Study demonstrates three biomarker-based categories, called biotypes, sorted psychosis cases more distinctly into subgroups based on brain biology compared to traditional diagnoses; schizophrenia & bipolar with psychosis. This demonstrates biotypes were more biological similar than traditional categories based on observable symptoms. For example, a fever can have many different causes, multiple psychosis-causing processes, operating in different pathways, can lead to similar symptoms.

The study included 1,872 patients with schizophrenia, schizoaffective disorder and bipolar disorder with psychosis, their first-degree relatives and healthy control subjects. The researchers examined key biological and behavioural measures linked to psychosis, e.g. memory tasks, eye-tracking, measurement of brainwaves. The study demonstrated three subgroups based on biomarkers, better than traditional clinical diagnoses. This was confirmed by external measures – social functioning, brain structure, and biomarker patterns in relatives.

• Subgroup biotype 1: Severe impairment in cognitive control (ability to flexibly control attention and information processing to meet own goals) and social function. Brain imaging demonstrates reduced grey matter in cortex, known to process higher-order information
• Subgroup biotype 2: Intermediate impairment in cognitive control, but accentuated brain responses to sensory input
• Subgroup biotype 3: Normal cognitive control, impaired sensorimotor reactivity, least social impairment, lowest positive and negative symptoms. Brain imaging demonstrate reduced grey matter in emotion-processing areas

Each biotype overlapped with clinical diagnoses, e.g. Biotype 1 cases, 59 percent had a schizophrenia diagnosis, while among Biotype 3 cases 44 percent had a bipolar disorder with psychosis diagnosis.

These results give support for the institute’s Research Diagnostic Criteria (RDoC) initiative, which frees scientists from designing research based on traditional diagnostic categories, encouraging them to explore groupings based on genomics, behavioural dimensions, physiological traits, or brain imaging findings. These biomarkers may help understand the development of the impairments and establish tailored treatment based on the biomarkers.

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