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Objective: The corpus callosum (CC) is known to be altered in patients with schizophrenia. However, its morphologic characteristics are less well studied in treatment-naive first-episode schizophrenia patients, as is the effect of antipsychotic treatment on this structure.Methods: T-1 weighted MRI scans were obtained from 160 antipsychotic-naïve first-episode schizophrenia patients (AN-FES) and 155 healthy controls (HCs) before treatment initiation. Among the patients, forty-four were available for follow-up studies after one year of antipsychotic treatment, and were divided into good-outcome (n = 31) and poor-outcome subgroups (n = 13) based on whether there was a 50% reduction in Positive and Negative Symptom Scale (PANSS) total scores from baseline. A computer algorithm was applied to automatically identify the mid-sagittal plane (MSP) and obtain morphological measurement parameters of the CC.Results: Compared with HCs, AN-FES patients showed a significant reduction of thickness in the posterior midbody of the CC. This deficit was correlated with severity of negative symptoms. After one year of antipsychotic treatment, there was no significant change in CC morphological measurements in schizophrenia patients, nor was there a significant difference of CC morphological measurements between good-outcome and poor-outcome subgroups at baseline or at 1-year follow-up.Conclusion: Thickness of the posterior midbody of the CC is reduced in the early course of schizophrenia before treatment. This alteration was not affected by antipsychotic treatment and was unrelated to treatment outcome at 1-year. [ABSTRACT FROM AUTHOR]

• Forty-two eligible papers with 4,217 participants were included in the analysis. • Lower TRP levels and higher circulating KYN/TRP ratios existed in subjects with SCZ. • Lower KYN levels were associated with medication-free persons with SCZ. • The KYN levels were higher in subjects with SCZ after antipsychotic treatments when compared with baseline. • The current evidence provides valuable insight of the potential roles of KYN pathway in the pathogenesis of SCZ. The kynurenine (KYN) pathway is postulated to play various roles in immune system dysregulation of schizophrenia (SCZ). We conducted a meta-analysis to explore the association between six key metabolites of KYN pathway (i.e., tryptophan (TRP), KYN, quinolinic acid (QUIN), and kynurenic acid (KYNA)) and SCZ. Priori Bonferroni adjustments were conducted for multiple comparisons. In total, 42 studies that examined the relationship between the metabolites in KYN pathway mentioned above and SCZ in 4217 participants and nine studies that examined alterations of these metabolites after antipsychotic treatments were included. The results demonstrate that (1) subjects with prescribed medication had significantly higher KYN levels when compared to controls; (2) higher KYN levels in cerebrospinal fluid (CSF), lower plasma KYN levels and higher CSF KYNA levels were associated with SCZ; (3) the KYN levels were higher in subjects with SCZ after antipsychotic treatments when compared with baseline. The evidence provides valuable insight of the potential underlying involvement of the KYN pathway in the pathogenesis of SCZ. [ABSTRACT FROM AUTHOR]

