Psychiatric Symptoms Of Schizophrenia Research Articles

Focused Ultrasound Stimulates the Prefrontal Cortex and Prevents MK-801-Induced Psychiatric Symptoms of Schizophrenia in Rats.

Treatment of schizophrenia remains a major challenge. Recent studies have focused on glutamatergic signaling hypoactivity through N-methyl-D-aspartate (NMDA) receptors. Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The aim of this study was to investigate the efficacy of LIPUS against psychiatric symptoms and anxiety-like behaviors. Rats assigned to 4 groups were pretreated with or without LIPUS for 5 days. The open field and prepulse inhibition tests were performed after saline or MK-801 (0.3 mg/kg) administration. Then, the neuroprotective effects of LIPUS on the MK-801-treated rats were evaluated using western blotting and immunohistochemical staining. LIPUS stimulation of the prefrontal cortex (PFC) prevented deficits in locomotor activity and sensorimotor gating and improved anxiety-like behavior. MK-801 downregulated the expression of NR1, the NMDA receptor, in rat medial PFC (mPFC). NR1 expression was significantly higher in animals receiving LIPUS pretreatment compared to those receiving only MK-801. In contrast, a significant increase in c-Fos-positive cells in the mPFC and ventral tegmental area was observed in the MK-801-treated rats compared to those receiving only saline; this change was suppressed by pretreatment with LIPUS. This study provides new evidence for the role of LIPUS stimulation in regulating the NMDA receptor and modulating c-Fos activity, which makes it a potentially valuable antipsychotic treatment for schizophrenia.

Negative-emotion-induced reduction in speech-in-noise recognition is associated with source-monitoring deficits and psychiatric symptoms in mandarin-speaking patients with schizophrenia

BackgroundPatients with schizophrenia (SCH) have deficits in source monitoring (SM), speech-in-noise recognition (SR), and auditory prosody recognition. This study aimed to test the covariation between SM and SR alteration induced by negative prosodies and their association with psychiatric symptoms in SCH. MethodsFifty-four SCH patients and 59 healthy controls (HCs) underwent a speech SM task, an SR task, and the assessment of positive and negative syndrome scale (PANSS). We used the multivariate analyses of partial least squares (PLS) regression to explore the associations among SM (external/internal/new attribution error [AE] and response bias [RB]), SR alteration/release induced by four negative-emotion (sad, angry, fear, and disgust) prosodies of target speech, and psychiatric symptoms. ResultsIn SCH, but not HCs, a profile (linear combination) of SM (especially the external-source RB) was positively associated with a profile of SR reductions (induced especially by the angry prosody). Moreover, two SR reduction profiles (especially in the anger and sadness conditions) were related to two profiles of psychiatric symptoms (negative symptoms, lack of insight, and emotional disturbances). The two PLS components explained 50.4% of the total variances of the release-symptom association. ConclusionCompared to HCs, SCH is more likely to perceive the external-source speech as internal/new source speech. The SM-related SR reduction induced by the angry prosody was mainly associated with negative symptoms. These findings help understand the psychopathology of SCH and may provide a potential direction to improve negative symptoms via minimizing emotional SR reduction in schizophrenia.

Network analysis of psychiatric symptoms in schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP).

Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia. Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed. A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P=0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P=0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P<0.01). Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.

Gut Microbiome: A Brief Review on Its Role in Schizophrenia and First Episode of Psychosis.

There is a growing body of evidence highlighting the role of gut microbiota as a biological basis of psychiatric disorders. The existing literature suggest that cognitive and emotional activities can be influenced by microbes through the microbiota–gut–brain axis and implies an association between alterations in the gut microbiome and several psychiatric conditions, such as autism, depression, bipolar disorder and psychosis. The aim of this review is to summarise recent findings and provide concise updates on the latest progress of the role of gut microbiota in the development and maintenance of psychiatric symptoms in schizophrenia and the first episode of psychosis. Despite the lack of consistent findings in regard to specific microbiome changes related to psychosis, the emerging literature reports significant differences in the gut microbiome of schizophrenic subjects compared to healthy controls and increasingly outlines the significance of an altered microbiome composition in the pathogenesis, development, symptom severity and prognosis of psychosis. Further human studies are, however, required, which should focus on identifying the drivers of microbiota changes in psychosis and establish the direction of causality between psychosis and microbiome alterations.

