Improvement In Negative Symptoms Research Articles

Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations.

Objective: Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology.Method: Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1–2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers.Results: Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5–17.5, all p < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7–21.0, all p < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, p < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (r ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers (r ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (r = 0.5, p < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (r = 0.5, p < 0.010).Conclusion: The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness.

The Role of Cytokines in Predicting the Efficacy of Acute Stage Treatment in Patients with Schizophrenia.

PurposeInflammatory response in schizophrenia (SCz) is related to its underlying pathological mechanism and might be significant in deciding a patient’s prognosis. The current study aims to investigate the differences in the serum inflammation level between schizophrenic patients and healthy controls and identify inflammatory markers that can predict clinical therapeutic effects in early-stage SCz patients at the 6-month follow-up.Patients and MethodsIn total, 71 subjects were recruited in this study, including 35 patients with Scz and 36 healthy controls. The 35 Scz patients, who were in the first-episode or acute relapse state at admission, had completed the 6-month follow-up. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) assessment results, demographic details, and blood samples were collected at the baseline and at follow-up. Data were analyzed using the Spearman correlation and multiple linear regression.ResultsSerum interleukin (IL-1β, IL-4, IL-6, and IL-8) levels were significantly elevated in SCz patients at baseline compared with healthy controls, with a reduced IL-8 level at the follow-up. Furthermore, a higher IL-6 level and lower IL-8 level was found to predict better improvement in negative symptoms. The higher IL-6 level also predicted lesser improvement in depressive symptoms. Finally, a higher interferon (IFN)-γ level predicted a lower therapeutic effect for excitatory symptoms.ConclusionThe serum levels of inflammatory markers were higher in patients with SCz than in healthy controls. These markers can be considered accurate predictors of therapeutic effects in patients with SCz.

Protective Effects of Two Halophilic Crude Extracts from Pseudomonas zhaodongensis and Bacillus stratosphericus against Memory Deficits and Anxiety- and Depression-Like Behaviors in Methionine-Induced Schizophrenia in Mice Focusing on Oxidative Stress Status.

Recently, the implication of oxidative stress in behavioral-like disorders has received a lot of attention. Many studies were interested in searching for new natural compounds with protective effects on behavioral-like disorders by focusing on oxidative stress as the main causal factor. Here, we assess the potential effect of cell-free extracts from halophilic bacteria on memory, anxiety, and depression-related behaviors in mice, as well as on cognitive deficits, negative symptoms, and some oxidative stress biomarkers in methionine-induced mice models of schizophrenia. Firstly, crude extracts of bacteria isolated from the Dead Sea were screened for their effects on memory and anxiety- and depression-like behaviors through Y-maze, elevated plus maze, and forced swimming test, respectively, using two doses 60 mg/kg and 120 mg/kg. Then, 120 mg/kg of two bacterial crude extracts, from two strains designated SL22 and BM20 and identified as Bacillus stratosphericus and Pseudomonas zhaodongensis, respectively, with significant contents of phenolic and flavonoid-like compounds, were selected for the assessment of cognitive and negative symptom improvement, as well as for their effects on oxidative stress status in methionine-induced mice models of schizophrenia using six groups (controls, methionine, crude extracts solely, and combinations of crude extracts and methionine). Results showed that the administration of the crude extracts caused a significant increase in the spontaneous alternations in the Y-maze task, the time spent in open arms of the elevated plus maze, and a decrease in immobility time in the forced swimming test in comparison with the control group. Furthermore, the administration of bacterial extracts seemed to diminish disorders related to cognitive and negative symptoms of schizophrenia and to improve the oxidative state in the temporal lobes, in comparison with the methionine group. Our findings suggest substantial antioxidant and anti-neuropsychiatric effects of the crude extracts prepared from Pseudomonas zhaodongensis strain BM20 and Bacillus stratosphericus strain SL22 and that further studies are needed to purify and to determine the active fraction from the extracts.

Role of Executive Function in Response to a Problem Solving Based Psychoeducational Intervention in Adolescents with Psychosis: The PIENSA Trial Revisited.