Objective purpose: The investigation and recording of those factors related to the poor or lack of drug compliance of patients with severe mental disorders. Methodology: A literature search was conducted in the Pubmed and Scopus databases, from 2010 to 2020, with a critical evaluation and synthesis of all data. The keywords used either individually or in combination were antipsychotic treatment, drug compliance, mentally ill, chronic illness, comorbidity. Results: Out of a total of three hundred and twenty studies, twelve were included. All in English and the last decade. Of the twelve studies, eight were quantitative, one study was qualitative, two cross-sectoral studies and one case study. The most commonly reported reasons for discontinuation of the medication were: side effects, concomitant use of alcohol and other substances, lack of information about the action of the drug and its exact dosage, lack of patient anesthesia, stigma, limited access and use of health services. Conclusions: Studies examining the factors that affect the medical compliance of the mentally ill have shown that non-compliance with medication is associated with an increased risk of relapse, hospitalization and suicide. Also, poor drug compliance or discontinuation of treatment is responsible for 40% of readmission and results in a significant increase in health expenditure. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood level of brain-derived neurotrophic factor (BDNF) may be used as a diagnostic and/or prognostic marker for schizophrenia. Previous studies were inconsistent. A systematic review was conducted to examine whether BDNF level is different in patients with first episode psychosis (FEP) compared to health controls (HC) and whether it changes after treatment. Methods: Literature search was done in PubMed, Web of Science, and Google Scholar following standard procedures. Hedges’ g was used as the measure of effect size (ES), which was pooled with random effects model. Publication bias and moderator effects were examined. Results: Search yielded 29 studies with a total sample size of 2912. First meta-analysis included 27 studies with FEP vs. HC comparison. Pooled ES was −0.63, p < 0.001, indicating that BDNF level was lower in FEP than in HC. Studies were heterogeneous, and moderator analysis showed that studies of younger patient, higher symptom severity, and more drug naïve had larger ES. Second meta-analysis examined change in BDNF levels before and after antipsychotic treatment in eight studies. A pooled ES of −0.003 (p = 0.96) showed no change in peripheral BDNF level after treatment. Conclusion: Peripheral BDNF level was decreased in FEP compared to HC, but it did not change after treatment.

Systemic Lupus Erythematosus (SLE) affects various systems in human including central and peripheral nervous systems. The Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe complication of SLE which causes a formidable challenge in term of diagnosis and its management. Acute confusional state (delirium) is a rare entity of numerous symptoms of NPSLE which is being overlooked even though it is associated with increased mortality. The present case report describe about the presentation of SLE consisting of hyperpigmentation maculopapular rashes over face, neck regions, lower back and extremities in a 36-yearold female with abrupt onset and fluctuating course of psychotic symptoms, acute confusional state and oddities in behaviours. Treatment with low dose of antipsychotic (aripiprazole) resolve the symptom with due consideration taken to rule out steroid induced manifestation of above symptoms. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious mental illness for which the mainstay of treatment is antipsychotics. Up to 30% of schizophrenia patients show limited response to antipsychotics. Identifying these patients before treatment could guide individualized treatment for improving outcomes in those not likely to show robust benefit from antipsychotics. Diffusion tensor imaging was performed with 56 drug-naïve first-episode schizophrenia patients and 69 matched healthy controls. Patients were followed clinically after one-year of antipsychotic treatment and classified at that point into groups of 17 poor outcome and 39 good outcome patients based on whether they showed at least a 50% reduction of Positive and Negative Syndrome Scale (PANSS) scores from baseline. Tract-based spatial statistics were applied to assess white matter microstructure in the two patient subgroups and healthy controls. Poor outcome patients showed reduced pretreatment fractional anisotropy (FA) in left cingulum and anterior thalamic radiation and increased FA in right superior and inferior longitudinal fasciculus compared with good outcome patients. FA in each of these four tracts was decreased in both patient subgroups relative to healthy controls. Considered together, the four altered tracts showed promising ability to differentiate poor from good outcome patients (sensitivity = 74.4%, specificity = 95.2%, AUC = 0.90, p < 0.001), and superior prediction of clinical outcome to baseline PANSS scores (p < 0.015). Prediction of outcomes using DTI features was not related to duration of untreated psychosis. Baseline alterations in white matter integrity may identify schizophrenia patients less likely to respond to treatment, which could be useful information for stratification in clinical trials and for individualized treatment planning. [ABSTRACT FROM AUTHOR]