Prof K C Dube Poster Award

Introduction –Several biomarkers have been implicated and studied in schizophrenia with mixed results.Aims –To study the correlation between serum lipids, Homocysteine, CRP in patients with schizophrenia.Methodology -37 males diagnosed with schizophrenia as per ICD-10 have been evaluated cross-sectionally. Their serum lipids, Homocysteine and CRP levels were correlated with symptoms severity (assessed on Positive and Negative Symptoms of Schizophrenia scale) and sexual function (assessed by Arizona Sexual Experience Scale).Results –Homocysteine was significantly associated with negative symptoms of schizophrenia (p < 0.01), serum Homocysteine and CRP were also associated with higher prevalence of sexual dysfunction (p < 0.05) while triglycerides levels were associated with general psychopathology symptoms (p < 0.05).Discussion –These three biomarkers were selected as they have been assessed in the past to evaluate the hypothesis of schizophrenia being a neuro-inflammatory disorder. The findings suggest that alteration in lipid levels may contribute to the severity of psychiatric symptoms in schizophrenia, and it may be postulated that homocysteine may accentuate negative signs of schizophrenia, possibly by deteriorating cognitive abilities.Conclusion -Impaired Homocysteine, CRP and serum lipids are implicated to symptoms and sexual problems in schizophrenia.

Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4.

Schizophrenia is a common neuropsychiatric disorder with complex pathophysiology. Recent reports suggested that complement system alterations contributed to pathological synapse elimination that was associated with psychiatric symptoms in schizophrenia. Complement component 3 (C3) and complement component 4 (C4) play central roles in complement cascades. In this study, we compared peripheral C3 and C4 protein levels between first-episode psychosis (FEP) and healthy control (HC). Then we explored whether single nucleotide polymorphisms (SNPs) at C3 or C4 genes affect peripheral C3 or C4 protein levels. In total, 181 FEPs and 204 HCs were recruited after providing written informed consent. We measured serum C3 and C4 protein levels using turbidimetric inhibition immunoassay and genotyped C3 and C4 polymorphisms using the Sequenom MassArray genotyping. Our results showed that three SNPs were nominally associated with schizophrenia (rs11569562/C3: A > G, p = 0.048; rs2277983/C3: A > G, p = 0.040; rs149898426/C4: G > A, p = 0.012); one haplotype was nominally associated with schizophrenia, constructed by rs11569562–rs2277983–rs1389623 (GGG, p = 0.048); FEP had higher serum C3 and C4 (both p < 0.001) levels than HC; rs1389623 polymorphisms were associated with elevated C3 levels in our meta-analysis (standard mean difference, 0.50; 95% confidence interval, 0.30 to 0.71); the FEP with CG genotype of rs149898426 had higher C4 levels than that with GG genotypes (p = 0.005). Overall, these findings indicated that complement system altered in FEP and rs149898426 of C4 gene represented a genetic risk marker for schizophrenia likely through mediating complement system. Further studies with larger sample sizes needs to be validated.

S234. DEPRESSION AND SEXUAL FUNCTIONING: TWO NEGLECTED AND PREVALENT DOMAINS IN PEOPLE WITH SCHIZOPHRENIA

BackgroundSexual function is highly neglected in individuals with schizophrenia (SZ). Clinicians usually underestimate the rates of sexual dysfunctions in these patients, and this group does not spontaneously complain about it.Sexual dysfunction in this population could reach up to 80% and its known to affect all domains of sexual function. Moreover, it may be linked to stigma and discrimination factors.Medication side effects on sexuality concern more than any other side effects, and it is known to be a major cause of poor quality of life and non-adherence to medication.Furthermore, the relationship between sexual dysfunction and other psychiatric symptoms in SZ is still unclear.Our aim was to describe the sexual dysfunction in chronic patients with SZ and its relation to negative, positive and depressive symptoms.MethodsA convenience and exploratory sample of 57 patients (age 43.75±10.38, 69% men, 86,2% single) were recruited from an university outpatient schizophrenia clinic, in Porto Alegre – Brazil. Participants were assessed using Arizona Sexual Experience Scale (ASEX), Medication Adherence Rating Scale (MARS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Inventory and demographic information.Sexual dysfunction was considered following the ASEX scoring criteria.ResultsSexual dysfunction was present in 51,8% of the patients, assessed by ASEX. Women showed increased sexual dysfunction than men (χ2=22,727, p < .001). There were no differences between patients that reported sexual dysfunction and the ones who did not regarding age, duration of illness and medication adherence assessed by MARS (p > .05). Additionally, there were no differences between groups on positive and negative symptoms assessed by PANSS.Interestingly, patients with sexual dysfunction had increased depressive symptoms compared to patients with a good perceived sexual function (t(54) = -3.326, p = .002). Calgary total scores were positively correlated with ASEX total scores (r = .369, p = .005).Nevertheless, we did not find significant correlations between ASEX total scores and other scales. Scores found on MARS (8.07±1.5) suggest that this sample is highly adherent to prescribed treatment.DiscussionThis is an exploratory and preliminary study that shows and reinforces the idea that sexual dysfunction is importantly prevalent and remains as a neglected issue in individuals with schizophrenia, as are the depressive symptoms. We showed that there is an association between these two domains, which might indicate a need for change of perspective for the pharmacological and psychosocial approaches currently used.In addition to the dopaminergic blockage by antipsychotics that lead to reduction in positive symptoms, we believe there is a need to look for depression symptoms to access, prevent and treat sexual dysfunction. Inattention to this event may result in abrupt treatment discontinuation and relapse.Curiously, the fact that we did not find any correlations between sexual evaluations and PANSS scores would suggest that sexual dysfunction in chronic patients could differ from others stages of the disease. The size of our sample and the fact that we did not access hormones and prolactin levels are important limitations of this study. However this is an exploratory study that provided clues on the subject, allowing to address further investigation taking into account the limitations.

