Clinical Psychopharmacology and Neuroscience最新文献

Objective: To investigate the role of neuroinflammation in the etiopathogenesis of autism spectrum disorder (ASD), we investigated the role of fractalkine and tumour necrosis factor alpha (TNF-α), which may be potential biomarkers for ASD. This study aimed to evaluate the serum levels of interleukin-1beta (IL-1β), interleukin-6 (IL-6), and high-sensitivity CRP (hs-CRP) and to investigate the relationship between fractalkine, TNF-α, IL-1β, IL-6, and hs-CRP and the severity of symptoms in ASD.

Methods: In this cross-sectional study, 44 children between the ages of 24-72 months diagnosed with ASD constituted the research group, and 44 healthy children of similar age and sex constituted the control group. Detailed mental status examinations were performed in both groups. Symptom severity of children diagnosed with ASD was evaluated using the Childhood Autism Rating Scale, Autism Behaviour Checklist and Repetitive Behaviours Scale-Revised Turkish Version. Peripheral venous blood samples were obtained from children in both groups and serum fractalkine, TNF-α, IL-1β, IL-6 and hs-CRP levels were measured by ELISA method.

Results: Serum fractalkine and IL-1β levels of children in the ASD group were significantly lower than those in the control group. No significant difference was found between the groups in serum TNF-α, IL-6 and hs-CRP levels. There was no correlation between ASD severity and fractalkine, TNF-α, IL-1β, and IL-6 levels.

Conclusion: Our study is the first to evaluate serum fractalkine levels in ASD in early childhood. Our findings suggest that fractalkine may play a role in the etiopathogenesis of ASD in early life and may be a potential biomarker for ASD.

Objective: This study aims to explore the relationship between symptom severity and cytokine levels in patients with tic disorders by evaluating these parameters at baseline and after a one-year follow-up.

Methods: A total of 44 tic disorder patients were recruited, 35 completed baseline assessments, and 20 completed endpoint assessments after one year. Based on changes in Yale Global Tic Severity Scale scores, patients were categorized into 'improved' and 'persistent' groups. Cytokine levels were measured using a Luminex^Ⓡ human cytokine multiplex assay at both time points.

Results: Significant increases were found in interferon (IFN)-α2, IFN-γ, interleukin (IL)-1β, IL-6, IL-10, IL-12 p40, IL-12 p70, and IL-13, while IL-1ra and IL-4 levels decreased. Changes in IFN-γ levels showed significant correlations with tic severity, with higher endpoint levels being linked to symptom worsening. Baseline IL-5 levels were significantly higher in the improved group compared to the persistent group.

Conclusion: This study underscores the potential of IFN-γ and IL-5 as biomarkers and therapeutic targets in tic disorders. The findings suggest that these cytokines could be instrumental in assessing tic disorder severity and developing targeted therapies. Further research involving larger cohorts is needed to validate these findings and explore cytokine-targeted therapies for tic disorders.

Objective: Intranasal (IN) esketamine represents a novel add-on treatment for treatment-resistant depression (TRD) with reported favourable effects on insomnia. IN esketamine treatment might similarly reduce the incidence of insomnia as an adverse event (AE). The present meta-analysis therefore investigated whether IN esketamine relative to placebo is associated with a lower incidence of insomnia as an AE in adults with TRD.

Methods: Data were retrieved from seven randomised placebo-controlled trials evaluating the safety and efficacy of IN esketamine combined with a monoaminergic antidepressant in the treatment of TRD that reported data on insomnia as an AE. The study population (n = 1,311) comprised adult patients (aged ≥ 18 years) with a primary diagnosis of major depressive disorder. A mixed-effects logistic regression model was employed to compare the incidence of insomnia as an AE between the IN esketamine and placebo group.

Results: Insomnia as an AE was reported by 52 patients (7.3%) in the IN esketamine group relative to 40 (6.7%) in the placebo group. IN esketamine compared to placebo was not associated with the odds of insomnia as an AE (OR = 1.07; 95% CI = 0.68-1.69; p = 0.76). There was no evidence for heterogeneity between the included trials.

Conclusion: IN esketamine does not affect the occurrence of insomnia as an AE in the treatment of TRD. This contrasts previous findings demonstrating beneficial effects of esketamine on insomnia severity relative to placebo, although AE reporting may not capture insomnia improvements in a population with frequent baseline insomnia.

