Treatment Outcome In Schizophrenia Research Articles

Assessing the Clinical Efficacy of Therapeutic Drug Monitoring for Risperidone and Paliperidone in Patients with Schizophrenia: Insights from a Clinical Data Warehouse.

This study investigated the usage patterns and impact of therapeutic drug monitoring (TDM) for risperidone and paliperidone in patients diagnosed with schizophrenia, utilizing retrospective real-world data sourced from a single center's Clinical Data Warehouse. Our study cohort comprised patients diagnosed with schizophrenia undergoing treatment with either risperidone or paliperidone. Data on demographic characteristics, comorbidities, medication utilization, and clinical outcomes were collected. Patients were categorized into two groups: those undergoing TDM and those not undergoing TDM. Additionally, within the TDM group, patients were further stratified based on their risperidone and paliperidone concentrations relative to the reference range. The findings revealed that patients in the TDM group received higher risperidone and paliperidone doses (320 mg/day and 252 mg/day, p = 0.0045) compared to their non-TDM counterparts. Nevertheless, no significant disparities were observed in hospitalization rates, duration of hospital stays, or compliance between the two groups (p = 0.9082, 0.5861, 0.7516, respectively). Subgroup analysis within the TDM cohort exhibited no notable distinctions in clinical outcomes between patients with concentrations within or surpassing the reference range. Despite the possibility of a selection bias in assigning patients to the groups, this study provides a comprehensive analysis of TDM utilization and its ramifications on schizophrenia treatment outcomes.

Illusory generalizability of clinical prediction models.

It is widely hoped that statistical models can improve decision-making related to medical treatments. Because of the cost and scarcity of medical outcomes data, this hope is typically based on investigators observing a model's success in one or two datasets or clinical contexts. We scrutinized this optimism by examining how well a machine learning model performed across several independent clinical trials of antipsychotic medication for schizophrenia. Models predicted patient outcomes with high accuracy within the trial in which the model was developed but performed no better than chance when applied out-of-sample. Pooling data across trials to predict outcomes in the trial left out did not improve predictions. These results suggest that models predicting treatment outcomes in schizophrenia are highly context-dependent and may have limited generalizability.

Long-acting antipsychotic treatments: focus on women with schizophrenia.

Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients' personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient's age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.

Predictors of 6-month follow-up Outcome of Drug Treatment in Schizophrenia in a tertiary hospital of Bangladesh

Background: Schizophrenia may have a better outcome in low- and middle-income countries. In Bangladesh short-term outcome of drug treatment of schizophrenia is also better. It is required to see the predictors of outcome of drug treatment of schizophrenia in Bangladesh.
 Objectives: General objective of this study is to assess the outcome of 6-month follow-up of patients with schizophrenia. Specific objective of this study is to find out the predictors of 6-month follow-up outcome of drug treatment in schizophrenia.
 Methods: Patients with a SCID-1/P diagnosis of schizophrenia (n=42) were assessed prospectively at baseline, at 6-week and at 6-month follow-up. Socio-demographic and relevant variables and questionnaire for family support and previous work record for the study were read in front of the patients and guardians and were filled up by the researcher. Psychopathological measurements were applied at base line by researcher and at 6-week and at 6-month by research assistant for the study population.
 Results: Follow-up data were available for 38 patients at 6-month and among them 86.85% achieved partial remission, 7.89% had not responded and 5.26% had relapsed. In multivariate analysis by General Linear Model Analysis of socio-demographic and relevant variables with the mean BPRS score as outcome in this study we found that age, education, marital status and history of previous work record were significantly associated with the 6-month treatment outcome. Conclusions: Drug treatment outcome of schizophrenia in Bangladesh is better in short-term follow-up. Increase family support and early management by drugs should be a target for intervention.
 Central Medical College Journal Vol 6 No 2 Jauly 2022 Page: 90-96

Predicting Treatment Response in Schizophrenia With Magnetic Resonance Imaging and Polygenic Risk Score.

