October 17, 2004

How does the brain change in schizophrenia?

Neuroplasticity and schizophrenia.

Frost DO, Tamminga CA, Medoff DR, Caviness V, Innocenti G, Carpenter WT.
Biol Psychiatry. 2004 Oct 15;56(8):540-3.

This article was based on a workshop sponsored by the International Congress on Schizophrenia Research that looked at how changes in the brain's structure and function (neuroplasticity) affect schizophrenia. The workshop brought together researchers specializing in schizophrenia as well as other doctors who try to understand how the brain works. By using neuroplasticity as a way to understand the illness, they wanted to find special ways to increase our knowledge and understanding of schizophrenia, its treatment and its prevention. This has already been done in other medical conditions For example, those who are deaf or blind from a young age show that lesions/cuts in one part of the brain can cause functional changes in other parts of the brain. This is evidence of neuroplasticity and how it can help us understand behavior changes.

Changes in the brain occur during normal brain development, help with learning and memory and occur in other diseases such as epilepsy. Since it is often difficult to look at brain cells directly, researchers have tried to look at the neuroplasticity in schizophrenia in indirect ways. They've looked at 1) observable behavioral changes (phenotypes) as they emerge, 2) early risk factors for schizophrenia and 3) the what happens over time due to the disease and its response to medication.

Based on this type of research, the workshop outlined different stages in the development of schizophrenia with respect to brain changes. These were:

1) Prodromal stage: This can be either months to years (slow onset) or can be as fast as weeks to months. With a slow onset, this could reflect increasing changes in the brain over time or a response to altered brain activity. In this stage, some changes in behavior are noticed, although not all patients with such symptoms will have schizophrenia. There is much more work needed at this stage to figure out the risk factors for later psychotic symptoms.

2) Psychosis onset stage: This is when symptoms of psychosis begin (eg hearing voices). There are two hypotheses for how neuroplasticity could contribute to schizophrenia. The Developmental hypothesis says that there are abnormal changes that occur early in life (perhaps even during conception of the baby) which reach critical levels and then result in the disease later on. The Two Hit hypothesis says that an early developmental defect could increase an individual's chances of becoming psychotic in response to a second trigger that occurs at the end of the teenage years. This then affects how the illness changes over time. Since the connections in the brain are complex, it may be difficult to bring the brain back to a "normal" state once psychosis develops. But, with medications, it may be possible to bring the brain back to a near-normal pattern, even while the underlying brain system remains abnormal.

3) Symptom stabilization phase: After taking regular medication, about 25-35% of patients can go back to a 'quiet period' where psychotic symptoms decrease. This could be because of brain plasticity that occurs with medications, where the brain adapts to the drugs and results in a state of reduced risk for relapse. But the early fluctuations in psychosis may have already affected social, cognitive and emotional functioning. More research is needed to figure out things that can help stabilize the brain.

4) Late-life heterogeneity phase: Long-term studies of schizophrenia show a reduction in psychosis and improved function with aging, although some patients can go into a rapidly progressing dementia after age 65. These aging-related changes could be due to hormones and more research is needed to understand these changes in older people.

In terms of future research, the workshop participants hoped to introduce new ways of looking at schizophrenia and call for more research to figure out which features of the brain are normal or abnormal at various ages, different stages of the disease and different behaviors due to the illness. More research is needed with children who are at high risk for the illness as well as the effects of chronic medicine on the brain over time. The idea of schizophrenia as a syndrome with a spectrum of those who have active psychosis and those who do not is also pushed forward by this article.

Click here to find this article on PubMed

Author: Farzin Irani


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