Objective: Schizophrenia mainly begins in adolescence and leads to impairments of social functioning. Alterations in the immune system, as represented by cytokine levels, has been linked to the pathophysiology of schizophrenia. Among a variety of cytokines, transforming growth factor-β (TGF-β) plays a role in several neural events, e.g., neurogenesis and synapse formation. To date, few studies have evaluated the relationship between cytokine concentrations and social functioning in subjects with ultra-high-risk state for psychosis (UHR). In this study, we investigated the ability of serum levels of TGF-β to predict the change of social functioning in UHR subjects.

Methods: Fifty-two UHR subjects were recruited at 7 hospitals. We measured social function with the Specific Levels of Functioning scale (SLOF) at baseline, 4, 16, 28, 40, and 52 weeks after sampling blood to measure TGF-β levels.

Results: TGF-β1 concentration at baseline was correlated with changes from baseline in the SLOF scores at 4, 28, and 40 weeks. Mixed model for repeated measures analyses revealed that serum levels of TGF-β1 at baseline associated positively with changes from baseline in the SLOF scores, which was most evident at the 40-week time point.

Conclusion: These results suggest that peripheral levels of TGF-β1 might be associated with longitudinal course of functional outcomes in UHR subjects.

Introduction: Tourette syndrome and chronic tic disorders are neurodevelopmental disorders characterized by involuntary motor and vocal tics, often beginning in childhood and causing significant distress. While medication and behavioral therapies are established treatments, chronic use of medication can cause side effects, and behavioral therapy faces limited provider availability and geographic barriers. Internet-based behavioral interventions are emerging as alternatives to improve treatment accessibility.

Methods: We performed a meta-analysis of five randomized controlled trials examining online delivery of comprehensive behavioral interventions for tics/habit reversal training or exposure and response prevention for tic disorders. Primary outcomes included Yale Global Tic Severity Scale scores and treatment response rate. A fixed-effect model was used, with heterogeneity and subgroup analyses to assess consistency.

Results: The overall Hedges' g was -0.26 (95% CI: -0.42 to -0.10, p = 0.0019), indicating a small but significant effect of online interventions. Treatment response odds ratio was 2.34 (95% CI: 1.55-3.52, p < 0.001), with no significant subgroup differences by control condtion, age, intervention, or delivery method.

Conclusion: In this meta-analysis, internet-based behavior therapy demonstrated modest yet statistically significant reductions in tic symptoms, marginally lower than those achieved with in-person. Nevertheless, their cost-effectiveness and potential to broaden treatment accessibility underscore the necessity for large-scale, methodologically rigorous trials that explore long-term outcomes, developmental considerations, and comorbidities. Our findings support the clinical utility and feasibility of internet-based behavior therapy for tic disorders. This approach may broaden treatment access for underserved communities and potentially improve patients' quality of life in the digital healthcare era.

Objective: Insomnia is a common symptom of major depressive disorder (MDD). However, the neural distinctions between MDD with and without insomnia remain unclear. This study investigated resting state functional connectivity (RSFC), specifically seeding the habenula and septal nuclei, to identify neurobiological abnormalities associated with insomnia in MDD.

Methods: Thirty-six patients with MDD and clinically significant insomnia (MDD_w/INS), 21 patients without insomnia (MDD_wo/INS), and 38 healthy controls underwent 3T resting-state fMRI. Seed-to-voxel RSFC analyses were conducted using the habenula and septal nuclei as seeds. Between-group comparisons and correlation analyses were adjusted for age, sex, years of education, and Hamilton Depression Rating Scale 17 items (HDRS-17) scores.

Results: The MDD cohort had a mean age of 35.6 years and mean illness duration of 7.3 years. Compared to the MDD_wo/INS group, the MDD_w/INS group exhibited significantly higher depressive symptom severity (HDRS-17: 19.4 ± 4.8 vs. 13.8 ± 4.3) but a shorter illness duration (6.4 ± 6.9 vs. 8.9 ± 6.8 years). RSFC was increased between the left habenula and the right Rolandic operculum and cuneus and between the right habenula and thalamic pulvinar in the MDD_w/INS group. In contrast, decreased RSFC was observed between the septal nuclei and right cerebellar Crus I. All altered RSFC patterns were significantly correlated with the severity of insomnia.

Conclusion: This study reveals distinct RSFC patterns associated with insomnia in MDD, emphasizing the role of the habenula and septal nuclei and their potential significance in modulating mood and sleep patterns in MDD.

Objective: The study was designed to compare the expression levels of IL-6 mRNA, long non-coding RNA (lncRNA) NRON (non-coding repressor of the nuclear factor of activated T cells [NFAT]) and TMEVPG1 (Theiler's murine encephalomyelitis virus persistence candidate gene 1) which play critical roles in the regulation of immune function, and to investigate relationship between expression levels and symptom type and the cognitive functions in patients with schizophrenia and schizoaffective disorder.