Background: Prior studies have separately demonstrated that magnetic resonance imaging (MRI) and schizophrenia polygenic risk score (PRS) are predictive of antipsychotic medication treatment outcomes in schizophrenia. However, it remains unclear whether MRI combined with PRS can provide superior prognostic performance. Besides, the relative importance of these measures in predictions is not investigated. Methods: We collected 57 patients with schizophrenia, all of which had baseline MRI and genotype data. All these patients received approximately 6 weeks of antipsychotic medication treatment. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. We divided these patients into responders (N = 20) or non-responders (N = 37) based on whether their percentages of PANSS total reduction were above or below 50%. Nine categories of MRI measures and PRSs with 145 different p-value thresholding ranges were calculated. We trained machine learning classifiers with these baseline predictors to identify whether a patient was a responder or non-responder. Results: The extreme gradient boosting (XGBoost) technique was applied to build binary classifiers. Using a leave-one-out cross-validation scheme, we achieved an accuracy of 86% with all MRI and PRS features. Other metrics were also estimated, including sensitivity (85%), specificity (86%), F1-score (81%), and area under the receiver operating characteristic curve (0.86). We found excluding a single feature category of gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), and surface curvature could lead to a maximum accuracy drop of 10.5%. These three categories contributed more than half of the top 10 important features. Besides, removing PRS features caused a modest accuracy drop (8.8%), which was not the least decrease (1.8%) among all feature categories. Conclusions: Our classifier using both MRI and PRS features was stable and not biased to predicting either responder or non-responder. Combining with MRI measures, PRS could provide certain extra predictive power of antipsychotic medication treatment outcomes in schizophrenia. PRS exhibited medium importance in predictions, lower than GMV, ALFF, and surface curvature, but higher than measures of cortical thickness, cortical volume, and surface sulcal depth. Our findings inform the contributions of PRS in predictions of treatment outcomes in schizophrenia.

Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services.

Background:Long-acting injectable (LAI) antipsychotic medications are used to optimise treatment outcomes in schizophrenia. Guaranteed medication delivery increases the responsibility of prescribers to monitor and manage adverse effects.Methods:In the context of a quality improvement programme conducted by the Prescribing Observatory for Mental Health, a clinical audit addressed documented side-effect monitoring in patients prescribed continuing LAI antipsychotic medication under the care of United Kingdom adult mental health services.Results:A total of 62 mental health services submitted data on 5169 patients prescribed LAI antipsychotic medication for more than a year. An assessment of side effects had been documented in the past year in 2304 (45%) cases. Post hoc analysis showed that extrapyramidal side effects were more likely to have been assessed and found to be present in those patients prescribed LAI haloperidol, flupentixol or zuclopenthixol. There was little other targeting of assessments to the known side effects profiles of individual LAI antipsychotic medications, but when dysphoria had been assessed it was most commonly found with LAI haloperidol treatment and when weight gain, sexual and prolactin-related side effects had been assessed, they were more often identified with LAI paliperidone.Conclusion:The data suggest a relatively low frequency of side-effect assessments, largely untargeted. This is likely to result in many adverse effects going unrecognised and unmanaged, thus failing to tackle their potential to confound mental state assessment and adversely affect physical health and adherence. Patients receiving LAI antipsychotic medication have regular contact with a healthcare professional who administers the medication, which provides an opportunity to potentially remedy this situation.

Plasma β-Endorphin Concentration and Antipsychotic Treatment Outcome in Schizophrenia: 1-Year Follow-Up.

BackgroundIncreased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of schizophrenia remains unclear. The aim of this study was to evaluate the impact of beta-endorphin (BE) on the course of schizophrenia and risk of relapse.Material/MethodsThe study included 25 patients hospitalized with schizophrenia and 47 controls. Their symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS) and composite index at five points: at the onset of hospitalization; after 4, 6 and 10 weeks of treatment; and after 12 months. β-endorphin plasma concentrations were assessed in patients at study enrollment and after 6 weeks of treatment. Data regarding rehospitalization during follow-up were also collected.ResultsPatients had higher BE concentration than controls at study enrollment (P=0.002) and after 6 weeks (P=0.000). BE levels increased during treatment (mean 0.538ng/mL vs. mean 0.624 ng/mL; P=0.007). No correlation was found between BE concentration and PANSS subscale score at any stage of the study. A higher BE level at study enrollment was related to a predominance of negative symptoms after 1 year, measured with composite index (R=−0.404; P=0.045). Patients who were later hospitalized again were significantly more likely to demonstrate an increase in BE levels over 6 weeks (P=0.001).ConclusionsIndividuals with schizophrenia demonstrated higher BE concentrations than healthy controls; this tendency was particularly apparent in those affected by negative symptoms. The imbalance in the endogenous opioid system might adversely alter the course of disease and predispose patients to persistence of negative symptoms, despite antipsychotic treatment.