Background: Impaired sensorimotor gating, commonly measured as disrupted prepulse inhibition (PPI) of the acoustic startle response, has been widely observed in psychotic diseases. However, most PPI studies published so far involve patients with long illness duration and different drug treatments. Few studies have investigated untreated patients at their first episode of psychotic symptoms.Method: PPI is an acoustic startle paradigm (30, 60-, 120-ms interstimulus intervals). Startle reactivity and habituation were succesfully assessed in 49 antipsychotic-naïve first-episode psychosis (FEP) patients and compared with 35 age- and gender-matched healthy control subjects. Mean age of patients was 28 years and 27 for controls. Patients treated with antipsychotics more than 30 days were not included in the study and twenty-three out of forty-nine patients received antipsychotic treatment with a mean treatment time of 13 days.Results: PPI was significantly lower in FEP patients, compared to healthy controls. The PPI deficiency found in these patients was not due to antipsychotic treatment since PPI did not differ between treated (n=23) and untreated patients n=(26). By using the latent curve modeling we identified a delayed habituation in patients treated with antipsychotics, suggesting that antipsychotic treatment should be considered as a confound when investigating habituation in schizophrenia.Conclusions: Our results suggest that acute pharmacological treatment does not normalize PPI in FEP patients but should be considered as a confound when investigating habituation in these patients. [ABSTRACT FROM AUTHOR]

There is no pharmacological treatment to remediate cognitive impairment in schizophrenia (SZ). It is imperative to characterize underlying pathologies of memory processing in order to effectively develop new treatments. In this longitudinal study, we combined functional magnetic resonance imaging during a memory encoding task with proton MR spectroscopy to measure hippocampal glutamate + glutamine (Glx). Seventeen SZ were scanned while unmedicated and after 6 weeks of treatment with risperidone and compared to a group of matched healthy controls (HC) scanned 6 weeks apart. Unmedicated patients showed reduced blood oxygen level dependent (BOLD) response in several regions, including the hippocampus, and greater BOLD response in regions of the default mode network (DMN) during correct memory encoding. Post hoc contrasts from significant group by time interactions indicated reduced hippocampal BOLD response at baseline with subsequent increase following treatment. Hippocampal Glx was not different between groups at baseline, but at week 6, hippocampal Glx was significantly lower in SZ compared to HC. Finally, in unmedicated SZ, higher hippocampal Glx predicted less deactivation of the BOLD response in regions of the DMN. Using 2 brain imaging modalities allowed us to concurrently investigate different mechanisms involved in memory encoding dysfunction in SZ. Hippocampal pathology during memory encoding stems from decreased hippocampal recruitment and faulty deactivation of the DMN, and hippocampal recruitment during encoding can be modulated by antipsychotic treatment. High Glx in unmedicated patients predicted less deactivation of the DMN; these results suggest a mechanism by which faulty DMN deactivation, a hallmark of pathological findings in SZ, is achieved. [ABSTRACT FROM AUTHOR]

• PBMC expression of key metabolic proteins was altered specifically in schizophrenia. • Insulin regulation was disrupted in schizophrenia. • Insulin receptor expression was associated with schizophrenia polygenic risk scores. • Peripheral metabolic markers predicted response to antipsychotics and side effects. Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy. [ABSTRACT FROM AUTHOR]

Although schizophrenia patients exhibit structural abnormalities in the striatum, it remains largely unknown for the role of the striatum subregions in the treatment response of antipsychotic drugs. The purpose of this study was to investigate the associations between the striatal subregions and improved clinical symptoms in first-episode drug-naïve (FEDN) schizophrenia. Forty-two FEDN schizophrenia patients and 29 healthy controls (HCs) were recruited. At baseline, the Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of patients, MRI scanner was used to obtain anatomical images of patients and HCs. After 12-week stable doses of risperidone treatment, clinical symptoms were obtained in 38 patients and anatomical images in 26 patients. After 12 weeks of treatment, the left nucleus accumbens volume decreased, whereas the left pallidum volume increased in schizophrenia patients. The decreased left nucleus accumbens volume was positively correlated with cognitive factor improvement measured by PANSS. Intriguingly, greater left nucleus accumbens volume at baseline predicted greater cognitive improvements. Furthermore, the responders who had >50 % improvement in cognitive symptoms exhibited significantly greater baseline left nucleus accumbens volume compared to non-responders. The left striatum volume at baseline and after treatment predicted the cognitive improvements in FEDN schizophrenia, which could be a potential biomarker for the development of precision medicine approaches targeting cognitive function., Competing Interests: All authors declare no conflict of interests., (© 2024 The Authors.)

Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone.

This study aims to better characterize the metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia. We performed a retrospective real-world study in a naturalistic setting that included inpatients with first-episode drug-naïve schizophrenia; metabolic profiles were measured at baseline and 2 weeks and 4 weeks after antipsychotic treatment. The metabolic profiles of medicated patients with first-episode schizophrenia were also included. Insulin resistance, based on the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C), increased significantly after 2 weeks of antipsychotic treatment, whereas fasting glucose (FG) decreased significantly. Regarding lipid metabolism, triglycerides (TG), cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) increased significantly after 2 weeks of antipsychotic treatment; however, high-density lipoprotein cholesterol (HDL-C) decreased significantly after 4 weeks of antipsychotic treatment. There were no statistically significant differences between the antipsychotic groups in any of the metabolic parameters evaluated. Our study revealed that insulin resistance and lipid metabolic abnormalities occurred as early as two weeks after the initiation of antipsychotic treatment. Our findings suggest that metabolic profiles should been monitored in the early stage of antipsychotics treatment in clinical practice. Further research is needed to explore the underlying mechanisms of the short-term effects of antipsychotics on metabolic parameters. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is one of the most severe psychiatric disorders and dysfunction of gray matter (GM) has been usually investigated by resting-state functional (f)MRI. However, functional organization of white matter (WM) in chronic schizophrenia remains unclear.Purpose: To investigate the WM functional alterations in chronic never-treated schizophrenia and the effects of long-term antipsychotic treatment.Study Type: Prospective.Subjects: Twenty-five never-treated, 41 matched antipsychotic-treated schizophrenia, and 25 healthy comparison subjects.Field Strength/sequence: Resting state (rs)-fMRI, T1 -weighted images (T1 WI), and diffusion tensor imaging (DTI) covering the whole brain were acquired with a 3.0T scanner.Assessment: Amplitude of low-frequency fluctuations (ALFF) in WM and the correlation coefficients between WM and GM were examined and compared among the three participant groups by two reviewers independently. Independent component analysis (ICA) was added to evaluate WM-fMRI signals. Statistical Tests: Analysis of covariance (ANCOVA); Pearson correlation analysis.Results: Never-treated patients demonstrated lower ALFF in splenium of corpus callosum (SCC) relative to treated patients and controls (P < 0.001, false discovery rate [FDR]-corrected). While the extracted independent component also located in SCC and showed significantly decreased connectivity in never-treated patients when compared to controls (P < 0.05, FDR-corrected). The correlation coefficients of WM-GM displayed greater reductions in the genu of corpus callosum (GCC), pontine crossing tract (PC), bilateral cingulum (hippocampus) (CGH), and bilateral corticospinal tract (CST) in treated patients relative to controls (P < 0.05, FDR-corrected).Data Conclusion: These findings provide new insight into WM functional alterations over the long-term course of schizophrenia with and without the potential effects of antipsychotic medication. Functional change and abnormal connectivity in SCC were both found greater in untreated patients than treated patients relative to healthy controls, suggesting that long-term antipsychotic treatment may show some protective effects on WM functional organization.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:752-763. [ABSTRACT FROM AUTHOR]

