A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders.

BACKGROUND: Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum. METHODS: PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment. RESULTS: Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003). CONCLUSIONS: Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn. PROSPERO: CRD42022359018.

Culturally Adapted Cognitive Behaviour Therapy (CaCBT) to Improve Community Mental Health Services for Canadians of South Asian Origin: A Qualitative Study.

BACKGROUND: South Asian (SA) Canadians are disproportionately affected by higher rates of mood and anxiety disorders. SA Canadians with depression report significant barriers to accessing mental health care and the highest proportion of unmet mental health needs. The Mental Health Commission of Canada (MHCC) advocates for culturally and linguistically relevant services for SA Canadians. Culturally adapted cognitive behavior therapy (CaCBT) has shown to be more effective than standard cognitive behavior therapy (CBT). Adapting CBT for the growing SA population in Canada will ensure equitable access to effective, culturally-appropriate mental health interventions. METHOD: The study used a qualitative design to elicit stakeholder consultation via in-depth interviews. This study is reported using the criteria included in Consolidated Criteria for Reporting Qualitative Studies (COREQ). The analysis follows an ethnographic approach and was informed by the principles of emergent design. RESULTS: Five themes were identified from the analysis, (i) Awareness and preparation: factors that impact the individual's understanding of therapy and mental illness. (ii) Access and provision: SA Canadians' perception of barriers, facilitators, and access to treatment. (iii) Assessment and engagement: experiences of receiving helpful treatment. (iv) Adjustments to therapy: modifications and suggestions to standard CBT. (v) Ideology and ambiguity: racism, immigration, discrimination, and other socio-political factors. CONCLUSIONS: Mainstream mental health services need to be culturally appropriate to better serve SA Canadians experiencing depression and anxiety. Services must understand the family dynamics, cultural values and socio-political factors that impact SA Canadians to reduce attrition rates in therapy.

Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.

Background and Hypothesis: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia. Study Design: A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed. Study Results: We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes. Conclusions: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge. Trial Registration: ClinicalTrials.gov: NCT03510741.