Antipsychotic Treatment Research Articles

Risk of hospitalization in synucleinopathies and impact of psychosis.

Few studies have investigated the risk of hospitalization among patients with synucleinopathies (Parkinson disease, Dementia with Lewy Bodies, Parkinson disease dementia, Multiple System Atrophy) with associated psychosis and the impact of antipsychotic treatments on hospital admissions and duration of the stay. To determine the risk of hospitalization among patients with synucleinopathies and in patients with associated psychosis. To evaluate the impact of antipsychotic treatments on hospital admission of patients with synucleinopathies and psychosis in an incident cohort study in Olmsted County, Minnesota (MN). We used the Rochester Epidemiology Project (REP) to define an incident cohort of patients with clinically diagnosed synucleinopathies (1991-2010) in Olmsted County, MN. A movement disorder specialist reviewed all medical records to confirm the clinical diagnosis of synucleinopathies using the NINDS/NIMH unified diagnostic criteria. We included 416 incident cases of clinically diagnosed synucleinopathies from 2,669 hospitalizations. 409 patients (98.3%) were admitted to the hospital at least once for any cause after the onset of parkinsonism. The median number of hospitalizations for a single patient was 5. In total, 195 (46.9%) patients met the criteria for psychosis: patients with psychosis had a 49% (HR = 1.49, p < 0.01) increased risk of hospitalization compared to patients without psychosis. Among patients with psychosis, 76 (39%) received antipsychotic medication. Treatment with antipsychotic medications did not affect the risk of hospitalization (HR = 0.93, p = 0.65). The median length of hospitalization among the entire cohort was 1 (IQR 0-4) day. There was no difference between hospitalization length for patients with no psychosis and patients with active psychosis (RR = 1.08, p = 0.43) or patients with resolved psychosis (RR = 0.79, p = 0.24). Psychosis increases the risk of hospitalization in patients with clinically defined synucleinopathies; however, it does not affect the length of hospital stays in our cohort. Antipsychotic treatment does not affect the risk of hospitalization in our study.

Association between the rs6313 polymorphism in the 5-HTR2A gene and the efficacy of antipsychotic drugs

BackgroundPrescribing the optimal antipsychotic treatment to schizophrenia is very important as it is well established that patients have different sensitivity to the available antipsychotic drugs. The genotype of the HTR2A T102C (rs6313) polymorphism has been suggested to affect the efficacy of antipsychotic drugs, but the results of different studies have been inconsistentMethodsIn this study, a meta-analysis was used to ascertain the association between allele and genotype polymorphism of rs6313 and the efficacy of antipsychotic drugs. Related studies publicated from January 1995 to December 2021 were retrieved from PubMed, Embase, ScienceDirect, and Web of Science databases. The correlations between allele and genotype polymorphism of rs6313 and the responder rate and scale score reduction rate of antipsychotics were analyzed. In addition, subgroup analyses were performed on time, drug, and ethnicity.ResultsA total of 18 studies were included. The meta-analysis showed that allele and genotype polymorphisms at the rs6313 locus overall were not associated with antipsychotic drug responder rate or scale score reduction rate. Ethnicity subgroup analysis showed that antipsychotic drugs were more effective in patients with allele T in the Caucasian population. Indian patients with the TT genotype had the lowest scale score reduction rate and poor drug treatment effect. East Asian patients with the TC genotype had better treatment effect, whereas in patients with the CC genotype, the treatment was less effective. Drug subgroup analysis showed that patients with the TC genotype treated with clozapine had the highest responder rate and score reduction rate.ConclusionsThe association between rs6313 polymorphism and the efficacy of antipsychotic drugs is mainly influenced by drug and ethnicity. Caucasian patients with the T allele respond better to drug therapy, and Asian patients with TC genotype. The TC genotype was also a good predictor of the efficacy of clozapine treatment.

Is There Any Risk for Metabolic Syndrome in Children and Adolescents with Psychiatric Disorders?

