Strategy For Schizophrenia Research Articles

Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus

Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Decreased insight, but not self-stigma or belief about medicine, is associated with greater severity of delusions in a sample of long-stay patients with schizophrenia: a cross-sectional study

BackgroundThere are, to date, limited and inconsistent findings concerning the relationship between insight and psychotic symptoms, despite some evidence in favor of the clinical and therapeutic relevance of the insight construct. We aimed to add to the pool of the available data in this area, by examining the correlations between the severity of insight and positive psychotic symptoms (delusions and auditory hallucinations), while accounting for self-stigma and attitudes towards medication, in a sample of long-stay inpatients with schizophrenia.MethodsA cross-sectional study was conducted at the Psychiatric Hospital of the Cross, between July and October 2021. A total of 82 patients diagnosed with schizophrenia (aged 55.55 ± 10.21 years, 54.9% males) were enrolled. The semi-structured psychotic symptom rating scales, the Birchwood Insight Scale, the Belief About Medicine Questionnaire, and the Internalized Stigma of Mental Illness were used.ResultsThe mean duration of illness in years was 30.15 ± 11.73, and the mean duration of hospitalization in years was 17.56 ± 9.24. Sixteen out of the 82 patients (19.5%) were considered as having poor insight. Bivariate analyses showed that higher chlorpromazine equivalent dose was significantly associated with more delusions, whereas higher insight was significantly associated with lower delusions. Multivariable analyses revealed that Higher chlorpromazine equivalent dose (Beta = 0.004) was significantly associated with more delusions, whereas higher insight (Beta = − 0.89) was significantly associated with less delusions. No significant associations were found between insight, self-stigma and hallucinations.ConclusionOur results imply that more impaired insight is associated with greater severity of delusions, above and beyond the effects of self-stigma and medication doses. These findings are valuable to aid clinicians and researchers improve their understanding of the relationship insight-psychotic symptoms, and could help personalize prevention and early intervention strategies in schizophrenia.

Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response.

The dorsolateral prefrontal cortex (DLPFC) has a crucial role in cognitive functioning and negative symptoms in schizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n = 20) and unaffected subjects (n = 20) followed by bioinformatic analysis to identify altered protein networks in schizophrenia (PXD024939 identifier in ProteomeXchange repository). Our results displayed a proteome profile in the DLPFC of 1989 proteins. 43 proteins were found significantly altered in schizophrenia. Analysis of this panel showed an enrichment of biological processes implicated in vesicle-mediated transport, processing and antigen presentation via MHC class II, intracellular transport and selenium metabolism. The enriched identified pathways were MHC class II antigen presentation, vesicle-mediated transport, Golgi ER retrograde transport, Nef mediated CD8 downregulation and the immune system. All these enriched categories were found to be downregulated. Furthermore, our network analyses showed crosstalk between proteins involved in MHC class II antigen presentation, membrane trafficking, Golgi-to-ER retrograde transport, Nef-mediated CD8 downregulation and the immune system with only one module built by 13 proteins. RAB7A showed eight interactions with proteins of all these pathways. Our results provide an altered molecular network involved in immune response in the DLPFC in schizophrenia with a central role of RAB7A. These results suggest that RAB7A or other proteins of this network could be potential targets for novel pharmacological strategies in schizophrenia for improving cognitive and negative symptoms.

Efficacy of Serotonin and Dopamine Activity Modulators in the Treatment of Negative Symptoms in Schizophrenia: A Rapid Review

Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional outcome of the disorder, and their treatment is difficult and rarely specifically investigated. Serotonin-dopamine activity modulators (SDAMs), of which aripiprazole, cariprazine, brexpiprazole, and lumateperone were approved for schizophrenia treatment, represent a possible therapy to reduce NS. The aim of this rapid review is to summarize the evidence on this topic to make it readily available for psychiatrists treating NS and for further research. We searched the PubMed database for original studies using SDAM, aripiprazole, cariprazine, brexpiprazole, lumateperone, schizophrenia, and NS as keywords. We included four mega-analyses, eight meta-analyses, two post hoc analyses, and 20 clinical trials. Aripiprazole, cariprazine, and brexpiprazole were more effective than placebo in reducing NS. Only six studies compared SDAMs with other classes of antipsychotics, demonstrating a superiority in the treatment of NS mainly for cariprazine. The lack of specific research and various methodological issues, related to the study population and the assessment of NS, may have led to these partial results. Here, we highlight the need to conduct new methodologically robust investigations with head-to-head treatment comparisons and long-term observational studies on homogeneous groups of patients evaluating persistent NS with first- and second-generation scales, namely the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. This rapid review can expand research on NS therapeutic strategies in schizophrenia, which is fundamental for the long-term improvement of patients' quality of life.