An improvement in negative symptoms and a reduction in the number of visits to the emergency department have been reported in a problem solving based psychoeducational group intervention (PE) for adolescents with psychosis relative to a nonstructured group (NS). One of the factors that may play a role on the response to PE treatment is executive function (EF), a crucial cognitive domain for problem-solving performance. We aimed to examine the role of EF in response to PE treatment versus an NS group. We examined the associations between changes in cognition and in clinical/functional variables within each treatment group using Spearman-ranked and partial correlation analyses. A total of 22 individuals (mean age: 16.3) were randomized to PE (N = 10) and NS (N = 12). We found an association between improvements in EF performance and a reduction in positive symptoms (rs = –0.756, p = 0.030 for semantic fluency), reduction in negative symptoms (r = 0.758, p = 0.029 for semantic; rs = –0,733, p = 0.025 for verbal fluency), and reduction in the number of visits to the emergency department (r = –0,743, p = 0.035 for semantic fluency) in the PE group. No associations were found in the NS group. Our results suggest that EF may play a role in the specific improvements observed in the PE group. This may have implications in the development of new areas of clinical intervention focusing on the role of cognitive functioning in response to psychosocial treatments in psychosis.

Deep Transcranial Magnetic Stimulation for the Treatment of Negative Symptoms in Schizophrenia: Beyond an Antidepressant Effect.

Negative symptoms of schizophrenia show limited response to both typical and atypical antipsychotics. Repetitive transcranial magnetic stimulation applied over the prefrontal cortex (PFC) has been proposed as an adjuvant to pharmacological treatment of negative symptoms in schizophrenia, but whether the improvements obtained are specific to negative symptoms or attributable to antidepressant effects is still unclear. The aim of the present study is to determine to which extent the improvements in negative symptoms of schizophrenia obtained after high-frequency stimulation of the bilateral PFC using deep TMS (dTMS) are attributable to antidepressant effects. Repetitive dTMS was administered to the PFC in a cohort of 16 patients with schizophrenia under successful pharmacological control of positive symptoms and predominant negative symptoms. Patients were treated using high-frequency (18 Hz) bilateral stimulation applied over the lateral PFC bilaterally using Brainsway H-2 coil. The effects of dTMS on negative symptoms were measured using the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scales. We then compared the improvements in negative symptoms obtained in patients showing depressive symptoms (≥7 points) with those found in patients without depression (>7 points), as determined by the Calgary Scale for Depression. Repetitive dTMS treatment induced significant improvements in negative symptoms as assessed using both Scale for the Assessment of Negative Symptoms and Positive and Negative Syndrome Scales. Comparison of the improvements obtained in patients with or without depression at the beginning of treatment revealed similar improvements in negative symptoms, irrespective of subjacent depression. Our data suggest that the beneficial effects of high frequency dTMS of the PFC cannot be attributed solely to its antidepressant effects.

Distinct striatum pathways connected to salience network predict symptoms improvement and resilient functioning in schizophrenia following risperidone monotherapy

Abnormal interactions between the striatum and salience network (SN) are considered as etiological and treatment-sensitive marker in schizophrenia. However, whether alterations in the intrinsic dynamics as reflected by resting-state functional connectivity (RSFC) between the striatum and salience network may predict treatment response to the widely used antipsychotic treatment strategies (risperidone, monotherapy) has not been examined systematically. To this end, treatment-naive first-episode schizophrenia patients (n = 41) underwent task-free resting-state fMRI assessment before (baseline) and after 8 weeks of risperidone monotherapy (n = 38). Intrinsic connectivity between striatal sub-regions and core salience processing nodes were examined and compared to carefully matched healthy controls (HC) to determine disorder-specific and treatment-predictive neural markers. Findings demonstrate hypo-connectivity of both ventral and dorsal striatal-SN pathways in patients at baseline. Importantly, specifically the dorsal striatal pathway at baseline could predict negative symptoms improvement in patients; while ventral striatal pathways could predict positive symptoms improvement. Together, results indicate that distinct striatal-SN pathways represent specific treatment-success markers for the effects of risperidone, suggesting that alterations in dorsal versus ventral striatal network markers may represent brain-based markers for specific symptomatologic improvements following risperidone mono-therapy.

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study.

The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate-left primary motor cortex/right dorsal rostral putamen-anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen-anterior cingulate cortex functional connectivity predicted improvement in general functioning. These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.

Predictors of study drop-out and service disengagement in patients at clinical high risk for psychosis.

