Clinical Psychopharmacology and Neuroscience最新文献

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.

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.

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.

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.

Objective: Pan-immune inflammation value (PIV) and systemic immune-inflammation index (SII) have recently been investigated as new inflammatory markers. The aim of this study was to investigate and compare the PIV and SII in different mood episodes in bipolar disorder (BD) and healthy controls (HC).

Methods: In this study, white blood cells, neutrophil, monocyte, lymphocyte, and platelet counts of 339 BD patients (138 manic, 100 depressive, and 101 euthymic patients) along with 117 HC were evaluated. The PIV and the SII were calculated using these parameters and compared between the groups.

Results: PIV (p < 0.001) and SII (p = 0.002) were significantly higher in the manic group than in the HC. A comparison of the HC with the depressed and euthymic groups indicated no significant difference in PIV (p = 0.086, p = 0.139, respectively) and SII (p = 0.555, p = 0.244, respectively), while neutrophil (p = 0.043, p = 0.042, respectively) and monocyte (p = 0.010, p = 0.023, respectively) counts were significantly higher. Compared to the depressed and euthymic patients, the manic patients had significantly higher PIV (p <0.001, p <0.001, respectively) and SII (p = 0.019, p = 0.034, respectively). PIV could to be predictive in distinguishing manic episode patients from the other groups.

Conclusion: Our findings highlight the role of the low-grade systemic inflammation in the pathophysiology of BD, particularly during the manic episode, and suggest that PIV could serve as an inflammation marker to distinguish the manic episode of BD from other phases.

Objective: Human endogenous retroviruses (HERVs) and associated sequences occupy ∼8% of the human genome and dysregulation of HERV transcripts may have significant impacts on human health including psychiatric disorders. HERV-K18 is still active in the human genome and its envelope gene encodes a superantigen (SAg) which may result in deregulation of the immune system. In the study, the possible associations of the two variants localized in the SAg-coding region of HERV-K18 with bipolar disorder type I (BD-I) were evaluated.

Methods: The subjects included 100 patients with BD-I and 100 age- and sex-matched healthy controls. The effects of the two HERV-K18 variants (HERV-8594 and HERV-8914) were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The possible associations of the genotypes/alleles in BD-I patients with several clinical and demographic data were also evaluated.

Results: HERV-8914 TT genotype had approximately 5.36 times higher risk of BD-I than those with the CC genotype (odds ratio, 5.386; 95% confidence interval, 1.602-18.110). Moreover, the prevalence of the CC genotype in patients with hypomania (31.25%) was found to be higher than that observed in patients without hypomania (10.71%) (Fisher's exact test = 5.931, p = 0.036).

Conclusion: This is the first study implying that HERV-K18 variations may be associated with the pathogenesis of BD-I.

Objective: Pathological anxiety is characterized by dysregulated arousal and lower heart rate variability associated with emotional dysregulation. This study explored the connection between peripheral and central autonomic nervous system activity during emotional processing in social anxiety disorder (SAD).

Methods: Thirty-two patients with SAD and 41 healthy controls engaged in a passive viewing task alternating between neutral and angry faces. The root mean square of successive differences (RMSSD) was measured during the resting state (baseline RMSSD) and emotional processing (task RMSSD). We examined the relationships between brain activation during emotional processing and these RMSSD measures.

Results: Unlike the controls, the SAD group exhibited a trend level toward significant correlations of baseline RMSSD with left anterior insula activity during neutral face processing (p = 0.058) and significant correlations with both left anterior insula and right amygdala activities during angry face processing (p = 0.027 and 0.046, respectively). In the controls, task-related RMSSD correlated with neural activities in the right amygdala and right dorsomedial prefrontal cortex during neutral face processing (p = 0.017 and 0.004, respectively), while in the SAD group, a correlation emerged with the right parahippocampal gyrus (p = 0.044). Notably, only in the control group did RMSSD, measured during neutral face processing, significantly correlate with neural activation during the processing of angry faces (p = 0.035).

Conclusion: This study delineates distinct autonomic and neural response patterns to emotional stimuli in SAD patients, highlighting increased autonomic readiness and diminished flexibility in response to social threats.