Objective: We aimed to investigate the risk of antipsychotic drug treatment in the development of metabolic syndrome (MetS) in children and adolescents and to determine which psychiatric disorder is more associated with MetS in the pediatric population. Methods: The sample consisted of 118 children and adolescents (88 used psychotropic medication). The hemogram, fasting blood glucose, lipid profile, weight, and blood pressure levels of all the participants and information regarding medication doses of the patient group at the sixth month of the treatment process were obtained. Results: Bipolar disorder (BPD) was the only psychiatric disorder associated with MetS. Quetiapine and valproic acid were found to have increasing effects on MetS. Weight gain and the increase in systolic and diastolic blood pressure significantly increased the likelihood of MetS. Hierarchical logistic regression analyses revealed that quetiapine increased the risk of MetS through weight gain, and valproic acid increased MetS risk through systolic blood pressure. Conclusion: Especially BPD and psychotropic use in children and adolescents disrupt metabolic regulation and pose a risk for MetS. Determining the risk factors causing MetS, especially in children and adolescents, plays a significant role in preventing mortality and morbidity at advanced ages.

Mental Health Staff's Perspectives on Tapering of Antipsychotic Medication: A Focus Group Study.

Contemporary practices of long-term antipsychotic maintenance treatment for schizophrenia are being challenged, and clinicians must consider the possibilities of reducing long-term maintenance use. However, research indicates that people with schizophrenia receive little support from mental health staff to reduce antipsychotic medication. This article reports a study which aimed to investigate interdisciplinary mental health staff's accounts of tapering of antipsychotic medication and to explore different positions that mental health staff assign to themselves and others. Six focus groups were conducted with 39 mental health staff from outpatient clinics, inpatient units, forensic mental health units, and community mental health services. The data analysis combined analyses of the interactions during focus groups and the thematic content. Results were considered from a discourse analytic perspective considering the function and consequence of accounts applied by the mental health staff. The mental health staff accounted for their perspectives on tapering from the following three distinctive positions: 1) No, patients will eventually realize that they need the medication, 2) Yes, but tapering means running a big risk of relapse in symptoms, and 3) Yes, we need to welcome risks to support personal recovery. Our findings indicated that there was reluctance among interdisciplinary mental health staff to let service users make decisions and limited possibilities for people with schizophrenia to have their request for tapering of their antipsychotic medication met by mental health staff.

The role of the gut microbiome in weight-gain in schizophrenia patients treated with atypical antipsychotics: Evidence based on altered composition and function in a cross-sectional study

ObjectivesWe aimed to explore the interconnection between the weight-gain in schizophrenia patients with atypical antipsychotic treatment and gut microbiome. MethodsThis study employed a cross-sectional design, encompassing a total of 88 schizophrenia patients with long-term atypical antipsychotic treatment. The 16S rRNA gene sequencing was used to identify gut microbiome contents. ResultsNo significant differences in alpha diversity between normal-weight and overweight schizophrenia treated with atypical antipsychotics. The beta diversity analysis showed that overweight patients clustered tightly while normal-weight patients clustered widely. For taxonomic composition, overweight patients had a lower relative abundance in Porphyromonadaceae at family level and Butyrivibrio at genus level, but higher relative abundance in Ruminococcus2 and Clostridium_XIVa at genus level than normal-weight patients. Function prediction revelated that four pathways (including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection and Meiosis-yeast) were significantly different between groups. Correlation analysis indicated that Klebsiella, Butyrivibrio, Unassigned, Methanosphaera, Holdemania, Anaerotruncus were negatively, while Veillonella was positively correlated with BMI in patients. ConclusionOur findings offer evidence that perturbations in the gut microbiome composition, encompassing taxa such as Porphyromonadaceae, Butyrivibrio, Ruminococcus2, and Clostridium_XIVa, in conjunction with distinct functional pathways including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection, and Meiosis-yeast, might contribute to the weight-gain in schizophrenia treated with atypical antipsychotics.

Antipsychotic effects on anthropometric outcomes in anorexia nervosa: a retrospective chart review of hospitalized children and adolescents

