Effects Of Antipsychotic Medication Research Articles

Risperidone effects on heterochromatin: the role of kinase signaling.

Epigenetic effects of anti-psychotic medications are poorly understood. We have appropriated a model whereby heterochromatin is established through 24- or 48-h lipopolysaccharide (LPS) treatment, and tested the epigenetic effects of risperidone along the adenylyl cyclase/protein kinase A (AC/PKA) pathway in human liposarcoma cells that express the LPS-sensitive Toll-like receptor (TLR)-4. Human SW872 cells were cultured with LPS and mRNA expression levels and epigenetic modifications of dimethylated lysine 9 of histone 2 (H3K9me2), geterochromatin protein 1γ (HP1γ) and phospho-H3S10 at promoters of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL1β were measured. Pharmacological manipulation of the AC/PKA pathway was achieved through treatment with a PKA inhibitor (H89), mitogen- and stress-activated kinase 1 (MSK1) inhibitor (SB-747651A) or forskolin. Twenty-four and 48-h LPS treatment establishes heterochromatin at selected promoters, corresponding to decreased mRNA expression. Concurrent risperidone treatment with LPS treatment can both 'block' and 'reverse' heterochromatin formation. Forskolin treatment resulted in a similar disassembling effect on heterochromatin. Conversely, inhibition of PKA by H89 or MSK1 both blocked 'normalizing' effects of risperidone on LPS-induced heterochromatin. Our results demonstrate that risperidone can disassemble heterochromatin, exerting this effect along the G-protein/AC/PKA pathway. This approach can also be utilized to investigate functional outcomes of single or combined pharmacological treatments on chromatin assemblies in human cells.

A longitudinal magnetic resonance spectroscopy study investigating effects of risperidone in the anterior cingulate cortex and hippocampus in schizophrenia

Magnetic Resonance Spectroscopy is a popular approach to probe brain chemistry in schizophrenia (SZ), but no consensus exists as to the extent of alterations. This may be attributable to differential effects of populations studied, brain regions examined, or antipsychotic medication effects. Here, we measured neurometabolites in the anterior cingulate cortex (ACC) and hippocampus, two structurally dissimilar brain regions implicated in the SZ pathophysiology. We enrolled 61 SZ with the goal to scan them before and after six weeks of treatment with risperidone. We also scanned 31 matched healthy controls twice, six weeks apart. Using mixed effect repeated measures linear models to examine the effect of group and time on metabolite levels in each voxel, we report an increase in hippocampal glutamate + glutamine (Glx) in SZ compared to controls (p = 0.043), but no effect of antipsychotic medication (p = 0.330). In the ACC, we did not find metabolite alterations or antipsychotic medication related changes after six weeks of treatment with risperidone. The coefficients for the discriminant function (differentiating SZ from HC) in the ACC were greatest for NAA (−0.83), and in the hippocampus for Glx (0.76), the same metabolites were associated with greater treatment response in patients at trend level. Taken together, our data extends the existing literature by demonstrating regionally distinct metabolite alterations in the same patient group and suggests that antipsychotic medications may have limited effects on metabolite levels in these regions.

Pituitary volume in individuals at elevated risk for psychosis: A systematic review and meta-analysis

BackgroundPituitary volume (PV) abnormalities, representing one of several markers of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been observed in psychosis, with variable patterns across illness stages. Typically, enlargements characterise first-episode patients, with reductions observed in those with chronic illness relative to healthy controls. Findings in high-risk populations have been inconsistent, highlighting the need for an updated review of the evidence. MethodsWe searched PubMed, PsycINFO, and EMBASE for studies examining PV in high-risk [clinical high-risk (CHR), family history of psychosis (FHx), schizotypal personality disorder (SPD), and psychotic-experiences (PEs)] and healthy individuals. Random effects models were used to examine group differences in PV (Hedges g) with stratified analyses and meta-regression employed to investigate the effect of high-risk category, transition status, age, sex, and antipsychotic medication. ResultsTen studies, yielding 11 effect sizes, were eligible for inclusion. Overall, high-risk individuals had significantly larger PV relative to healthy controls (g = 0.16 [95% CI: 0.01 to 0.32] p = 0.04), despite showing a reduction in whole brain volume (g = −0.17, [95% CI. −0.30 to −0.03] p = 0.020). Individual sub-group analyses for CHR and FHx groups showed no significant differences relative to controls; however, larger PV increases characterised those who later transitioned to psychosis (g = 0.55, [95% CI. 0.06 to 1.04] p = 0.028). Larger effect sizes were positively associated with the proportion of high-risk individuals receiving antipsychotic medication. ConclusionsPV enlargements characterise high-risk individuals and are more pronounced among those who later develop psychosis. We provide recommendations for future studies.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness

BackgroundThere are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).MethodsIn a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation.ResultsWritten informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms.ConclusionsThe use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)

Pulmonary embolism in a patient with neuroleptic malignant syndrome.

Venous thromboembolism is one of the complications in patients prescribed antipsychotic medications. Neuroleptic malignant syndrome (NMS) is a rare side effect of antipsychotic medications in this population. In this case, a young patient, who presented with NMS after a recent start of antipsychotic medications, had developed a pulmonary embolism despite standard of care measures of venous thromboprophylaxis and early mobilization. A low threshold of VTE suspicion and effective preventive measures are both required in order to avoid this preventable complication in this population.

Neurological soft signs and grey matter abnormalities in individuals with ultra-high risk for psychosis.

Neurological soft signs (NSSs), conventionally defined as subtle neurological abnormalities, are frequently found in individuals with schizophrenia. Many neuroimaging studies have also reported that NSSs are associated with grey matter changes in patients with schizophrenia at different stages of the illness. However, these findings may be confounded by the effect of antipsychotic medications, chronicity, and duration of untreated psychosis. Examining NSSs in individuals with ultra-high risk (UHR) for psychosis may help to identify the neuroanatomical substrates of NSSs related to the illness itself and to avoid these potential confounding effects. A sample of 21 individuals with UHR were included in the present study. NSSs were rated using the abridged version of the Cambridge Neurological Inventory. Grey matter volume was assessed using optimized voxel-based morphometry on images acquired by a high-resolution 3-T magnetic resonance imaging scanner. We found that higher NSS scores in individuals with UHR were associated with decreased grey matter volume at the superior and medial frontal cortex, the rectal cortex, the pre- and post-central cortex, the insula, the caudate, and the cerebellum. Our results suggest that these brain structural characteristics may represent the neuroanatomical substrate of NSSs in individuals with UHR. These findings contribute to the understanding of the intrinsic features of psychosis associated with NSSs and may provide insights into pre-schizophrenia pathophysiology.

Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach

Tardive dyskinesia (TD) is a side effect of antipsychotic medications used to treat schizophrenia (SCZ) and other mental health disorders. No study has previously used pyrosequencing to quantify DNA methylation levels of the DLGAP2 gene; while the quantitative methylation levels among CpG sites within a gene may be correlated. To deal with the correlated measures among three CpG sites within the DLGAP2 gene, this study analyzed DNA methylation levels of the DLGAP2 gene using a linear mixed model (LMM) in a Chinese sample consisting of 35 SCZ patients with TD, 35 SCZ without TD (NTD) and 34 healthy controls (HCs) collected in Beijing, China. The initial analysis using the non-parametric Kruskal-Wallis test revealed that three groups (TD, NTD and HC) had significant differences in DNA methylation level for CpG site 2 (p = 0.0119). Furthermore, the average methylation levels among the three CpG sites showed strong correlations (all p values < 0.0001). In addition, using the LMM, three groups had significant differences in methylation level (p = 0.0027); while TD, NTD and TD + NTD groups showed higher average methylation levels than the HC group (p = 0.0024, 0.0151, and 0.0007, respectively). In conclusion, the LMM can accommodate a covariance structure. The findings of this study provide first evidence of DNA methylation levels in DLGAP2 associated with SCZ with TD in Chinese population. However, TD just showed borderline significant differences to NTD in this study.

Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review.

