Why hasn’t the outcome of schizophrenia changed since the 1950s? 

Although there has been much research done on the etiology and treatment methods of schizophrenia since the 1950s, little progress has been made in terms of clinical outcomes. A few disheartening statistics demonstrate this well: the life expectancy of someone with schizophrenia is still almost 15 years shorter on average than that of a neurotypical person, and only 10% of people with schizophrenia will ever hold a job. However, medications that treat psychosis, the symptom most prominently associated with schizophrenia, are highly effective. In fact, after just 4 to 10 weeks of antipsychotic treatment, two-thirds of first-episode patients with schizophrenia do not show any signs of psychosis. 

Issues with consistent medication use in the schizophrenic population are partially to blame for the poor prognosis of schizophrenic patients in the long run. However, a unique hypothesis about this problem is proposed in this article; namely, that cognitive decline, not psychosis, should be the defining factor of schizophrenia. Psychologists Emil Kraepelin and Eugen Bleuler both believed that cognitive decline played a much more central role in schizophrenia than psychosis did. Since antipsychotics are so effective in controlling psychotic symptoms, but the prognosis for people with schizophrenia is not getting any better, it is logical to conclude that psychosis may be playing too large of a role in our current conception of schizophrenia.

What role does cognitive decline play in the development of schizophrenia? 

It has long been taught that schizophrenia begins in early adulthood. This conception has proven to be too simplistic. Foreboding signs of schizophrenia may begin a full 10 years or more before recognizable symptoms emerge. These signs are subtle, and consist of unusual cognitive, motor, and social behavior. Cognitive impairment, presenting as a lowered IQ, has been found to be quite a consistent similarity between children who later develop schizophrenia. This deficient IQ level can be seen long before psychosis emerges in the patient. Various longitudinal studies have found that relatively poor cognitive performance begins as early as age four in people who later develop schizophrenia. It is important to make the distinction that these strong links have been found between low cognitive ability and schizophrenia development, but not necessarily psychosis development.

How is abnormal brain maturation related to schizophrenia? 

After a groundbreaking study by Johnstone et al. was published in 1976, it has been known that patients with schizophrenia have reduced brain volume. More research has been done since, and it is clear that brain volumes are consistently smaller in patients with psychosis compared to neurotypical people. Further, studies were done on intracranial volume (ICV, also known as skull size) that showed that there were small but significant reductions in ICV in patients with schizophrenia versus controls. This is relevant because ICV is a very accurate indicator of brain expansion, meaning that patients with schizophrenia have stunted brain growth compared to the rest of the population. Some of this brain loss occurs far before symptoms of schizophrenia arise. In recent research concerning the brain-age gap (the difference between the actual age of a person and the examined age of their brain), it has been found that the brain age of schizophrenic patients is on average 3.6 years older than their chronological age. This abnormal maturation of the brain may begin whilst the patient is still an adolescent.

How do genetics affect the risk of developing schizophrenia? 

Schizophrenia was found to be a heritable disease shortly after it was defined as a disorder in the early 1900s. Genetics have been found to account for up to 85% of the risk of developing the disease. Using twin studies, it was found that 25% of the variance for the risk of developing schizophrenia was explained by cognitive impairment (lower IQ). Furthermore, 4% of the variance of lower IQ was itself explained by brain volume. Therefore, it can be concluded that abnormal brain development leads to cognitive deficits which play a large part in the genetic determination of developing schizophrenia. It is difficult for schizophrenia researchers to pin down the genetic causes of the disease on a more microscopic scale. Over 200 loci in the human genome have been implicated in increasing the risk of schizophrenia, however, each gene only accounts for a tiny proportion of genetic risk.

What should be the focus of future schizophrenia research be? 

The focus of schizophrenia research has long been on psychosis, as it has been seen as the diseases’ defining symptom for quite some time. Shifting the eye of schizophrenia research to cognitive decline during childhood and adolescence may help to identify cases earlier as well as help to improve the prognosis of schizophrenia which is currently a devastating disease in many ways. To study the cognitive decline in children who may develop schizophrenia in the future, it is important to put resources into large longitudinal studies that combine genetics, cognition, and brain imaging. This may also speed up the process of developing early interventions for youths who are at high-risk for the disease.