Clinical Psychopharmacology and Neuroscience最新文献

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.

Dopamine supersensitivity psychosis (DSP) is characterized by treatment resistance, tardive dyskinesia, and worsening psychotic symptoms due to long-term antipsychotic use. A 52-year-old woman with treatment-resistant schizophrenia and possible DSP continued to experience persistent psychotic symptoms despite high-dose antipsychotic treatment. Through close follow-up, symptom improvement was observed following the gradual reduction of antipsychotic doses and the introduction of the aripiprazole long-acting injectable (LAI) two-injection start regimen. This approach may offer a rapid and effective strategy for stabilizing dopamine receptors in patients with DSP. This case highlights the potential role of aripiprazole LAI in DSP management and symptom improvement in complex clinical presentations.

Objective: ADHD, a prevalent neurodevelopmental disorder affecting 5-7% of children and adolescents, is characterized by inattention, hyperactivity, and impulsivity, impacting social and academic functioning. Its complex etiology includes genetic, environmental, and inflammatory factors. In the present research, we aimed to compare serum CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin and zinc levels in drug-naive ADHD patients and healthy controls.

Methods: This study included 50 drug-naïve ADHD patients (aged 8-18) and 37 healthy controls. Psychiatric diagnoses were based on DSM-5 criteria. Blood samples were analyzed for inflammatory markers, including CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin, and zinc. Statistical analyses were performed using SPSS.

Results: The study found no significant differences in age, sex, or BMI between individuals with ADHD and the control group. Regarding inflammatory markers, ADHD patients demonstrated significantly lower levels of TWEAK and higher levels of CRP compared to controls. However, no differences were observed in the levels of TNF-α, IL-6, IFN-γ, zinc, or neopterin. When examining ADHD subtypes, it was noted that individuals with the inattentive subtype had markedly lower TWEAK levels and higher CRP levels than the control group.

Conclusion: This finding particularly supports that TWEAK levels could be a significant marker both for ADHD and the predominantly inattentive subtype. Additionally, a correlation was identified between IFN-γ levels and psychosomatic symptoms, and this positive correlation suggests that this cytokine may be associated with specific ADHD symptoms. This study highlights the role of neuroinflammatory processes in ADHD and the etiological distinction of the predominantly inattentive ADHD subtype from other subtypes in the literature. Future research should validate these findings through larger and longitudinal studies.

Objective: International treatment guidelines recommend psychotherapy as the first-line treatment for anorexia nervosa (AN). Adaptation of Western evidence-based treatments to different cultures through personalization has become increasingly important, but evidence remains limited. This study examined the feasibility and effectiveness of AN outpatient psychotherapies in Korea.

Methods: A total of 160 adult patients diagnosed with AN (mean age = 25.3 years) were recruited from an eating disorder (ED) clinic in Korea. They received one of the following psychotherapy programs: motivational enhancement therapy with nutrition (MET with nutrition) (n = 47); Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) augmented by New Maudsley Model for Collaborative Care (NMCC) (n = 20); or Specialist Supportive Clinical Management (SSCM) (n = 93). Treatments were administered face-to-face by trained therapists, following protocols tailored to each individual. Demographic and ED-related clinical data were collected through standardized interviews and questionnaires at baseline and at the end of treatment.

Results: Overall dropout rate was 40.3%, with a lower rate observed in MANTRA augmented by NMCC and SSCM than MET with nutrition. All three psychotherapies increased body mass index (BMI), with minimal group differences. Individuals with lower baseline BMI and those who attended more sessions experienced greater BMI increases across all psychotherapies.

Conclusion: Psychotherapies for AN were feasible and showed promise in terms of effectiveness among Korean patients. Despite comparable BMI increases, the therapies led by experienced therapists and with greater personalization had lower dropout rates. Further studies using randomized controlled trials are needed while controlling for variables outside treatments.