortical, subcortical, and ventricular volumes were computed after segmentation with FreeSurfer. Repeated measures analysis of variance was used to evaluate longitudinal changes in brain volume at 96 regions.

Results: Acute alcohol administration increased bilateral lateral ventricular volumes, which lasted until 90 min after the end of alcohol injection. On the other hand, the volumes of total gray matter, left precentral cortex, left caudal middle frontal cortex, and left superior frontal cortex decreased after alcohol administration, but these changes disappeared 90 min after the end of alcohol administration.

Conclusion: Acute injection of moderate doses of alcohol may enlarge ventricle volumes and reduce gray matter volumes. The transient volume changes caused by acute administration of alcohol may be related to changes in CSF flow and water content of brain tissue, which warrants further study.

Aims: Fatty acid binding protein 4, adipocyte (Fabp4), is well known for its role in peripheral lipid metabolism, but its potential role in brain function remains largely unexplored. This study aimed to investigate Fabp4 expression in the adult mouse brain and explore gene expression changes in Fabp4 knockout (KO) mice to assess its potential impact on brain function.

Methods: We conducted in situ hybridization to assess Fabp4 expression in key brain regions of adult mice. In parallel, differential gene expression analysis using RNA-seq was conducted in the prefrontal cortex of Fabp4 KO mice to identify genes affected by Fabp4 deficiency.

Results: No Fabp4 expression was detected in the brains of mice, suggesting a lack of direct involvement in the central nervous system. However, Fabp4 KO mice exhibited significant changes in gene expression in the brain, with 31 genes upregulated and 30 downregulated. Downregulated genes were linked to histone methylation and metabolic processes, while upregulated ones were associated with synaptic organization.

Conclusion: Although Fabp4 is not expressed in the brain, its deficiency leads to substantial changes in gene expression, likely mediated by peripheral metabolic pathways and epigenetic regulation. These changes may explain the previously observed autism-like behaviors and increased dendritic spine density in Fabp4 KO mice. This study sheds light on the role of systemic lipid metabolism in neurodevelopmental disorders such as autism spectrum disorder (ASD) and highlights epigenetic mechanisms as potential mediators of these effects.

Aim: Strokes are the second most common cause of mortality and disability worldwide. Ischemic strokes account for the main part of strokes. Recently, the epigenetic changes that occur during biological aging through DNA methylation have gained attention. The National Institutes of Health Stroke Scale (NIHSS) scores measure physical and cognitive function. We hypothesized that there are associations between acute changes in the NIHSS score and biological aging in patients with ischemic stroke. We conducted epigenetic clock analyses to investigate the association between the difference in NIHSS (dNIHSS) and epigenetic clock in patients with ischemic stroke.

Methods: We used two publicly available DNA methylation data sets from Caucasian patients with ischemic stroke in Spain. The discovery data set consists of 59 patients with ischemic stroke, and the replication dataset consists of 62. Acceleration of several epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, GrimAge2, DNA methylation-based telomere length, and DunedinPACE), GrimAge components, and GrimAge2 components was analyzed with standard multiple regression analyses with dNIHSS. We obtained information on dNIHSS between discharge and baseline for each patient. We integrated these results from the two data sets using meta-analyses.

Results: There was no significant association in the epigenetic age acceleration. The predictive value of only Cystatin C showed a significant association with dNIHSS in the GrimAge components.

Conclusions: We could not find a significant association between the severity during the acute phase of ischemic stroke and epigenetic clocks. We may be able to find different findings with a larger sample size and longitudinal data such as NIHSS scores at fixed intervals.

Background: Cerebrospinal fluid (CSF) levels of orexin show a cyclic diurnal variation in healthy subjects, which is diminished in patients with certain diseases. However, possible circadian variations in orexin levels in critically ill patients remain unknown. In this study, we evaluated the orexin concentrations in the CSF and their diurnal variation in patients undergoing thoracic aortic aneurysm repair with lumbar intrathecal catheterization for CSF drainage after non-neurosurgery.

Methods: Eligible patients with a lumbar intrathecal catheter placed for CSF drainage following aortic surgery at a single-center ICU between September 2019 and February 2020 were included. Catheters were placed before anesthesia induction, and CSF was collected at the time of catheter placement, ICU admission, and daily at 6:00, 12:00, 18:00, and 24:00 until the catheter was removed or for up to 5 days after admission to the ICU.