Despite the existence of many preclinical studies, scientific evidence is lacking on the clinical use of alpha-lipoic acid (ALA) for central nervous system disorders. Therefore, we aimed at revising the literature concerning the use of ALA for the treatment of psychiatric and neurological conditions and to point out what is missing for the introduction of this antioxidant to this purpose. For this systematic review we performed a search using PubMed and SCOPUS databases with the following keywords: "alpha-Lipoic Acid AND central nervous system OR psychiatric disorders OR neurological disorders OR mood disorders OR anxiety OR psychosis OR Alzheimer OR Parkinson OR stroke". The total number of references found after automatically and manually excluding duplicates was 1061. After primary and secondary screening 32 articles were selected. Regarding psychiatric disorders, the studies of ALA in schizophrenia are advanced being ALA administration related to the improvement of schizophrenia symptoms and side effects of antipsychotic medication. In neurological disorders, ALA as a supplement was effective in the prevention of Alzheimer disease progression. For stroke, the use of the supplement ALAnerv® (containing 300mg ALA) presented important results, since it was observed a reversal of clinical parameters and oxidative imbalance in these patients. For other neurological conditions, such as encephalopathy, multiple sclerosis, traumatic brain injury, mitochondrial disorders and migraine, the results are still preliminary. Overall, there is a need of well-designed clinical trials to enhance the clinical evidences of ALA effects for the treatment of neurological and psychiatric conditions.

Systematic review of case reports of oropharyngeal dysphagia following the use of antipsychotics

ObjectiveThe purpose of this systematic review was to examine the effect of antipsychotic medication on dysphagia based on clinical case reports. Patients and methodsLiterature searches were performed using the electronic databases PubMed and Embase. In PubMed, we used the MeSH terms “antipsychotic agents” OR “tranquilizing agents” combined with “deglutition disorders” OR “deglutition”. In Embase, we used the Emtree terms “neuroleptic agents” combined with “swallowing” OR “dysphagia”. Two reviewers assessed the eligibility of each case independently. ResultsA total of 1043 abstracts were retrieved, of which 36 cases met the inclusion criteria; 14 cases were related to typical antipsychotics and 22 to atypical antipsychotics. Dysphagia occurred together with extrapyramidal symptoms in half of the cases and was the only prominent symptom in the other half. The most common strategy against dysphagia was changing to another antipsychotic (n=13, 36.1%). ConclusionsThe data from this review indicate that antipsychotics can increase the prevalence of dysphagia.

Nocturnal Enuresis is an Under-recognised Side Effect of Clozapine: Results of a Systematic Review

Abstract Objectives Clozapine is an effective antipsychotic medication licenced for the management of treatment resistant schizophrenia. Due to its non-selective pharmacology, it has a broad range of side effects. Nocturnal enuresis secondary to the use of clozapine has been documented in the literature but may be overlooked, the link between drug and symptom being clinically unnoticed. Patients may not mention urinary symptoms due to supervening psychosis, co-existing symptomatology, embarrassment or shame. By raising awareness of the phenomenon, early recognition and patient support may improve compliance with clozapine medication, and consecutively, overall mental health. Consequently, this systematic review investigates the prevalence of nocturnal enuresis secondary to clozapine use. Methods A literature search on clozapine and nocturnal enuresis was used to identify the relevant papers. Papers providing the prevalence data on Clozapine associated nocturnal enuresis were selected for data extraction. Results 47 papers were initially identified. Eight papers focused on the prevalence of clozapine associated nocturnal enuresis (CANE). Point prevalence (nocturnal enuresis at the time of assessment), 1-month prevalence and episode prevalence (nocturnal enuresis since beginning of clozapine) were given. Papers included patients with schizophrenia, schizoaffective disorder, bipolar affective disorder and psychotic depression, taking clozapine medication. The prevalence of CANE ranged from 10–42%. Point prevalence was 21–27%, 1-month prevalence was 10–39% and episode prevalence was 15–42%. Clozapine was more likely to cause nocturnal enuresis compared to other psychotropic medication. Conclusion The prevalence of CANE may be greater than previously thought. However, in order to determine an accurate prevalence of clozapine associated nocturnal enuresis, larger studies with strict inclusion criteria, common definition of diagnosis and prevalence are required. By establishing an accurate prevalence, physician awareness can be improved, and patients can becounselled on the risk of developing the side effect, thus improving early identification and reducing discontinuation rates.

Management of common adverse effects of antipsychotic medications.