People with severe mental illness (SMI) have numerous risk factors that may predispose them to food insecurity (FI); however, the prevalence of FI and its effects on health are under-researched in this population. The present study aimed to describe the prevalence of FI and its relationship to lifestyle factors in people with SMI. This cross-sectional study recruited people with SMI receiving long-acting injectable (LAI) antipsychotic medication from community services at three sites in Sydney, Australia. Assessments were completed on physical health and lifestyle factors. χ2 Tests, independent-samples t tests and binary logistic regression analyses were calculated to examine relationships between lifestyle factors and FI. In total, 233 people completed the assessments: 154 were males (66 %), mean age 44·8 (sd 12·7) years, and the majority (70 %) had a diagnosis of schizophrenia. FI was present in 104 participants (45 %). People with FI were less likely to consume fruits (OR 0·42, 95 % CI 0·24, 0·74, P = 0·003), vegetables (OR 0·39, 95 % CI 0·22, 0·69, P = 0·001) and protein-based foods (OR 0·45, 95 % CI 0·25, 0·83, P = 0·011) at least once daily, engaged in less moderate to vigorous physical activity (min) (OR 0·997, 95 % CI 0·993, 1·000, P = 0·044), and were more likely to smoke (OR 1·89, 95 % CI 1·08, 3·32, P = 0·026). FI is highly prevalent among people with SMI receiving LAI antipsychotic medications. Food-insecure people with SMI engage in less healthy lifestyle behaviours, increasing the risk of future non-communicable disease. [ABSTRACT FROM AUTHOR]

Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone. [ABSTRACT FROM AUTHOR]

Aim: Immunopathogenesis remains a widely appreciated etiopathological model of schizophrenia. Persistent efforts have aimed to identify schizophrenia biomarkers indexing immune system abnormalities and also immuno‐dampening effects of antipsychotic medications. Although data arising from published reports are encouraging, such studies are limited to a few immune parameters and not focused on a specific pathway. Th17 cells‐mediated immuno‐inflammatory responses have emerged as a potential mechanism in various neuropsychiatric conditions, including schizophrenia. The Th17 pathway is distinctly regulated through a coordinated action of multiple cytokines and transcription factors. In this study, we explored whether antipsychotic medication has any effect on the cytokines and transcription factors of the Th17 pathway. Methods: A total of 27 drug‐naive schizophrenia patients were recruited and followed up for 3 months after initiation of antipsychotic medication. Lymphocyte gene expression levels of two transcription factors (STAT3 and RORC) and one of their upstream regulators, IL6, were quantified before and after treatment. Plasma levels of cytokines, such as interleukin (IL)‐1β, IL‐6, IL‐17A, IL‐23, and IL‐33, were also analyzed before and after treatment. Results: Treatment with antipsychotic medication for 3 months resulted in significant downregulation of STAT3 gene expression as well as reduction in plasma levels of IL‐1β, IL‐6, and IL‐17A. Significant reduction in total scores for the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms was also observed in schizophrenia patients after 3 months of antipsychotic treatment. Conclusion: Our findings suggest possible immuno‐modulatory effects of antipsychotic medication on the critical regulators, such as IL‐6 and STAT3, of the Th17 pathway in schizophrenia patients. The IL‐6/STAT3 signaling axis involved in the transcriptional regulation of Th17 cells might appear as an important target of antipsychotic treatment in schizophrenia patients. Alternatively, irrespective of the effect of antipsychotic drugs, the IL‐6/STAT3 signaling axis might be crucially involved in ameliorating psychotic symptoms. [ABSTRACT FROM AUTHOR]

Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations. Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms. A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping. Results: We found that two studied genetic variants, namely DRD2 rs4436578*C and HTR2A rs6314*A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578*C variant remained significant while the rs6314*A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected. The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians. [ABSTRACT FROM AUTHOR]