Study drop-out during follow-up and service disengagement frequently occur in patients at clinical high risk for psychosis (CHR-P). However, little is known about their predictors. Therefore, we aimed to analyze the rate and reasons for drop-out and service disengagement in CHR-P patients and investigate their sociodemographic and clinical predictors. Data from 200 patients of the prospective Früherkennung von Psychosen (FePsy) study were analyzed with competing risks survival models, considering drop-out and transition to psychosis as competing events. To investigate whether symptoms changed immediately before drop-out, t tests were applied. Thirty-six percent of patients dropped out within 5years. Almost all drop-outs also disengaged from our service. Hence, study drop-out was used as a proxy for service disengagement. Patients with more severe baseline disorganized symptoms and a late inclusion into the study were significantly more likely to disengage. Immediately before disengagement, there was significant improvement in negative symptoms only. A considerable proportion of CHR-P patients disengaged from our clinical study and service. Patients who were included during a later study period with more assessments disengaged more often, which might have been due to more frequent invitations to follow-up assessments and thereby increasing participation burden. Hence, our study provides a cautionary note on high-frequency follow-up assessments. Larger-scale studies evaluating predictors on multiple domains would help to further elucidate drop-out and disengagement.

A functional HTR1A polymorphism, rs6295, predicts short-term response to lurasidone: confirmation with meta-analysis of other antipsychotic drugs.

Stimulation of the serotonin (5-HT)1A receptor (HTR1A) has been shown to contribute to the mechanism of action of some atypical antipsychotic drugs (APDs), including clozapine and lurasidone. A meta-analysis of rs6295, a functional polymorphism located at the promoter region of HTR1A, showed association with clinical response in schizophrenic patients treated with atypical APD. We have now tested whether other SNPs related to rs6295 predict response to lurasidone. We first evaluated whether rs358532 and rs6449693, tag SNPs for rs6295, predicted response to lurasidone, using data from two clinical trials of acutely psychotic schizophrenia patients with European (EUR, n = 171) or African (AFR, n = 131) ancestry; we then determined if those findings could be replicated in a third trial of lurasidone of similar design. Weekly changes (up to 6 weeks) in the Positive and Negative Syndrome Scale (PANSS) Total score and its five subscales were used to assess response. In EUR, a significant association, or trends for association, were observed for PANSS Total (p = 0.035), positive (p = 0.039), negative (p = 0.004), and disorganization (p = 0.0087) subscales, at week 1-6. There was a trend for replication with PANNS Total (p = 0.036) in the third trial. No significant association was observed in AFR or the placebo group. Meta-analysis of five studies, including the three with lurasidone, showed that rs6295 was associated with improvement in positive (p = 0.023) and negative (p ≤ 0.0001) symptoms in EUR patients with schizophrenia. This is the first study to show a significant association between functional HTR1A polymorphisms and treatment response to lurasidone. The meta-analysis provides additional evidence that rs6295 could be a race-dependent biomarker for predicting treatment response to APDs in schizophrenic patients with European Ancestry.

Reduced connectivity in anterior cingulate cortex as an early predictor for treatment response in drug-naive, first-episode schizophrenia: A global-brain functional connectivity analysis

BackgroundAntipsychotic medications may have acute effect on brain functional connectivity (FC) after only a few days of treatment. It is unclear if early changes in FC can predict treatment response in patients with schizophrenia. MethodsThe study included 32 patients with drug-naive, first-episode schizophrenia and 32 healthy controls. Resting-state functional magnetic resonance imaging was obtained from the patients at two time-points (pre-treatment baseline and 1 week after treatment) and healthy controls at baseline. Patients were treated with olanzapine for 8 weeks, and clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at three time points (baseline, 1 week and 8 weeks after treatment). Imaging data were analyzed using global-brain FC (GFC) and support vector regression (SVR). ResultsAt baseline, an increased GFC was observed in bilateral anterior cingulate cortex (ACC) in patients compared with healthy controls. After 1 week of olanzapine treatment, patients showed decreased GFC in bilateral ACC compared to the baseline values. SVR analysis suggested a positive relationship between GFC changes in bilateral ACC at week 1 and improvement in negative symptoms at week 8 (r = 0.957, p < 0.001). ConclusionAn early decrease in GFC in bilateral ACC may serve as a predictor for treatment response in patients with schizophrenia. If further confirmed, our finding may be able to help clinicians decide, during the early treatment course, whether the patient should stay on the chosen antipsychotic medication or switch to a different one.

