Psychiatry and Clinical Psychopharmacology最新文献

Background: Pregabalin, prescribed for various neurological and psychiatric conditions, has demonstrated increasing potential for abuse. Despite its psychoactive effects and growing misuse, pregabalin remains absent from standard urine drug screening panels in Türkiye. To assess the prevalence of pregabalin abuse through comprehensive biochemistry laboratory data and to underscore the necessity of including pregabalin in routine toxicological screening protocols.

Methods: This retrospective study analyzed urine drug screening results from 2019 to 2024 obtained in a tertiary hospital's biochemistry laboratory. Analysis was performed using a validated liquid chromatography system coupled with a tandem mass spectrometry method, which included pregabalin, gabapentin, and over 140 other substances. Data were stratified by year, clinical department, and co-detected substances. Urine pregabalin concentrations were statistically compared between single-use and polydrug use groups using the Mann-Whitney U-test.

Results: Pregabalin was detected in 15%-18% of analyzed urine samples annually, sometimes exceeding methamphetamine detection rates. The majority of positive cases originated from probation services and the Alcohol and Substance Use Disorder Treatment Center outpatient clinics. Notably, urine samples with co-detected substances exhibited significantly higher pregabalin concentrations (P < .05). The most frequently co-used drugs were cannabis and methamphetamines. However, a significant subgroup used pregabalin as the sole psychoactive substance. These individuals would be misclassified as "negative" in routine screening panels that exclude pregabalin. To describe this diagnostic blind spot, the term "incomplete negativity" is proposed, referring to toxicology reports that falsely appear negative due to limited panel scope, not true drug abstinence.

Conclusion: Pregabalin abuse remains under-recognized due to current technical and regulatory limitations. Inclusion of pregabalin in routine drug panels is both feasible and urgently needed. The concept of incomplete negativity, introduced in this study, underscores the need to revise national toxicology practices and expand screening panels to include pregabalin. A multidisciplinary approach involving clinical psychiatry, medical biochemistry, and public health authorities is crucial. Recognizing this diagnostic gap is essential for effective clinical and legal responses to substance use disorders.

Objective: The aim of the present study was to investigate NOD-like receptor-3 (NLRP-3)-mediated inflammasome activation in macrophage and microglia cells, which is one of the early step mechanisms in the formation of proinflammatory cytokines, in an autism model and also investigate the possible effect of vortioxetine (VTX), which has a multimodal mechanism of action, in the treatment of autism in a valproic acid (VPA)-induced experimental rat model of autism spectrum disorder (ASD).

Materials and methods: Male Sprague-Dawley rats were divided into 3 groups: Control (n = 12), ASD (n = 16), and ASD + VTX (n = 16). The VTX (5 mg/kg/day) or saline was administered to the male offspring born from pregnant rats administered VPA (400 mg/kg) or saline, between postnatal 30-45 days. Open field, body splash, and social interaction tests were performed in groups on postnatal days 46-52. The NLRP3 inflammasome components such as NLRP3, caspase-1, and ASC levels were investigated in the prefrontal cortex by real-time polymerase chain reaction. Data were analyzed using 1- or 2-way analysis of variance (ANOVA) and Tukey's multiple comparison tests, and differences of P < .05 were considered statistically significant.

Results: The ASD model showed increases in locomotor activity and repetitive behaviors like grooming despite decreases in sociability and social interactions. These findings as well as observational malformations supported the formation of an autism model. It was found that sniffing and following behaviors as social interaction markers were significantly increased and avoidance behavior was reduced with VTX treatment. In molecular analyses, NLRP3 inflammasome components, NLRP3, ASC, and caspase-1 were increased in the ASD model. It was observed that VTX treatment statistically significantly reduced the increased NLRP3, caspase-1, and ASC gene expressions in ASD.

Conclusion: In light of the findings of the study, it was thought that the NLRP-3 pathway may have an important role in the neurobiology of ASD. VTX, as a multimodal antidepressant, has some beneficial effects for the improvement of the behavioral and molecular parameters of ASD.

Background: Methamphetamine causes cognitive impairment. Glial cell line derived neurotrophic factor (GDNF), a survival factor of dopaminergic and motor neurons, has been studied not only for its protective role against neurodegenerative diseases but also for its role in cognitive function. This study examined the relationship between methamphetamine-induced cognitive dysfunction and serum GDNF levels.

Methods: Thirty-eight male outpatients dependent on methamphetamine completed a clinical and neuropsychological battery, the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease, and were tested using an enzyme-linked immunosorbent assay.