Medication compliance in outpatients with schizophrenia in one veterans hospital in Taiwan

Medication compliance is an important determinant in schizophrenia treatment outcomes. This study aimed to investigate medication compliance in cases of patients receiving a single antipsychotic medication among adult outpatients with schizophrenia, and examine whether their antipsychotic therapy and other factors may affect the medication compliance. Subjects with schizophrenia who had received any single outpatient first- or second-generation antipsychotic therapy from the Yuli Veterans Hospital, Taiwan, during August and November 2006 were identified from medical chart reviews. The selected subjects were surveyed for information including their medication compliance, sociodemographics, treatment-related side effects, social support, and perceived treatment-related benefits. Their physicians were also surveyed on their medication compliance, Clinical Global Impression (CGI) scores, and comorbid mental illness(es). Good medication compliance was defined as consumption of more than 75% of prescribed antipsychotics in the previous month. Subjects were categorized into this group when both their self-reported consumption and their physicians' estimation were higher than 75%. A logistic regression model was adopted to evaluate the association of each factor with medication compliance. Of the 76 subjects surveyed, 39 (51%) received second-generation antipsychotics (amisulpride, risperidone, or olanzapine), while 37 (49%) received first-generation antipsychotics (haloperidol or sulpiride). Thirty-eight (50%) consumed more than 75% of prescribed medications in the previous month. The average age was 41, and 62% of the sample was male. Education level and employment type were significantly different between individuals with good and poor medication compliance. The regression result indicated that education of above nine years was significantly associated with an increased likelihood of good medication compliance. Employment and perceived treatment benefits were marginally significantly correlated with good medication compliance. Second-generation antipsychotics, however, had no correlation with good medication compliance.

M191. EFFECT OF BREXPIPRAZOLE ON ENGAGEMENT IN PATIENTS WITH SCHIZOPHRENIA: POST-HOC ANALYSIS OF THREE STUDIES

BackgroundIn schizophrenia, a patient’s quality of life and level of psychosocial functioning is dependent on two key domains: the severity of their psychotic symptoms, and the side effects of antipsychotic medication. In addition, people with schizophrenia experience motivation deficits, thus patient engagement is a key component of successful schizophrenia treatment outcomes.The present analyses investigated the effect of brexpiprazole (a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all at similar potency) on patient engagement. The concept of patient engagement stems from the collective post-marketing experience with brexpiprazole, and has been established in patients with MDD and an inadequate response to antidepressant treatments treated with adjunctive brexpiprazole.To explore the concept of engagement in schizophrenia, 11 out of the 30 items in the Positive and Negative Syndrome Scale (PANSS) were identified as relevant to capture patient improvement and well-being beyond an improvement of the core symptoms of schizophrenia.MethodsThe studies [Vector (NCT01396421), Beacon (NCT01393613) and Lighthouse (NCT01810380)] included patients aged 18–65 years experiencing an acute exacerbation of schizophrenia (DSM-IV-TR criteria), and who would benefit from hospitalization or continued hospitalization. Eligible patients were randomized to 6 weeks treatment with placebo or brexpiprazole ranging from doses of 0.25 to 4 mg/day depending on the study. The primary efficacy analysis in all three studies was the mean change in PANSS Total score from baseline (randomization) to Week 6. The PANSS was administered at weekly intervals.Items N1, N2, N3, N4, N5, N6, G6, G7, G13, G15, and G16 were selected from the PANSS as relevant items to capture patient engagement.In the present analysis, data were pooled for patients allocated to placebo and to a brexpiprazole dose in the range of 2–4 mg. Mean changes from baseline on the selected PANSS items were analyzed using a mixed model repeated measures approach. A Principal Component Analysis (PCA) was performed to validate whether changes in the selected items clustered together. Standardized effect sizes were also calculated.ResultsIn the short-term studies, the PANSS scale was completed at baseline by a total of 1,378 patients, brexpiprazole 2–4 mg (n=863); placebo (n=515). At Week 6, an improvement (p<0.05) was observed on 10 out of the 11 selected items from the PANSS scale, with LS mean differences versus placebo in the range of -0.11 to -0.24.The PCA showed that the majority of the selected items cluster together, confirming the importance of the selected items for patient engagement/re-engagement with their lives. The standardized effect size for brexpiprazole versus placebo was -0.31 for the combined 11 selected items and of a similar magnitude as the effect size of the PANSS Total score (-0.32).Discussion11 items from the PANSS scale were selected to capture patient re-engagement. The clustering, as shown by the PCA, validated the selection of the specific engagement items. The results of these exploratory post-hoc analyses suggest that treatment with brexpiprazole, in addition to improving symptoms of schizophrenia, has the potential to also improve patient well-being and engagement with life.

