Neuropsychopharmacology Reports最新文献

Aims: Alzheimer's disease (AD) is a leading cause of dementia, with increasing prevalence. Mutations in genes like MAPT, PSEN1, and PSEN2 are risk factors, leading to the development of several AD model mice. Recent hypotheses suggest AD brain pathology involves abnormal neurodevelopment, decreased pH, and neural hyperexcitation. However, it remains unclear to what extent these pathologies are reflected in the gene expression changes of AD models. This study aims to compare gene expression patterns in the brains of multiple AD model mice with those related to these three factors, evaluating the extent of overlap.

Methods: We conducted a comprehensive search of public databases, collecting 20 gene expression datasets from the hippocampus of AD model mice. These datasets were compared with gene sets related to hippocampal maturation, brain pH, and neural hyperexcitation to statistically assess overlap. Pathway enrichment analysis explored the biological relevance of these gene expression changes.

Results: The extent of overlap with maturity-, pH-, and hyperexcitation-associated genes varied across AD models, showing significant correlations between lower maturity, lower pH, and increased neural hyperexcitation. In MAPT mutant and APP+PSEN1 homozygous transgenic mice, these signatures became more pronounced with age. Pathway meta-analysis revealed that genes associated with maturity, pH, and hyperexcitation in AD models are involved in synaptic and channel functions, as well as inflammatory responses, consistent with previous studies.

Conclusion: These findings suggest that pathophysiological changes related to maturity, pH, and neural hyperexcitation play varying roles across individual AD model mice. Our recent study found a negative correlation between disease progression and actual pH levels in human AD patients. Considering the results presented in this study, maturity and neural hyperexcitation, which are correlated with pH, may also be linked to disease progression. Thus, gene expression changes in these factors could be useful markers for assessing the pathology in AD models.

Aim: Anhedonia is a key symptom of major depressive disorder (MDD), however, its burden in patients with MDD is not well understood. We aimed to assess the impact of anhedonia on health-related quality of life (HRQoL), health-care resource utilization (HRU), and work productivity in subjects with MDD and anhedonia (MDD-ANH) compared to subjects with MDD without ANH (MDD non-ANH).

Methods: A cross-sectional web-based survey was conducted across six countries/territories. Adult participants were categorized as MDD-ANH, MDD non-ANH, and General Population based on self-reported MDD diagnosis, Patient Health Questionnaire (PHQ-9), and Snaith-Hamilton Pleasure Scale (SHAPS). Multivariate/generalized linear regression modeling (GLMs) and mediation analysis were used to assess anhedonia's impact on HRQoL/function, HRU, and work productivity.

Results: Among 11 383 respondents, 20.1% were identified with MDD (MDD-ANH: 12.7%; MDD non-ANH: 7.3%) and 79.9% as General Population. Subjects with MDD-ANH, compared with MDD non-ANH demonstrated significantly worse or lower sexual functioning, HRQoL (RAND mental/physical component summary, health state utility (EuroQol) Index scores, all p < 0.001), and higher HRU (psychiatrist visits). Work productivity (higher absenteeism/overall work productivity or daily life impairment scores; all p < 0.05) was significantly worse in subjects with MDD-ANH compared with MDD non-ANH.

Conclusion: Anhedonia in patients with MDD had a significant negative impact on HRQoL, sexual functioning, work productivity, and HRU, emphasizing the need for focus on anhedonia management in MDD patients in the Asia-Pacific region.

Aim: We aimed to create a rat model of drug-induced parkinsonism and tardive dyskinesia by chronic administration of haloperidol and examine the expression of direct and indirect pathway markers in the striatum of the model rats.

Methods: We treated 21 rats, 14 with haloperidol decanoate and 7 with placebo. The number of vacuous chewing movements per 2 min was counted, and haloperidol-treated rats were classified into two groups: mild and severe tardive dyskinesia. Other behavioral analyses were also conducted. After a 6-month treatment period, rat brains were removed, and protein expression was evaluated by Western blotting.