Results: Sociodemographic data, including years of methamphetamine use and abstinence period, showed no correlation with serum levels of GDNF. Additionally, among the neurocognitive tests, only the performance on the trail making test B was significantly inversely correlated with serum GDNF levels.

Conclusion: Unlike the reports on cerebrospinal fluid GDNF concentration, previous reports on the relationship between serum GDNF levels and cognitive function in neurodegenerative and psychiatric diseases have demonstrated mixed results. This study is significant, as it is the first study on the relationship between serum GDNF and cognitive function in patients with methamphetamine dependence.

Background: According to the cognitive model known as poor-me/bad-me paranoia, the feeling of deservedness in the formation of persecutory delusions predicts the individual's self-esteem and depressive symptoms. Internalized stigma is associated with poor outcomes in many areas of functioning throughout the course of psychotic disorders and may also be related to the bad-me/poor-me distinction, as both cognitive phenomena are thought to stem from social-cognitive biases regarding how the individual is represented in the minds of others. This study aims to investigate whether the bad-me/poor-me distinction is related to internalized stigma in individuals with persecutory delusions.

Methods: The type of paranoia was determined based on the content of delusions. Sociodemographic data form, Rosenberg Self-Esteem Scale, Internalized Stigma of Mental Illness Scale, Beck Depression Inventory, and Perceived Social Support Scale were administered to the participants. Group differences and variables affecting stigma perception were examined.

Results: In the bad-me group, depression scores, total stigma perception, and alienation scores were higher, while stigma resistance scores were lower. A positive and significant relationship was found between self-esteem and family support. Paranoia type and depressive symptoms were identified as stronger predictors of alienation than self-esteem and perceived social support.

Conclusion: The relationship between paranoia subtype and stigma perception may be important in risk assessment and in identifying therapeutic intervention targets. However, further studies are needed to better understand the relationships among persecutory delusions, self-esteem, depression, and stigma perception.

Objective: To assess the prevalence of postoperative anxiety and depression among elderly patients with hip fractures and to examine their associations with functional recovery, pain, and quality of life during the rehabilitation process.

Methods: A cross-sectional study was conducted involving 218 elderly patients (≥60 years old) who underwent surgical treatment for hip fractures between August 2022 and January 2025. Psychological assessments were performed using the Zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Functional and clinical rehabilitation outcomes were evaluated at hospital discharge, 1-month, and 3-month follow-ups using the Harris hip score (HHS), visual analog scale (VAS), and short form health survey (SF-36). The prevalence of anxiety and depression and their correlation with rehabilitation indicators were determined by calculating the Pearson correlation coefficient.

Results: The prevalence of postoperative anxiety and depression was 36.70% and 38.53%, respectively, with mild severity being the most common. Anxiety and depression levels were significantly associated with age (≥70 years), marital status, presence of diabetes, and lack of regular rehabilitation exercise. At 3 months post surgery, patients with anxiety and/or depression exhibited significantly lower HHS and SF-36 scores and higher VAS scores compared to those without psychological comorbidities (P < .05). Correlation analyses revealed negative correlations between SAS/SDS scores and HHS (r = -0.356/-0.358) and SF-36 scores (r = -0.319/-0.426) and positive correlations with VAS scores (r = 0.160/0.260); all were statistically significant (P < .05).

Conclusion: Anxiety and depression are prevalent among elderly patients following hip fracture surgery and are significantly associated with impaired functional recovery, increased pain, and reduced quality of life. Early psychological assessment and timely intervention should be integrated into postoperative care to optimize rehabilitation outcomes in this vulnerable population.

Citicoline and phosphatidylserine are considered safe compounds with potential cognitive and behavioral benefits in the management of attentiondeficit/hyperactivity disorder (ADHD). However, their safety profiles have not been sufficiently characterized. A case is presented of a 7-year-old boy with ADHD who developed marked irritability, agitation, and a suicide attempt shortly after starting a combination of methylphenidate, phosphatidylserine (100 mg/day), and citicoline (250 mg/day). During the clinical stabilization period, when the family restarted the phosphatidylserine and citicoline combination against medical advice, the patient experienced similar side effects and suicidal thoughts; however, these symptoms completely resolved after discontinuation of the supplements. Although citicoline and phosphatidylserine are generally well-tolerated, this case highlights the potential for serious side effects in sensitive pediatric patients, particularly when used concomitantly with stimulants. The temporal relationship between the initiation of supplementation and the onset of symptoms, as well as the resolution of symptoms following discontinuation, suggests a possible causal relationship. It may be beneficial to review mood symptoms and conduct a risk assessment before adding such supplements.

