‘Risk circuits’ for schizophrenia refined

By Eleanor McDermid, Senior medwireNews Reporter

A study sheds further light on the brain circuits that may underlie risk for schizophrenia.

The researchers used functional magnetic resonance imaging to look at connectivity between the striatum and prefrontal cortex (PFC), which has long been of interest in psychosis, partly because of the reputed role of some of this circuitry in associative learning and reward-based decision making.

They found that, compared with 26 mentally healthy controls, 19 patients with first-episode schizophrenia and 25 of their unaffected first-degree relatives showed altered connectivity between the PFC and all striatal regions except the dorsorostral putamen.

“Collectively, these results indicate that functional abnormalities of corticostriatal systems are apparent from the earliest stages of psychosis and may be more extensive than previously thought,” write lead study author Alex Fornito (Monash University, Clayton, Victoria, Australia) and team in JAMA Psychiatry.

The most prominent abnormality shared by the patients and their relatives was a gradient of connectivity such that there was hypoconnectivity between dorsal caudate and prefrontal regions but hyperconnectivity between ventral caudate and prefrontal regions.

Patients had more widespread connectivity abnormalities than their relatives, including some that were significantly associated with the severity of psychosis symptoms. However, the fact that unaffected relatives shared many abnormalities indicates that some connectivity changes cannot be a consequence of psychosis or its treatment, says the team. “Rather, they likely reflect a state-independent vulnerability marker.”

Fornito et al say that the presence of hyperconnectivity in patients and relatives indicates a general reorganization of frontostriatal systems, with greater integration between dorsal and ventral systems, given that controls had no significant functional connectivity between some of these regions – for example, between the superior ventral caudate and dorsolateral PFC.

The researchers stress that their methodology cannot directly determine whether the abnormal activity stems from the striatal or prefrontal areas. Nevertheless, they say that they might have pinpointed a “possible site of primary pathology” within the affected circuitry.

“The dorsal, associative striatum receives direct afferents from the PFC, but only projects back to the PFC indirectly via the pallidum and thalamus,” they explain. “The fact that we observed a risk-related reduction of functional connectivity between the PFC and dorsal caudate, but not along the striato-pallido-thalamic pathway, suggests that the abnormality lies in the direct afferent input provided to the dorsal caudate from the PFC rather than efferent outflow emanating from the striatum.”

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.