Imaging and Genetic Biomarkers Predicting Transition to Psychosis

Abstract

The search for diagnostic and prognostic biomarkers in schizophrenia care and treatment is the focus of many within the research community. Longitudinal cohorts of patients presenting at elevated genetic and clinical risk have provided a wealth of data that has informed our understanding of the development of schizophrenia and related psychotic disorders.Imaging follow-up of high-risk cohorts has demonstrated changes in cerebral grey matter of those that eventually transition to schizophrenia that predate the onset of symptoms and evolve over the course of illness. Longitudinal follow-up studies demonstrate that observed grey matter changes can be employed to differentiate those who will transition to schizophrenia from those who will not prior to the onset of the disorder.In recent years our understanding of the genetic makeup of schizophrenia has advanced significantly. The development of modern analysis techniques offers researchers the ability to objectively quantify genetic risk; these have been successfully applied within a high-risk paradigm to assist in differentiating between high-risk individuals who will subsequently become unwell and those who will not.This chapter will discuss the application of imaging and genetic biomarkers within high-risk groups to predict future transition to schizophrenia and related psychotic disorders. We aim to provide an overview of current approaches focussing on grey matter changes that are predictive of future transition to illness, the developing field of genetic risk scores and other methods being developed to aid clinicians in diagnosis and prognosis.

Structural and functional imaging markers for susceptibility to psychosis

“…Several volumetric differences in gray matter have been reported in high-risk patients compared with healthy controls, the most consistent being volume reductions in hippocampal/parahippocampal areas, cingulate cortex, as well as the medial and lateral frontal cortex and medial parietal cortex [ 21 , 31 – 33 ]. Studies comparing high-risk subjects with (CHR-T) and without (CHR-NT) later transition to psychosis indicates that some of these volume reductions might be relevant for the prediction of future psychotic transition.…”

Early Detection and Prevention of Schizophrenic Psychosis—A Review

“…Reduced volumes of the amygdala and insula, by contrast, were primarily registered in UHR individuals who later developed bipolar disorder [ 94 , 95 ]. When comparing high-risk subjects who transitioned to psychosis with high-risk individuals who did not, the former group was characterized by reduced GMV of the prefrontal cortex (and specifically the orbitofrontal cortex), the temporal cortex (in particular, the medial temporal gyrus), and the cerebellum [ 96 , 97 , 98 ]. Furthermore, GMV reduction was also reported for limbic system structures—(anterior) cingulate cortex, insula, and hippocampus—albeit less frequently [ 96 , 97 ].…”

Predicting major mental illness: ethical and practical considerations

“…Across studies, subthreshold symptom severity, poorer functioning and a family history of schizophrenia are consistent clinical predictors of transition. 6 , 7 Biological approaches tend to have focused on neuroimaging indices, usually involving complex machine learning analyses, some of which have since been replicated and validated in independent samples, 8 but these clinical and neuroimaging research streams have largely progressed in parallel. Indeed, the only study we are aware of which has systematically evaluated various combinations of clinical and biological parameters, and validated the predictive algorithm across multiple sites, reported no advantage of including imaging data.…”

“…One rarely remarked upon limitation of the ‘psychosis’ prediction studies done to date is that most include a range of psychotic disorders as part of the group of about one-third or so considered to have become psychotic. 7 But, a notable minority of these have brief or transient psychoses that do not typically need ongoing treatment. And others have for example delusional disorders that are often treated, with some clinical trial justification, differently from schizophrenia.…”

“…Although transition rates vary, the generally observed rate of transition to ‘psychosis’ is 30–40% over 2–3 years of follow-up. Across studies, subthreshold symptom severity, poorer functioning and a family history of schizophrenia are consistent clinical predictors of transition 6 , 7 . Biological approaches tend to have focused on neuroimaging indices, usually involving complex machine learning analyses, some of which have since been replicated and validated in independent samples, 8 but these clinical and neuroimaging research streams have largely progressed in parallel.…”