Abstract Background Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients. Methods This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment. Results The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group. Conclusions The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Abstract Background Severe and persistent mental illnesses, such as schizophrenia and bipolar disorder, are associated with increased risk of obesity compared to the general population. While the association of lurasidone and lower risk of weight gain has been established in short and longer-term clinical trial settings, information about lurasidone’s association with weight gain in usual clinical care is limited. This analysis of usual clinical care evaluated weight changes associated with lurasidone treatment in patients with schizophrenia or bipolar disorder. Methods A retrospective, longitudinal analysis was conducted using de-identified electronic health records from the Humedica database for patients who initiated lurasidone monotherapy between February 2011 and November 2013. Weight data were analyzed using longitudinal mixed-effects models to estimate the impact of lurasidone on patient weight trajectories over time. Patients’ weight data (kg) were tracked for 12-months prior to and up to 12-months following lurasidone initiation. Stratified analyses were conducted based on prior use of second-generation antipsychotics with medium/high risk (clozapine, olanzapine, quetiapine, or risperidone) versus low risk (aripiprazole, ziprasidone, first-generation antipsychotics, or no prior antipsychotics) for weight gain. Results Among the 439 included patients, the mean age was 42.2 years, and 69.7% were female. The average duration of lurasidone treatment across all patients was 55.2 days and follow-up duration after the index date was 225.1 days. The estimated impact of lurasidone on weight was − 0.77 kg at the end of the 1-year follow-up. Patients who had received a prior second-generation antipsychotic with medium/high risk for weight gain were estimated to lose an average of 1.68 kg at the end of the 1-year follow-up. Conclusions Lurasidone was associated with a reduction in weight at 1 year following its initiation in patients with schizophrenia or bipolar disorder. Stratified analyses indicated that weight reduction was more pronounced among patients who had received second-generation antipsychotics associated with a higher risk of weight gain prior to lurasidone treatment. These findings are consistent with the results of prior short- and long-term prospective studies and suggest that lurasidone is associated with low risk for weight gain in patients with schizophrenia or bipolar disorder.

Abstract Recent preclinical studies point to muscarinic and GABA B receptors as novel therapeutic targets for the treatment of schizophrenia. This study was aimed to assess the role of muscarinic and GABA B receptor interactions in animal models of schizophrenia, using positive allosteric modulators (PAMs) of GABA B receptor (GS39783), muscarinic M 4 (VU0152100) and M 5 (VU0238429) receptor, and partial allosteric agonist of M 1 receptor (VU0357017). DOI-induced head twitches, social interaction and novel object recognition tests were used as the models of schizophrenia. Analyses of DOI-induced increases in sEPSCs (spontaneous excitatory postsynaptic currents) were performed as complementary experiments to the DOI-induced head twitch studies. Haloperidol-induced catalepsy and the rotarod test were used to examine the adverse effects of the drugs. All three activators of muscarinic receptors were active in DOI-induced head twitches. When administered together with GS39783 in subeffective doses, only the co-administration of VU0152100 and GS39783 was effective. The combination also reduced the frequency but not the amplitude of DOI-induced sEPSCs. Neither VU0357017 nor VU0238429 were active in social interaction test when given alone, and also the combination of VU0152100 and GS39783 failed to reverse MK-801-induced deficits observed in this test. All muscarinic activators when administered alone or in combination with GS39783 reversed the MK-801-induced disruption of memory in the novel object recognition test, and their actions were blocked by specific antagonists. None of the tested compounds or their combinations influenced the motor coordination of the animals. The compounds had no effect on haloperidol-induced catalepsy and did not induce catalepsy when administered alone. Pharmacokinetic analysis confirmed lack of possible drug-drug interactions after combined administration of GS39783 with VU0357017 or VU0152100; however, when the drug was co-administered with VU0238429 its ability to pass the blood-brain barrier slightly decreased, suggesting potential drug-drug interactions. Our data show that modulation of cholinergic and GABAergic systems can potentially be beneficial in the treatment of the positive and cognitive symptoms of schizophrenia without inducing the adverse effects typical for presently used antipsychotics. [ABSTRACT FROM AUTHOR]