BackgroundOff-label antipsychotic use is not uncommon in youth with anorexia nervosa (AN), aiming to enhance suboptimal weight restoration, yet its efficacy remains debated, especially in youth.MethodsRetrospective chart review of consecutively admitted inpatients (ages 8–18 years) with restricting/binge-purge AN, comparing youth with versus without antipsychotic treatment regarding baseline factors, treatment, and anthropometric outcome characteristics including all patients and matched subgroups. Matched subsamples were also compared regarding faster versus slower weight change (median split). Furthermore, within-subject analyses compared weight gain trajectories before versus after antipsychotic use in antipsychotic-treated youth. These results were then compared in a pre-/post design with the matched control group without antipsychotic treatment, using the mean duration until antipsychotic use in the antipsychotic-treated group as the dividing timeline, controlling for a potential order effect, in that later rather than earlier antipsychotic treatment for AN may be more successful.ResultsOf 294 youth with AN (median age = 15.2 (interquartile range = 14.0, 16.6) years, females = 96.6%, restricting subtype = 81.0%, hospitalization duration = 98.2 ± 43.2 days), 44 (15.0%) underwent 52 antipsychotic trials (olanzapine = 63.5%). In multivariable analyses, antipsychotic use was independently associated with younger age, childhood physical abuse history, comorbid borderline personality traits, and lower pre-antipsychotic weight gain (p < 0.0001). In unmatched groups, antipsychotic-treated versus non-treated youth had significantly lower discharge anthropometric parameters, longer inpatient treatment, and lower weight change/week (p < 0.001–p = 0.005), without significant differences between olanzapine and non-olanzapine antipsychotics (p = 0.27–0.44). Non-significant antipsychotic effects on weight outcomes were confirmed in (1) matched subgroups of antipsychotic-treated versus non-treated youth (n = 43 each), (2) youth with faster versus slower weight gain (n = 21 vs. n = 22), and (3) antipsychotic-treated youth when comparing weight change before versus after antipsychotic use (n = 31). Moreover, in antipsychotic-treated youth, weight change/week remained significantly lower versus matched non-antipsychotic-treated youth (n = 31) both before (p = 0.053) and after (p = 0.006) the median time (5 weeks) until antipsychotic use.ConclusionsIn this naturalistic study, clinician's antipsychotic choice, given to a more severely ill subgroup of adolescents with AN, did not significantly improve overall worse weight change trajectories during inpatient treatment, even in matched subgroups. Randomized trials in individuals reflecting real-world samples are needed to evaluate the utility of antipsychotic treatment in youth with AN.

Correlates of severity in a clinical staging model of schizophrenia: a cross-sectional study among 158 subjects

BackgroundClinical staging has been widely used to predict and optimize the treatment of medical disorders. Different models have been proposed to map the development, progression, and extension of psychiatric disorders over time, mainly for schizophrenia. The primary objective of this study was to classify patients with psychosis according to the McGorry staging model and compare factors between the different stages.MethodsThis was a cross-sectional study, collecting data from 158 patients hospitalized for schizophrenia/psychosis. The survey included the Mini International Neuropsychiatric Interview (MINI), Positive and Negative Symptom Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Yong Mania Rating Scale (YMRS), Clinical Global Impression (CGI) scale, and the McGorry staging model.ResultsPatients have been classified into three clinical stages: relapse of psychotic disorder (43%), multiple relapses (47.5%), and persistent and severe illness (9.5%). A higher mean duration of hospitalization, psychotic symptoms (PANSS total scale and subscales), chlorpromazine equivalent dose, and number of antipsychotic treatments were found among participants in Stage 4 as compared to the other groups. However, a significantly higher mean GAF scale was found among participants in stage 3b as compared to the other groups.ConclusionEach stage in the McGorry staging model of schizophrenia is associated with well-defined clinical presentations, which help decide the appropriate treatment. Using such models in psychiatry can improve the diagnostic process and potential therapeutic interventions for patients suffering from mental disorders.

Frequency of sexual dysfunction in outpatients with severe mental illness in Greece.

Patients with psychosis can develop sexual dysfunction, which may be related to the disease itself, psychosocial factors, somatic comorbidities, and the use of psychotropic medication. We aimed to investigate the type and frequency of sexual dysfunction in patients diagnosed with schizophrenia or bipolar disorder in order to assess the side effects of antipsychotics in sexual function. This is a multicenter, cross-sectional study, involving patients diagnosed with schizophrenia (79.3%) or bipolar disorder (20.7%) treated in the Department of Psychiatry and Community Mental Health Centers from November 2018 to December 2019. Patients were enrolled in the study after signed informed consent. Demographic and clinical data were collected from patients through a semi-structured interview. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) was administered to assess sexual function. A total of 87 outpatients on antipsychotics were recruited in the study. The mean age was 43.6 years, while the mean duration of the disease was 16.9 years. Overall, only 9.1% of patients spontaneously reported sexual dysfunction. Patients treated with oral first-generation antipsychotics had more difficulties in achieving orgasm and decreased erection capacity. In contrast, patients treated with oral second-generation antipsychotics had decreased ejaculation capacity. Patients on antipsychotic combination therapy were associated with higher rates of sexual anhedonia. These results suggest that sexual dysfunction is a side effect of antipsychotic treatment, which was spontaneously rarely reported by patients. It seems essential to obtain a psychosexual clinical history before initiating antipsychotic treatment to evaluate following changes and adopt an individualized strategy to manage sexual dysfunction induced by antipsychotics.