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

Fostering coping as a mechanism of symptom change in cognitive behavioural therapy for psychosis

IntroductionCognitive behavioural therapy for psychosis (CBTp) has been repeatedly shown to ameliorate psychotic symptoms. However, so far we have little understanding of the mechanisms of change in CBTp. In this study, we tested whether improved cognitive and behavioural efforts to manage taxing external or internal demands (=coping) constitute a mechanism of change in CBTp. MethodsUsing data from a published trial for a secondary analysis, we tested whether the continuous symptomatic improvement of patients (n = 57) who received up to 45 sessions of CBTp and completed weekly self-assessments of symptoms (suspiciousness, individualised positive and negative symptoms, and individualised symptoms of depression) was mediated by preceding improvement in self-assessed coping using multilevel analysis. A reverse model in which symptom improvement predicted improved coping was also tested. ResultsContinuous improvement in suspiciousness, negative symptoms, and depression over the course of CBTp was preceded by improvement in coping. Improvement in suspiciousness or positive symptoms did not predict subsequent improvement in coping, whereas improvement in negative symptoms and depression predicted subsequent improvement in coping. ConclusionCoping constitutes a mechanism of change, albeit to a different extent for different symptom clusters. Further research needs to explore how best to utilise this mechanism and optimise its integration with other active ingredients of CBTp to maximise therapeutic gain.

Predicting Symptomatic and Functional Improvements over 1 Year in Patients with First-Episode Psychosis Using Resting-State Electroencephalography

ObjectiveAlthough early intervention from the beginning of a psychotic episode is essential for a better prognosis, biomarkers predictive of symptomatic and functional improvement in early psychotic disorders are lacking. This study aimed to investigate whether the spectral power of resting-state electroencephalography (EEG) can be used as a predictive marker of the 1-year prognosis in patients with first-episode psychosis (FEP). MethodsTwenty-four patients with FEP and matched healthy control (HC) subjects were examined with resting-state EEG at baseline. The symptomatic severity and functional status of FEP patients were assessed at baseline and reassessed after 1 year of usual treatment. Repeated measures analysis of variance was conducted to compare EEG spectral powers across the groups. Multiple regression analysis revealed EEG spectral powers predictive of symptomatic and functional improvement in FEP patients at the 1-year follow-up. ResultsDelta band power in the frontal and posterior regions was significantly higher in patients with FEP than in HCs. Higher delta band power in the posterior region predicted later improvement of positive symptoms and general functional status. Lower delta band power in the frontal region predicted improvement of negative symptoms and general functioning after 1 year. ConclusionThese results suggest that increased delta absolute power is observed from the beginning of psychotic disorders. Furthermore, decreased delta power in the frontal region and increased delta power in the posterior region might be used as a predictive marker of a better prognosis of FEP, which would aid early intervention in clinical practice.

Effect of Adjunctive Estradiol on Schizophrenia Among Women of Childbearing Age

Several lines of evidence suggest that estradiol influences the course of schizophrenia, and a previous randomized controlled trial demonstrated that transdermal estradiol improved symptoms in female patients of childbearing age. However, many initial positive findings in schizophrenia research are not later replicated. To independently replicate the results of the effect of estradiol on schizophrenia in women of childbearing age. An 8-week randomized, placebo-controlled trial performed in the Republic of Moldova between December 4, 2015, and July 29, 2016, among 200 premenopausal women aged 19 to 46 years with schizophrenia or schizoaffective disorder as defined by the DSM-5. Patients were randomized to receive a 200-μg estradiol patch or placebo patch changed twice a week added to their antipsychotic treatment. The primary outcome was the positive subscale of the Positive and Negative Syndrome Scale (PANSS; lower scores indicated fewer symptoms and higher scores indicated more symptoms), analyzed with mixed models for repeated measures on an intention-to-treat basis. A total of 100 women (median age, 38 years; interquartile range, 34-42 years) were randomized to receive an estradiol patch and 100 women (median age, 38 years; interquartile range, 31-41 years) were randomized to receive a placebo patch; the median age at baseline for the entire group of 200 women was 38.0 years (range, 19.5-46.0 years). At baseline, the mean positive PANSS score was 19.6 for both groups combined; at week 8, the mean positive PANSS score was 14.4 in the placebo group and 13.4 in the estradiol group. Compared with placebo, participants receiving add-on estradiol patches had statistically significant improvements in the primary outcome measure, PANSS positive subscale points (-0.94; 95% CI, -1.64 to -0.24; P = .008; effect size = 0.38). Post hoc heterogeneity analyses found that this effect occurred almost entirely in 100 participants older than 38.0 years (46 in placebo group vs 54 in estradiol group; difference, -1.98 points on the PANSS positive subscale; 95% CI, -2.94 to -1.02; P < .001). Younger participants did not benefit from estradiol (difference, 0.08 points on the PANSS positive subscale; 95% CI, -0.91 to 1.07; P = .87). Breast tenderness was more common in the estradiol group (n = 15) than in the placebo group (n = 1) as was weight gain (14 in estradiol group vs 1 in placebo group). The results independently replicate the finding that transdermal estradiol is an effective add-on treatment for women of childbearing age with schizophrenia and extend it, finding improvements in negative symptoms and finding that the effect could be specific to those older than 38 years. The results should be viewed in the context of the differences in the natural course of schizophrenia between females and males. ClinicalTrials.gov identifier: NCT03848234.

