Brain structural and neurofunctional correlates of liability to psychosis : a multimodal neuroimaging approach

Schizophrenia is one of the most debilitating and still not entirely understood mental diseases. Improvements in the treatment came hand in hand with an introduction of antipsychotics and thus with better understanding of neurobiology underlying its symptoms. Postmortem and imaging studies uncovered increase of ventricular volumes and reduction of total gray matter, white matter and whole brain volume. To distinguish which abnormalities were caused by illness itself and which (at least partially) by used medication was not possible. Recently, some studies appeared, that showed possible contribution of antipsychotics to the brain volume deficits or abnormalities. We reviewed existing publications in this field and contributed to discussion between research groups.
Corresponding to the staging in serious physical diseases (e.g. oncological and cardiovascular) the research in the prodromal stages of psychosis has progressed in the last period of time. Vulnerability- and psychosis-associated structural and functional brain abnormalities in a population at high clinical risk to develop psychosis were intensively studied over the past decade. Aiming to improve understanding of the psychosis in very early stages, we focused on prodromal stages of psychosis and published a meta-analysis. We reviewed the results from studies comparing at-risk mental state (ARMS) individuals with and without subsequent transition to psychosis and characterized neuroimaging markers of ongoing psychosis.
Additionally, we introduced a new concept of splitting ARMS population according to the duration of the Ôpsychosis risk syndromeÕ and their probability to develop psychosis. Based on this new concept we provided volumetric voxel-based and functional neuroimaging analysis of first episode of schizophrenia patients, ARMS individuals and healthy controls.
We found association between structural and functional abnormalities corresponding to the different transition probabilities and duration of ARMS. These abnormalities correlated with impairments in functioning and with negative symptoms. ARMS individuals with lower transition probability showed strikingly more gray matter volume in insula not only as compared to the ARMS with higher transition probability, but also as compared to the healthy controls. This higher gray matter volume can reflect protective Ð resilience factors or mechanisms. Thus, insular abnormalities distinguished different transition probabilities and resilience factors. Better understanding of resilience mechanisms can contribute to prevention and/or early treatment of individuals with high clinical risk for psychosis.
In future, by improving the understanding of emerging psychosis, we may be able to selectively treat those patients with the highest risk for psychosis. The treatment will be thus more efficient, selectively targeted and can integrate resilience-based non-pharmacological interventions to clinical psychiatry.