Results: All haloperidol-treated rats exhibited vacuous chewing movements. The frequency of exploratory behavior and rotarod test performance was lower in the mild and severe tardive dyskinesia groups. The number of vacuous chewing movements and frequency of exploratory behavior were positively correlated in haloperidol-treated rats. The expression of dynorphin, a direct pathway marker, decreased in the severe tardive dyskinesia group. The expression of enkephalin, an indirect pathway marker, decreased both in the mild and severe tardive dyskinesia groups. The expression of dopamine D1 and D2 receptors also decreased with haloperidol treatment.

Conclusion: Both direct and indirect pathways are involved in haloperidol-induced movement disorders.

Pituitary adenylate cyclase-activating polypeptide (PACAP) affects rodents' stress-related behaviors, such as anxiety-like behavior or fear conditioning. However, previous studies have investigated the effect of intracerebroventricular, but not hippocampal, injection of this PAC1R-selective antagonist (PACAP-6-38) on anxiety-like behavior. However, it has been reported that administration of PACAP-6-38 to the dorsal hippocampus reduces the fear response in a fear conditioning test. Therefore, this study aimed to determine whether the effect of dorsal hippocampal PACAP-6-38 injection in Sprague-Dawley rats can affect anxiety-like behavior assessed by an elevated plus-maze test. As a result, rats treated with PACAP-6-38 spent longer time in open arms than those with saline, suggesting that this drug has an anxiolytic effect. In conclusion, the role of PACAP in the dorsal hippocampus can promote anxiety-like behavior.

Background: Cefepime, a fourth-generation cephalosporin, has neurotoxic side effects such as encephalopathy. Baseline conditions, including blood-brain barrier (BBB) impairment and renal dysfunction, are known to associate with elevated central nervous concentration of cefepime. Although BBB dysfunction occurs with depression or cancer, currently, neither is regarded as a risk factor for cefepime-induced encephalopathy.

Case presentation: A 79-year-old woman with a history of depression and rectal cancer was hospitalized for a bacterial liver abscess. Brain metastasis and other causes for delirium were excluded, and no renal dysfunction was observed. However, 11 days after cefepime and metronidazole administration, the patient suddenly developed confusion, disorientation, and myoclonus, with no apparent changes on brain magnetic resonance imaging. Electroencephalography revealed a consistent tri-phasic wave pattern. Clinical symptoms were well consistent with cefepime-induced encephalopathy; hence, cefepime and metronidazole were discontinued, followed by rapid physical and mental recovery, with no aftereffects.

Conclusions: In terms of BBB dysfunction, depression and cancer might be possible occult risk factors for cefepime-induced encephalopathy. Doctors need to pay attention to encephalopathy risk when administering cefepime in patients with depression or cancer because the psychiatric symptoms of encephalopathy, depression, and delirium from other causes are often confusing, leading to misdiagnosis and a poor prognosis.

Although no psychotropic medication is specifically effective for dissociative symptoms, certain abusive substances can markedly alter these symptoms. Regarding psychotropic medications, a positive response was observed in certain patients with dissociative symptoms who also have attention deficit hyperactivity disorder (ADHD), for which methylphenidate extended release (MER) was administered. A is a female in her twenties and has dissociative identity disorder (DID) and ADHD. Primary personality A1 is usually on duty but always on guard, as her other personality, A2, often attempts to disturb A1. A1's job is also hampered by careless mistakes due to her ADHD. After A was put on MER, A1 felt that A2's presence suddenly faded away while on duty and she could focus better on her job as a result. B is a middle-aged male with DID and ADHD whose life is disturbed by the occasional appearance of a violent and disruptive personality. When MER was administered for his ADHD symptoms, it helped him stay alert, and his violent episodes decreased significantly. C is a young male university student with occasional dissociative "foggy" episodes that leave him with amnesia. He is diagnosed with depersonalization-derealization disorder (DDD) and ADHD. After MER was administered for his ADHD symptoms, his dissociative episodes diminished markedly, and his job performance improved significantly as a result. When MER is administered for patients with dissociative conditions and comorbid ADHD, it appears to have positive effects on their dissociative symptoms, including increasing the threshold separating different personalities or diminishing depersonalization symptoms.