Objectives: There are many antipsychotic medications that have been shown to be associated with the prolongation of the rate-corrected QT (QTc) interval on the electrocardiogram (ECG). Studies have shown that QTc prolongation is associated with increased risk of arrhythmias and sudden cardiac death. This study aims to identify and study the risk profile of patients on high-dose antipsychotic and to examine the prevalence of rate and rhythm abnormalities, in particular, QTc prolongation. We hope that this study could throw a light on current practice patterns and also could potentially guide us towards safe practice in the future. Methods: We recruited 37 adult outpatients who are on high-dose antipsychotic from the 3 outpatient clinics of the Institute of Mental Health in Singapore. Baseline characteristics risk profiling was performed to identify their pre-existing risk, including checks on Calcium, Potassium and Magnesium levels to rule out confounders. 12 lead ECG was done and reviewed manually by our resident physician. Results: It showed that rate abnormality was detected in 8 patients (22%) and QTc interval prolongation was detected in nearly 12 patients (32.4%) but of those only 3 patients had significantly prolonged QT interval needing the primary treating team to review their psychopharmacology regime. Conclusion: QTc Prolongation was positively linked with a number of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Abstract Objective: To describe a rare case of a patient who developed psychotic symptoms after a right stroke that disappeared with antipsychotic treatment, but appears to need low-dose maintenance antipsychotic therapy. Case description: A 65-year-old man presented at the psychiatric emergency service with a history of persistent delusional jealousy, visual illusions and agitation with onset about 1 month after a right posterior cerebral artery ischemic stroke. These symptoms only disappeared with therapeutic dosages of an antipsychotic drug (3 mg/day of risperidone). At 2-year follow-up, he no longer had delusional activity and the antipsychotic treatment was gradually discontinued over the following year. However, 1 week after full cessation, the patient once more became agitated and suspicious and was put back on risperidone at 0.25 mg/day, resulting in rapid clinical remission. One year after the return to low-dose risperidone, the patient's psychopathology is still under control and he is free from psychotic symptoms. Comments: Psychosis is a relatively rare complication after stroke. To our knowledge, no cases of post-stroke psychosis that apparently require continuous low-dose antipsychotic treatment have been reported to date. Our case suggests that low-dose maintenance antipsychotic therapy may be needed for certain patients with post-stroke psychosis, especially for those with risk factors and non-acute onset.

Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs). According to multivariate analysis, antipsychotic-naïve FEP patients had significantly higher levels of taurine and spermine, whereas values of proline (Pro), alpha-aminoadipic acid (alpha-AAA), kynurenine (Kyn), valine (Val), tyrosine (Tyr), citrulline (Citr), tryptophan (Trp), and histidine (His) were diminished compared to CSs. Increased levels of taurine and spermine, as well as reduced levels of alpha-AAA and Kyn probably reflect the compromised function of N-methyl-D-aspartate (NMDA) receptors in patients. The decreased levels of Pro (AA modulating the function of glutamate decarboxylase) likely reflect the imbalanced function of gamma-aminobutyric acid (GABA) system in the brain of FEP patients. The alterations in ratio between Tyr and phenylalanine (Phe) can be taken as a sign of compromised function of dopaminergic system. These metabolic shifts were reinstated by 7-month antipsychotic treatment. Serum metabolic profiles can be regarded as important indicators to investigate clinical course of SCH and treatment response.

Introduction One of the common side effects of antipsychotic drugs is excessive sedation. The treatment with antipsychotics often manifests as an increase in slow wave activity in electroencephalography (EEG). The aim of this study was to analyze EEG recordings of patients treated with a non-sedative antipsychotic drug sertindole with regard to its adverse effects and clinical efficacy. Patients and methods EEG recordings of 45 patients (27 females, mean age 30.1 ± 8.7 years) with schizophrenia were analyzed. EEG recordings were categorized based on abnormalities severity. The clinical efficacy was rated on the Clinical Global Impression Scale. Results Abnormalities from mild to moderate were found in 29 % of the group. Clinical improvement was observed in 80 % of patients. Sedation/daytime sleepiness was present in 7 % of patients. Other side effects were prolongation of QTc (11 %, severe 4 %), insomnia (9 %), extrapyramidal symptoms (7 %), and heart palpitations (2 %). Conclusions Patients treated with sertindole do not show side effects similar to those found during treatment with other antipsychotic drugs. Increased slow wave activity in EEG and sedation were absent in the majority of the investigated patients. [ABSTRACT FROM AUTHOR]