PRELIMINARY STUDY ON THE EFFECT OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION ON NEGATIVE SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA

Back Ground: Negative symptoms of schizophrenia have been demonstrated to be the most relevant predictor of increased future socio-occupational dysfunction and poorer quality of life which is linked to impaired functioning of the prefrontal cortex, mainly reduced activation of the dorsolateral prefrontal cortex. Repetitive Trans-cranial Magnetic Stimulation (rTMS) is a relatively safe and non-invasive tool to modulate neuronal activity. High-frequency rTMS might have role in improvement of negative symptoms of schizophrenia. Aim of work: The Aim of this study to explore the effects of highfrequency rTMS stimulation to the DLPFC on negative symptoms observed in schizophrenia patients. Patients and Methods: 40 patients with schizophrenia who accept and there guardians to participate in the study and sign the written informed consent were assessed by Positive and Negative Syndrome Scale for Schizophrenia (PANSS), before the rTMS sessions and after the sessions. Meanwhile the operator allocated the subjects to active or sham group then the subjects of the study received active or Sham rTMS . The rTMS was delivered for 3 sessions /week during six weeks, each session lasts for 13 minutes. Results: There was a statistical significance between active and sham group as regard PANSS Negative subdomain scale, used before and after the rTMS sessions (P value= 0.001 ) Also there was a statistical significant difference among active group before and after the rTMS stimulation( P value<0.001). Conclusion: This study suggests that high frequency rTMS applied to DLPFC may be of benefit in alleviating negative symptoms in schizophrenic patients. A larger sample size is needed to confirm our findings.

Gray matter volume changes following antipsychotic therapy in first-episode schizophrenia patients: A longitudinal voxel-based morphometric study

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients.

Animal-assisted therapy for schizophrenia and related disorders: A systematic review

Animal-assisted therapy (AAT) is increasingly researched as a potential treatment for physical and mental illness, including schizophrenia. The aim of the current paper is to systematically review randomised controlled trials (RCTs) to assess the effectiveness of AAT for schizophrenia and related disorders. We searched PubMed, PsycINFO, CINAHL, EMBASE, The Cochrane Library, CAB Abstracts, and Web of Science for RCTs of AAT for schizophrenia and related disorders. Primary outcomes were mental state and behaviour, clinical global response, and quality of life and wellbeing. Studies were eligible if they were RCTs that had compared AAT, or other animal-assisted intervention, to any control group using any participants with a clinical diagnosis of schizophrenia (or related disorder), regardless of age, gender, setting, or severity and duration of illness. Seven studies were identified for the review. Meta-analysis was not possible due to heterogeneity of studies, including marked differences in outcome measures and interventions. Five out of seven studies included symptoms as an outcome measure, with one reporting improvements in negative symptoms and one study reporting improvements in positive and emotional symptoms. The remaining studies reported no significant effects of AAT. Three studies included quality of life as an outcome measure but did not find any significant effects. Two studies did, however, report improvements in various measures of self-view. The use of AAT for schizophrenia remains inconclusive and there is currently not enough evidence to draw any firm conclusions due to heterogeneity of studies, risk of bias, and small samples. Rigorous, large-scale RCTs are needed to assess the true impact of AAT on schizophrenia.