The benefits of antipsychotic medications are sometimes obscured by their adverse effects. These effects range from relatively minor tolerability issues (e.g., mild sedation or dry mouth) to very unpleasant (e.g., constipation, akathisia, sexual dysfunction) to painful (e.g., acute dystonias) to disfiguring (e.g., weight gain, tardive dyskinesia) to life-threatening (e.g., myocarditis, agranulocytosis). Importantly, adverse effect profiles are specific to each antipsychotic medication and do not neatly fit into first- and second-generation classifications. This paper reviews management strategies for the most frequent side effects and identifies common principles intended to optimize net antipsychotic benefits. Only use antipsychotics if the indication is clear; only continue antipsychotics if a benefit is discernible. If an antipsychotic is providing substantial benefit, and the adverse effect is not life-threatening, then the first management choice is to lower the dose or adjust the dosing schedule. The next option is to change the antipsychotic; this is often reasonable unless the risk of relapse is high. In some instances, behavioral interventions can be tried. Finally, concomitant medications, though generally not desirable, are necessary in many instances and can provide considerable relief. Among concomitant medication strategies, anticholinergic medications for dystonias and parkinsonism are often effective; beta-blockers and anticholinergic medications are useful for akathisia; and metformin may lead to slight to moderate weight loss. Anticholinergic drops applied sublingually reduce sialorrhea. Usual medications are effective for constipation or dyslipidemias. The clinical utility of recently approved treatments for tardive dyskinesia, valbenazine and deutetrabenazine, is unclear.

Positive and negative symptoms in schizophrenia: A longitudinal analysis using latent variable structural equation modelling

BackgroundRecent network models of schizophrenia propose it is the consequence of mutual interaction between its symptoms. While cross-sectional associations between negative and positive symptoms are consistent with this idea, they may merely reflect their involvement in the diagnostic process. Longitudinal analyses however may allow the identification of possible causal relationships. The European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. MethodsEuroSC includes 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures were repeated after 12 and 24 months. Latent variable structural equation modelling was used to investigate the direction of effect between positive and negative symptoms assessed with the Positive and Negative Syndrome Scale, controlling for the effects of depressed mood and antipsychotic medication. ResultsThe structural model provided acceptable overall fit [χ2 (953) = 2444.32, P < 0.001; CFI = 0.909; RMSEA = 0.046 (90% CI: 0.043, 0.048); SRMR = 0.052]. Both positive and negative symptoms were persistent, and strongly auto-correlated. There were also persistent cross-sectional associations between positive and negative symptoms. While the path from latent positive to negative symptoms from T1 to T2 approached conventional levels of statistical significance (P = 0.051), that from T2 to T3 did not (P = 0.546). Pathways in the reverse direction were uniformly non-significant. ConclusionsThere was no evidence that negative symptoms predict later positive symptoms. The prediction of negative symptoms by positive symptoms was ambiguous. We discuss implications for conceptualization of schizophrenic processes.

The Effects of Antipsychotic Treatment on Presynaptic Dopamine Synthesis Capacity in First-Episode Psychosis: A Positron Emission Tomography Study

BackgroundElevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore, it is unknown whether antipsychotic efficacy is linked to reductions in dopamine synthesis capacity. We conducted a prospective [18F]-dihydroxyphenyl-L-alanine positron emission tomography study in antipsychotic naïve/free people with first-episode psychosis commencing antipsychotic treatment. MethodsDopamine synthesis capacity (indexed as influx rate constant) and clinical symptoms (measured using Positive and Negative Syndrome Scale) were measured before and after at least 5 weeks of antipsychotic treatment in people with first-episode psychosis. Data from a prior study indicated that a sample size of 13 would have >80% power to detect a statistically significant change in dopamine synthesis capacity at alpha = .05 (two tailed). ResultsA total of 20 people took part in the study, 17 of whom were concordant with antipsychotic medication at therapeutic doses. There was no significant effect of treatment on dopamine synthesis capacity in the whole striatum (p = .47), thalamus, or midbrain, nor was there any significant relationship between change in dopamine synthesis capacity and change in positive (ρ = .35, p = .13), negative, or total psychotic symptoms. ConclusionsDopamine synthesis capacity is unaltered by antipsychotic treatment, and therapeutic effects are not mediated by changes in this aspect of dopaminergic function.

