Neuropsychopharmacology Reports最新文献

Controlling for confounding factors in postmortem brain studies of psychiatric disorders is crucial, particularly in gene expression analyses. Potential confounding factors include sex, age at death, medication history, agonal state, postmortem interval (PMI), tissue storage duration, tissue pH, and RNA integrity number (RIN). pH and RIN are considered particularly important in gene expression analysis because they accurately reflect mRNA quality. We previously found that pH and RIN affected the levels of genes related to the cell cycle and RNA processing, respectively, and both affected genes involved in energy production and the immune system. In this study, we investigated the influence of confounding factors on gene expression profiles in psychiatric disorders. We measured gene expression levels in the prefrontal cortex of 25 deceased patients with schizophrenia, 10 with bipolar disorder, and 21 nonpsychiatric controls via RNA sequencing, and identified genes associated with pH, RIN, PMI, sex, age at death, tissue storage duration, and antipsychotic drug dose. We identified key molecular pathways through Ingenuity Pathway Analysis. The total number of mRNA variants significantly correlated with gene expression, and each confounding factor was as follows: 139 for sex, 87 for age, 99 for PMI, 35 386 for pH, 11 373 for RIN, and 13 414 for storage duration. We identified strong associations with metabolic, immune, energy production, and DNA repair pathways. The expression of certain genes was strongly associated with different confounding factors; therefore, it is necessary to consider these factors when interpreting the gene expression profile in brain tissue.

The relationship between depression and alcohol consumption has not yet been confirmed, and no large-scale studies have examined this association in Asian college students. This study examined the correlation between excessive drinking and depression in Japanese college students. We solicited the participation of undergraduate and graduate students aged 20 years or older who underwent annual health examinations between April 2019 and January 2020 at two universities in Japan. A self-administered questionnaire was used to assess the frequency of alcohol drinking, the amount of alcohol consumed per day, binge drinking during the past month, Center for Epidemiologic Studies Depression Scale score, and demographic data. A total of 4535 students were analyzed, specifically 2775 men (61.2%) and 1760 women (38.8%). Of these, 1076 men (66.3%) and 548 women (33.7%) were classified as excessive drinkers. Further, 1474 students (32.5%) had depression, of whom 528 (35.8%) were excessive drinkers. In a logistic regression analysis, depression was found to be inversely associated with heavy drinking (odds ratio 0.59 [0.36-0.98]), even after adjusting for several variables. This study found a negative association between excessive alcohol use and depression among Asian college students. More detailed research should investigate the relationship between alcohol consumption and depression by age group and race.

Objectives: Ketamine is a prototypical rapid-acting antidepressant for treatment-resistant bipolar depression (TRBD), yet many patients do not achieve a meaningful response. This study explored features of ketamine nonresponse in TRBD.

Methods: In a post hoc analysis of a naturalistic study, 35 TRBD patients received a four-week ketamine regimen (intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg). Response was measured using the Montgomery-Åsberg Depression Rating Scale, and baseline sociodemographic and clinical features were compared between responders and nonresponders.

Results: Fourteen patients (40%) were nonresponders. They had a higher median number of psychiatric comorbidities (2 vs. 1; p = 0.0366), were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%; p = 0.0153), and had greater prior benzodiazepine use (64.3% vs. 23.8%; p = 0.0332). No significant links emerged between individual comorbidities or baseline suicidality and response.

Conclusion: Ketamine demonstrates a favorable safety and tolerability profile for short time use in TRBD regardless of isolated baseline characteristics, although a more severe comorbidity burden and benzodiazepine use appear to be associated with nonresponse.

Trial registration: NCT04226963 and NCT05565352.

Background: Olanzapine is a second-generation atypical antipsychotic drug which is commonly used in the treatment of schizophrenia. It has been associated with metabolic adverse effects such as weight gain, hyperglycaemia, dyslipidaemia, and this has been shown to contribute to the reduction of life expectancy of patients with schizophrenia. This systematic review aimed to assess whether adjunctive aripiprazole is effective at reducing metabolic adverse effects caused by olanzapine.

