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ICOSR 2015—Neuroimaging: Can It Help Reduce Risk for Schizophrenia?

10 May 2015

As part of our ongoing coverage of the 2015 International Congress on Schizophrenia Research (ICOSR), held March 29 through April 1 in Colorado Springs, we bring you session summaries from some of the participants in the Young Investigator program. We are, as always, grateful for the gracious assistance of conference directors Carol Tamminga and Chuck Schulz, as well as meeting staff Cristan Tamminga and Dorothy Denton. For this report, we thank Anna Docherty of Virginia Commonwealth University in Richmond.

May 10, 2015. In the morning sessions on Monday, March 30, at the International Congress on Schizophrenia Research in Colorado Springs, Tyrone Cannon of Yale University in New Haven, Connecticut, led a symposium on the topic of early detection and prevention of psychosis. The focus was largely on neuroimaging findings and the results from prevention trials.

Stephan Ruhrmann of the University of Cologne, Germany, presented information from a comprehensive meta-analysis of 45 clinical high-risk studies, indicating that brief limited intermittent psychotic syndrome (BLIPS) was highly predictive of transition to psychosis. Ruhrmann reviewed recommendations on early intervention and offered criteria for intervention research from the European Psychiatric Association, including a focus on improvement of functioning and postponement of the first episode. He described a staged intervention model with CBT and then, if necessary, a low-dose trial of second-generation antipsychotic medication. He encouraged the use of complementary measures in prevention and intervention studies such as mismatched negativity EEG and structural MRI, the measurement of symptoms during the period prior to follow-up, and the longitudinal modeling of internal and external protective and risk factors.

The next speaker, Raquel Gur of the University of Pennsylvania in Philadelphia presented compelling data from a longitudinal study of the Philadelphia Neurodevelopmental Cohort, a community-based sample comprising ~9,500 individuals 8-21 years of age. The researchers have found that significant developmental indicators of risk occur as early as eight years of age, with deficits in neurocognitive performance across several domains that were more pronounced for accuracy than for speed. The deficits implicate executive control and social cognition systems. MRI volumetric analysis indicates an overall lower intracranial volume in the psychosis spectrum group, and reduced volume specific to gray matter in several cortical and subcortical regions. Interestingly, those who remained on the psychosis spectrum at follow-up had performed worse on measures of social cognition, facial memory, and verbal reasoning speed, and these trajectories were significantly associated with multimodal neuroimaging parameters.

Diana Perkins of the University of North Carolina, Chapel Hill, then presented research identifying predictors of onset of psychosis in the context of the North American Prodrome Longitudinal Study (NAPLS). Her talk focused specifically on markers of neuroinflammation, oxidative stress, hypothalamic-pituitary-adrenal axis activation, and synaptic plasticity, and the implications of these findings for targeted interventions. She reviewed innate and adaptive types of immune response and a possible “proinflammatory state” in schizophrenia, evidenced by mouse studies of cognitive function and manipulation of CD4+ T lymphocytes and also by increased antibodies in high-risk individuals. Perkins noted that pathways involving T helper cell differentiation and dendritic cell maturation appear promising, and examination of plasma analyte and leukocyte gene expression may help identify vulnerability constructs for psychosis. Overall, blood-based assays appear to show promise in stratifying psychosis risk.

The final speaker, Christos Pantelis of the University of Melbourne, Australia, reviewed findings from a series of MRI and neurocognition studies mapping the trajectories from clinical high risk for psychosis to 10 years' follow-up. The most pronounced brain changes in relation to conversion to psychosis were observed at the earliest stages of illness, particularly at transition to a first-episode psychosis. He emphasized the relevance of developmental factors and the need for more longitudinal research examining the complexity of the trajectory in these early stages of illness, especially with episodes of relapse and remission. Such work could illuminate both risk and resilience factors relevant to illness progression or amelioration and provide novel approaches to intervention. Using PET imaging, his group identified differences in microglial activity (relevant to neuroinflammation) in first-episode patients compared to matched controls and in comparison with chronic schizophrenia patients. Using MRS, Pantelis and colleagues also identified significant increases in glutathione and glutamate in response to the administration of EPA (fish oil), which may have neuroprotective effects.—Anna Docherty.