Improvement In Negative Symptoms Research Articles

Gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia.

This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES). 82 patients with FES, including 50 male patients and 32 female patients, were enrolled in the present study. Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were respectively conducted to evaluate the clinical symptoms and cognitive function of patients with FES at baseline and after treatment. Repeated measure ANOVA was performed to compare gender differences in cognitive domains scores between baseline and 2-month follow-up. Stepwise liner regression model was performed to explore the effect factors of cognitive improvements in patients. There was no significant difference in age of onset, education years, PANSS scores, duration of untreated psychosis and Olanzapine equivalent doses between male and female patients (all p > 0.05). In the comparisons of cognition function, male patients exhibited better performance in social cognition compared with female patients at baseline (t = 3.20, p < 0.05). After treatment, improvements of attention/vigilance and working memory were both found in male patients and female patients (attention/vigilance, F = 11.867, p < 0.05; working memory, F = 18.265, p < 0.05). In addition, improvement of speed of information processing was only found in female patients (F = 11.65, p < 0.01). Significant interaction between time and gender was found in speed information of processing (F = 4.140, p = 0.045). Stepwise liner regression model revealed that improvements of negative symptoms promote improvements of cognitive function in female patients (all p < 0.05). Our findings revealed gender differences of cognitive improvements in patients with FES after 2-month treatment. It provides new evidence for gender differences in cognitive symptoms of schizophrenia, and also provides preliminary clues for further individualized cognitive intervention strategies.

Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.

It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients. The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12. Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC. Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial

ObjectiveNegative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). MethodThis is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. ResultsTwo distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. ConclusionsThe 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

The trace amine-associated receptor 1 agonists - non-dopaminergic antipsychotics or covert modulators of D2 receptors?

A major effort of the pharmaceutical industry has been to identify and market drug treatments that are effective in ameliorating the symptoms of psychotic illness but without the limitations of the current treatments acting at dopamine D2 receptors. These limitations include the induction of a range of adverse effects, the inadequate treatment response of a substantial proportion of people with schizophrenia, and the generally poor response to negative and cognitive features of the disease. Recently introduced drug treatments have gone some way to avoiding the first of these, with a reduced propensity for weight gain, cardiovascular risk and extrapyramidal motor effects. Despite claims of some small improvements in negative symptoms, these drugs have not demonstrated substantial increases in efficacy. Of the drugs currently in development as antipsychotic agents, several are misleadingly described as having novel 'non-dopaminergic' mechanisms that may offer improvements in addressing the limitations of adverse effects and efficacy. It will be argued, using the trace amine-associated receptor 1 agonist as an example, that several of these new drugs still act primarily through modulation of dopaminergic neurotransmission and, in not addressing the primary pathology of schizophrenia, are therefore unlikely to have the much-needed improvements in efficacy required to address the unmet need associated with resistance to current treatments.

Interaction between baseline BMI and baseline disease severity predicts greater improvement in negative symptoms in first-episode schizophrenia.

Several studies have reported that baseline symptom severity in patients with schizophrenia (SCZ) is associated with the efficacy of antipsychotic medication. Overweight/obesity is common in SCZ and has also been reported to be correlated with therapeutic response to antipsychotics. This study aimed to evaluate whether baseline body mass index (BMI) and disease severity were associated with improvements in negative symptoms in patients with first-episode and medication-naïve (FEMN) SCZ. A total of 241 FEMN patients were recruited in this study and treated with oral risperidone over 3months. Clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) and BMI was assessed at baseline and 3-month follow-up. We found that baseline BMI was correlated with the baseline severity of symptoms. Baseline BMI or baseline disease severity was associated with improvement in negative symptoms after 3months of treatment. Linear regression analysis indicated that the interaction of BMI and disease severity at baseline was associated with improvement in negative symptoms in the early stage of SCZ after controlling for sex, age, and dose of risperidone. Our study suggests that the interaction of baseline BMI and disease severity may play a role in predicting negative symptom improvement after 3months of risperidone treatment.

Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia

Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.

New Therapeutic Targets and Drugs for Schizophrenia Beyond Dopamine D2 Receptor Antagonists.

Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.

Attachment styles and associated psychosocial factors in patients at ultra-high risk for psychosis: A systematic review.

Patients with an ultra-high risk of psychosis (UHR) are more likely to transition to psychosis. Attachment style has also been associated with psychosis and other symptoms. To review attachment styles in UHR patients and to analyze related psychosocial factors. Ours is the first systematic review of attachment in this population. We performed a systematic review of attachment and related psychosocial factors in UHR patients following the PRISMA methodology. We identified five studies. The results revealed high rates of insecure attachment in this population (more than 80%). The UHR sample presented high levels of depression, anxiety, social anxiety, emotional reactivity, trauma, and poor mentalization. Premorbid social adjustment was a predictor of improvement in disorganization and negative symptoms. The rate of transition to psychosis was 10%. Attachment patterns accounted for 16.8% of the variance. This vulnerability for psychosis was also associated with poor mentalization. Early detection of patients with UHR and insecure attachment is crucial, since early intervention to address symptoms, mentalization, and attachment is feasible and may lead to an improvement in the remaining associated psychosocial related factors (secure style: better global functioning and less affective and anxious symptoms). PROSPERO ID440957.

Effects of right prefrontal theta-burst transcranial magnetic stimulation or transcranial direct current stimulation on apathy in patients with schizophrenia: A multicenter RCT

Apathy is a core negative symptom associated with an unfavorable functional outcome. Noninvasive brain stimulation has shown promise in the treatment of schizophrenia but has not been tested specifically for apathy.We conducted a randomized controlled trial of intermittent theta-burst (iTBS) transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) targeted at the right dorsolateral prefrontal cortex (DLPFC) in patients diagnosed with a psychotic disorder suffering from apathy. The study was a multicenter, randomized, placebo-controlled, and rater-blinded trial. Patients (N = 88) were randomized into active iTBS, active tDCS, sham iTBS or sham tDCS treatment, daily for two weeks (excluding weekends). Effects were measured post-treatment and at four week and ten week follow-up. Primary outcome was apathy severity (Apathy Evaluation Scale, clinician-rated). Additional measures included assessment of negative symptoms, depression, anhedonia and quality of life.No significant difference in improvement of apathy or negative symptoms was observed for real versus sham treatment with either iTBS or tDCS, though all groups improved to a small extent. We conclude that two weeks of brain stimulation over the right DLPFC with either iTBS or tDCS is not effective for improving apathy or negative symptoms. Longer and more intensive protocols may yield different results.

OXTR polymorphisms associated with severity and treatment responses of schizophrenia

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = −0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

Activation of Metabotropic Glutamate Receptor 3 Modulates Thalamo-accumbal Transmission and Rescues Schizophrenia-like Physiological and Behavioral Deficits

BackgroundPolymorphisms in the gene encoding for metabotropic glutamate receptor 3 (mGlu3) are associated with an increased likelihood of schizophrenia diagnosis and can predict improvements in negative symptoms following treatment with antipsychotics. However, the mechanisms by which mGlu3 can regulate brain circuits involved in schizophrenia pathophysiology are not clear. MethodsWe employed selective pharmacological tools and a variety of approaches including whole-cell patch-clamp electrophysiology, slice optogenetics, and fiber photometry to investigate the effects of mGlu3 activation on phencyclidine (PCP)-induced impairments in thalamo-accumbal transmission and sociability deficits. A chemogenetic approach was used to evaluate the role of thalamo-accumbal transmission in PCP-induced sociability deficits. ResultsWe first established that PCP treatment augmented excitatory transmission onto dopamine D1 receptor–expressing medium spiny neurons (D1-MSNs) in the nucleus accumbens (NAc) and induced sociability deficits. Our studies revealed a selective increase in glutamatergic synaptic transmission from thalamic afferents to D1-MSNs in the NAc shell. Chemogenetic silencing of thalamo-accumbal inputs rescued PCP-induced sociability deficits. Pharmacological activation of mGlu3 normalized PCP-induced impairments in thalamo-accumbal transmission and sociability deficits. Mechanistic studies revealed that mGlu3 activation induced robust long-term depression at synapses from the thalamic projections onto D1-MSNs in the NAc shell. ConclusionsThese data demonstrate that activation of mGlu3 decreases thalamo-accumbal transmission and thereby rescues sociability deficits in mouse modeling schizophrenia-like symptoms. These findings provide novel insights into the NAc-specific mechanisms and suggest that agents modulating glutamatergic signaling in the NAc may provide a promising approach for treating negative symptoms in schizophrenia.

