Schizophrenia researchers have long been puzzled about why the illness normally begins in adolescence when important risk factors, such as genetic loading and neonatal brain damage, are present from birth or sooner. Many believe that the answer to this puzzle could tell us a lot about the cause of the illness. We now have some good clues to this mystery.

We know, for example, that normal brain development leads to the loss of 30 to 40 percent of the connections (synapses) between brain cells during the developmental period from early life to adolescence. Brain cells themselves do not diminish in number during this period, only their connectivity. It appears that we may need a high degree of connectivity between brain cells in infancy to enhance our ability to learn language rapidly (toddlers learn as many as twelve new words a day). The loss of neurons during later childhood and adolescence, however, improves our ‘working memory’ and our efficiency to process complex linguistic information. When we are listening to someone talking, for example, and we miss part of a phrase or sentence because someone nearby coughs or sneezes, our working memory allows us to fill in the blank, using a memory store of similar familiar phrases we have heard before.

We now know that, for people with schizophrenia, this normally useful process of synaptic pruning has been carried too far, leaving fewer synapses in the frontal lobes and medial temporal cortex. In consequence, there are deficits in the interaction between these two areas of the brain in schizophrenia which reduce the adequacy of working memory. One intriguing computer modeling exercise suggests that decreasing synaptic connections and eroding working memory in this way not only leads to abnormalities in the ability to recognize meaning when stimuli are ambiguous but also to the development of auditory hallucinations.

It is possible, therefore, that this natural and adaptive process of synaptic elimination in childhood, if carried too far, could lead to the development of schizophrenia. If true, this would help explain why schizophrenia persists among humans despite its obvious functional disadvantages and its association with reduced fertility. The genes for synaptic pruning may help us refine our capacity to comprehend speech and other complex stimuli, but, when complicated by environmental assaults resulting in brain injury, the result could be symptoms of psychosis. As yet, this formulation is speculative, but it allows us to see more clearly how the environment may interact with our innate qualities to increase our predisposition to schizophrenia.