Results: Three patients (Patients A, B, and C) who underwent thoracic aortic aneurysm repair were included. Patients B and C received sedatives or hypnotics during the orexin measurement period. The baseline orexin levels for Patients A, B, and C were 219.9, 312.3, and 403.8 pg/mL, while the mean orexin levels were 319.4 ± 82.6, 372.4 ± 56.0, and 306.3 ± 48.3 pg/mL, respectively. For all three patients, orexin levels showed diurnal variations, but no consistent periodic changes.

Conclusion: CSF orexin concentrations for patients undergoing thoracic aortic aneurysm repair in the ICU were within the reported range compared to those of previously reported healthy subjects; however, consistent periodic diurnal variations were not observed.

Aim: Psychopharmacotherapy plays an important role in the treatment of mentally disordered offenders (MDOs) with schizophrenia spectrum disorders. However, there have been few large-scale reports from multiple forensic psychiatric wards. This study aimed to clarify the current state of antipsychotic medications for MDOs with schizophrenia spectrum disorders in Japanese forensic psychiatric wards.

Methods: Medical information, including age, sex, psychiatric diagnosis, index offense, seclusion or restraint experience during hospitalization, and medication for patients discharged from 32 forensic wards nationwide between September 1, 2019 and December 31, 2021 was provided by the Database Scientific Utilization Project of Japanese forensic psychiatric wards. We analyzed the data of MDOs with schizophrenia spectrum disorders who were prescribed psychotropic medications at the time of discharge, especially focusing on comparing differences between the three groups (clozapine, long-acting injection (LAI), and other medications).

Results: A total of 362 MDOs with schizophrenia spectrum disorders were prescribed psychotropic medications at discharge. The prescription rates of clozapine and LAI were 23.2% and 24.9%, respectively. Additionally, the rate of antipsychotic polypharmacy was 37.8%. Among the three groups, the clozapine group had the highest rate of seclusion experience (46.4%), a long mean length of hospitalization (1758 days), and the lowest rate of antipsychotic polypharmacy (4.8%). Olanzapine was the most commonly prescribed antipsychotic medication.

Conclusion: This study revealed the current state of antipsychotic medications for MDOs admitted to forensic psychiatric wards in Japan. Future studies are needed to clarify the relevance of antipsychotic medications in the prognosis of MDOs.

Aim: To evaluate the relationship between cognitive impairment and work productivity loss in patients with bipolar disorder.

Methods: We enrolled outpatients with bipolar disorder aged 18-59 years undergoing treatment and actively employed or on sick leave. Baseline demographic, medical resource use, and employment data were collected. We evaluated work productivity, cognitive impairment, quality of life (QOL), depressive symptoms (defined as a Patient Health Questionnaire-9 [PHQ-9] score of ≥ 10), and sleep disturbance. This interim analysis examined correlations among baseline symptom scores and correlations of each symptom score with work productivity loss and QOL.

Results: Among 211 participants, cognitive impairment was moderately correlated with depressive symptoms (r = 0.595) and insomnia (r = 0.481), and depressive symptoms and insomnia were highly correlated (r = 0.719) (all p < 0.001). Work productivity loss (presenteeism) was moderately correlated with cognitive impairment (r = 0.474), depression (r = 0.577), and insomnia (r = 0.547) (all p < 0.001). Depression had the strongest influence on presenteeism (multiple regression analysis, regression coefficient: 22.98; p < 0.001). Among participants without severe depressive symptoms (PHQ-9 ≤ 19), cognitive impairment (13.91, p = 0.007) and insomnia (13.80, p = 0.016) strongly affected presenteeism. Among participants without moderately severe or severe depressive symptoms (PHQ-9 ≤ 14), insomnia affected presenteeism (23.14, p = 0.011). QOL was moderately negatively associated with cognitive impairment (r = -0.653), depression (r = -0.699), and insomnia (r = -0.559) (all p < 0.001). In multiple regression analysis, cognitive impairment (-0.12, p < 0.001), depression (-0.12, p = 0.010), and insomnia (-0.16, p < 0.001) were significantly associated with QOL.

Conclusions: Treatment should focus on improving the core symptoms of bipolar disorder, insomnia, and cognitive impairment.

Trial registration: UMIN Clinical Trials Registry (UMIN000051519).