A miR-137–Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing

BackgroundmiR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing. MethodsUsing RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). ResultsIn 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. ConclusionsThe functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.

Baseline BMI is associated with clinical symptom improvements in first-episode schizophrenia: a longitudinal study.

Background: There is sufficient evidence of the high prevalence of obesity in schizophrenia (SZ) compared to the general population. Previous studies have reported that weight gain correlated with the response to antipsychotics in patients with SZ. Nonetheless, the relationship between body mass index (BMI) and therapeutic benefits remains unclear. This study was designed to investigate the association between baseline BMI and improvements in clinical symptoms after treatment with antipsychotics in first-episode and medication-naïve SZ (FEMNS). Methods: A total of 241 FEMNS patients were enrolled and received risperidone over 12weeks. The severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS) and BMI was measured at baseline and 12-week follow-up. Results: We found that risperidone treatment raised the body weight of FEMNS patients and baseline BMI was negatively correlated with the improvement in negative symptoms (r = -0.14, p = 0.03) after 12-week treatment. Linear regression analysis indicated that baseline BMI was an independent predictor of response to risperidone in the early stage of SZ. Conclusion: The current study suggests a close relationship between baseline BMI and improvement in negative symptoms in SZ.

High-definition transcranial direct current stimulation for treating cognitive and negative symptoms in chronic schizophrenia – A sham-controlled proof of concept study

Objectives: Cognitive and negative symptoms are core symptoms of schizophrenia affecting interpersonal and socio-occupational functioning. Impaired dorsolateral prefrontal cortex (DLPFC) function is implicated in negative and cognitive symptoms. Conventional transcranial direct current stimulation (tDCS) to DLPFC has attracted interest as an add-on treatment for these symptoms. High-definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. Studies suggest that an increased number of sessions may increase the effectiveness of stimulation. Hence, we aimed to evaluate the efficacy of 20 sessions of HD-tDCS over the left DLPFC in the improvement of cognitive and negative symptoms in chronic schizophrenia (&gt;2 years continuous illness). Material and Methods: Twenty patients with chronic schizophrenia with predominantly cognitive and negative symptoms were enrolled in this sham-controlled trial. Participants received 20 sessions of HD-tDCS at 2 mA for 20 min, that is, twice daily over 10 days. Montreal cognitive assessment and scale for assessment of negative symptoms were used to assess outcome variables. Assessments were carried out at baseline, 2 weeks, and 6 weeks, respectively. Results: Significant improvement was noted in both active and sham groups across all outcome variables over time. However, a statistically significant decrease in negative symptoms in the active group was noted, which was maintained at the end of 6 weeks, but there was no statistically significant improvement in cognitive symptoms between the active and sham groups at 6 weeks. The stimulation protocol was well tolerated. Conclusion: HD-tDCS has substantial potential in the treatment of negative symptoms; however, its role in cognitive symptoms needs further evaluation.

Sarcosine May Induce EGF Production or Inhibit the Decline in EGF Concentrations in Patients with Chronic Schizophrenia (Results of the PULSAR Study).