Review of pharmacogenomics of psychiatric comorbidities in autism spectrum disorder.

Approximately 70% of individuals diagnosed withautism spectrum disorder (ASD) receive at least one psychotropic medication to treat comorbidities. However, the response to treatment with these drugs is far from satisfactory, with 30-50% of treated patients not responding adequately or developing severe and long-lasting side effects. There is strong evidence of the clinical utility of pharmacogenetics for the personalization of antipsychotic and antidepressant treatments in adult populations. However, the use of pharmacogenetic interventions for the personalization of treatment in ASD populations is minimal. The aim of this review is to summarize the findings of pharmacogenetic studies conducted in subjects with ASD and illustrate their utility in the personalization of treatment with psychoactive drugs in this population group.

Association Between Abnormal Metabolic Parameters and Receiving Subsequent Interventions in Children and Adolescents Initiating Second-Generation Antipsychotics.

Objectives: This study aimed to examine the association between abnormal readings of metabolic parameters detected during second-generation antipsychotic (SGA) treatment and the likelihood of receiving subsequent adverse drug event interventions. Methods: This was a nested case-control study conducted on patients 1-17 years of age with at least two prescriptions of SGAs between January 2010 and January 2019 using TriNetX EMR data. Following an incident density sampling procedure, patients who received the SGA metabolic adverse event intervention (mAEI) (case) were matched with three nonrecipients (controls). The abnormal readings of metabolic parameters within 30 days before the initiation of mAIEs were further identified. These metabolic parameters include body mass index (BMI) and laboratory parameters such as cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, blood glucose, HbA1c, thyroid hormones, liver enzymes, and prolactin. The association of abnormal metabolic parameters with subsequent mAEIs was assessed using a conditional logistic regression model, after adjusting for demographic and other clinical risk factors. Results: One thousand eight hundred eighty-four children and adolescents met the inclusion criteria and were prescribed SGA mAEIs. The most common types of mAEIs prescribed were weight management pharmacotherapy (40.6%), switching from a high or medium metabolic risk profile SGA to a low-risk one (30.9%), nonpharmacological treatment (25.4%), and switching from SGA polytherapy to monotherapy (11.7%). The conditional logistic regression analysis on matched mAEI recipients and nonrecipients showed that patients with an abnormal BMI had 43% higher odds of receiving mAEI (odds ratio [95% confidence interval]: 1.43 [1.13-1.79]). However, the presence of an abnormal laboratory reading was not associated with the initiation of mAEIs. Conclusions: The prescribing of mAEIs were associated with the presence of obesity, but not with abnormal readings of other metabolic parameters, suggesting that additional data are needed to clarify the long-term implication of SGA metabolic adverse events other than weight gain and to inform the appropriate timing for interventions.

Long-Acting Injectable Antipsychotic Treatment for Schizophrenia in Asian Population: A Scoping Review.

Evidence of comparative benefits of long-acting injectable (LAI) antipsychotics in Asian patients with schizophrenia has been inconsistent. This scoping review aimed to synthesize the current evidence in the past ten years and provide an overview of efficacy, safety, treatment adherence, patient attitudes, and healthcare resource utilization of LAI in this population. A systematic search was conducted with a pre-defined search strategy in six electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, CINAHL, and PsycArticles. A total of 46 studies were included, including 15 cohort studies, 13 single-arm trials, 10 randomized controlled trials, four mirror-image studies, three cross-sectional studies, and one controlled clinical trial. Paliperidone palmitate once-monthly injection (27/46) and risperidone LAI (14/46) were the most frequently investigated LAIs. Compared with oral antipsychotic medications (OAMs), LAIs demonstrated a lower rate of relapse/hospitalization and comparable improvement in efficacy. Adverse events (AEs) were similar between LAIs and OAMs, although types and incidence varied. Significant reduction in the length of hospitalization and number of outpatient visits/inpatient admission was observed after initiation of LAIs. These findings suggest that LAI demonstrated comparable efficacy and safety among Asian populations with schizophrenia in comparison to OAMs. Better adherence and lower relapse were observed in patients receiving LAIs from published evidence. Future research is warranted to better understand the comprehensive performance of LAI in specific population or context.

Deviant spontaneous neural activity as a potential early-response predictor for therapeutic interventions in patients with schizophrenia.