Mscs-derived evs as potential treatment in a phencyclidine model of schizophrenia

Background & Aim Schizophrenia is a debilitating mental disorder, a major contributor to the global health burden of disease. Although antipsychotic medication is very effective against the positive symptoms of the disease, such as hallucinations, such an effective treatment for the negative symptoms is not available. Phencyclidine (PCP) has been validated in rodents as a model for schizophrenia, shown to reliably induce both positive and negative symptoms in a multitude of behavioral tests. It was previously shown in our lab that behavioral phenotypes of PCP-treated mice can be alleviated after intracranial transplantation of mesenchymal stem cells (MSC). Methods, Results & Conclusion In this study, we assessed the feasibility of intranasal delivery of MSCs-derived EVs to improve the positive and negative symptoms in a PCP model of schizophrenia. Our results show that mice treated with MSCs-EVs are beneficial for preventing both positive and negative symptoms in a PCP-model of schizophrenia. While PCP-treated mice showed a deficiency in social interaction and increased vulnerability to amphetamine, mice co-administered with PCP and MSCs-EVs behaved similarly to the sham group, treated with saline. Immunohistochemical studies demonstrated that the EVs prevented loss of Paravalbumin-expressing GABAergic neurons in the PFC of treated mice, where EVs were most congregated. We believe MSCs-derived EVs may be an invaluable treatment for schizophrenia. With the convenient intranasal administration and ability to arrive at the site of damage in the diseased brain, they may offer an unprecedented improvement in negative symptoms.

Repetitive transcranial magnetic stimulation as an adjunctive treatment for negative symptoms and cognitive impairment in patients with schizophrenia: a randomized, double-blind, sham-controlled trial.

Purpose: Effective treatment options for negative symptoms and cognitive impairment in patients with schizophrenia are still to be developed. The present study was to examine potential benefits of repetitive transcranial magnetic stimulation (rTMS) to improve negative symptoms and cognition in this patient population.Methods: The study was a 4-week, randomized, double-blind sham-controlled trial. Patients with schizophrenia were treated with adjunctive 20-Hz rTMS for 4 weeks or sham condition to the left dorsolateral prefrontal cortex (DLPFC). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative symptom scale (PANSS) negative subscale at baseline and week 4. Cognitive function was measured using the MATRICS Consensus Cognitive Battery (MCCB) at the same two time points. In addition, possible moderators for rTMS treatment efficacy were explored.Results: Sixty patients (33 in the treatment group, 27 in the sham group) completed the study. There was a significant decrease in negative symptoms after 4-week rTMS treatment as measured by the SANS total score and the PANSS negative symptom subscale score. However, there was no significant improvement in cognition with rTMS treatment. Stepwise multiple linear regression analysis suggested that the baseline severity of positive symptoms may predict poorer improvement in negative symptoms at week 4.Conclusion: Twenty-Hz rTMS stimulation over left DLPFC as an adjunctive treatment might be beneficial in improving negative symptoms of schizophrenia. Future studies with a longer treatment duration and a larger sample size are needed.Clinical trial ID: NCT01940939.

Positive affect treatment for depression and anxiety: A randomized clinical trial for a core feature of anhedonia.

Loss of pleasure or interest in activities (i.e., anhedonia) is a risk factor for suicidality, treatment nonresponse, and relapse. Extant treatments that focus on reducing negative affect have limited effects upon positive affect (a core feature of anhedonia). We investigated whether a novel intervention aimed at increasing reward sensitivity was more efficacious for positive affect than a cognitive-behavior treatment aimed at reducing threat sensitivity, in individuals with clinically severe symptoms of depression or anxiety, and functional impairment. The Treatment for Affective Dimensions trial was offered in a 2-site randomized study at outpatient treatment centers in Los Angeles and Dallas. Ninety-six patients were randomized to 15 weekly, individual sessions of Positive Affect Treatment (PAT) or Negative Affect Treatment (NAT). The primary outcome was improvement in positive affect (Positive and Negative Affect Schedule-Positive) from pretreatment to 6-month follow-up (6MFU). Secondary outcomes were improvements in negative affect (Positive and Negative Affect Schedule-Negative), suicidal ideation, and symptoms (Depression Anxiety Stress Scales). PAT resulted in greater improvements in positive affect, p = .009, d = .52, and higher positive affect at 6MFU, p = .002, d = .67, than NAT. Participants in PAT also reported lower negative affect, p = .033, d = .52, and lower symptoms of depression, p = .035, d = .34, anxiety, p < .018, d = .30, and stress, p = .006, d = .43 at 6MFU. Finally, probability of suicidal ideation at 6MFU was lower in PAT than NAT (1.7% vs. 12.0%), p < .001. Compared to NAT, PAT demonstrated better outcomes (at 6MFU) on positive affect, depression, anxiety, stress, and suicidal ideation, for patients with symptomatic pretreatment levels of these outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).