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New Imaging Study Shows How Schizophrenic Brains Regenerate

A new study points the way toward future new therapies and maybe even, eventually, a cure.

To say that cures are rarely discussed within the context of mental illness would be an understatement. The reality is much closer to never and this becomes even more true as the mental illness in question becomes more severe. A very large portion of common schizophrenic symptoms, known as negative symptoms, aren't even treatable—successfully nuking the vast hydra that is schizophrenia in any curative sense is hard to fathom. We don't even really know what causes it (but have some good ideas).


A group of researchers led by the Lawson Health Research Institute's Lena Palaniyappan published a study this week in Psychology Medicine offering new evidence that the brain is capable of reorganizing itself in ways that may lead to a reversal of the effects of schizophrenia: hinting at a cure, that is.

The Lawson group's work is based on MRI scans of 98 schizophrenic subjects and 83 control subjects. Of particular interest in the scans was the varying thicknesses of the brain's cortical layers between the two groups and also among schizophrenic subjects that have had the disorder for longer and shorter periods of time. It's been suggested that neural degeneration in this region is at the root of schizophrenia, though this is still widely debated, and this is where the study begins.

"Robust changes in grey matter are observed using structural magnetic resonance imaging (MRI) in patients with schizophrenia both before and after the onset of psychosis, and are linked to the clinical features of the illness," Palaniyappan and her team note. "Rather controversially, these neuroanatomical changes have been argued to be progressive in nature, indicating a deteriorating pathophysiological process."

Image: Palaniyappan et al

The progressive tissue-loss model of schizophrenia is justifiably controversial. As Palaniyappan's paper points out, MRI studies supporting this idea have found neurodegeneration occurring at rates so extreme that, if they were to continue through the progression of the illness, would result in there being literally no brain matter left after a couple of decades. And yet, even with such extreme rates of observed tissue loss, this deterioration doesn't seem to match very well the severity of clinical deterioration in patients. Moreover, some studies have even reported increases in cortical sizes as the disease progresses.


"In light of this evidence, neuroprogression, if present, is likely to be limited not only in time but also in spatial distribution, and occur alongside compensatory changes in the opposite direction," Palaniyappan writes. The brain heals, in other words, or at least has the capacity to. Indeed, researchers have previously observed clinical improvements coinciding with grey-matter increases.

The difficulty in making sense out of these neurological changes is in relating changes in one part of the brain to changes in other parts. So far, researchers have mostly just focused on degeneration/regeneration in parts of the brain where those processes occur the most consistently across patients. The approach taken by Palaniyappan and her team was to use pattern analysis to look at covariance widely across the brain—a pairing up of different regions and followed by an analysis of how each region changed in relation to the other.

The researchers' main finding is that, in terms of overall grey matter volume, schizophrenic brains become more "normal" the longer they're schizophrenic. That is, the largest deviations occur early in the illnesses onset. Moreover, patients with the most dramatic deviations from normal early in the illness were not necessarily the most likely to be better or worse off later in the illness than patients with less deviation.

"Taken together, these observations are suggestive of a compensatory/remodelling process contributing to the cortical thickness variations in schizophrenia," the paper concludes.

"These findings are important not only because of their novelty and the rigour of the study, but because they point the way to the development of targeted treatments that potentially could better address some of the core pathology in schizophrenia," offers the Lawson Institute's Jeffrey Reiss in a statement. "Brain plasticity and the development of related therapies would contribute to a new optimism in an illness that was 100 years ago described as premature dementia for its seemingly progressive deterioration."