Methods: The study included 84 participants (27 patients with schizophrenia, 27 with schizoaffective disorder, and 30 healthy subjects). The lncRNA (TMEVPG1 and NRON) and IL-6 mRNA expression analysis was measured with the real-time PCR method. The Wisconsin Card Sorting Test, the Stroop Test, Clinical Global Impression Scale, Positive and Negative Symptoms Scale, Young Mania Rating Scale and the Hamilton Depression Rating Scale were applied.

Results: The lncRNA TMEVPG1 expression level was determined to be higher in the patient groups than controls. The TMEVPG1 was able to differentiate schizophrenia cases from the controls. In the schizoaffective group, a positive correlation was determined between NRON expression and positive symptomatology, and an increase in NRON expression was determined to make a moderate contribution to cognitive dysfunction. NRON expression was decreased as the dose of antipsychotic drug increased in the schizophrenia group.

Conclusion: The results of this study demonstrated that there are significant differences between schizophrenia and schizoaffective disorder in terms of inflammatory markers and their relationship between the symptom type or cognitive functions.

Incomplete hippocampal inversion (IHI) is associated with epilepsy and schizophrenia, often leading to persistent auditory verbal hallucinations (AVH). This case study discusses a 23-year-old with diagnosed with schizophrenia, intellectual disability, and a seizure disorder, having AVH non-responsive to multiple antipsychotics. Magnetic resonance imaging indicated left hippocampal IHI. In view of the increased risk of seizure with clozapine, transcranial direct current stimulation (tDCS) was administered, targeting the left temporoparietal junction using cathodal stimulation and left dorsolateral prefrontal cortex using anodal stimulation. Following 20 sessions over 10 days, AVH significantly improved, with Scale for the Assessment of Positive Symptoms and Auditory Hallucination Rating Scale scores reducing by over 70%, maintaining at a 3-month follow-up. This case highlights tDCS as an effective adjunctive treatment for AVH in schizophrenia with structural brain abnormalities, emphasizing the need for further research into tDCS effects on hippocampal-temporoparietal connectivity.

Borderline personality disorder (BPD) is a complex psychiatric disorder characterized by emotional instability, impulsivity, and self-destructive behavior. In BPD, impulsivity is particularly concerning because it can lead to suicidal behavior, self-injury, and aggressive behavior. Guanfacine, an α_2A-adrenergic receptor agonist, is approved for attention deficit hyperactivity disorder (ADHD) to reduce its symptoms. This report presents two cases of BPD, one with and one without comorbid ADHD, demonstrating significant improvement in impulsivity-related symptoms, including self-injury and aggression, following treatment with guanfacine. Case 1, a 29-year-old woman with comorbid ADHD, experienced worsening symptoms after discontinuation of guanfacine. Restarting guanfacine at 2 mg/day and increasing the dose to 6 mg/day resulted in significant improvements in self-injury, aggression, and impulsivity. Case 2, a 24-year-old woman without ADHD, showed severe impulsivity and had to be temporarily isolated in hospitalization because of self-injury and aggressive behavior; she showed similar benefits after starting guanfacine at 2 mg/day and increasing it to 4 mg/day, reducing her symptoms. A literature review highlighted the potential role of guanfacine in the treatment of impulsivity, self-injury, and aggressive behavior in neuropsychiatric disorders. Guanfacine is thought to improve prefrontal cortex (PFC) dysfunction. Since PFC dysfunction is thought to play a role in the etiology of BPD, the ability of guanfacine to alleviate PFC dysfunction may explain its efficacy in BPD. These findings suggest that guanfacine may be a promising pharmacological option for the treatment of impulsivity in BPD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction as well as repetitive behaviors and restricted interests. The genetic mechanism underlying ASD is as complex and heterogeneous as the clinical presentation of the disorder itself. Megalencephaly-capillary malformation syndrome (MCAP) is a rare genetic disorder that is associated with mutations in the ADGRV1 and PIK3CA genes. To the best of our knowledge, there is only one case report in the literature that documents the coexistence of MCAP and ASD. In this case study, we present the case of a 14-year-old girl diagnosed with both ASD and MCAP who was admitted to our clinic. Diagnosing ASD in patients with genetic syndromes can be challenging due to pre-existing cognitive and medical issues. This case underscores the importance of regular child psychiatry follow-ups for children with genetic syndromes to ensure timely and accurate diagnosis of ASD.