The association between childhood trauma and treatment outcomes in schizophrenia spectrum disorders

Childhood trauma exposure has been associated with poorer treatment outcomes in schizophrenia. Most studies to date have been conducted in naturalistic settings in which the outcome may have been mediated by factors such as poor adherence and substance abuse. We compared the effects of high vs low childhood trauma exposure on the treatment response over 24 months in 78 patients with first-episode schizophrenia spectrum disorders who received standardised treatment with a long acting injectable antipsychotic. Compared to the low childhood trauma group (n = 37), the high childhood trauma group (n = 41) received higher doses of antipsychotic medication and were less likely to achieve remission. When age, sex and cannabis use were controlled for, patients with high levels of childhood trauma had a slower treatment response for positive and disorganized symptom domains, although differences did not differ significantly at 24 months. While there were no differences in functional outcomes, self-rated quality of life was the domain that most clearly differentiated the high and low childhood trauma groups. High childhood trauma exposure was associated with lower quality of life scores at baseline, a lesser degree of improvement with treatment, and lower quality of life scores at 24 months.

Influence of demographic profile and symptoms on insight among people with schizophrenia

Introduction: Insight facilitation is an integral step to achieve good treatment outcome in schizophrenia. Low insight always leads to poor drug adherence and treatment resistance. The study aimed to examine how demographic profile and symptoms influencing the insight among people with schizophrenia. Methods and Materials: Objectives were to assess socio-demographic variables, the symptoms, and insight among people with Schizophrenia and to understand the influence of those variables on the insight. The descriptive research design opted for the study. Sample size of the quantitative study was 53, and subjects were selected as per the study inclusion and exclusion criteria. The population of the study was patients who were attending the outpatient department of psychiatry at the National Institute of Mental Health and Neuro Sciences (NIMHANS). Results: Age and age at the onset of illness were not associated with insight. Male participants had better insight compared to female participants. Persons with middle school or primary school education reported better insight than illiterate, graduates or professional graduates. Participants from the urban area had better insight than participants from the rural area. Insight and positive and negative symptoms were negatively correlated. Conclusion: The demographic factors and symptoms influence the insight among people with Schizophrenia. Hence such factors must be considered while insight facilitation for increasing the adherence to the treatment. &#x0D; Keywords: Insight, schizophrenia, positive, negatives symptoms, age, gender, education, domicile

Prescribing practice of long-acting injectable antipsychotics

Introduction: Nonadherence to treatment is one of the main problems that prevent treatment outcomes in schizophrenia. Long-acting injectable antipsychotic (LAIA) simplifies the treatment process and improves the adherence and health-related outcomes. The prescription pattern of antipsychotics in psychiatric and nonpsychiatric wards is well studied. Whereas the patterns of long-acting injectable (LAI) are not yet documented. Hence, this study was aimed to assess the pattern and prescription of LAI in a university hospital in Saudi Arabia. Materials and Methods: This single-centered, retrospective study was conducted in a university teaching hospital in Khobar city over a period of 6 months. Patients of all ages and either gender with a psychiatric diagnosis or received at least a single depot injection over a period of 1 year were included in the study. Results: A total of 101 patients were included in the study; a male predominance was observed in (64%) our study patients. One half of the study patients have a long history (10 years and more) of psychiatric problems. Of the total 313 medications, 176 (55.7%) and 137 (43.3%) were psychotropic and nonpsychotropic medications, respectively. Zuclopenthixol (n = 48) and haloperidol (n = 10) were the commonly prescribed first-generation LAIAs, whereas risperidone (40) was the only one second-generation LAIA preferred in the study site. Befere the Initiation of LAIA ,majority (67%)of the patients received a trial of antipsychotices orally. Conclusion: The study delivers the evidence of LAIA utilization in a psychiatric unit of a tertiary care teaching hospital in Saudi Arabia. LAIAs were the choice not solitary for schizophrenic-like ailments. The utilization pattern is similar to both-generation LAIs. More studies are required to focus the safety and efficacy concerns of LAIA.

The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

Effects of chronic physical illness on treatment outcomes among patients with schizophrenia.