Lower sertraline plasma concentration in patients co-medicated with clozapine-Implications for pharmacological augmentation strategies in schizophrenia.

Augmentation of antipsychotic treatment with antidepressants represents a common and beneficial treatment strategy in patients suffering from schizophrenia. Combining clozapine and the selective serotonin reuptake inhibitor (SSRI) sertraline represents a clinically important strategy in patients with therapy-resistant schizophrenia, but there is limited knowledge about mutual pharmacokinetic interactions. In the present study, we assessed the impact of clozapine on sertraline plasma concentrations. Based on a therapeutic drug monitoring (TDM) database, sertraline plasma concentrations were compared between two groups: patients receiving a combined treatment with sertraline and clozapine (N= 15) and a matched control group receiving sertraline but no clozapine (N= 17). Group differences with respect to raw and dose-adjusted concentrations were assessed using nonparametric tests. Comedication with clozapine was associated with 67% lower median sertraline plasma concentrations (16 vs. 48 ng/mL; p= .022) and 28% lower median dose-adjusted plasma concentrations (C/D; 0.21 vs. 0.29 (ng/mL)/(mg/day); p= .049) as compared to the control group. Scatter plots revealed a complex relationship between the dosage of clozapine and dose-adjusted sertraline concentrations composed of an initial decrease at clozapine doses below 300 mg, an increase between 300 and 600 mg and a final decrease at 800 mg which was best modeled by a third order polynomial term. Cotreatment with clozapine may lead to reduced sertraline plasma concentrations which may be explained by clozapine-induced gastrointestinal hypo-mobility already present at low doses and cytochrome P450 3A4 inducing properties at high clozapine doses. For this drug combination, clinicians should consider TDM to confirm therapeutically effective plasma concentrations of sertraline.

Maternal immune activation induces methylation changes in schizophrenia genes.

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.

The Feasibility and Effectiveness of Home-based Cognitive Remediation in Clinically Stable Schizophrenia Patients Attending a North Indian Tertiary Care Institution

Background: Cognitive deficits are one of the core symptoms of Schizophrenia that compromises real-world functioning, adversely impacts rehabilitation, and negatively influence the quality of life. Studies evaluating interventions for cognitive remediation in Schizophrenia are scarce in India. This study aimed to evaluate the effectiveness of the add-on home-based cognitive remediation strategy in schizophrenia in comparison to the schizophrenic patients receiving treatment as usual. 
 Methods: The research was carried out in a North Indian tertiary care teaching hospital. Clinically stable patients diagnosed with schizophrenia were randomly assigned to study and control groups. The control group had received treatment as usual, whereas the study group had received 8 weeks of home-based manual-based cognitive remediation in addition to the treatment as usual. Assessment of psychopathology, cognitive functioning, disability, and quality of life was done at baseline, completion at 8 weeks and 16 weeks follow up.
 Results: A total of 186 patients with schizophrenia were screened based on selection criteria. 74 patients were included in the study. During the intervention, 17 patients were dropped out, making the sample size of the study group to be 28 and the control group to be 29. At the baseline, the socio-demographic, as well as clinical variables, were comparable. After cognitive remediation intervention, the study group had better cognitive functioning, less disability, and better quality of life in comparison to the control group. The benefits were sustained in the study group at the end of two-month follow-up period. The effect size of home-based cognitive remediation was found to be moderate (Cohen’s d 0.4 to 0.69) at the end of the intervention.
 Conclusion: Home-based cognitive remediation is a feasible and effective strategy of intervention in patients with schizophrenia which has at least a short-lasting effect and it is also useful in limiting the disability and improving the quality of life.

Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10−4) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10−10). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, PCDHA2, PCDHA3 and PCDHA5, were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia.

