Clozapine has been the most effective antipsychotic in schizophrenia for almost 40 years, yet it is still routinely held back until patients have failed multiple alternatives over many years — a “third-line, after years of failure” default that a 2026 Current Opinion review by Davani et al. argues is no longer supported by the evidence.1 …
A 2026 resting-state fMRI study of 800 adults found intra-thalamic hypoconnectivity across schizophrenia, bipolar disorder, and major depression, but schizophrenia showed far broader subcortical dysconnectivity than bipolar disorder or depression.1 The calibrated read is that these diagnoses may share a thalamic vulnerability while diverging in striatal and limbic circuitry. Research Highlights Shared thalamic deficit: In …
A 2026 PRONIA preprint involving 727 discovery-sample participants found that early mental illness severity cut across psychosis risk, recent psychosis, and recent depression: groups with higher symptom severity also had poorer functioning, higher schizophrenia and depression polygenic risk, and lower gray matter volume. Research Highlights Severity crossed diagnostic labels: Ye et al. stratified 727 participants …
A 2026 SEEearly baseline report found that 53.3% of 184 young people with early schizophrenia-spectrum psychosis were not in employment, education, or training at study entry, even though 97.8% had at least a lower- or upper-secondary school-leaving qualification.1 Psychosis had already interrupted the bridge from school into training, college, or competitive work. Research Highlights NEET …
A 2026 Han Chinese case-control preprint linked the MTHFR C677T variant to schizophrenia with type 2 diabetes: the 677T allele appeared in 81.67% of alleles in the comorbid group vs. 60.00% in controls (p = 0.009), while MTHFR promoter methylation was nearly saturated in both groups (95.00% vs. 90.00%; p = 1.000). Research Highlights Genetic …
Cognitive impairment in first-episode schizophrenia (FES) is the symptom that does the most work blocking employment, relationships, and independent living — and the symptom current antipsychotics barely move. A 2026 RCT by Hu et al. in Psychological Medicine tested whether 20 sessions of low-frequency rTMS targeting the right orbitofrontal cortex (OFC) could improve cognition where …
Mukai et al.’s 499-person Phase 2b schizophrenia trial tested whether higher, sustained PDE10A inhibition could turn MK-8189 into a non-D2 antipsychotic; it did not. At week 6, MK-8189 missed the PANSS total endpoint at 16 mg (−2.8 points vs. placebo; 95% CI −8.3 to 2.6; P = 0.241) and 24 mg (−0.7 points; 95% CI …