Previous studies have established significant differences in the neuroimaging characteristics between healthy controls (HCs) and patients with schizophrenia (SCZ). However, the relationship between homotopic connectivity and clinical features in patients with SCZ is not yet fully understood. Furthermore, there are currently no established neuroimaging biomarkers available for the diagnosis of SCZ or for predicting early treatment response. The aim of this study is to investigate the association between regional homogeneity and specific clinical features in SCZ patients. We conducted a longitudinal investigation involving 56 patients with SCZ and 51 HCs. The SCZ patients underwent a 3-month antipsychotic treatment. Resting-state functional magnetic resonance imaging (fMRI), regional homogeneity (ReHo), support vector machine (SVM), and support vector regression (SVR) were used for data acquisition and analysis. In comparison to HCs, individuals with SCZ demonstrated reduced ReHo values in the right postcentral/precentral gyrus, left postcentral/inferior parietal gyrus, left middle/inferior occipital gyrus, and right middle temporal/inferior occipital gyrus, and increased ReHo values in the right putamen. It is noteworthy that there was decreased ReHo values in the right inferior parietal gyrus after treatment compared to baseline data. The observed decrease in ReHo values in the sensorimotor network and increase in ReHo values in the right putamen may represent distinctive neurobiological characteristics of patients with SCZ, as well as a potential neuroimaging biomarker for distinguishing between patients with SCZ and HCs. Furthermore, ReHo values in the sensorimotor network and right putamen may serve as predictive indicators for early treatment response in patients with SCZ.

Value of gym-based group exercise versus usual care for young adults receiving antipsychotic medication: study protocol for the multicenter randomized controlled Vega trial

Background Exercise is recommended to protect physical health among people with severe mental illness and holds the potential to facilitate long-term recovery. An inclusive exercise community provides an opportunity for life skill training and social connectedness and may reduce the experience of loneliness and internalized stigmatization which together may improve personal recovery. Using a pragmatic randomized design, we aim to examine the effectiveness of a gym-based exercise intervention tailored to young adults in antipsychotic treatment (i.e., Vega Exercise Community) compared to usual care. It is hypothesized that the Vega Exercise Community will be superior to usual care for personal recovery at four months.Methods The trial will be conducted at four sites in Denmark from which 400 participants, aged 18 to 35 years, who are in current treatment with antipsychotic medications for the management of schizophrenia spectrum or affective disorders, will be recruited. Participants will be randomized (2:1) to Vega Exercise Community or usual care. Vega Exercise Community includes three weekly group-based exercise sessions hosted in commercial functional training centers delivered by certified Vega instructors. After four months, participants in Vega Exercise Community will be randomized (1:1) to minimal versus extended support with regards to sustained physical activity. Data will be collected at baseline, four, six and 12 months. The primary outcome is personal recovery assessed by Questionnaire about the Process of Recovery at four months. Behavioral symptoms, health-related quality of life, metabolic health, and program costs will be evaluated to further determine the effectiveness and cost-effectiveness of the Vega Exercise Community. Finally, the quality of life and physical and mental health of the participants’ primary relative will be evaluated.DiscussionThe results of this trial may have important implications for health, sustained physical activity, and recovery for individuals in treatment with antipsychotics. Given the pragmatic design, positive results may readily be implemented by mental health care professionals to promote exercise as an integrated part of treatment of severe mental illness.Trial registrationClinical Trials.gov (NCT05461885, initial registration June 29th, 2022). WHO Universal Trial Number (UTN): U1111-1271–9928.

Protocolo terapéutico de uso de benzodiacepinas y antipsicóticos

Benzodiazepines are drugs used for anxiety, insomnia, or as muscle relaxants. They act as gamma-aminobutyric acid receptor (GABA) modulators, reducing neuronal excitability. The choice of one benzodiazepine or another will depend on the desired potency and its pharmacokinetic factors. They must be used only as short-term treatment and in combination with other treatments, such as cognitive behavioral therapy. Antipsychotics are effective drugs for the symptomatic treatment of diseases that progress with psychotic symptoms as well as impulsiveness, hostility, or aggressiveness. Their main mechanism of action is dopamine receptor blocking. They are classified as typical or atypical. Variability in the individual response makes it so that there is no one first-line antipsychotic treatment, but rather treatment must be chosen based on efficacy, tolerability, pharmacological properties, and the patient's individual characteristics.

A Functional Connectome-Based Neural Signature for Individualized Prediction of Antipsychotic Response in First-Episode Psychosis.