Delays and barriers to the commencement of clozapine in eligible people with a psychotic disorder: A literature review

While the majority of individuals with a first episode of psychosis (FEP) achieve symptomatic remission with the appropriate treatment, there is a small but significant proportion who do not achieve remission of symptoms despite adequate treatment with at least two antipsychotic medications (termed treatment resistance). Clozapine is indicated in individuals who fulfil the criteria for treatment-resistant schizophrenia, however, despite it being the most effective antipsychotic medication, there can be delays in the commencement of clozapine in eligible patients. A systematic search was performed to identify articles reporting either the time taken to commence clozapine (or delays) in eligible individuals or articles reporting barriers to the commencement of clozapine. The initial search generated 5588 articles and of these, 18 were eligible. 13 studies described delays in commencing clozapine and five studies reported on the barriers to the commencement of clozapine. The duration of delay from when an individual was deemed eligible for clozapine treatment to the time of clozapine commencement ranged from 19.3 weeks to 5.5 years. In addition, the duration of illness prior to clozapine initiation ranged from 1.1 to 9.7 years. It was found that some clinicians were more inclined to prescribe antipsychotic polypharmacy or doses higher than recommended than to prescribe clozapine. Delays in commencing clozapine have been consistently demonstrated. Early intervention for psychosis services are the ideal settings to identify individuals with persistent positive psychotic symptoms and commence clozapine if indicated.

A Study of Sexual Dysfunction in a Sample of Medicated and non Medicated Egyptian Female Patients with Schizophrenia

Background: the relationship between sexuality and schizophrenia is complex. It may be related to both the psychopathology and the pharmacotherapy, as the sexual functions may be affected by symptoms itself, living with a severe chronic mental health illness, and the adverse effects of antipsychotics or other medications. Systematic studies have revealed that sexual dysfunction is highly prevalent in both untreated and treated schizophrenia patients, affecting 30–80% of women and 45–80% of men. The prevalence of sexual dysfunction may be higher in patients with schizophrenia than in patients treated for other mental disorders. Aim of the Work: to compare a group of females with Schizophrenia to healthy female control group regarding frequency and type of sexual dysfunction. Patients and Methods: this study was sought to extend our knowledge about the association of schizophrenia and its treatment with sexuality problems. It was done at Institute of Psychiatry, Faculty of Medicine, Ain Shams University to determine the rate of occurrence of sexual dysfunctions in married females with schizophrenia in comparison to control group. It included 90 females diagnosed as schizophrenia (divided into 3 groups of 30s 1-untreated patients 2-patients treated with typical anti psychotics 3- patients treated with Atypical antipsychotics) and 30 females as a control group. Results: the study revealed high prevalence of sexual dysfunction among all patients group yet it was highest among the drug naive group as 100% of them had sexual dysfunction. Conclusion: the relation between schizophrenia and female sexuality is complex it could be the result of side effect of antipsychotic medications yet the high prevalence of sexual dysfunction among drug naive patients, suggest that sexual dysfunction is an integral part of the disease.

A Study of Sexual Dysfunction in a Sample of Medicated and non Medicated Egyptian Female Patients with Schizophrenia

Background: the relationship between sexuality and schizophrenia is complex. It may be related to both the psychopathology and the pharmacotherapy, as the sexual functions may be affected by symptoms itself, living with a severe chronic mental health illness, and the adverse effects of antipsychotics or other medications. Systematic studies have revealed that sexual dysfunction is highly prevalent in both untreated and treated schizophrenia patients, affecting 30–80% of women and 45–80% of men. The prevalence of sexual dysfunction may be higher in patients with schizophrenia than in patients treated for other mental disorders. Aim of the Work: to compare a group of females with Schizophrenia to healthy female control group regarding frequency and type of sexual dysfunction. Patients and Methods: this study was sought to extend our knowledge about the association of schizophrenia and its treatment with sexuality problems. It was done at Institute of Psychiatry, Faculty of Medicine, Ain Shams University to determine the rate of occurrence of sexual dysfunctions in married females with schizophrenia in comparison to control group. It included 90 females diagnosed as schizophrenia (divided into 3 groups of 30s 1-untreated patients 2-patients treated with typical anti psychotics 3- patients treated with Atypical antipsychotics) and 30 females as a control group. Results: the study revealed high prevalence of sexual dysfunction among all patients group yet it was highest among the drug naive group as 100% of them had sexual dysfunction. Conclusion: the relation between schizophrenia and female sexuality is complex it could be the result of side effect of antipsychotic medications yet the high prevalence of sexual dysfunction among drug naive patients, suggest that sexual dysfunction is an integral part of the disease.