Aim: The COVID-19 pandemic has had negative physical and psychological impacts worldwide. However, there has been a lack of real-world evidence concerning the predictors of severe psychological distress (SPD) among the general population in Japan during the COVID-19 pandemic. The aim of this study was to examine predictors of SPD during the COVID-19 pandemic.

Methods: We investigated the predictors of new-onset SPD in the general Japanese population using data from a large-scale internet-based cohort study.

Results: We included 16 489 study participants (age range = 16-81, mean age = 52.7, percentage of male = 50%) in the analysis. Over the course of 1 year from baseline, the estimated proportion of participants who experienced SPD was 5.2% with inverse probability weighting. The predictors of SPD included younger age, being never married, being unemployed, having a higher education background, scoring higher on the Fear of Coronavirus-19 Scale, experiencing more adverse childhood experiences, reporting poorer subjective health status, and COVID-19 with oxygen therapy. Our internet-based survey of the Japanese population may have selection bias, limiting the generalizability to other countries and cultures.

Conclusion: This study revealed that being afflicted with COVID-19 requiring oxygen therapy is the most significant predictor of SPD. In addition, we found that vulnerability to social isolation, such as never being unmarried, anxiety toward COVID-19, and susceptibility to stress, are predictors of the emergence of SPD. Therefore, the implementation of online support systems and ensuring access to accurate information may protect against SPD during the COVID-19 pandemic in Japan.

Background: While drugs are sometimes taken during deliberate self-harm (DSH), no study has attempted to analyze drugs in the blood of DSH patients and compare them with prescribed medications or other drugs. In this study, drugs were analyzed from the blood of DSH patients, and the detected, prescribed, and suspected drugs were documented.

Methods: Patients who practiced DSH and were transferred to the emergency sites of Fukuoka University Hospital between April 2021 and September 2022 participated in the study. Psychiatrists assessed information such as the history of psychiatric treatment and recent methods of DSH, as well as prescribed drugs within 1 month of presenting to the hospital. Blood samples were analyzed using LC-MS/MS. Participants were divided into groups according to whether or not they were prescribed psychotropics within 1 month.

Results: Fifty-five patients were enrolled in the study. Forty had been prescribed psychotropics within 1 month of hospital admission. However, non-prescribed drugs (NPD) were detected in 42 of the 55 participants (76%). The detection of NPD was significantly high among patients with overdose of medications and OTC drugs (p = 0.036), but NPD were also detected in patients who engaged in other methods (n = 14), and in patients without prescribed medication (n = 10).

Discussion: This is the first study focused on the drug analysis of blood from patients engaging in DSH. Approximately 80% of the DSH patients in this study had taken NPD, revealing a large discrepancy between prescribed medications and those detected in the blood.

Patients with epilepsy often require long-term treatment with antiseizure medications, and their impact on daily activities, particularly driving, is of significant concern. The recently published "Guideline for Evaluating Effects of Psychotropic Drugs on the Performance to Drive a Motor Vehicle" in Japan provides a framework that can be referred to for not only the evaluation of new drugs but also the reevaluation of approved drugs. This study conducted a literature review regarding the effects of carbamazepine, valproate, lamotrigine, lacosamide, and levetiracetam, which are frequently prescribed for epilepsy, on driving performance following the guideline's tiered evaluation approach. Analyses of pharmacological, pharmacodynamic, and adverse events suggested that these drugs primarily affect arousal function. Driving studies showed that acute administration of carbamazepine, but not chronic monotherapy with carbamazepine, valproate, lamotrigine, and levetiracetam, significantly impairs driving performance. Epidemiological studies have not identified a definitive association between these drugs and traffic accidents. Initial administration of these five antiseizure medications may affect driving performance, warranting special attention, but the influence appears to diminish with continued use. Nevertheless, while long-term administration of these five drugs may not have a clinically meaningful effect on driving performance, safe driving is not guaranteed for each individual patient, and appropriate individualized guidance is important in clinical practice.