The Shape of the Neuron in Schizophrenia

Schizophrenia is defined by its core symptomatology, which includes thought disorder, psychosis (including delusions, hallucinations, and paranoia), and negative symptoms, the latter which include things like apathy, depression, and executive dysfunction.

Schizophrenia is also defined, however, by its characteristic regression. Unlike many cases of autism (regressive variants aside), the symptoms are largely present at the outset of postnatal development. Meanwhile, most first episodes in schizophrenia don’t occur until late adolescence or early adulthood, with the exception of rarer, more severe childhood- and adolescent-onset schizophrenia. Though it’s not considered strictly as a neurodegenerative disorder, it does share some commonalities with later onset dementias like Alzheimer’s. In fact, Alzheimer’s patients, depending upon the stage of their illness, can present with paranoia and delusions, as well as apathy, depression, and executive dysfunction. And as I covered in a previous blog, overt psychosis aside, acute schizophrenia can share many of the same symptoms that occur in autism, such as sensory issues, orientation to details, and the incapacity to see the “bigger picture”.

The regression that’s seen in schizophrenia may well be resultant from a loss of dendritic spines. Numerous studies, in fact, have shown again and again that there is reduced spine density in neurons of schizophrenics [1]. This is accompanied by reports of cortical volume loss without consistent loss in neuronal numbers. Imagine how a progressive loss of communicative fibers affects cognition. Like autism, schizophrenia may be a condition in part defined by “underconnectivity”, especially of disparate areas.

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To the right you can see an example of the loss of branching complexity in schizophrenia. Image borrowed from here.

What happens to the neurons just preceding the first episode? One thought is that, under some specific stressor, the molecular state of the neurons themselves regress. You’re familiar with the concept of “cellular differentiation” in which an immature cell, say a stem cell, differentiates and matures, both in shape and in molecular composition, to become another form of cell, perhaps a terminally-differentiated cell. This means, in theory, that this cell can no longer multiply and has achieved its final cellular identity.

Molecular studies show that a neuron, without particular in vitro coaxing, will never again be a progenitor cell; however, studies also suggest that neurons have the inherent capacity for a certain level of repair and regeneration. In order to grow and repair, the molecular state of the neuron appears to regress moderately, once again expressing telltale markers which are typically only associated with neural progenitors, such as certain chloride import and export channels. In addition, the neurons probably also reflect these molecular changes in changes to branching complexity and overall shape and form. As such, it’s possible that branches regress alongside the recapitulation of stem-like molecular markers.

It’s easy to envision a stressor triggering such events. And with neurons’ capacities to regress, it is also easy to see how regressive autism and schizophrenia may come about, if for different reasons. Both of these conditions have been shown to exhibit stem cell-like markers, such as increased chloride importer and decreased chloride exporter levels.

For most cases of schizophrenia, something about adolescence and its passing seems to increase vulnerability. Meanwhile, those cases who develop symptoms even earlier tend to be much more extreme, often also exhibiting some sort of intellectual or developmental condition prior to the first episode, suggesting that their thresholds for vulnerability are comparatively lower.

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