Effects of omega-3 polyunsaturated fatty acids supplements on psychopathology and metabolic parameters in schizophrenia: A meta-analysis of randomized controlled trials.

Several monotherapy and augmentation strategies have been introduced to improve the treatment of schizophrenia. The benefits of omega-3 polyunsaturated fatty acids in patients with mental disorders is becoming increasingly acknowledged. However, its role in the treatment of schizophrenia raises complex considerations about which there has been little consensus. The aim of this study was to synthesize the findings of randomized controlled trials that were conducted to determine the efficacy and safety of omega-3 polyunsaturated fatty acids in patients with schizophrenia. The MEDLINE, Embase, Cochrane, Scopus, and Web of Science databases were searched for relevant literature. The primary outcome was changes in psychopathology and the secondary outcomes were changes in metabolic parameters and safety profiles. Twenty double-blind randomized controlled trials in 1494 patients were included. Omega-3 polyunsaturated fatty acids augmentation was associated with significantly improved psychopathology in patients with schizophrenia, particularly general psychopathology and positive symptoms but not negative symptoms. Patients who were severely ill and received omega-3 polyunsaturated fatty acids containing eicosapentaenoic acid >1 g/d showed significant improvement. A favorable effect of omega-3 polyunsaturated fatty acids supplements on serum triglycerides was also demonstrated. Omega-3 polyunsaturated fatty acids are well-tolerated and safe in patients with schizophrenia. These findings tentatively support the use of omega-3 polyunsaturated fatty acids as a potential augmentation strategy in schizophrenia. Further research in larger samples is warranted to clarify the optimal dosage and the correct proportions of omega-3 polyunsaturated fatty acids to administer, together with elucidation of the underlying mechanisms.

Coping Strategies in Patients with Schizophrenia at Naimata Mental Hospital

Schizophrenia is one of the most common medical diagnoses of mental disorders and is a severe mental disorder that is influenced by biological, psychological and environmental factors. Schizophrenics have cognitive and behavioral disorders, so they have difficulty in determining appropriate coping. Koping is meant a process in order to change the cognitive domain and or behavior constantly to regulate and control external and internal demands and pressures. The purpose of this study was to determine coping strategies in schizophrenia the maintenance stage patients in the inpatient ward of the Naimata Kupang mental hospital. This type of research is descriptive research with a quantitative approach. The population in this study were 70 patients with Schizophrenia. The sample in this study were 30 patients with schisophrenia. The results obtained are that there is no impact from physical health and education on the application of coping strategies to Schizophrenia patients. The impact of positive beliefs (Emotion Focused Coping), problem solving skills (Problem Focused Coping), social and occupational support or socioeconomic status on the application of coping strategies to schizophrenia patients. The type of Emotion Focused Coping used is the highest type of Distancing and the Escape-Avodiance type while for the type of use of Problem Focused Coping there are Confrontative-Coping, Planfull Problem Solving and Seeking Social Support. Hospitals and families are expected to always provide support to patients both in the form of verbal and non verbal, material, and motivational support to be able to support the healing process of schizophrenic patients.

Language in schizophrenia and aphasia: the relationship with non-verbal cognition and thought disorder

ABSTRACTObjective: To determine the relationship between language abnormalities and broader cognitive impairment and thought disorder by examining language and cognition in schizophrenia and aphasia (a primary language disorder).Methods: Cognitive and linguistic profiles were measured with a battery of standardised tests, and compared in a clinical population of n = 50 (n = 30 with schizophrenia and n = 20 with aphasia) and n = 61 non-clinical comparisons (n = 45 healthy controls and n = 16 non-affected first-degree relatives of patients with schizophrenia).Results: Both clinical groups showed linguistic deficits. Verbal impairment was more severe in participants with aphasia, whereas non-verbal performance was more affected in participants with schizophrenia. In schizophrenia, but not in aphasia, verbal and non-verbal performance were associated. Formal thought disorder was associated with impairment in executive function and in grammatical, but not naming, tasks.Conclusion: While patients with schizophrenia and aphasia showed language impairments, the nature and cognitive basis of these impairments may be different; language performance disassociates from broader cognitive functioning in aphasia but may be an intrinsic expression of a broader cognitive impairment in schizophrenia. Thought disorder may represent a core malfunction of grammatical processing. Results suggests that communicative ability may be a valid target in cognitive remediation strategies in schizophrenia.

