The impact of childhood trauma exposure on social functioning in schizophrenia: the moderated mediation role of oxytocin and oxytocin receptor gene polymorphisms.

BACKGROUND: Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia. METHODS: The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected. RESULTS: Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = -46.951, p < 0.001), and lower plasma oxytocin levels (t = -5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033-0.044]). CONCLUSIONS: The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

Lymphocyte-related ratios in methamphetamine-induced psychotic disorder in Taiwan, comparing with patients with schizophrenia.

The lymphocyte-related ratios, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) are new measures of inflammation within the body. Few studies have investigated the inflammatory response of patients with methamphetamine-induced psychotic disorder. Clinically, the psychotic symptoms and behavioural manifestation of methamphetamine-induced psychotic disorder are often indistinguishable from paranoid schizophrenia. We aimed to determine the differences in these inflammatory markers between patients with methamphetamine-induced psychotic disorder, patients with schizophrenia and healthy individuals. A total of 905 individuals were recruited. The NLR and MLR were found to be higher in both patients with methamphetamine-induced psychotic disorders and patients with schizophrenia compared with healthy controls. There was no significant difference between the three groups in PLR. When compared with the control group, the methamphetamine-induced psychotic disorder group was significantly higher in NLR 27% (95%CI = 11 to 46%, p = 0.001), MLR 16% (95%CI = 3% to 31%, p = 0.013) and PLR 16% (95%CI = 5% to 28%, p = 0.005). NLR of the group with methamphetamine-induced psychotic disorder was 17% (95%CI = 73% to 94%, p = 0.004) less than the group with schizophrenia, while MLR and PLR did not differ significantly between the two groups. This is the first study that investigated the lymphocyte-related ratios in methamphetamine-induced psychotic disorder when compared with patients with schizophrenia and healthy individuals. The results showed that both patients with methamphetamine-induced psychotic disorder and patients with schizophrenia had stronger inflammatory responses than the healthy control. Our finding also indicated that the inflammatory response of methamphetamine-induced psychotic disorder was between those of patients with schizophrenia and healthy individuals.

Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes.

BACKGROUNDS: A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups. METHODS: This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups. RESULTS: The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups. CONCLUSIONS: Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

Asthma and early smoking associated with high risk of panic disorder in adolescents and young adults.

PURPOSE: Studies have reported a strong link between asthma and panic disorder. We conducted a 17-year community-based large cohort study to examine the relationship between asthma, early smoking initiation, and panic disorder during adolescence and early adulthood. METHODS: A total of 162,766 participants aged 11-16 years were categorized into asthma and nonasthma groups at baseline and compared within the observation period. Covariates during late childhood or adolescence included parental education, cigarette smoking by family members of participants, and participant's gender, age, alcohol consumption, smoking, and exercise habits. Data for urbanicity, prednisone use, allergic comorbidity, and Charlson comorbidity index were acquired from the National Health Insurance Research Database. The Cox proportional-hazards model was used to evaluate the association between asthma and panic disorder. RESULTS: Our findings revealed that asthma increased the risk of panic disorder after adjustment for key confounders in the Cox proportional hazard regression model (adjusted HR: 1.70, 95% CI 1.28-2.26). Hospitalizations or visits to the emergency department for asthma exhibited a dose-response effect on the panic disorder (adjusted HR: 2.07, 95% CI 1.30-3.29). Patients with asthma with onset before 20 years of age who smoked during late childhood or adolescence had the greatest risk for panic disorder (adjusted HR: 4.95, 95% CI 1.23-19.90). CONCLUSIONS: Patients newly diagnosed with asthma had a 1.7-times higher risk of developing panic disorder. Smoking during late childhood or adolescence increased the risk for developing the panic disorder in patients with asthma.

Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome.

BACKGROUND/PURPOSE: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. METHODS: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. RESULTS: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. CONCLUSION: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Psychological distress assessment among patients with suspected and confirmed COVID-19: A cohort study.