Relationship of poor insight to neurocognition, social cognition, and psychiatric symptoms in schizophrenia: A meta-analysis

BackgroundPoor insight (unawareness) about having a mental disorder is considered to be a core feature of the disorder. Further, poor insight has been associated with another core feature of schizophrenia, neurocognitive deficits. However, previous meta-analyses have shown that poor insight is more strongly related to positive symptoms and social cognition than to neurocognitive functioning. MethodA meta-analysis of 123 studies of schizophrenia patients (combined n = 14,932) was conducted to determine the magnitude of the relationship between poor insight and neurocognition, social cognition, and positive symptoms, as well as negative symptoms, disorganization, and depression. The neurocognitive constructs were defined empirically using dimensions identified by the MATRICS initiative. ResultsMeta-analytic findings showed that relationships were weak between poor insight and the six neurocognitive domains (r's range from −0.04 to −0.13), but that poor insight was moderately correlated with one aspect of social cognition, theory of mind (r = −0.23, p < .01). In addition, poor insight was moderately associated with reality distortion (r = 0.28, p < .01), disorganization (r = 0.29, p < .01), and negative symptoms (r = 0.20, p < .01). DiscussionOrganizing the neurocognitive variables using the MATRICS domains continues to demonstrate that the relationship between insight and neurocognition is relatively weak. In comparison, we found moderate correlations between insight and theory of mind and several symptom domains. These moderate relationships are generally consistent with previous meta-analyses but are demonstrated more rigorously by examining more studies within the same meta-analysis.

&lt;p&gt;Efficacy of low-dose D&lt;sub&gt;2&lt;/sub&gt;/D&lt;sub&gt;3&lt;/sub&gt; partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study&lt;/p&gt;

ObjectiveSome lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375–0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability.MethodsTen subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit.ResultsSAS total scores decreased significantly during the study in patients with DIP (P<0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood.ConclusionA low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected.

Microduplications at the 15q11.2 BP1–BP2 locus are enriched in patients with anorexia nervosa

Microduplication at 15q11.2 have been reported in genetic association studies of schizophrenia and autism. Given the potential overlap in psychiatric symptoms of schizophrenia and autism with anorexia nervosa (AN), we were inspired to test the association of this CNV locus with the genetic susceptibility of AN using ParseCNV, a highly quality controlled CNV pipeline developed by our group. The CNV analysis was performed in 1017 AN cases and 7250 controls using the Illumina HumanHap610 SNP arrays data. We uncovered association of the 15q11.2 microduplication with AN with P = 0.00023, while no genetic association between the microdeletion of this region and AN was identified. Among four genes in this region that are not imprinted, NIPA1 has the highest expression in brain and encodes a magnesium transporter protein on early endosomes and the cell surface in neurons. Targeting at Mg2+ uptake mediated by NIPA1 presents an interesting research topic for the explorations of novel therapy for AN and other neurobehavioral diseases, such as schizophrenia and autism.

Microduplications at the 15q11.2 BP1-BP2 Locus are Enriched in Patients with Anorexia Nervosa

Microduplication at 15q11.2 have been reported in genetic association studies of schizophrenia and autism. Given the potential overlap in psychiatric symptoms of schizophrenia and autism with anorexia nervosa (AN), we were inspired to test the association of this CNV locus with the genetic susceptibility of AN using PareseCNV, a highly quality controlled CNV pipeline developed by our group. The CNV analysis was performed in 1,017 AN cases and 7,250 controls using the Illumina HumanHap610 SNP arrays data. We uncovered association of the 15q11.2 microduplication with AN with P=0.00023, while no genetic association between the microdeletion of this region and AN was identified. Among four genes in this region that are not imprinted, NIPA1 has the highest expression in brain and encodes a magnesium transporter protein on early endosomes and the cell surface in neurons. Targeting at Mg2 uptake mediated by NIPA1 presents an interesting research topic for the explorations of novel therapy for AN and other neurobehavioral diseases, such asschizophrenia and autism. Funding: The study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia to the Center for Applied Genomics, The Children’s Hospital of Philadelphia Endowed Chair in Genomic Research to HH and by U01HG006830 from the NHGRI (eMERGE). Declaration of Interest: None declared. Ethical Approval: This study was approved by the Research Ethics Board of the Children's Hospital of Philadelphia.