Methods: A systematic review was conducted for this study. A systematic search strategy was developed, recorded, and applied to multiple databases. The literature search found a total of 853 results with the final inclusion of 7 research articles. Based on specific inclusion and exclusion criteria, a wide range of study designs were included in the review, such as randomized control trials (RCTs), open label trials, and case series. Key outcomes were identified, which included glucose levels, lipid profile, body weight, BMI, and waist circumference. The results were recorded and analyzed using narrative synthesis.

Results: Statistically significant decreases in fasting triglycerides were consistent across multiple studies. Adjunctive aripiprazole shows potential weight loss benefits, with some studies reporting significant reductions in weight and BMI. Effects on cholesterol and fasting glucose showed reductions, and others showed minimal or no impact. Psychiatric symptom control remained stable in most studies, suggesting that aripiprazole does not negatively affect schizophrenia symptoms while potentially providing metabolic advantages.

Conclusion: Adjunctive aripiprazole had variable effects on metabolic parameters in patients on olanzapine therapy; however, reductions in triglycerides appeared consistent among most of the data, and some studies reported significant weight loss. This highlighted that aripiprazole does have some effect in reducing metabolic adverse effects caused by olanzapine.

Dextromethorphan and bupropion in combination are approved to treat major depressive disorders in adults. This case report describes a patient with a history of treatment-resistant depression who presented to the emergency department after overdosing on approximately 30 tablets of dextromethorphan-bupropion 45-105 mg in a suicide attempt. The patient required intubation, gastrointestinal decontamination, and changes in her antidepressant medications. The patient reported no suicidality by the end of her hospitalization, and she was discharged on paroxetine 40 mg daily and quetiapine 200 mg at night. Clinicians should be cautious and vigilant when prescribing or considering these medications together, particularly in populations at risk of overdose.

Masataka et al.'s cannabis gateway study misrepresents the 43.8% probability of cannabis users transitioning to illegal drugs as "rare," and misuses regression via the Table 2 Fallacy. These critical issues discredit their conclusion.

Background: Although opioid analgesics may influence sleep in patients with chronic pain, the association between strong opioid use and sleep characteristics remains unclear. This study aimed to explore differences in sleep status among chronic pain patients with varying levels of opioid use.

Methods: A total of 29 patients with chronic non-cancer pain who had been under treatment for more than 6 months were included. Patients were divided into four groups based on their opioid use: non-opioid users (n = 11), weak opioid users (n = 8), and strong opioid users receiving either < 60 mg/day (n = 5) or ≥ 60 mg/day (n = 5) in morphine-equivalent doses. Pain and psychological factors were assessed using the Numerical Rating Scale, Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, and Japanese Perceived Stress Scale. Subjective sleep status was assessed using the Athens Insomnia Scale. Objective sleep parameters, including total sleep duration, wakefulness after sleep onset (WASO), and sleep efficiency, were measured over seven nights using the wearable device. Sleep data were analyzed using a linear mixed-effects model with the opioid-naive group as the reference. Model 1 was unadjusted; Model 2 adjusted for age, sex, pain intensity, catastrophizing, anxiety, depression, and stress.

Results: Patients in the ≥ 60 mg/day group showed shorter total sleep duration, longer WASO, and lower sleep efficiency in Model 1 compared to non-opioid users. These trends remained in Model 2, although statistical significance decreased. In contrast, those receiving < 60 mg/day showed trends toward shorter WASO and higher sleep efficiency. Subjective insomnia symptoms were more frequent in both strong opioid groups, especially in the high-dose group.

Conclusion: Among patients with chronic non-cancer pain, high-dose strong opioid use tended to be associated with poorer sleep, while low-dose use was linked to more favorable sleep characteristics.

Background: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a type of autoimmune encephalitis, characterized by acute onset neuropsychiatric symptoms, predominantly affects young females and is often associated with ovarian teratomas. Although small cell lung cancer (SCLC) is a known cause of paraneoplastic encephalitis, its association with anti-NMDAR encephalitis is rare and often carries a poor prognosis due to limited response to immunotherapy.