Evaluation of the relationship between family burden, family functioning and coping strategies in schizophrenia

Amac: Kronik hastaliklar aile yukunu arttirir, aile islevlerini etkiler. Bu calismada, sizofreni hastalari ve bakim verenlerde aile yukunun duzeyi ile sosyodemografik ozellikler, klinik bulgular, aile islevleri ve basa cikma tutumlari arasindaki iliskinin incelenmesi amaclanmistir. Gerec ve Yontem: Calismaya Recep Tayyip Erdogan Universitesi Egitim ve Arastirma Hastanesi Psikiyatri Poliklinigine ardisik sira ile basvuran, 100 sizofreni tanili hasta ve 100 hasta yakini dahil edildi. Hastalara Pozitif ve Negatif Sendrom Olcegi (PNSO), Sosyal Islevsellik Olcegi (SIO) uygulanirken; hasta yakinlarina Basa Cikma Tutumlarini Degerlendirme Olcegi (COPE), Algilanan Aile Yuku Olcegi (AAYO) ve Aile Degerlendirme Olcegi (ADO) uygulandi. Bulgular: Hasta grubunun %57’si kadin (n:57), %43’u erkek (n: 43) olup, yas ortalamasi 37,4±10’dur. Ortalama hastalik suresi 14,9±8 yil olarak bulunmustur. Bakim verenlerin cogunlugunu (%63’unu) kadinlar olusturmustur. Yas ortalamasi 47,5± 11’dir. Hastaya bakim verme sureleri 11,4 ±7 yil, birlikte gecirdikleri ortalama zaman 12,8 ±8 saat olarak belirlenmistir. Hastalarin semptomlari, hastalik sureleri, hastalarin islevselliklerindeki bozulma derecesi ve bozulmus aile islevlerinin aile yuku ile iliskili oldugu saptanmistir (p<0,05). Sonuc: Bu calismada sizofreni tanili hastalarin pozitif ve negatif belirtilerinin siddeti arttikca oznel aile yuku, nesnel aile yuku ve toplam yukun arttigi, sosyal islevsellik duzeyi azaldikca aile yukunun arttigi, hasta yakinlarinin en sik pozitif yeniden yorumlama ve gelisme, aktif basa cikma, plan yapma basa cikma yontemlerini kullandiklari belirlenmistir. Sizofreni tanili hastalara bakim verenlerde aile yukunu azaltmak icin semptomlarin kontrol altina alinmasi, hastalarin sosyal islevselliklerinin iyilestirilmesi, bakim vermekte olan kisilerin hastalik ve aile islevleri hakkinda egitilmesi hastalara bakim verenlerin stresli durumlar karsisinda basvurduklari olumlu bas etme tutumlari, tedavi hedefini belirlemede ve tedavinin etkinliginin izlenmesi surecinde yardimci olacaktir.

Galantamine-Memantine Combination as an Antioxidant Treatment for Schizophrenia.

The objective of this article is to highlight the potential role of the galantamine-memantine combination as a novel antioxidant treatment for schizophrenia. In addition to the well-known mechanisms of action of galantamine and memantine, these medications also have antioxidant activity. Furthermore, an interplay exists between oxidative stress, inflammation (redox-inflammatory hypothesis), and kynurenine pathway metabolites. Also, there is an interaction between brain-derived neurotrophic factor and oxidative stress in schizophrenia. Oxidative stress may be associated with positive, cognitive, and negative symptoms and impairments in white matter integrity in schizophrenia. The antipsychotic-galantamine-memantine combination may provide a novel strategy in schizophrenia to treat positive, cognitive, and negative symptoms. A "single antioxidant" may be inadequate to counteract the complex cascade of oxidative stress. The galantamine-memantine combination as "double antioxidants" is promising. Hence, randomized controlled trials are warranted with the antipsychotic-galantamine-memantine combination with oxidative stress and antioxidant biomarkers in schizophrenia.

Many ways to forget – Neurophysiology of directed forgetting mechanisms in schizophrenia

Numerous studies have shown dysfunctional mechanism of interaction between bottom-up emotional and top-down cognitive processes in persons with schizophrenia (SCZ). During the emotional directed forgetting (DF) paradigm participants have to apply volitional mechanisms to resist automatic emotional enhancement of the memory. Here we sought to compare mechanisms underlying emotional DF in SCZ and in healthy persons (HC). Eighteen SCZ and eighteen HC completed a DF paradigm with neutral and negative pictures. EEG was recorded during study and test phase of the task. We analyzed both the behavioral outcomes and event-related potential components, indicating emotional enhancement of memory (Late Positive Potential elicited by pictures) and DF strategies (N2/P3 elicited by forget/remember cues during study-phase; “old/new” and “reversed old/new” effects during test-phase of the task). Directed forgetting effects and emotional enhancement of memory were observed in both groups, even despite overall lower recognition rates in SCZ. Furthermore, cue presentation elicited similar pattern of N2/P3s in SCZ and in HC. However, “reversed old/new” effect was observed only in HC for negative stimuli. Patients may show similar reaction to affective stimuli as healthy controls during the emotional DF task. However, further investigation is needed to elicit the specific mechanisms underlying the DF strategies in SCZ.

23. FRONTAL CORTEX DEVELOPMENT AND RISK FOR PSYCHOPATHOLOGY: MOLECULAR AND GENETIC MEDIATORS AS POSSIBLE BIOMARKERS?

Overall : This panel includes 4 females and 1 male, 2 early career scientists, 2 clinicians. From 5 different countries, 3 different continents.Prefrontal cortex (PFC) dysfunction is associated with alterations in cognitive processing impaired in schizophrenia. The development of the PFC is a protracted process, which peaks in adolescence and ends only in early adulthood. Its extended development renders the PFC particularly susceptible to environmental influences, but we know very little about the underlying neurobiological mechanisms. More importantly, we need to understand how risk or protective factors can affect PFC development. This could have an impact towards the development of early and/or preventive treatments for cognitive dysfunctions relevant to a number of psychiatric disorders including schizophrenia.We will discuss recently-discovered processes involved in different stages of prefrontal cortex development, including gestation and adolescence, and how alterations to these events may lead to schizophrenia-relevant phenotypes. A multidisciplinary group of preclinical and human researchers will discuss recently-identified molecular, genetic, and hormonal events that shape PFC development. We will also show compelling new evidence that disruption to these developmental processes is linked to psychiatric conditions. The data we will present include:(1) Signaling events implicated in the migration of newborn neurons into emerging cortical layers and their relevance to schizophrenia and autism spectrum disorder (Helen Cooper).(2) Mechanisms related to adolescent axonal growth and connectivity in the PFC and how they are disrupted by ongoing experiences (Cecilia Flores).(3) Findings from human and mouse studies regarding the impact of the 22q11.2 microdeletion on PFC development and cognitive maturation (Francesco Papaleo).(4) The molecular development of the postnatal human cortex, including the maturation of interneurons, molecular changes in neurotransmitter signaling pathways, synaptic development and developmental changes in those immune related molecules that may impact synaptic development (Maree Webster).Collective discussion of these data (Maude Schneider) will highlight important implications for prevention and early intervention strategies in schizophrenia.

25. OLIGODENDROCYTE-BASED IMPAIRMENT OF BRAIN CONNECTIVITY AS TARGET FOR NEW TREATMENT STRATEGIES IN SCHIZOPHRENIA

Overall : This symposium has a translational approach. First, we present human post-mortem and in-vivo imaging studies on the pivotal role of oligedondrocyte loss and dysfunction with consecutive impairments of brain connectivity in schizophrenia. Natalya Uranova will show morphometric data on ultrastructural alterations of oligodendrocytes, myelin damage and degeneration and disturbed oligodendrocyte-axon interactions in post-mortem prefrontal white matter in schizophrenia. Adrienne Lahti will report diffusion tensor imaging data suggesting impaired axonal and myelin integrity. Because, MR Spectroscopy permits the non-invasive measurement of neurometabolites, such as N-acetylaspartate, a marker of neuronal integrity, and glutamate, which can be neurotoxic when overproduced, this technique provides further understanding of the relationship between white matter microstructure and neuronal function.Second, we present data from cell culture and animal models suggesting that restoration of oligodendrocyte function (in terms of energy metabolism, maturation and myelin production) is a promising target for the development of novel treatment strategies in schizophrenia. Proteomic studies in postmortem brain by Daniel Martins-de-Souza have suggested a schizophrenia-related energy metabolism dysfunction in oligodendrocytes. These findings have been followed up using oligodendroglia cell lines and induced pluripotent stem cell-derived cerebral organoids, supporting the notion that alterations in glycolysis in oligodendrocytes are pivotal to the overall energy dysfunction in schizophrenia brains. Lan Xiao′s lab has shown that oligodendrocyte dysfunction and impaired myelination in the prefrontal cortex is correlated with schizophrenia-like behavior in mice undergoing prolonged social isolation. Enhancing oligodendrocyte generation and myelin repair by FDA-approved compounds, like quetiapine (an APD) or clemastine (a histamine antagonist) successfully reversed the above phenotype.