Antipsychotics

Antipsychotics are used to treat a variety of disorders. They are commonly used in the management of psychiatric symptoms of schizophrenia and bipolar disorder. However, among other uses, they also have shown efficacy in treating symptoms of autism, nausea/vomiting, and hiccups. In the case of psychiatric uses, long-term maintenance treatment is typically needed to avoid relapse of symptoms. Antipsychotic choice based on the efficacy is difficult; therefore, in many cases side-effect profile of an agent becomes relevant when deciding on a treatment regimen. Side effects of antipsychotics include extrapyramidal symptoms, metabolic adverse effects, hematologic changes, anticholinergic effects, and QTc prolongation. As clinicians, it is important to be aware of these side effects and their monitoring parameters. These can be managed by discontinuing a drug, decreasing dosage, changing the drug to a different antipsychotic, and using another drug for their treatment. This review contains 5 tables and 97 references Key Words: antipsychotics, atypical antipsychotics, clozapine, D2 receptor, extrapyramidal symptoms, FDA-approved, REMS, typical antipsychotics

Adjunctive therapy with statins in schizophrenia patients: A meta-analysis and implications

There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis). Inclusion criteria were the following: RCTs, the adult schizophrenia patients, received antipsychotics plus statins or placebo, and the PANSS or SANS scores. Exclusion criteria were as follows: no data reported and multiple reports of the same study. A meta-analysis was used to compare psychiatric symptoms in schizophrenia patients with or without statins adjunctive therapy. The 6 RCTs included in the analysis represented 339 participants (169 in treatment group versus 170 in placebo group). A test for overall effect demonstrated that the PANSS positive scale and negative scale significantly reduced in participants receiving compliant with statins. Our meta-analyses first clarified that adjunctive therapy with statins could improve psychiatric symptoms, either negative symptoms or positive symptoms.

Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders.

There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.

Sluggishness of Early-Stage Face Processing (N170) Is Correlated with Negative and General Psychiatric Symptoms in Schizophrenia.

Patients with schizophrenia consistently exhibit abnormalities in the N170 event-related potential (ERP) component evoked by images of faces. However, the relationship between these face-specific N170 abnormalities in patients with schizophrenia and the clinical characteristics of this disorder has not been elucidated. Here, ERP recordings were conducted for patients with schizophrenia and healthy controls. The amplitude and latency of the N170 component were recorded while participants passively viewed face and non-face (table) images to explore the correlation between face-specific processing and clinical characteristics in schizophrenia. The results provided evidence for a face-specific N170 latency delay in patients with schizophrenia. The N170 latency in patients with schizophrenia was significantly longer than that in healthy controls when images of faces were presented in both upright and inverted orientations. Importantly, the face-related N170 latencies of the left temporo-occipital electrodes (P7 and PO7) were positively correlated with both negative and general psychiatric symptoms in these patients. The N170 amplitudes were weaker in patients than in controls for inverted images of both faces and non-faces (tables), with a left-hemisphere dominance. The face inversion effect (FIE), meaning the difference in N170 amplitude between upright and inverted faces, was absent in patients with schizophrenia, suggesting an abnormality of holistic face processing. Together, these results revealed a marked symptom-relevant neural delay associated with face-specific processing in patients with schizophrenia, providing additional evidence to support the demyelination hypothesis of schizophrenia.

PM539. Evaluation of plasma and cerebrospinal fluid G72 protein levels and their correlations with psychiatric symptoms in schizophrenia and major depression

PM539. Evaluation of plasma and cerebrospinal fluid G72 protein levels and their correlations with psychiatric symptoms in schizophrenia and major depression

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network.

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile.

A commentary on "Antipsychotic-induced Parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders".

A commentary on "Antipsychotic-induced Parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders".

統合失調症における探索眼球運動異常と精神症状との関係

統合失調症における探索眼球運動異常と精神症状との関係

P.3.d.068 Varenicline effects on smoking, cognition and psychiatric symptoms in schizophrenia

We report an incident of delayed onset of true vocal fold paralysis with continuous interscalene brachial plexus block. A 51 year old woman underwent left shoulder manipulation and lysis of adhesions with fluoroscopy and general anesthesia. An interscalene brachial plexus block was performed and a catheter with a continuous infusion pump was placed for postoperative pain control. Following hospital discharge, approximately 8 hours after the initial catheter bolus the patient developed hoarseness, dysphagia, and dyspnea, secondary to left vocal fold palsy. The patient was admitted for observation and the catheter was discontinued with no intubation required. By the next morning, the patient’s dysphagia and dyspnea had resolved and her hoarseness improved.