Background: A potential link between increase in total cholesterol and triglycerides and clinical improvement has been observed during antipsychotic drug treatment in chronic schizophrenia patients, possibly due to drug related effects on lipid biosynthesis. We examined whether changes in serum lipids are associated with alleviation of psychosis symptoms after one year of antipsychotic drug treatment in a cohort of first-episode psychosis (FEP) patients.Methods: A total of 132 non-affective antipsychotic-treated FEP patients were included through the Norwegian Thematically Organized Psychosis (TOP) project. Data on antipsychotic usage, serum lipids (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (TG)), body mass index (BMI) and clinical state were obtained at baseline and after 12months. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptoms. Mixed-effects models were employed to examine the relationship between serum lipids and psychotic symptoms while controlling for potential confounders including BMI.Results: An increase in HDL during one year of antipsychotic treatment was associated with reduction in PANSS negative subscores (B=-0.48, p=0.03). This relationship was not affected by concurrent change in BMI (adjusted HDL: B=-0.54, p=0.02). No significant associations were found between serum lipids, BMI and PANSS positive subscores.Conclusion: We found that an increase in HDL level during antipsychotic treatment is associated with improvement in negative symptoms in FEP. These findings warrant further investigation to clarify the interaction between lipid pathways and psychosis. [ABSTRACT FROM AUTHOR]

A number of patients with meningiomas and psychiatric disorders will suffer psychiatric symptom recurrence following tumorectomies. The present study reported a retrospective analysis regarding 42 cases of patients with meningiomas using complete clinical follow-up data from June 2005 to June 2013. The patients were divided into the systemic antipsychotic (SP) group (n=20) following 6months of postoperative SP therapy and the none-SP (NSP) group (n=22), who did not receive postoperative antipsychotic treatment. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) at the time points of prior to surgery, immediately following surgery, and 6 months, 12 months and 3 years following surgery. The effective rate, recurrence rate, rehospitalization rate and survival analysis were calculated. The BPRS score and PANSS scores (including PANSS positive, PANSS negative, PANSS general psychopathology and PANSS overall) in the SP group at 6 months, 12 months and 3 years following surgery were significantly decreased compared with the NSP group (P<0.05). The effective rate was 95, 90 and 90% at 6 months, 12 months and 3 years, respectively, in the SP group, whilst it was 68.2, 63.6 and 59%, respectively, in the NSP group, which was statistically significant (χ2=4.89, χ2=4.01 and χ2=5.12; P<0.05). The recurrence rate of the SP group was 0, 5 and 10% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 22.7, 31.8 and 54.5%, respectively, which was statistically significant (χ2=5.16, χ2=4.89 and χ2=9.34; P<0.05). The rehospitalization rate of the SP group was 0, 0 and 5% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 13.6, 22.7 and 36.4%, respectively, and the data at 12 months and 3 years was statistically significant (χ2=5.16 and χ2=6.12; P<0.05). Kaplan-Meier survival analysis indicated that the accumulative survival rates of recurrence and rehospitalization in the SP group were improved compared with the NSP group. The log-rank of recurrence was χ2=9.369 (P=0.002) and the log-rank of rehospitalization was χ2=6.330 (P=0.012). In conclusion, postoperative SP therapy is of great importance to the consolidation of mental symptoms in patients with meningiomas and psychiatric symptoms, and it may significantly reduce the recurrence and rehospitalization rates. [ABSTRACT FROM AUTHOR]

Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naïve first-episode psychosis patients (n=43) at baseline and following symptom remission, and in healthy controls (n=77). At baseline GSK3B total level was higher in patients (p<0.001). In schizophrenia spectrum patients (n=25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n=18) (p<0.001; p=0.027; p=0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular. [ABSTRACT FROM AUTHOR]