Adolescent brain remodeling goes awry in schizophrenia

By Eleanor McDermid, Senior medwireNews Reporter

A crucial reorganization process that occurs in the adolescent brain may be disturbed in those who go on to develop schizophrenia, a study suggests.

The process involves the selective development of some strong long-distance connections. Normally, connectivity strength weakens with increasing distance (the negative anatomical distance function, or ADF), because of the higher metabolic cost of long-distance connections. But selective strong long-distance connections emerge during normal adolescent development, to produce an efficient adult brain.

Jianfeng Feng (University of Warwick, Coventry, UK) and colleagues now report significantly stronger negative ADF in 28 patients with schizophrenia than in 28 age-matched siblings without schizophrenia and 60 mentally healthy controls.

Also, the mean anatomical distance of the connections was significantly shorter in the patients than their siblings or the controls, indicating continued strong preference for shorter connections in the brains of the schizophrenia patients.

Patients and siblings both had an increase in the proportion and strength of short-range connections. However, while both also had a significant reduction in the proportion of long-range connections (>75.5 mm), siblings had an increase in the strength of these long-range connections, relative to controls, whereas patients had a reduction.

This suggests “some degree of recovery or compensation” in the siblings, the researchers write in Schizophrenia Bulletin. “This observation is strikingly reminiscent of the structural studies that demonstrate ‘normalization’ of deficits along the developmental trajectory in siblings.”

They add: “While higher genetic loading in patients could be invoked to explain the lack of such ‘recovery,’ another possibility is the effect of environmental agents such as cannabis and stimulants.”

The pronounced negative correlations between connection distance and strength affecting the long-range links were apparent in the frontal, insular, and subcortical regions in schizophrenia patients. Siblings, by contrast, had less marked negative correlations in the frontal and subcortical regions, and an unexpected positive correlation for the salience network.

The differences between patients and siblings in the salience network mostly involved connections between the insula and part of the orbitofrontal cortex (the rectus gyrus).

“These observations are interesting in the context of structural studies, which show that the anatomical changes pertaining to the insula is only apparent in patients and not siblings,” comments the team.

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