BACKGROUND: Global pandemic resulted from the coronavirus disease-19 (COVID-19) demands mental health concerns on the affected population. We examine the time-course shift of psychological burden among suspected and confirmed COVID-19 patients. METHODS: Participants with suspected or confirmed COVID-19 were included in the cohort. Consecutive surveys were conducted upon hospital admission, discharge, and during outpatient follow-up by adapting the 5-item brief symptom rating scale (BSRS-5) assessing psychological symptoms including anxiety, depression, hostility, interpersonal sensitivity, and insomnia. The sixth measure to observe suicidal ideation was also included. RESULTS: A total of 109 eligible patients participated in the study, in which 83.49% reported no distress upon hospital admission, while 2.75%, 3.66%, and 10.1% patients were assessed as being with severe, moderate and mild psychological distress, respectively. Overall, age, sex, and history of contact did not significantly differ between patients with and without psychological distress. Multivariate logistic regression revealed that patients admitted during April-May (OR: 7.66, 95% CI: 1.46-40.28) and presented with symptoms including sore throat (OR: 4.24, 95% CI: 1.17-15.29) and malaise (OR: 5.24, 95% CI: 1.21-22.77) showed significantly higher risk of psychological distress. Cough symptom interestingly showed lower risk of emotional distress (OR: 0.25, 95% CI: 0.08-0.81). Subsequent surveys upon hospital discharge and during outpatient follow-up revealed steadily declining distress among all cohort. CONCLUSION: At least 16.5% of our cohort reported psychological distress upon hospital admission, with distinct time-dependent decline. Access to mental health support, alongside with promoting positive activities for good mental health are pivotal for those directly affected.

Methylphenidate and mortality in children with attention-deficit hyperactivity disorder: population-based cohort study.

BACKGROUND: Little is known about methylphenidate (MPH) use and mortality outcomes. AIMS: To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis. METHOD: This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4-17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan. RESULTS: The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67-0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01-1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70-0.98). CONCLUSIONS: MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.

New use for old drugs: The protective effect of atypical antipsychotics on hepatocellular carcinoma.

It has been encouraged to use large existing data like insurance claims data to investigate the new indications of old drugs. New strategies of research are warranted to identify feasible drugs. We conducted a dual research model with a population-based case-control study using Taiwan's National Health Insurance Research Database and an in vitro study to investigate the association between atypical antipsychotic and Hepatocellular carcinoma (HCC) risk. The study herein consists of two components. The first is a population-based case-control study using existing data from the Taiwan National Health Insurance Research Database. The second component was an in vitro study in which HCC cell lines (Huh7 and Hep G2) were treated with risperidone, quetiapine and clozapine. after treatment of the foregoing antipsychotics, the HCC cell lines were assessed for cell proliferation, invasion and apoptosis. Multivariate conditional logistic regression analysis revealed that antipsychotic use was independently and inversely associated with HCC risk (adjusted odds-ratio [aOR]:0.85, 95% CI: 0.81-0.89). The protective effect was dose-dependent: compared to the low cumulative defined daily dose (cDDD) group (0-29 cDDD), the 30-89 cDDD and ≥90 cDDD groups were associated with significantly reduced risk for HCC (aOR: 0.56, 95% CI: 0.41-0.76; aOR: 0.37, 95% CI: 0.27-0.50, respectively). In vitro study results indicated that risperidone, quetiapine and clozapine significantly inhibited cell proliferation, invasion and induced apoptosis in human HCC cell lines. Our results herein suggested that antipsychotic use might reduce the risk of HCC and may provide evidence for new uses of old drugs.

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods: Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results: Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions: Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.

Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder.

OBJECTIVES: The association between older-age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late-onset bipolar disorder (LOBD) and early-onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. METHODS: We recruited 95 outpatients aged over 55 with a DSM-IV-TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10-year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. RESULTS: No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. CONCLUSIONS: Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

Topiramate mitigates weight gain in antipsychotic-treated patients with schizophrenia: meta-analysis of randomised controlled trials.

OBJECTIVE: Weight gain is one of the most challenging issues in patients with schizophrenia treated with antipsychotics. Several meta-analyses have been conducted to review the efficacy of topiramate in reducing weight, however, several issues regarding the methodology had arisen of which make the results remain ambiguous. METHODS: We conducted a meta-analysis of randomised controlled trials about the use of topiramate in patients with schizophrenia for weight reduction. Ten double-blinded randomised placebo-controlled trials and seven open-label randomised controlled trials included 905 patients. RESULTS: Patients treated with topiramate experienced a greater reduction in body weight and BMI. Patients in countries of the lower overweight population showed more significant BMI reduction. Besides, studies from the Middle East and South Asia showed the greatest effect in body weight change, followed by East Asia, then Europe/America. Topiramate group was outperformed control group with significant psychopathology improvement. No difference between two groups regarding the overall side effects. CONCLUSIONS: Topiramate was significantly superior to control group in mitigating weight gain and psychopathology in antipsychotic-treated patients with schizophrenia. The effects of topiramate augmentation need further investigations in larger definitive studies using methodological rigor and thorough assessments.

