Abstract
Background: Bipolar disorder and schizophrenia are severe neuropsychiatric disorders that are highly heritable. Although both disorders partly share clinical characteristics, it is unclear whether bipolar disorder patients have similar lower IQ as that observed in schizophrenia patients. In the first part of this thesis we investigate Intelligence Quotient (IQ) and
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educational performance in bipolar disorder patients, schizophrenia patients, relatives and controls. In order to illuminate determinants for cognitive dysfunction in bipolar disorder patients, we investigate the relationship of brain volume, genetic vulnerability for schizophrenia, medication use and the experience of trauma with cognitive function in these patients. In the second part of this thesis, we focus on the non-clinical variant of psychosis, psychotic-like experiences. Specifically, we study advanced paternal age and cannabis use as possible risk factors for psychotic-like experiences in adolescents and young adults from the general population.
Method: We used data of three Dutch studies, Bipolar Genetics, Dutch Genetic Risk and Outcome in Psychosis (GROUP) and CannabisQuest. We estimated IQ by four subtests (Information, Block Design, Digit Symbol Coding and Arithmetic) of the Wechsler Adult Intelligence Scale-III (WAIS-III). We compared IQ and educational performance of bipolar disorder type I patients (BD-I), schizophrenia patients, parents, siblings and healthy controls in a cross-sectional design. Subsequently, we investigated the relationship between IQ and brain volume in BD-I patients using structural T1 images of the brain. We also examined the role of medication use and a history of trauma as potential confounders of the relationship between brain volume and IQ. In addition, we calculated polygenic schizophrenia scores and investigated the relationship with IQ in BD-I patients, relatives and controls. Furthermore, we studied the relationship of advanced paternal age and psychotic-like experiences in adolescents and young adults from the general population. To examine the relationship between change in cannabis use and psychotic-like experiences we used a longitudinal design. We used analyses of variance, regression and mixed-effects models for our analyses.
Results: Patients with BD-I were more likely to have completed the highest level of education (OR=1.88 [1.66-2.70]) despite having a lower IQ compared with controls (β=-9.09, SE=1.27, p<0.001). In contrast, schizophrenia patients showed a lower IQ and completed lower educational levels compared with controls. Siblings of both patient groups had a significantly lower IQ than controls, but did not differ on educational performance. Parents of BD-I patients did not differ on IQ from parents of schizophrenia patients, but had completed higher educational levels. The lower IQ we found in BD-I patients was only partly mediated by smaller brain volume. Lithium use, but not a history of trauma nor polygenic schizophrenia scores was related to lower IQ in BD-I patients. In addition, advanced paternal age was not associated with psychotic-like experiences. However, change in cannabis use was associated with a change in frequency of psychotic-like experiences; decreased cannabis use was associated with a decrease in total psychotic-like experiences (β=-0.096, p=0.01) and increased cannabis use was related to increased positive symptoms (β=0.07, p=0.02) at follow-up.
Conclusion: The main finding of this thesis is that BD-I patients have higher educational performance, but lower general cognitive function after illness onset compared with healthy controls. This is in stark contrast to cognitive function in schizophrenia patients, in which cognitive decline precedes the first psychosis by almost a decade and remains present after illness onset. Of the determinants that we investigated we found that smaller brain volume and lithium use only partly explained lower IQ in BD-I patients, suggesting that other (illness-related) factors influenced cognitive function.
Overall, this thesis provides support for the notion that cognitive function is a distinctive characteristic of neuropsychiatric disorders.
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