Cognitive impairment is ubiquitous in patients with schizophrenia (1
) and is considered core to the pathophysiology of the illness (2
). According to the neurodevelopmental model of schizophrenia, subtle behavioral, motor, and cognitive deviations are already apparent in childhood, years before overt clinical symptoms of adult schizophrenia manifest (3
). Childhood cognitive deficits precede the appearance of adult schizophrenia (4
). In a recent meta-analysis (8
), it was estimated that on average, individuals who develop adult schizophrenia exhibit an 8-point deficit (0.5 standard deviations) in their childhood IQ. Although the premorbid cognitive deficit in schizophrenia is now well documented, three fundamental questions pertinent to the neurodevelopmental model remain unresolved.
The first question concerns the developmental course of cognitive functions prior to the onset of illness. Three hypotheses put forward to describe the developmental course of premorbid cognitive functioning in schizophrenia are illustrated in . The developmental deterioration hypothesis (9
) predicts premorbid decline in cognitive performance. The developmental deficit hypothesis (13
) predicts static cognitive impairment, manifested as deficits that emerge early and remain stable. The developmental lag hypothesis (14
) predicts growth in cognitive abilities, but growth that lags behind the more rapid growth in healthy individuals.
Schematic Representation of Three Hypotheses of the Developmental Course of Premorbid Cognitive Functioning in Schizophreniaa
The second question is whether different cognitive functions follow similar or different developmental courses. Cross-sectional studies of premorbid cognitive functioning in schizophrenia conclude that most, if not all, cognitive functions are impaired. However, there is considerable variation in the magnitude of impairment across functions (4
). Some evidence suggests that the developmental course may differ for verbal versus nonverbal cognitive functions (4
). This hypothesis should be tested for multiple specific cognitive abilities.
The third question is whether neurodevelopmental deficits are specific to schizophrenia or are common to other psychiatric disorders. Evidence from research in cognitive epidemiology (20
) shows that low IQ elevates the risk of many psychiatric conditions, most notably depression (21
). Such findings underscore the need to test the disorder specificity (versus disorder generality) of cognitive deficits.
The existing literature does not provide adequate answers to these three questions because of the following five reasons. First, many studies have used follow-back analyses of clinical samples and samples of convenience that may not represent the population of individuals with schizophrenia. Second, most previous studies have assumed, but not tested, the specificity of premorbid cognitive deficits in schizophrenia. Third, most epidemiological studies examine an omnibus index of cognitive functioning, namely IQ. Such indexes summarize the overall integrity of the brain, but they cannot be used to test hypotheses about specific cognitive functions. Fourth, many studies have used retrospective assessments that can only serve as a proxy for actual cognitive performance, have a narrow range of scores, usually index global cognitive functioning, and are not time specific. Fifth, most longitudinal studies have collected cognitive data at only one point in time. Studying developmental change requires measuring cognitive functioning on multiple occasions prior to illness. Some studies have measured cognitive functioning on multiple occasions but using different tests at each occasion, making it difficult to evaluate change in specific functions.
In the present study, we report data from a multidisciplinary health and development investigation that has followed more than 1,000 children in the general population from birth to age 32 years. We identified case subjects meeting diagnostic criteria for schizophrenia or depression through age 32 years, spanning the peak age period for these psychiatric disorders. Multiple cognitive functions were repeatedly assessed from childhood to early adolescence prior to the onset of schizophrenia or depression.