The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia.

Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia.

Ovarian cancer and antidepressants.

BACKGROUND: The association between antidepressant use and ovarian cancer remains unclear. This study aimed to assess the ovarian cancer risk with antidepressant use in the general population. METHODS: Taiwan's National Health Insurance Research Database was used to identify 957 patients with ovarian cancer and 9570 controls. We used a conditional logistic regression model for data analysis, excluding a 1-year latent period before the diagnosis of ovarian cancer to account for the quantification of treatment duration. RESULTS: We found no increased risk of developing ovarian cancer among antidepressant users. Neither the duration of antidepressant use nor the average dose had a significant effect on the risk of ovarian cancer. In addition, timing of antidepressant use was not linked to ovarian cancer risk. However, we found the estimate of ovarian cancer risk increased slightly among subjects under 50 years (adjusted OR = 2.03, 95% CI [0.82, 5.02]), although this association was still statistically insignificant (p = 0.12). CONCLUSIONS: There was no association between risk of ovarian cancer and use of antidepressant drugs. Whether or not there is possible risk of using antidepressant whose mechanism of action involves dopamine and norepinephrine warrants further investigation.

Tramadol-related psychosis in a patient with bipolar I disorder.

INTRODUCTION: Tramadol hydrochloride (HCl) is a centrally acting synthetic opioid analgesic. Psychotic symptoms are relatively rare in reported adverse events. Here, we report a patient who presented with tramadol-related psychotic symptoms. CASE: A 59-year-old female had underlying bipolar I disorder and received lithium treatment with stable affective status. 1 month before hospitalisation, she had been taking tramadol HCl/acetaminophen for joint pain. She then developed obvious persecutory delusion. However, her clinical picture did not meet the criteria of any mood episode. After treatment of risperidone in addition to lithium, she was discharged without any psychotic symptom. She remained euthymic without any psychotic symptom on monotherapy of lithium (300 mg) three tablets once daily. CONCLUSIONS: Tramadol HCl is commonly prescribed in clinical practice and psychotic symptoms related to it are uncommon. We should be careful about the rare but important adverse events while prescribing tramadol HCl.

Targeting cravings in substance addiction with transcranial direct current stimulation: insights from a meta-analysis of sham-controlled trials.

Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.

The interplay of childhood trauma, oxytocin, and impulsivity in predicting the onset of methamphetamine use.

BACKGROUND: Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma. OBJECTIVE: To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD. PARTICIPANTS AND SETTING: The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. METHODS: Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained. RESULTS: Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use. CONCLUSIONS: The findings reveal the complex interplay among childhood trauma, oxytocin, impulsivity, and methamphetamine use, emphasizing the importance of considering these factors in prevention and intervention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.

Higher orexin-A levels are associated with treatment response to clozapine in patients with schizophrenia: A cross-sectional study.

BACKGROUND: Clozapine is the primary antipsychotic (APD) for treatment-resistant schizophrenia (TRS). However, only 40% of patients with TRS respond to clozapine, constituting a subgroup of clozapine-resistant patients. Recently, the neuropeptide orexin-A was shown to be involved in the pathophysiology of schizophrenia. This study evaluated the association of orexin-A levels with the clozapine response in patients with TRS. METHODS: We recruited 199 patients with schizophrenia, including 37 APD-free and 162 clozapine-treated patients. Clozapine-treated patients were divided into clozapine-responsive (n = 100) and clozapine-resistant (n = 62) groups based on whether they had achieved psychotic remission defined by the 18-item Brief Psychiatric Rating Scale (BPRS-18). We compared blood orexin-A levels among the three groups and performed regression analysis to determine the association of orexin-A level with treatment response in clozapine-treated patients. We also explored the correlation between orexin-A levels and cognitive function, assessed using the CogState Schizophrenia Battery. RESULTS: Clozapine-responsive patients had higher orexin-A levels than clozapine-resistant and APD-free patients. Orexin-A level was the only factor significantly associated with treatment response after adjustment. Orexin-A levels were negatively correlated with BPRS-18 full scale and positive, negative, and general symptoms subscale scores. We also observed a positive correlation between orexin-A levels and verbal memory, visual learning and memory, and working memory function. CONCLUSIONS: This cross-sectional study showed that higher levels of orexin-A are associated with treatment response to clozapine in patients with TRS. Future prospective studies examining changes in orexin-A level following clozapine treatment and the potential benefit of augmenting orexin-A signaling are warranted.

Linking childhood trauma to the psychopathology of schizophrenia: the role of oxytocin.

Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia.