The latest medical research on Schizophrenia
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Request AccessPsychotic Experiences and Risk of Suicidal Thoughts and Behaviors: A Systematic Review and Meta-Analysis of Longitudinal Population Studies.
Schizophrenia BulletinSince a prior systematic review and meta-analysis reported an association between psychotic experiences (PEs) and suicidal thoughts and behaviors, a large number of new studies have been published on the topic, including several novel studies on the association between PEs and transition from suicidal ideation to attempt.
Two authors independently searched PubMed, Embase, CINAHL, and PsycINFO databases from inception until July 2023, conducted data extraction, and assessed study quality using the Newcastle-Ottawa Quality Assessment Scale. Random-effects models were used to calculate pooled odds ratios (ORs) for the association of PEs and subsequent suicide ideation, suicide attempts, suicide death, and transition from suicidal ideation to attempt, first for the total population, and second stratified by age group. Secondary analyses assessed the mediating role of co-occurring psychopathology.
Twenty studies from 18 different samples (n = 81,861) were identified. Individuals who reported PEs had increased odds of subsequent suicidal ideation (k = 12, OR = 1.90, 95% CI = 1.65-2.19), suicide attempt (k = 13, OR = 2.95, 95% CI = 2.21-3.94), transition from suicidal ideation to suicide attempt (k = 3, OR = 2.83, 95% CI = 1.60-4.99), and suicide death (k = 1, OR = 4.39, 95% CI = 1.63-11.80). This heightened risk was stable across childhood, adolescence, and adulthood. PEs predicted suicide attempts over and above co-occurring psychopathology (k = 8, OR = 2.85, 95% CI = 2.06-3.95).
Individuals reporting PEs are at increased risk of all types of suicidal thoughts and behaviors. In addition, PEs are particularly important risk markers for future suicidal behaviors, including in individuals already reporting suicidal ideation. This risk is in excess of what is explained by co-occurring psychopathology.
Yoga-Based Group Intervention for Inpatients with Schizophrenia Spectrum Disorders-Feasibility, Acceptability, and Preliminary Outcomes of a Rater-Blinded Randomized Controlled Trial.
Schizophrenia BulletinThe efficacy of yoga as an adjunctive treatment for schizophrenia spectrum disorders (SSD) has garnered interest. While yoga may positively influence various symptom domains, further investigation is needed due to the limited number, quality, and generalizability of studies. This study assessed the feasibility and acceptability (primary outcome) of a yoga-based group intervention (YoGI) developed in a participatory approach and explored its preliminary effectiveness.
In addition to the primary outcomes, this preregistered randomized controlled trial examined rater-blinded general psychopathology, positive- and negative symptoms, and self-rated depression, anxiety, stress, body mindfulness, mindfulness, psychological flexibility, cognition, social functioning, quality of life, and medication regime at baseline and postintervention as secondary outcomes.
Fifty inpatients with SSD received either TAU (n = 25) or YoGI + TAU (n = 25) for four weeks. Outcomes showed 95% protocol adherence of YoGI, feasibility, and retention rates of 91% and 94%, respectively, and a dropout rate of 6%. ANCOVA revealed significant between-group postintervention improvements for YoGI + TAU in positive symptoms, depression, cognitive fusion, and a mindfulness subscale. Medium-to-large pre- to postintervention effects were found for body mindfulness, positive, negative, and general psychopathology, cognitive fusion, depression, anxiety, stress, quality of life, and attention in YoGI + TAU, while within-group changes were consistently smaller in TAU. No severe adverse events were reported.
This trial supports the feasibility and acceptability of YoGI for inpatients with SSD and provides preliminary evidence of YoGI's benefits beyond TAU. Further robust, multicentric RCTs are warranted to deepen our understanding of YoGI's therapeutic potential and inform clinical interventions for SSD.
Mitochondrial Dysfunction and Cognitive Impairment in Schizophrenia: The Role of Inflammation.
Schizophrenia BulletinThe complex immune-brain interactions and the regulatory role of mitochondria in the immune response suggest that mitochondrial damage reported in schizophrenia (SZ) may be related to abnormalities observed in immune and brain functions.
Mitochondrial DNA copy number (mtDNA CN), a biomarker of mitochondrial function, was assessed in peripheral blood leukocytes (PBLs) of 121 healthy individuals and 118 SZ patients before and after 8 weeks of antipsychotic treatment, and a meta-analysis related to blood mtDNA CN was conducted. Plasma C-reactive protein (CRP) levels in SZ patients were obtained from the medical record system. Spearman correlation analysis and hierarchical linear regression were used to analyze the relationships among mtDNA CN, CRP levels, and cognitive function. A mediation model was constructed using the PROCESS program.
Our results revealed the decreased mtDNA CN in PBLs from SZ patients (P = .05). The meta-analysis supported the decreased blood mtDNA CN in SZ patients (P < .01). The mtDNA CN in PBL was positively correlated with working memory (P = .02) and negatively correlated with plasma CRP levels (P = .039). Furthermore, a lower mtDNA CN in PBL in SZ patients was a significant predictor of worse working memory (P = .006). CRP acted as a mediator with an 8.0% effect.
This study revealed an association between peripheral mitochondrial dysfunction and cognitive impairment in SZ, with inflammation acting as a mediating effect. Therefore, mitochondrial dysfunction might provide novel targets for new treatments for cognitive impairment in SZ.
The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis.
Schizophrenia BulletinWeight gain and metabolic complications are substantial adverse effects associated with second-generation antipsychotics. However, comprehensive guidelines for managing antipsychotic-induced weight gain are lacking.
This review included all double-blind, placebo-controlled studies investigating metformin's effectiveness in addressing antipsychotic-related weight gain. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov for relevant studies from the inception to 2024. A random-effects model was used for the meta-analysis.
This meta-analysis, including 20 studies with 1070 patients, revealed that metformin significantly surpassed placebo in attenuating weight gain in patients receiving antipsychotics. The mean weight change with metformin was -3.32 kg [95% confidence interval (CI): -4.57 to -2.07]. Additionally, metformin use resulted in a marked decrease in body mass index [-1.24 kg/m2 (95% CI: -1.70 to -0.77)]. Metformin could maintain the effects from 12 to 24 weeks.
This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research to validate our findings.
Transcriptomic Analysis of the Amygdala in Subjects with Schizophrenia, Bipolar Disorder and Major Depressive Disorder Reveals Differentially Altered Metabolic Pathways.
Schizophrenia BulletinThe amygdala, crucial for mood, anxiety, fear, and reward regulation, shows neuroanatomical and molecular divergence in psychiatric disorders like schizophrenia, bipolar disorder and major depression. This region is also emerging as an important regulator of metabolic and immune pathways. The goal of this study is to address the paucity of molecular studies in the human amygdala. We hypothesize that diagnosis-specific gene expression alterations contribute to the unique pathophysiological profiles of these disorders.
We used a cohort of subjects diagnosed with SCZ, BPD or MDD, and nonpsychiatrically ill control subjects (n = 15/group), together with our bioinformatic 3-pod analysis consisting of full transcriptome pathway analysis, targeted pathway analysis, leading-edge gene analysis and iLINCS perturbagen analysis.
We identified altered expression of metabolic pathways in each disorder. Subjects with SCZ displayed downregulation of mitochondrial respiration and nucleotide metabolism pathways. In comparison, we observed upregulation of mitochondrial respiration pathways in subjects with MDD, while subjects with BPD displayed enrichment of pathways involved in carbohydrate metabolism. Several pathways associated with brain metabolism including immune system processes and calcium ion transport were also differentially altered between diagnosis groups.
Our findings suggest metabolic pathways, including downregulation of energy metabolism pathways in SCZ and upregulation of energy metabolism pathways in MDD, are uniquely altered in the amygdala in these disorders, which may impact approaches for therapeutic strategies.
Probiotic Formulation for Patients With Bipolar or Schizophrenia Spectrum Disorder: A Double-Blind, Randomized Placebo-Controlled Trial.
Schizophrenia BulletinProbiotic augmentation offers a promising treatment for bipolar disorder (BD) and schizophrenia spectrum disorder (SSD). By targeting microbiome deviations, they may improve both gut and brain health.
In this double-blind, randomized, placebo-controlled trial with the multi-strain probiotic formulation Ecologic BARRIER, we aimed to improve psychiatric and cognitive symptoms, intestinal permeability, and gastrointestinal symptoms in patients with BD or SSD. A total of 131 patients were randomized 1:1 to receive either the probiotic supplement (n = 67) or a placebo (n = 64) for 3 months, in addition to treatment-as-usual. The primary outcomes were symptom severity assessed by the Brief Psychiatric Rating Scale and cognitive functioning by the Brief Assessment of Cognition in Schizophrenia.
No significant effect of probiotics was observed on psychiatric symptoms, but borderline significant improvement was observed in the cognition category of verbal memory (Linear Mixed Model (LMM) 0.33; adjusted P = .059). Probiotics beneficially affected markers of intestinal permeability and inflammation, including zonulin (LMMserum = -18.40; adjusted P = .002; LMMfecal = -10.47; adjusted P = .014) and alpha-1 antitrypsin (LMM 9.26; adjusted P = .025). Indigestion complaints significantly decreased in male participants in the probiotics group (LMM = -0.70; adjusted P = .010). Adverse events were similar between groups.
Our study observed significant advantages of probiotics for gut health in BD and SSD, with excellent safety and tolerability. A borderline effect on verbal memory was also indicated. These results underscore the need for further research into microbiome-targeted interventions for patients with complex brain disorders.
Retina in Clinical High-Risk and First-Episode Psychosis.
Schizophrenia BulletinAbnormalities in the retina are observed in psychotic disorders, especially in schizophrenia.
Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28).
Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs.
The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.
Protective Factors Predict Resilient Outcomes in Clinical High-Risk Youth with the Highest Individualized Psychosis Risk Scores.
Schizophrenia BulletinStudying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator.
CHR participants (N = 572) from NAPLS3 were assessed on the Risk Calculator. Those who scored in the top half of the distribution and had 2 years of follow-up (N = 136) were divided into those who did not convert to psychosis (resilient, N = 90) and those who did (nonresilient, N = 46). Groups were compared based on candidate protective factors that were not part of the Risk Calculator. Better functional outcome was also examined as an outcome measure of resiliency. Study Results: Exploratory analyses suggest that Hispanic heritage, social engagement, desirable life experiences, premorbid functioning and IQ are all potential protective factors that predict resilient outcomes. Reduced startle reactivity, brain area and volume were also associated with greater resilience.
The primary focus of CHR research has been the risk and prediction of psychosis, while less is known about protective factors. Clearly, a supportive childhood environment, positive experiences, and educational enrichment may contribute to better premorbid functioning and brain development, which in turn contribute to more resilient outcomes. Therapies focused on enhancing protective factors in the CHR population are logical preventive interventions that may benefit this vulnerable population. Future CHR research might use similar models to develop a "protective index" to predict resilient outcomes.
The Effects of Cognitive Remediation on Negative Symptoms in Schizophrenia-Spectrum Illness: A Meta-analytic Investigation of Efficacy.
Schizophrenia BulletinThe number of clinical efficacy trials of Cognitive Remediation (CR), a behavioral intervention consisting of cognitive task practice and/or strategy training to improve cognitive skills in schizophrenia, has increased substantially over the past 25 years. While recent reviews have highlighted the effects of CR on cognition and function, CR effects on negative symptoms remain understudied. Given the overlap between negative symptoms and cognition, CR effects might be expected.
Electronic databases were evaluated up to September 2023 using a broad range of search terms. Sixty-nine unique, controlled trials that used negative symptoms as an outcome were meta-analyzed. Data were independently extracted with excellent (>98%) reliability. Random effects models assessed the effects of CR on summary and expressive vs. experiential negative symptoms. Moderator analyses evaluated a broad array of treatment and participant factors.
The meta-analysis (5319 participants) revealed that CR produced a small effect size improvement on summary negative symptoms (Hedge's g = 0.179). Sample differences in age, duration of illness, symptoms, and antipsychotic dosage did not serve as a barrier to treatment benefit. CR also produced small-to-moderate improvements in alogia (Hedge's g = 0.312) but not experiential negative symptoms. Programs of CR that utilized bridging activities that relate training of cognitive skills to activities of daily living produced greater improvement in negative symptoms (g = 0.281 vs 0.055). Longer CR programs also produce larger effects on negative symptoms.
CR produces small, consistent reductions in negative symptoms in people with schizophrenia. Variations in CR effects may be linked to different treatment ingredients.
Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.
Schizophrenia BulletinAngiogenesis triggered by inflammation increases BBB permeability and facilitates macrophage transmigration. In the midbrain, we have discovered molecular alterations related to the blood-brain barrier (BBB), including endothelial cell changes associated with macrophage diapedesis, in neuroinflammatory schizophrenia and bipolar disorder, but changes in angiogenesis are yet to be reported. Hypothesis: We expected to discover molecular evidence of altered angiogenesis in the midbrain in individuals with schizophrenia and bipolar disorder compared to controls, with these changes more evident in "high" inflammation schizophrenia as compared to "low" inflammation.
In a case-control post-mortem cohort including schizophrenia (n = 35), bipolar disorder (n = 35), and controls (n = 33), we measured mRNA (RT-PCR) and protein (multiplex immunoassays) and performed immunohistochemistry to determine levels and anatomical distribution of angiogenesis-related molecules in the ventral midbrain.
We found large changes in angiogenesis factors in bipolar disorder high inflammatory subgroup (increased angiopoietin-2 and SERPINE1 mRNAs, but decreased angiopoietin-1, angiopoietin-2, and TEK receptor proteins). In schizophrenia high inflammatory subgroup, we found a robust increase in SERPINE1 mRNA and protein levels. However, we found no significant changes in angiopoietins in schizophrenia. We found that VEGFA mRNA level was increased in high inflammation schizophrenia, but only reached statistical significance compared to one low inflammatory subgroup.
Thus, angiogenesis signaling pathways appeared to be involved in the BBB alterations when inflammation is also present in the midbrain of schizophrenia and bipolar disorder, with increased levels of SERPINE1 in schizophrenia high inflammatory subgroup and with a putative suppression of angiopoietin signaling in bipolar disorder high inflammatory subgroup.
Language, Motor Ability and Related Deficits in Children at Familial Risk of Schizophrenia or Bipolar Disorder.
Schizophrenia BulletinIt is known that impairments in linguistic ability and motor function tend to co-occur in children, and that children from families with parental mental illness such as schizophrenia tend to perform poorly in both domains, but the exact nature of these links has not yet been fully elucidated.
In this study, we leveraged the first wave of the Danish High Risk and Resilience Study (VIA 7), which includes both genetic data and measures covering multiple developmental domains. The VIA 7 cohort comprises 522 7-year-old children born to parents with schizophrenia (N = 202), bipolar disorder (N = 120) or neither (N = 200). We investigated the relationships between linguistic ability and motor function using correlation and regression analyses, focusing on developmental coordination disorder (DCD) and specific language impairment (SLI) and their potential associations with the three risk groups.
We found significant correlations between most measures of language and motor function and significant associations of DCD and SLI with language and movement measures, respectively, the largest effect being that of DCD on receptive language, with a significant interaction effect: DCD was associated with poorer performance in children from schizophrenia families compared to bipolar disorder and control families. Both disorders showed higher prevalence among children with familial high risk of mental illness. We did not find significant evidence of genetic overlap between DCD and SLI.
Our results suggest strong links between the domains of motor function and linguistic ability. Children of parents with schizophrenia are at high risk of comorbid language and movement disorders.
Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial.
Schizophrenia BulletinIn the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing.
A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel.
This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).
This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up.