Cognitive Deficits in Schizophrenia: Understanding the Biological Correlates and Remediation Strategies.

Cognitive deficits are one of the core symptoms of schizophrenia that evolve during the course of schizophrenia, after being originated even before the onset of illness. Existing pharmacological and biological treatment modalities fall short to meet the needs to improve the cognitive symptoms; hence, various cognitive remediation strategies have been adopted to address these deficits. Research evidences suggest that cognitive remediation measures improve the functioning, limit disability bettering the quality of life. The functional outcomes of cognitive remediation in schizophrenia are resultant of neurobiological changes in specific brain areas. Recent years witnessed significant innovations in cognitive remediation strategies in schizophrenia. This comprehensive review highlights the biological correlates of cognitive deficits in schizophrenia and the remedial measures with evidence base.

Memantine as an Augmentation Treatment for Schizophrenia: Limitations of Meta-Analysis for Evidence-Based Evaluation of Research.

The action of memantine on N-methyl-D-aspartate (NMDA) glutamatergic receptors and the other pharmacodynamic actions of this drug suggest that it may benefit patients with schizophrenia. Many randomized controlled trials (RCTs) have examined this possibility. These RCTs have been meta-analyzed by at least 2 groups of authors. In one meta-analysis (8 RCTs, pooled N = 448), memantine (20 mg/d for 6-12 weeks) augmentation of antipsychotic drug therapy was found to attenuate the severity of negative symptoms and improve cognitive functioning; in both regards, the effect was large. Memantine was also associated with a small but statistically significant reduction in general psychopathology. Whereas memantine did not significantly attenuate positive symptom, depression, total psychopathology, and global illness ratings, it was also not associated with an increased risk of individual adverse events, discontinuation due to adverse events, or all-cause discontinuation. The findings of the other meta-analysis, which examined much the same body of literature, were largely similar. On the surface, these results suggest that memantine may be considered for the reduction of negative symptoms and cognitive impairment in schizophrenia. However, an examination of the individual RCTs and a careful look at the findings of the meta-analyses identify so many important concerns that it is probably premature to draw conclusions about the usefulness of memantine as an augmentation strategy in schizophrenia. At best, it may be stated that there is a signal that supports the study of memantine in schizophrenia patients who are specifically impaired by negative symptoms and cognitive complaints. This is a good example of a situation in which meta-analysis did not provide a trustable evidence-based interpretation of literature.

Altered Volume and Functional Connectivity of the Habenula in Schizophrenia.

The pathogenesis of schizophrenia (SCH) is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb) nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs). Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC) in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG). A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS) scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.

Caregiver burden and coping strategies in schizophrenia: a hospital based study

Introduction: Schizophrenia is a severe mental illness which not only affects the patients but also causes significant distress to the caregivers, who use various strategies to minimize their distress. It is important to know about their suffering in order to include them in the treatment program.Objective: To assess the severity of burden and coping strategies among the caregiversMethod: 36 admitted cases of patients and their caregivers were enrolled. Patients were assessed using PANSS while caregivers were assessed using BAS and COPE Inventory.Result: 47.2% caregivers reported suffering from severe burden. The most severely affected areas were physical and mental health, taking responsibility, caregiver's routine and patient's behavior. Caregivers used both problem oriented and emotion oriented strategy to minimize the distress. The choice of coping strategy and severity of burden was not influenced by the patient's symptoms.Conclusion: Caregivers of patients with schizophrenia suffered from significant burden and require additional care to help them alleviate their problems.