Neuropsychopharmacology Reports最新文献

Aim: The Internet Gaming Disorder Scale is a 9-item screening instrument developed based on the diagnostic criteria for Internet Gaming Disorder (IGD) in the DSM-5. This study aimed to examine the reliability and validity of the Internet Gaming Disorder Scale for children (IGDS-C) in Japanese clinical and nonclinical populations.

Methods: The study included clinical outpatients aged 9-29 with problematic game use and nonclinical adolescents aged 12-18 who played online games at least once a week. Reliability was examined by calculating internal consistency and test-retest reliability. Validity was assessed using Spearman's correlation and Confirmatory Factor Analysis (CFA).

Results: A total of 746 participants (93 clinical, 653 nonclinical) were eligible for statistical analysis. Reliability results revealed acceptable internal consistency (Cronbach's α = 0.87) and test-retest reliability (intraclass correlation coefficient = 0.62). CFA results (Comparative Fit Index = 0.92, Tucker-Lewis Index = 0.90, root mean square error of approximation = 0.10, standardized root mean square residual = 0.05, factor loadings = 0.59-0.71) and significant correlations with the GAMES test, psychological distress, and gaming hours verified the validity of the IGDS-C.

Conclusion: The study verified the reliability and validity of the IGDS-C in Japanese clinical and nonclinical participants, suggesting that it generally reflects the severity of IGD well.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T⁺ Itpr3^tf/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.

Aim: Selective serotonin reuptake inhibitors are thought to exert a clinical effect through various mechanisms, including through alteration in synaptic plasticity. Repetitive transcranial magnetic stimulation can induce temporary changes in synaptic excitability in cerebral cortex that resemble long-term potentiation and long-term depression that serve as a measure of synaptic plasticity in vivo. A version of repetitive transcranial magnetic stimulation called continuous theta burst stimulation can induce inhibition of cortical excitability that can be measured through a motor evoked potential. Previous work has suggested that this response can be modulated by administration of selective serotonin reuptake inhibitors.

Method: Thirty-one healthy volunteers received both fluoxetine 20 mg and placebo in randomly ordered sessions, followed by spaced continuous theta burst stimulation to motor cortex. Changes in Motor Evoked Potentials were then recorded over 60 min.

Results: The response to spaced continuous theta burst stimulation did not differ significantly between fluoxetine and placebo sessions. Spaced continuous theta burst stimulation produced a paradoxical excitatory response in an unexpected number of participants.

Conclusion: A single dose of fluoxetine 20 mg does not influence the response to continuous theta burst stimulation. Previous results suggesting an effect of selective serotonin reuptake inhibitors on inhibitory non-invasive brain stimulation protocols may be due to insufficiently large sample sizes.

Aim: This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment-resistant depression (TRD).

Methods: This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM-5 and ICD-10 criteria and treated using the NeuroStar TMS System. For 3-6 weeks, 10-Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD-17, HAMD-24, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t-tests and repeated measures ANOVA.

Results: Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: -0.50 kg, 95% CI: -0.14 to 0.56, p = 0.24; average BMI reduction: -0.21, 95% CI: -0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD-17, HAMD-24, and MADRS scores significantly increased post-treatment.

Conclusion: rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism.

Schizophrenia causes cognitive dysfunction. The assessment of cognitive function is important in the treatment of schizophrenia. The Wechsler Adult Intelligence Scale (WAIS) is used to assess cognitive function in patients with psychiatric disorders. For clinical use, a short form of the WAIS-III was developed in Japan specifically for patients with schizophrenia, allowing the estimation of IQ using the Similarities and Symbol Search. In the present study, we examined whether the same tasks could be used on the short form of the WAIS-IV. The subjects were 110 patients with schizophrenia. Using methods consistent with those employed in developing the WAIS-III short form, exploratory factor analysis was conducted to confirm the factor structure of intelligence in patients with schizophrenia. Regression analysis demonstrated that the Similarities and Symbol Search had sufficient explanatory power for estimating full-scale IQ. Additionally, correlation analysis revealed a positive relationship between estimated IQ, and social functioning. These findings indicate that the short form of the WAIS-IV, consisting of the Similarities and Symbol Search, meets the necessary criteria for practical use. This short form provides an efficient alternative for estimating cognitive function in patients with schizophrenia while maintaining enough validity.

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.

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.

Aim: There are limited reports regarding psychotropic prescriptions in first-visit patients with major depressive disorder (MDD). The objective of this study is to clarify the prescription patterns of psychotropics and their association with symptoms among first-visit patients with MDD in Japan.

Methods: In this cross-sectional analysis, we examined 376 first-visit patients diagnosed with MDD. Depressive symptoms were evaluated using the Quick Inventory of Depressive Symptomatology Japanese version (QIDS-J). To assess personality traits, we administered the Japanese version of the Ten Item Personality Inventory (TIPI-J), and psychotic symptoms were evaluated using the PRIME Screen-Revised (PS-J).

Results: Among the first-visit patients with MDD, 31.4% (118/376) were prescribed antidepressants, and 18.1% (68/376) received benzodiazepines. Overall, 40.2% (151/376) of the patients were prescribed at least one psychotropic medication. In a multivariate logistic regression model using the forced entry method, missing data on educational attainment and the view of myself domain of the QIDS-J were negatively associated, while the concentration/decision-making domain of the QIDS-J was positively associated with antidepressant prescription.

Conclusion: More than half of the first-visit patients did not receive any psychotropic medication. Psychiatrists appear to consider specific symptoms and personality traits when deciding whether to prescribe medications, which may also be influenced by patient preferences. Further studies, including longitudinal analyses, are needed to explore these associations in more detail.