Schizophrenia Is a Disorder of Aberrant Neurodevelopment: A Synthesis of Evidence from Clinical and Structural, Functional and Neurochemical Brain Imaging Studies

Article excerpt

Byline: Ganesan. Venkatasubramanian

Schizophrenia as a Disorder of Aberrant Neurodevelopment

Several reasons have been advanced to support the view that schizophrenia is a neurodevelopmental disorder.[sup] [1] The primary reason is that the onset of schizophrenia has a cumulative age incidence distribution or developmental function, that is nonlinear with a peak change in slope or acceleration that usually takes to occur during young adulthood. Given the plausibility of the existence of brain abnormalities in schizophrenia at the onset of the illness, it further seems reasonable to conceive the onset of schizophrenia as a neurodevelopmental disorder. Further support has been provided by epidemiological studies showing premorbid intellectual deficits dating back to the early development[sup] [2] and neuropathological studies showing altered cerebral cytoarchitecture indicative of a developmental rather that acquired encephalopathy.[sup] [3]

The main neurodevelopmental hypotheses for schizophrenia set forth in the last 10 years are relatively restricted and share three assumptions:[sup] [4]

*The primary pathogenetic defect is an early derangement of the orderly development of the central nervous system that occurs in the pre- or perinatal period; *The period of active operation of the causative agent is of short duration, meaning that it is essentially static; *The behavioral consequences of this static process remain relatively latent until long after the primary pathogenetic process has run its course.

Furthermore, aspects of illness suggesting neurodevelopmental deviation may not apply to all individuals and some authors have argued for neurodevelopmental and non-neurodevelopmental subtypes of the disorder[sup] [5] and even neurodegenerative subtypes of the disorder.[sup] [6]

However, neurodegenerative hypotheses of schizophrenia have been criticized mainly because of the following reason: gliosis, which is regarded as a necessary neuropathological hallmark of neuronal degeneration, has not been found in a number of carefully controlled postmortem studies in patients with schizophrenia. These neuropathological studies provide strong evidence against a classic neurodegenerative pathogenesis of schizophrenia.[sup] [1],[4] In addition, the failure of the first prospective CT studies of schizophrenia to show the same age-disproportionate progressive increase in ventricle-brain ratio after onset of illness that is seen in disorders such as Huntington's disease also rejects neurodegeneration.[sup] [4]

Some researchers have proposed another alternative that schizophrenia is a progressive neurodevelopmental disorder. This postulates that developmental mechanisms, such as apoptosis and pruning, can continue to go awry over many years without resulting in excessive gliosis. This accounts for both the neuropathological findings implicating prenatal pathology and the imaging findings (especially the recent Magnetic Resonance Imaging studies that report evidence for progressive brain changes in schizophrenia).[sup] [4] Thus, although schizophrenia is argued by a few as a neurodegenerative disorder,[sup] [6],[7] majority of the existing evidence points towards a neurodevelopmental etiopathogenesis.[sup] [1],[4]

Neurodevelopmental Hypothesis of Schizophrenia - Evidence Base

The tenets of the neurodevelopmental hypothesis of schizophrenia derive from observations of epidemiological, clinical and brain imaging evidence for neurodevelopmental deviance.[sup] [8] These include studies on schizophrenia patients examining obstetrical complications, age-at-onset (AAO), sex differences, minor physical anomalies (MPAs), neurological soft signs (NSS) and structural brain abnormalities. Other stigmata include abnormal dermatoglyphics and childhood neuromotor precursors of adult schizophrenic illness. This research paper attempts at providing an overview of evidence for neurodevelopmental basis for schizophrenia with specific focus on highlighting relevant Indian studies supporting this concept. …