Clinical Psychopharmacology and Neuroscience最新文献

The decision to use multiple long-acting injectable antipsychotics (LAIAs) is difficult since there is no evidence base for their use in treatment guidelines. In this case series, we aimed to present our experiences with the use of triple LAIAs in four patients diagnosed with schizophrenia. The study included four treatment-resistant schizophrenia cases who were followed in the inpatient ward of a university hospital, who could not use clozapine due to non-compliance with treatment, who did not benefit from multiple electroconvulsive therapy procedures, who did not respond to dual antipsychotic treatments and who were using triple LAIAs. The clinical histories of the cases were analysed retrospectively by experienced psychiatrists. All patients responded to the treatment with a decrease in their psychotic symptoms and the number of hospitalizations without any significant side effects. Also, improvement in daily functioning and adherence to treatment was observed in all cases. Based on these results, the use of multiple LAIAs can be safely applied, especially in appropriate treatment-resistant schizophrenia patients and with close follow-up by a clinician.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.

Objective: Dysregulation of the Wnt/β-catenin signaling system has been increasingly associated with the pathogenesis of autism spectrum disorder (ASD). Nevertheless, regulators of this system remain unexamined in patients with ASD. This study aimed to examine serum concentrations of Dkk-1, PORCN, Notum, and Tiki-1 in preschool children with ASD.

Methods: A total of 60 children diagnosed with ASD and 50 healthy controls, aged 18 to 60 months, were included in the study. Serum levels of the target molecules were quantified utilizing enzyme-linked immunosorbent assay kits. Autism severity and behavioral traits were evaluated utilizing the Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (AuBC).

Results: Serum concentrations of Dkk-1 and PORCN were significantly higher in the ASD group relative to controls. However, no significant difference for serum Notum and Tiki-1 levels was detected between the groups. Correlation analyses revealed significant positive associations between serum PORCN, Notum, and Tiki-1 levels and multiple AuBC subscale and total scores. No significant correlations were found between any of the molecules and CARS scores.

Conclusion: These data indicate that regulators of the Wnt/β-catenin pathway, notably Dkk-1 and PORCN may play a potential role in the pathogenesis of ASD. This study presents new data confirming the significance of Wnt/β-catenin pathway regulators in ASD and underscores the necessity for further research.

Objective: Biological processes are the sum of metabolic reactions that result in intermediate and end metabolite products. These processes are the reflection of genetic regulation and are profoundly impacted by environmental influence and changes, including those associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to assess the untargeted plasma metabolomic profile of children and adolescents with ADHD and to compare them with healthy controls and to study associations of dysregulated metabolic parameters with the clinical and socio-demographic parameters of ADHD.

Methods: This study involved 42 registered cases of ADHD among children aged 6 to 16 years, diagnosed based on DSM-5 criteria. Each case was matched by age and gender with 24 healthy controls. The severity of ADHD was evaluated using the ADHD Rating Scale, while behavioral issues were assessed through the Child Behavior Checklist. The gas chromatography-mass spectrometry technique was employed to examine changes in plasma metabolite content.

Results: We identified a total of 45 metabolites in the ADHD subtypes, which exhibited altered levels compared to the control group. The content of these metabolites and associated metabolic pathways showed significant differences between ADHD subjects and controls. Furthermore, we analyzed biomarkers derived from the compounds with the greatest fold changes in accumulation levels.

Conclusion: The identification and analysis of these metabolites and metabolic pathways represent a promising new approach for tracking disease progression in ADHD. The findings of this study indicate that metabolite-based biomarkers may hold considerable potential for effective disease management.

Methylphenidate is generally well tolerated, but it often causes sleep disturbances, less commonly suppresses appetite, and may lead to neurological and movement disorders such as tics, dyskinesia, and psychosis. Among movement disorders, acute dyskinesias are particularly rare but clinically significant, as highlighted in recent pharmacovigilance data. Dopamine receptor hypersensitivity and excessive dopamine signaling, disturbances in other neurotransmitter systems, and genetic predisposition are some of the mechanisms thought to contribute to dyskinesia. In the literature, most cases of dyskinesia reported with methylphenidate consist of orofacial and limb dyskinesias or a combination of these. Additionally, acute cases of dyskinesia have been reported following the combined use of methylphenidate and sodium valproate in childhood. To our knowledge, our case is the first case of isolated lingual dyskinesia in which similar drug-related movement disorders are also identified in the family. It is known that the patient's mother also experienced acute movement disorders after taking psychotropic drugs. Furthermore, the presence of epilepsy diagnosis, sodium valproate use, and multiple neurodevelopmental disorders in our case is noteworthy. While our case demonstrates that dyskinesia can occur even at standard low treatment doses after the first dose, it emphasizes the importance of considering dyskinesia as a potential side effect in cases with a family history of similar drug-related side effects and epilepsy comorbidity.