Identification of robust biomarkers that predict individualized response to antipsychotic treatment at the early stage of psychotic disorders remains a challenge in precision psychiatry. The aim of this study was to investigate whether any functional connectome-based neural traits could serve as such a biomarker. In a discovery sample, 49 patients with first-episode psychosis received multi-paradigm fMRI scans at baseline and were clinically followed up for 12 weeks under antipsychotic monotherapies. Treatment response was evaluated at the individual level based on the psychosis score of the Brief Psychiatric Rating Scale. Cross-paradigm connectivity and connectome-based predictive modeling were employed to train a predictive model that uses baseline connectomic measures to predict individualized change rates of psychosis scores, with model performance evaluated as the Pearson correlations between the predicted change rates and the observed change rates, based on cross-validation. The model generalizability was further examined in an independent validation sample of 24 patients in a similar design. The results revealed a paradigm-independent connectomic trait that significantly predicted individualized treatment outcome in both the discovery sample (predicted-versus-observed r=0.41) and the validation sample (predicted-versus-observed r=0.47, mean squared error=0.019). Features that positively predicted psychosis change rates primarily involved connections related to the cerebellar-cortical circuitry, and features that negatively predicted psychosis change rates were chiefly connections within the cortical cognitive systems. This study discovers and validates a connectome-based functional signature as a promising early predictor for individualized response to antipsychotic treatment in first-episode psychosis, thus highlighting the potential clinical value of this biomarker in precision psychiatry.

Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia

BackgroundMotivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia.MethodsForty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed.ResultsOverall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter.ConclusionMotivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

Weight gain, gender, and antipsychotics: a disproportionality analysis of the FDA Adverse Event Reporting System database (FAERS)

ABSTRACT Introduction Side effects are a very important aspect of antipsychotic treatments. Weight gain is an important side effect that jeopardizes the uninterrupted therapy administration, especially in patients with psychiatric conditions. This case-non-case pharmacovigilance study aims at investigating in a real-world adverse event reporting system whether several antipsychotics increase the risk of weight gain reporting, and the differences among men and women as far as weight gain as a reported adverse event is concerned. Areas covered Adverse event reports submitted to the FDA Adverse Event Reporting System of the Food and Drug Administration of the United States (FAERS) of 24 major antipsychotics were extracted, cleaned, and analyzed to determine which of these drugs were correlated with weight gain. The Reported Odds Ratio (ROR) and the adjusted Reported Odds Ratio (aROR) were calculated for each antipsychotic using logistic regression models. Demographics like age, gender, and concomitant insulin use were taken into consideration for each drug. Expert opinion Women had a statistically significant increase in weight gain reporting compared to men, while the men's group was associated with a reduced weight gain reporting in every antipsychotics in the logistic regression analyses. Out of the 24 antipsychotics included in our analysis, Aripiprazole, Brexpiprazole, Olanzapine, and Haloperidol had statistically significantly more weight increase reporting compared to the others.

Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis.

Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.

Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory

The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients.

Reward and punishment learning deficits among bipolar disorder subtypes

BackgroundReward sensitivity is an essential dimension related to mood fluctuations in bipolar disorder (BD), but there is currently a debate around hypersensitivity or hyposensitivity hypotheses to reward in BD during remission, probably related to a heterogeneous population within the BD spectrum and a lack of reward bias evaluation. Here, we examine reward maximization vs. punishment avoidance learning within the BD spectrum during remission. MethodsPatients with BD-I (n = 45), BD-II (n = 34) and matched (n = 30) healthy controls (HC) were included. They performed an instrumental learning task designed to dissociate reward-based from punishment-based reinforcement learning. Computational modeling was used to identify the mechanisms underlying reinforcement learning performances. ResultsBehavioral results showed a significant reward learning deficit across BD subtypes compared to HC, captured at the computational level by a lower sensitivity to rewards compared to punishments in both BD subtypes. Computational modeling also revealed a higher choice randomness in BD-II compared to BD-I that reflected a tendency of BD-I to perform better during punishment avoidance learning than BD-II. LimitationsOur patients were not naive to antipsychotic treatment and were not euthymic (but in syndromic remission) according to the International Society for Bipolar Disorder definition. ConclusionsOur results are consistent with the reward hyposensitivity theory in BD. Computational modeling suggests distinct underlying mechanisms that produce similar observable behaviors, making it a useful tool for distinguishing how symptoms interact in BD versus other disorders. In the long run, a better understanding of these processes could contribute to better prevention and management of BD.