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine (n = 28) or placebo (n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

Optimizing antidepressant and clozapine co-prescription in clinical practice: A systematic review and expert recommendations.

To synthesize the information relevant for clinical practice on clozapine-antidepressant co-prescription concerning pharmacokinetic drug-drug interactions (DDI), adverse drug reactions (ADRs) associated with the co-prescription, antidepressant add-on for clozapine-resistant symptoms and antidepressant add-on for clozapine-induced ADRs. Articles were identified with MEDLINE, Web of Sciences and PsycINFO search from inception through April 2023. Data were synthesized narratively. ADRs are most often induced by the co-prescription of antidepressants that inhibit CYP enzymes (fluvoxamine, fluoxetine, paroxetine). Fluvoxamine add-on is hazardous because of its potent inhibition of clozapine metabolism and has few indications (lowering daily number of clozapine tablets, reducing norclozapine-induced metabolic disturbances and other dose-dependent clozapine-induced ADRs). ADR frequency may be reduced by therapeutic drug monitoring and knowledge of other factors impacting clozapine metabolism (pneumonia, inflammation, smoking, etc.). Improvement of negative symptoms is the most documented beneficial effect of antidepressant add-on for clozapine-resistant psychotic symptoms. The add-on antidepressant should be chosen according to its safety profile regarding DDI with clozapine: antidepressants inhibiting clozapine metabolism or increasing the anticholinergic load should be avoided. Other indications of antidepressant add-on (affective or obsessive compulsive symptoms, sialorrhea, and enuresis) are poorly documented. Antidepressant add-on to clozapine is associated with potential benefits in clozapine users as this strategy may contribute to reduce the burden of clozapine-resistant symptoms or of clozapine-induced ADRs. Further studies are needed to determine whether antidepressant add-on can reduce the risk of clozapine discontinuation.

Significant improvement of psychotic symptoms in treatment-resistant schizophrenia with clozapine in an adolescent with SHINE syndrome: a case report

This report highlights a rare single-gene cause of early-onset, treatment-resistant schizophrenia, and its unique responsiveness to clozapine therapy. This case describes a pediatric female who was diagnosed with early-onset schizophrenia and catatonia in her early adolescence, and was later found to have DLG4-related synaptopathy, also known as SHINE syndrome. SHINE syndrome is a rare neurodevelopmental disorder caused by dysfunction of the postsynaptic density protein-95 (PSD-95), encoded by the DLG4 gene. After failing three antipsychotic drug treatments, the patient was started on clozapine, which resulted in significant improvements in positive and negative symptoms. This case illustrates the impact of clozapine in treatment-resistant early-onset psychosis and exemplifies practical implications for genetic testing in early-onset schizophrenia.

Predictors of cognitive changes in patients with schizophrenia undergoing electroconvulsive therapy.

Previous studies on the effects of electroconvulsive therapy (ECT) on cognition in schizophrenia have been inconclusive. This study aimed to identify factors that may predict cognitive improvement or deterioration in patients with schizophrenia after-ECT. Patients with schizophrenia or schizoaffective disorder with predominantly positive psychotic symptoms, who were treated with ECT at the Institute of Mental Health (IMH), Singapore, between January 2016 and January 2018, were assessed. Montreal Cognitive Assessment (MoCA), Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Function (GAF) were performed before and after ECT. Patients with clinically significant improvement, deterioration or no change in MoCA scores were compared on demographics, concurrent clinical treatment and ECT parameters. Of the 125 patients analysed, 57 (45.6%), 36 (28.8%) and 32 (25.6%) showed improvements, deterioration and no change in cognition respectively. Age and voluntary admission predicted MoCA deterioration. Lower pre-ECT MoCA and female sex predicted MoCA improvement. Patients showed improvements in GAF, BPRS and BPRS subscale scores on average, except for the MoCA deterioration group, who did not show statistically significant improvement in negative symptom scores. Sensitivity analysis showed that nearly half the patients (48.3%) who were initially unable to complete MoCA pre-ECT were able to complete MoCA post-ECT. The majority of patients with schizophrenia demonstrate improved cognition with ECT. Patients with poor cognition pre-ECT are more likely to see improvement post-ECT. Advanced age may be a risk factor for cognitive deterioration. Finally, improvements in cognition may be associated with improvements in negative symptoms.

