When Does Schizophrenia Begin?

For some illnesses, pathological changes begin years before symptoms appear. Alzheimer’s disease is a prime example. Although symptoms of dementia often are not apparent until persons reach their 70s or 80s, measurable changes in their brains start 20 or more years earlier. The possibility of detecting Alzheimer’s disease prior to the manifestation of clinical symptoms and initiating treatment in order to delay symptom onset may be achievable. Furthermore, for individuals who are at high risk to develop this disorder, it may be possible that treatments initiated prior to the beginning of the disease process may actually prevent the illness.

What about other brain disorders – in particular schizophrenia? Schizophrenia is a chronic disorder associated with “positive” symptoms such as hallucinations and delusions, “negative” symptoms such as social withdrawal and decreased motivation, and “cognitive” symptoms such as poor working memory and problems with attention. Positive symptoms usually become clinically evident during adolescence or early adulthood and are often the symptoms that trigger psychiatric evaluation and treatment. Can changes in brain function be detected prior to the appearance of overt psychotic symptoms? If so, this might provide an opportunity to initiate potentially preventative treatments.

A study published in JAMA Psychiatry by Josephine Mollon and colleagues attempts to address this question. These investigators analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC). This study recruited over 14,000 women living in Avon, England who gave birth to children between April 1, 1991, and December 31, 1992. Data have been collected on this cohort of children at regular intervals ever since.

Cognitive development was assessed at 18 months, 4 years, 8 years, 15 years, and 20 years of age. A variety of verbal and non-verbal skills were measured. At age 18, individuals underwent extensive psychological testing and were evaluated for the presence of various psychiatric disorders, including schizophrenia.

Analysis of these longitudinal data revealed that individuals who developed schizophrenia by age 18 had impaired development of verbal skills between 18 months and 4 years of age compared to controls without psychotic symptoms. This slower rate of developing verbal skills stabilized by the age of 8. Similarly, development of non-verbal cognitive skills was impaired between 18 months and 4 years of age, but these skills continued to lose ground throughout all ages examined. To be clear, individuals who went on to develop schizophrenia did develop verbal and non-verbal skills but at a slower rate than controls, and thus they were substantially impaired by the age at which clinical symptoms developed.

These data strongly support the idea that schizophrenia is a developmental disorder, i.e., a disorder that is caused by abnormal development of brain circuitry during the earliest years of life.

This work suggests that intervention strategies initiated in very young children may be able to delay symptoms and/or decrease the severity of symptoms. Strategies targeted toward augmenting language development or training children in non-verbal tasks may allow new brain wiring at an age when the brain is highly plastic and most capable of new programming. It is likely that the earlier an intervention takes place, the greater the possibility of success.

This study is important in that it demonstrates that abnormalities contributing to schizophrenia begin at a very early age. It also raises the possibility that the abnormalities may be partially, if not fully, reversible prior to the start of clinically evident symptoms. Cognitive impairment is a major cause of disability in those suffering from schizophrenia. If the early abnormalities are reversible or correctable, it may be possible to prevent some of the devastating outcomes associated with schizophrenia.

This post was written by Eugene Rubin MD, PhD and Charles Zorumski MD