This case report describes the clinical response and safety of intranasal esketamine (Spravato®) in a 61-year-old female with treatment-resistant depression (TRD), a history of electroconvulsive therapy (ECT) poor response, and structural brain abnormalities secondary to left frontal lobe tissue loss from traumatic brain injury in 2008. Despite multiple antidepressant trials, atypical antipsychotic augmentation, and 6 ECT sessions since 2019, the patient achieved only partial remission. In 2024, she received four 56 mg doses of Spravato over 2 weeks while maintaining duloxetine, fluvoxamine, and clozapine therapy. Montgomery-Åsberg Depression Rating Scale (MADRS) scores improved from severe to mild depression, with resolution of suicidal ideation and symptom stabilization. Anxiety symptoms decreased and nightmares ceased post-treatment. Transient dizziness occurred approximately 10 minutes post-administration in all sessions, resolving with 90 minutes of bed rest. No severe adverse events (dissociation, psychosis, or hypertensive crises) were observed. Although limited by an abbreviated treatment regimen and a single-case design, this case suggests that esketamine may be considered in carefully selected TRD patients with structural brain abnormalities and prior ECT poor response, pending validation from larger studies.

Background: Buspirone shows a certain efficacy in patients with generalized anxiety disorder (GAD), but its combination therapy with mindfulness-based cognitive therapy (MBCT) remains unclear. To compare buspirone + MBCT versus buspirone alone for GAD in a retrospective cohort.

Methods: According to the treatment regimens, patients were assigned to the experimental group (n = 50) to receive 120 minutes of MBCT sessions per week plus buspirone, or the control group (n = 50) to receive buspirone only. Comprehensive evaluations were conducted at 5 time points (baseline (Week 0, W0), W1, W2, W4, and W8), including clinician-rated measures (Hamilton Anxiety Scale [HAMA]), self-reported symptoms (Hospital Anxiety and Depression Scale - Anxiety [HADS-A]), sleep parameters (Pittsburgh Sleep Quality Index [PSQI] and Athens Insomnia Scale [AIS]), and morning serum cortisol levels (enzyme-linked immunosorbent assay; μg/mL). Group-by-time effects were modeled with repeated-measures mixed models; 2-sided α = 0.05.

Results: The combination therapy demonstrated superior outcomes across all measures from W1 onward (all P < .05). By W8, the experimental group showed significantly greater reductions in HAMA (6.1 ± 1.5 vs. 10.1 ± 1.8, P < .001), HADS-A (4.2 ± 1.6 vs. 5.6 ± 1.8, P < .001), PSQI (5.1 ± 2.0 vs. 7.2 ± 2.2, P < .001), and AIS (2.6 ± 1.5 vs. 3.9 ± 1.6, P < .001). Cortisol levels decreased more substantially in the combination group (209.8 ± 33.1 μg/dL vs. 264.0 ± 48.5 μg/dL, P < .001). Treatment effects emerged rapidly, with significant differences in HAMA (P < .001) and cortisol (P < .001) evident by W1. Adverse events were mild and comparable.

Conclusion: Adding MBCT to buspirone was associated with faster and greater clinical and biomarker improvements; prospective randomized trials are warranted.

Background: Previous observational studies provided inconsistent results in the relationship between schizophrenia (SCZ) and lung cancer (LUCA), with substantial between-study variance. The causality from SCZ to LUCA remains unknown. The aim was to conduct a Mendelian randomization (MR) analysis to investigate the impact of SCZ on LUCA.

Methods: The SNP-phenotype association data were acquired from genome-wide association studies (GWAS) analysis for each corresponding phenotype, including SCZ (53 386 cases and 77 258 controls), LUCA (29 266 cases and 56 450 controls), lifetime smoking (462 690 participants), and alcoholic drinks per week (2 428 851 participants). Univariable and multivariable MR analysis were conducted to evaluate the potential causal effect of SCZ on LUCA and a mediation approach to quantify the relative contribution of risk factors. Sensitivity and additional analyses were performed to further validate the robustness of the results.

Results: Univariable MR analysis demonstrated that genetically predicted SCZ causally increases the risk of carcinogenesis of LUCA (OR = 1.068, 95% CI = 1.024-1.114, P = .002). Approximately 27.6% (95% CI 9.2-47.3%) of the effect is mediated by lifetime smoking exposure, 5.9% (95% CI 1.6-12.3%) by drinks per week, and 31.4% (95% CI 9.2-56.5%) by both mediators combined. Consistent results were observed during sensitivity analyses and additional analyses.

Conclusion: This study provides genetic evidence for the causal relationship between genetically predicted SCZ and a higher risk of LUCA, which could be reduced by adopting population-level interventions targeting smoking cessation and alcohol reduction.