Effect of Music Therapy on The Improvement of Clinical Symptoms and Cognitive Functions of Schizophrenia Patients Receiving Risperidone Therapy

Background: Music therapy as a non-pharmacotherapy management has not been widely used. Data about effectiveness, ideal number of sessions and types/methods of music therapy have not been widely studied in Indonesia. Therefore, this study was designed to answer these problems so that music therapy can be applied appropriately. Objective : To determine the effect of music therapy on the improvement of clinical symptoms and cognitive function of schizophrenic patients that are receiving risperidone therapy. Methods : This study was an experimental study with comparative analysis. Sampling with consecutive sampling on the population of patients who were hospitalized in the Regional Special Hospital of South Sulawesi Province. The treatment group received risperidone therapy and music therapy (active and receptive) 6-8 sessions with a duration of 45 minutes/session, the control group only received risperidone 2-4 mg/day. The instruments used were the PANSS and the MoCA - Indonesian version, examined in the second and fourth weeks after music therapy. Results: There was a significant difference between the treatment group compared to the control group in decreasing the PANSS score for negative symptoms (p=0.000), general psychopathology (4th week p=0.011) and cognitive function (4th week p=0.000) especially on visuospatial components (p=0.001), attention (p=0.009) and abstraction (p=0.011). There was no significant difference between the treatment group compared to the control group in decreasing the PANSS score for positive symptoms (p=0.0.102) Conclusion: Music therapy can be a non-pharmacological therapy of choice to support the improvement of negative symptoms, cognitive function and general psychopathology in the stabilization phase of schizophrenic patients receiving risperidone.

Process-outcome relations in music therapy versus music listening for people with schizophrenia viewed through a mediational model: the role of the therapeutic alliance.

Examine whether change in clinical outcomes for patients with schizophrenia and negative symptoms randomized to either Music Therapy (MT) or Music Listening (ML) is associated to moderators and mediators, with focus on alliance, attendance and dropout. An exploratory post-hoc analysis of data from an original randomized controlled trial (RCT) investigating the effect of MT vs. ML for people with schizophrenia and negative symptoms. Inclusion to the study was implemented through screening of referred patients for symptoms of schizophrenia and negative symptoms. A total of 57 patients were randomly assigned, 28 to MT and 29 to ML. Session logs and notes were included in this study. Statistical analysis investigated moderator and mediator relation to outcome variables: Negative symptoms, functioning, quality of life, and retention to treatment. On average, participants in MT attended 18.86 sessions (SD = 7.17), whereas those in ML attended 12.26 (SD = 9.52), a statistically significant difference (p = 0.0078). Dropout at 25 weeks was predicted by intervention, with dropout being 2.65 (SE = 1.01) times more likely in ML than in music therapy (p = 0.009). Helping alliance score at weeks was explained by intervention, with mean score being 0.68 (SE = 0.32) points lower in ML than in MT (p = 0.042). The number of sessions attended was also explained by intervention, with participants in ML attending on average 6.17 (SE = 2.24) fewer sessions than those randomized to MT (p = 0.008). Though both groups improved significantly, improvements in negative symptoms, depression, and functioning tended to be higher in ML, whereas improvements in alliance and quality of life tended to be higher in MT. The analysis could not detect a direct link between helping alliance score and outcome variables. However, the analysis documented a stronger alliance developed in the MT group, a lower dropout rate, as well as higher attendance in treatment.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02942459.