Case presentation: An 80-year-old male with no psychiatric history presented with flu-like symptoms, followed by the acute onset of neuropsychiatric symptoms, including pressured speech, agitation, memory impairment, and abnormal behavior. Autoimmune encephalitis was suspected due to mildly elevated cerebrospinal fluid (CSF) white cell count and a mass in the right upper lung detected by whole-body computed tomography (CT) on the first day of hospitalization. High-dose intravenous corticosteroids were administered on Day 1, resulting in prompt and sustained improvement in symptoms. CSF was later confirmed positive for anti-NMDAR antibodies, and a bronchoscopy biopsy of the pulmonary mass diagnosed SCLC. The patient recovered without neurological deficits and was discharged in stable condition on hospital Day 30.

Conclusion: This was a rare case of anti-NMDAR encephalitis associated with SCLC in an elderly male patient. Diagnosis in elderly individuals is often challenging because of the atypical presentations and lower tumor association. Nevertheless, timely intervention initiation may lead to favorable outcomes. Clinicians should consider autoimmune encephalitis, including anti-NMDAR encephalitis, when evaluating acute onset neuropsychiatric symptoms in elderly individuals and initiate early immunotherapy alongside tumor screening.

Background: Since research on the pathophysiology of psychiatric disorders diagnosed by symptoms has not succeeded, a data-driven analysis incorporating biological and cross-disease perspectives has been proposed. We have reported a new subgroup of psychiatric disorders by a data-driven analysis of subcortical volumes of brain MRI in 5602 subjects, including patients with psychiatric disorders and controls. This subgroup of patients is characterized by enlarged ventricle and cognitive impairment (EVCI) with a high proportion of schizophrenia, electroencephalography abnormalities, and rare pathological copy number variations.

Case presentation: Of the nine patients with EVCI, eight patients had schizophrenia, and one patient had autism spectrum disorder. Early onset of age was observed in eight patients with schizophrenia. Treatment responses were poor in seven patients with schizophrenia, and two of three treatment-resistant schizophrenia patients responded to clozapine. Four patients showed ischemic changes in cerebral white matter. In electroencephalography, abnormal findings were observed in five patients, borderline findings in two patients, and normal findings in two patients. Rare pathogenic copy number variations were found in three patients (22q11.21 deletion, 7q11.23 duplication, and 7q36.2 deletion).

Conclusions: The results of this case series showed additional clinical features of treatment response and ischemic changes in cerebral white matter, which could be a clue to the treatment and diagnosis of EVCI. This case series might help elucidate the pathophysiology of EVCI.

Objective: To examine the characteristics associated with happiness in Japanese individuals with schizophrenia.

Methods: A self-reported online survey was conducted in 2022 among individuals aged 20-75 years, including 223 and 1776 individuals with and without schizophrenia, respectively. We used a modified Poisson regression to assess the factors associated with happiness by calculating the age- and sex-adjusted prevalence ratios (PRs). We examined within-schizophrenia group differences by age and sex strata, and compared these stratified PRs between groups with and without schizophrenia.

Results: Among participants with schizophrenia, happiness was significantly associated with self-rated health status (PR = 1.75), Ikigai (PR = 5.02), depressive symptoms (PR = 0.43), perceived stress (PR = 0.52), cognitive social capital (PR = 2.07), structural social capital (PR = 1.70), social support (PR = 2.40), close friends (PR = 1.88), close relatives (PR = 2.34), and a cohabiting partner (PR = 1.57). Within the schizophrenia group, sex differences were significant for cognitive social capital (men: PR = 3.45; women: PR = 1.43) and cohabiting partners (men: PR = 2.26; women: PR = 1.25), whereas no significant age differences were found. Factors demonstrating a stronger association in participants with schizophrenia than in those without schizophrenia included: Ikigai (with, PR = 5.02; without, PR = 2.91), cognitive social capital (with, PR = 2.07; without, PR = 1.49), and structural social capital (with, PR = 1.70; without, PR = 1.24).

Conclusion: Happiness in individuals with schizophrenia is associated with physical, mental, and social factors, with social factors exhibiting sex-related differences.