Previous research has demonstrated the high prevalence of medical comorbidity and multimorbidity among patients with schizophrenia. However, little is known regarding the potential effects of chronic physical illness (CPI) on schizophrenia treatment outcomes. In the present report, we aim to provide an updated review of the relevant literature. We searched MEDLINE for studies published between 2017 and 2018. After screening 683 articles, we included six studies of adequate quality. Five of these studies reported significant associations between several CPIs and different schizophrenia treatment outcomes, whereas the remaining study did not. Significant effects were low to moderate in size. CPIs with significant effects on treatment outcomes included metabolic syndrome, cardiovascular disease, and asthma. No significant effects were observed for diabetes, chronic obstructive pulmonary disease, hepatitis, hypertension, hyperlipidemia, or lung conditions. One study reported a significant association between the total number of CPIs and the overall number of psychiatric rehospitalizations. In addition to increasing the risk of premature mortality, accumulating evidence indicates that various CPIs affect schizophrenia treatment outcomes. Thus, researchers and healthcare practitioners should increase efforts to raise awareness regarding the importance of physical health among patients with schizophrenia. Further high-quality studies are required, particularly those targeting the potential effects of individual CPIs.

Study on risk factors of extrapyramidal symptoms induced by antipsychotics and its correlation with symptoms of schizophrenia

BackgroundExtrapyramidal symptoms (EPS) are one of the most common and neglected side effects during the treatment of schizophrenia. The risk factors of EPS in Chinese patients with schizophrenia and its...

Improving Cognition to Increase Treatment Efficacy in Schizophrenia: Effects of Metabolic Syndrome on Cognitive Remediation's Outcome.

Cognitive impairment, typically more severe in treatment resistant patients, is considered a hallmark of schizophrenia and the prime driver of functional disability. Recent evidence suggests that metabolic syndrome may contribute to cognitive deficits in schizophrenia, possibly through shared underlying mechanisms. However, results are still contradictory and no study has so far examined the influence of metabolic syndrome on cognitive outcome after cognitive remediation therapy (CRT). Based on these premises, this study aims to investigate the relationship between metabolic syndrome and cognition, specifically considering cognitive outcome after treatment. Secondary objectives include the analysis of the association between cognitive impairment and psychopathological status and, in a subgroup of patients, the evaluation of the effect of Sterol Regulatory Element Binding Transcription Factor 1 (SREBF-1) rs11868035 genetic polymorphism, previously associated with metabolic alterations, on both cognition and metabolic syndrome. One-hundred seventy-two outpatients with schizophrenia were assessed for metabolic parameters and neurocognitive measures and 138 patients, who completed CRT, were re-evaluated for cognition. A subsample of 51 patients was also genotyped for rs11868035 from peripheral blood sample. Results show a negative impact of metabolic syndrome on executive functions and global cognitive outcome after CRT. Data also revealed a significant effect of SREBF-1 polymorphism, with a higher prevalence of metabolic syndrome and worse processing speed performance among G/G homozygous subjects, compared the A allele carriers. Overall these findings support the hypothesis that metabolic alterations may hamper the capacity to restore cognitive deficits, as well as they highlight the need to further explore possible converging mechanisms underlying both cognitive and metabolic dysfunction. At the clinical level, results point to the importance of a comprehensive assessment including the metabolic status of patients and of individualized strategies addressing metabolic dysfunction in order to potentiate treatment outcome in schizophrenia.

PR284: Papillary bleeding index at hospital discharge predicts schizophrenia treatment outcomes; A prospective cohort study

PR284: Papillary bleeding index at hospital discharge predicts schizophrenia treatment outcomes; A prospective cohort study

Treatment outcomes in schizophrenia: qualitative study of the views of family carers

BackgroundSchizophrenia is a complex, heterogeneous disorder, with highly variable treatment outcomes, and relatively little is known about what is important to patients. The aim of the study was to understand treatment outcomes informal carers perceive to be important to people with schizophrenia.MethodQualitative interview study with 34 individuals and 8 couples who care for a person with schizophrenia/schizoaffective disorder. Interviews were transcribed verbatim and analysed by a thematic framework based approach.ResultsCarers described well-recognised outcomes of importance, alongside more novel outcomes relating to: Safety (of the patient/others); insight (e.g. into non-reality of psychotic phenomena); respite from fear, distress or pain; socially acceptable behaviour; getting out of the house; attainment of life milestones; changes in personality and/or temperament; reduction of vulnerability to stress; and several aspects of physical health.ConclusionsThese findings have the potential to inform the development of patient- or carer- focused outcome measures that take into account the full range of domains that carers feel are important for patients.

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms.

Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103). Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4). This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.