Psychiatry and Clinical Neurosciences最新文献

Neurodevelopmental disorders (NDDs), such as schizophrenia (SCZ), Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning disabilities, and intellectual disabilities (ID), are highly prevalent. One significant genetic factor associated with NDDs is copy number variations (CNVs), which are structural changes in the genome that involve deletions or duplications of DNA segments. CNVs are known to significantly elevate the risk of developing NDDs and are increasingly being studied for their role in these conditions. While CNVs encompass a wide range of genetic alterations, emerging evidence suggests they may disrupt key biological processes, such as synaptic development and function in the brain, which are critical for learning and behavior. This review synthesizes findings from genetics, molecular biology, and related fields to explore the link between CNVs and synaptic pathology with therapeutic investigations. By understanding how CNVs compromise synaptic function, we identify paths to more targeted and effective therapies for neurodevelopmental disorders associated with CNVs.

The antidepressant effect of zuranolone appears to be sustained beyond the treatment period in postpartum depression, whereas in major depressive disorder it may not persist after treatment discontinuation.

Aim: Recent neuropathological studies suggest that the accumulation of neurodegenerative disease-associated proteins in subcortical structures may contribute to mood symptoms. Animal models have highlighted the role of the paraventricular thalamic nucleus (PVT) in bipolar disorder (BD) pathophysiology. However, neuropathological investigations in the thalamus in BD remain limited. This study aimed to examine neurodegenerative pathology in the thalamus and medial temporal region including the hippocampus in patients with BD.

Methods: Postmortem brain tissues of the thalamus and medial temporal region of nine patients with BD and nine age-matched controls were obtained from Matsuzawa Hospital, with additional medial temporal samples of 14 BD cases acquired from the Stanley Foundation Brain Bank. Immunohistochemical analyses were performed using antibodies against phosphorylated tau, amyloid-β, α-synuclein, TDP-43, and granulovacuolar degeneration (GVD) markers including CHMP2B and CK-1δ.

Results: The 23 BD cases exhibited a significantly greater burden of tau pathologies, including higher neurofibrillary tangle Braak stages (P = 0.015) and more severe argyrophilic grain Saito stage (P = 0.029), compared with the nine controls. Notably, CHMP2B-positive GVD was significantly more frequently observed in the PVT of BD cases than in the controls (five of nine vs. zero of nine, P = 0.029).

Conclusions: These findings suggest that neurodegenerative processes, particularly tau pathology and CHMP2B-positive GVD in the PVT may play a role in BD pathophysiology.

Aim: This study aimed to evaluate the likelihood of discontinuing dual orexin receptor antagonists in patients continuously prescribed hypnotics using a large-scale claims database in Japan.

Methods: The cohort comprised 4422 patients identified from insurance claims data, who were newly prescribed a single hypnotic with more than three consecutive prescriptions over 3 months. The outcome was defined as the absence of a hypnotic prescription for 90 consecutive days after the final prescription. Kaplan-Meier and Cox proportional hazards analyses were used to compare the hazards of discontinuing hypnotics among four classes: benzodiazepines, non-benzodiazepines, dual orexin receptor antagonists, and melatonin receptor agonists, adjusting for age, sex, and the number of diagnostic categories based on the International Statistical Classification of Diseases, Tenth Revision.

Results: Kaplan-Meier analysis revealed significant differences among the hypnotic classes (P < 0.001), with dual orexin receptor antagonists demonstrating the highest rate of discontinuation. Multivariable Cox regression indicated a significantly higher likelihood of discontinuing dual orexin receptor antagonists than that of benzodiazepines (hazard ratio = 1.40; P < 0.001). Older age (hazard ratio = 0.995; P < 0.001) and a higher number of International Statistical Classification of Diseases, Tenth Revision diagnostic categories (hazard ratio = 0.975; P < 0.001) were significantly associated with a lower likelihood of discontinuation.

Conclusion: Dual orexin receptor antagonists are more likely to be discontinued than benzodiazepines after continuous hypnotic prescription, highlighting their potential clinical utility in insomnia treatment.