Dementia is a neuropsychiatric disorder that primarily affects the elderly, leading to a widespread decline in cognitive function and significant impairment of occupational, social, and personal functioning. In addition to cognitive deficits, dementia is frequently comorbid with behavioral and psychological symptoms of dementia (BPSD), such as agitation. When present, these secondary symptoms can exacerbate the clinical course of the disease, reduced treatment responsiveness, increased rates of admission to long-term care facilities, extended hospitalization, higher risk of personal injury and a substantial socioeconomic burden. Given these consequences, early management of BPSD-particularly agitation-is critical to mitigating these risks. Although antipsychotics are commonly prescribed to manage agitation, risperidone remains the only agent approved by regulatory authorities for this indication. Recently, however, brexpiprazole, a medication with a pharmacological profile distinct from that of risperidone, received U.S. FDA approval (on May 11, 2023) for the treatment of agitation associated with Alzheimer's disease. Agitation is among the most prevalent BPSD manifestations, with symptoms ranging from verbal to physical aggression. Given its recent approval and unique pharmacodynamic properties, brexpiprazole may have strong potential as a therapeutic option for this population. This paper aims to review the pharmacological mechanisms, clinical evidence, and future perspectives of brexpiprazole as a novel therapeutic option for managing agitation in patients with Alzheimer's disease.

Background: Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique that modulates cortical excitability through stochastic resonance. While promising, its safety and efficacy in psychiatric disorders remain underexplored.

Objective: To systematically evaluate the efficacy and safety of tRNS in various psychiatric disorders.

Methods: A systematic review was conducted per PRISMA guidelines and registered on PROSPERO (CRD420251040192). Databases searched included CENTRAL-Cochrane Central Register of Controlled Trials, PubMed, Scopus, and Web of Science. Studies were included from their inception to 30th April, 2025. Studies involving tRNS in psychiatric populations, regardless of study design, were included. The risk of bias was assessed using JBI tools.

Results: 22 studies were included (642 individuals), spanning ADHD, depression, schizophrenia, dyslexia, and other conditions. Most studies used 20-minute tRNS sessions over 1-4 weeks. ADHD and dyslexia showed consistent improvements in overall executive function and reading & phonological skills, respectively. Schizophrenia studies demonstrated significant reductions in negative symptoms and auditory hallucinations. Effects in depression were mixed, with some studies reporting substantial symptom relief, while others found no significant benefit. Across disorders, tRNS was generally well-tolerated with only mild, transient adverse effects.

Conclusion: tRNS appears to be a safe, well-tolerated, and potentially effective intervention for specific psychiatric symptoms, especially in ADHD, dyslexia, and schizophrenia. However, inconsistent protocols and mixed outcomes in mood disorders highlight the need for standardized protocols and further research.

Objective: This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months.

Methods: In a prospective cohort, 1,086 outpatients with depressive disorders received stepwise antidepressant treatment following a naturalistic protocol. Baseline serum samples were analyzed for biomarkers from six systems: immune (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-4, interleukin-10), metabolic (leptin, ghrelin, total cholesterol), neurotrophic (brain-derived neurotrophic factor), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine). Remission, defined as a Hamilton Depression Rating Scale scores ≤ 7, was assessed at 12 weeks and 12 months. Logistic regression models with biomarker-by-sex interaction and stratified analyses were used, adjusting for clinical covariates.

Results: Higher baseline serotonin predicted 12-week remission in males but not in females. At 12 months, lower leptin and higher folate predicted remission only in males, while lower cortisol predicted remission only in females. These showed significant biomarker-sex interactions. No sex-specific interactions were found for immune markers.

Conclusion: Baseline serum biomarkers across biological systems showed sex-specific associations with treatment outcomes. Neurotransmitter, metabolic, endocrine, and nutritional markers may offer predictive value for sex-tailored, biomarker-informed treatment strategies in depression.

To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide's potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

Objective: Patients with panic disorder (PD) are approximately four times more likely to experience suicidal thoughts and attempts compared to healthy controls (HCs). Despite the elevated risk compared to HCs, the relationship between cortical thickness (CT) in PD and suicidality remains underexplored.

Methods: We recruited 161 right-handed participants, including 82 PD patients and 79 HCs, and assessed them using a comprehensive battery of psychological scales, including the Scale for Suicidal Ideation (SSI), Early Trauma Inventory Self Report-Short Form, Neuroticism-Extraversion-Openness Personality Inventory-Neuroticism (NEO-N), State-Trait Anxiety Inventory-Trait Anxiety (STAI-T), Panic Disorder Severity Scale (PDSS), and Beck Depression Inventory.

Results: In whole-brain vertex-wise group comparison, patients with PD demonstrated significantly lower CT values in the insula, lateral occipital sulcus, and precentral gyrus compared to HCs. Notably, paradoxical significant positive correlations were observed between SSI total scores and CT in the above-mentioned regions within the PD cohort. Pearson's correlation analyses further indicated that CT in these regions may be linked to high levels of early trauma, trait anxiety (e.g., NEO-N, STAI-T), panic symptom severity (e.g., PDSS), and treatment response in patients with PD.

Conclusion: This study suggest that suicidality in PD may be associated with CT in specific EFN regions related to suicidal brain and that CT in these regions could play a critical role in anxiety symptomatology in PD.