Academic journal article Indian Journal of Psychiatry

What Is Schizophrenia: A Neurodevelopmental or Neurodegenerative Disorder or a Combination of Both? A Critical Analysis

Academic journal article Indian Journal of Psychiatry

What Is Schizophrenia: A Neurodevelopmental or Neurodegenerative Disorder or a Combination of Both? A Critical Analysis

Article excerpt

Byline: Swapnil. Gupta, Parmanand. Kulhara

The etiology of schizophrenia has been the focus of intensive research for a long time. Perspectives have changed drastically with the development of new investigative techniques. Clinical observations made by Kraepelin, Clouston, Bender, and Watt are now being complemented by neuroimaging and genetic studies to prove the neurodevelopmental hypothesis. At the same time, neuropathological and longitudinal studies of schizophrenia often support a neurodegenerative hypothesis. To provide a theoretical basis to the available evidence, another hypothesis called the progressive neurodevelopmental model has also emerged. This review presents some key evidence supporting each of these theories followed by a critical analysis of each.


Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. The study of the etiology of schizophrenia is ongoing although perspectives have changed. Various factors ranging from psychodynamic to autoimmune to genetic have been reported to be invoked in the causation of this disorder.

The proposition that schizophrenia may have its roots in early brain development dates back to Kraepelin and Bleuler, both having noted neurological and behavioral abnormalities in the childhood histories of their adult patients. Several others like Bender[sup] [1] and Watt[sup] [2] described similar abnormalities, but the theory that schizophrenia might be a developmental disorder was first proposed by Thomas Clouston[sup] [3] who called it a "developmental insanity". Advancing investigative technology spawned enthusiastic research in the neurobiology of schizophrenia. As scientists uncovered more facts about normal neural development and neurogenesis, the neural abnormalities found in schizophrenia were thought to be a result of aberrant neurodevelopment. As this course was pursued more actively, more and more evidence supporting a neurodevelopmental theory of schizophrenia emerged. Evidence accumulated from various types of studies, including those of obstetric complications, facial dysmorphogenesis, genetic neuroimaging, and neuropathological studies. This theory, however, left several vital questions unanswered. For example, how could a purely neurodevelopmental disorder manifest for the first time in an adolescent or an adult?

The neurodegenerative hypothesis has its beginnings in the descriptions of schizophrenia given by Kraepelin who popularized the term "dementia praecox," where inherent to its definition was the assertion of a chronic downhill course that is typical of neurodegenerative disorders. Studies of various types including neuroimaging, cognitive functions, and postmortem brain histopathology have been done to find support for this hypothesis.

Thorough analyses of both these theories as well as the redefinition of the concepts of neurodevelopment and neurodegeneration have led to a third possibility. A unifying hypothesis has been proposed that conceptualizes schizophrenia as a progressive neurodevelopmental disorder. The term may at first glance seem contradictory but has been made acceptable by the redefinition of the boundaries of neurodevelopment and neurodegeneration.

The following review attempts to re-examine the strengths and weaknesses of both these theories. A head-to-head comparison of the two theories is fallacious for two reasons: (i) n0 o researcher has ever claimed that schizophrenia is entirely neurodevelopmental or solely neurodegenerative, (ii) these theories are complementary rather than exclusive, because they can individually explain certain phenomena observed in the onset and course of schizophrenia, and put together, they can explain the onset as well as the course and outcome.

Normal neurodevelopment It must be remembered that development is a process that occurs in the normal human brain as a function of age. …

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