The relation of atypical antipsychotic use and stress with weight in individuals at clinical high risk for psychosis.

Atypical antipsychotics (AT) and stress are related to weight gain in individuals with severe mental illness. This cross-sectional study examines AT use, stressful life events, and baseline weight in a sample of youth at clinical high risk for psychosis. Results showed that dependent and desirable life events moderated the relationship between AT use and weight after controlling for demographic factors and selective serotonin reuptake inhibitor antidepressant (AD) use. The relation of AD and weight was explored as a secondary analysis and showed no relation between AD use and weight. Further, stress did not moderate the relationship between AD medication and weight after controlling for antipsychotic use. Results suggest that stress exposure may exacerbate the relationship between ATs and increased weight in clinical high-risk populations. Findings have implications for the development of interventions to address psychosocial factors that worsen or buffer the adverse effects of antipsychotic medication on weight.

Beneficial and adverse effects of antipsychotic medication on cognitive flexibility are related to COMT genotype in first episode psychosis

This study evaluated the ability to flexibly shift cognitive set and to consistently maintain a new response preference using the Penn Conditional Exclusion Test (PCET). The relationship of performance errors with catechol-O-methyltransferase (COMT) rs4680 (Val158Met) genotype (Met carriers vs. Val homozygotes) on test performance before and after antipsychotic treatment in 32 first episode psychosis (FEP) patients was examined. After treatment, patients demonstrated a mixture of beneficial and adverse cognitive outcomes that varied in relation to COMT genotype. Met carriers showed decreased perseverative and regressive errors, reflecting improved cognitive flexibility and enhanced stability of behavioral preferences, respectively. In contrast, Val homozygotes exhibited an increase in regressive errors after treatment. These findings suggest that Val homozygotes may be vulnerable to adverse effects of antipsychotic medication on cognitive processes that maintain consistent adaptive response preferences, an ability linked to the striatum in rodent models.

Increased resting perfusion of the hippocampus in high positive schizotypy: A pseudocontinuous arterial spin labeling study.

Arterial spin labeling (ASL) provides absolute quantification of resting tissue cerebral blood flow (CBF) as an entirely noninvasive approach with good reproducibility. As a result of neurovascular coupling, ASL provides a useful marker of resting neuronal activity. Recent ASL studies in individuals at clinical high risk of psychosis (CHR) have reported increased resting hippocampal perfusion compared with healthy controls. Schizotypy refers to the presence of subclinical psychotic‐like experiences in healthy individuals and represents a robust framework to study neurobiological mechanisms involved in the extended psychosis phenotype while avoiding potentially confounding effects of antipsychotic medications or disease comorbidity. Here we applied pseudo‐continuous ASL to examine differences in resting CBF in 21 subjects with high positive schizotypy (HS) relative to 22 subjects with low positive schizotypy (LS), as determined by the Oxford and Liverpool Inventory of Feelings and Experiences. Based on preclinical evidence that hippocampal hyperactivity leads to increased activity in mesostriatal dopamine projections, CBF in hippocampus, midbrain, and striatum was assessed. Participants with HS showed higher CBF of the right hippocampus compared to those with LS (p = .031, family‐wise error corrected). No differences were detected in the striatum or midbrain. The association between increased hippocampal CBF and HS supports the notion that hippocampal hyperactivity might be a central characteristic of the extended psychosis phenotype, while hyperactivity in subcortical dopamine pathways may only emerge at a higher intensity of psychotic experiences.

Negativsymptome der Schizophrenie – ein Überblick

Negative Symptoms in Schizophrenia - an Overview Abstract. Negative symptoms in schizophrenia comprise the symptom-dimensions of apathy (avolition, anhedonia and social withdrawal) and reduced expression (alogia and blunted affect). Negative symptoms are of a high relevance for the illness course, since they strongly affect functional outcome and quality of life. A diagnostic differentiation is recommended in primary negative symptoms (regarded as an integral part of schizophrenia) and secondary negative symptoms (regarded as a result of positive symptoms, comorbid depression, effects of antipsychotic medication, substance abuse or social deprivation). The following overview will present the various aspects of negative symptoms, the underlying pathophysiology and describe current diagnostic and therapeutic recommendations based on the concept of primary and secondary negative symptoms.