Murray et al. (2004) revisited: is bipolar disorder identical to schizophrenia without developmental impairment?

In 2004, Murray et al. (1) suggested that the main difference between bipolar disorder (BPD) and schizophrenia (Sz) was a larger prevalence of developmental impairments in the latter. A number of recent articles in Acta Psychiatrica Scandinavica suggest that categories of affective and non-affective psychosis may be similar in their pattern of associations with measures as diverse as social cognition (2), brain volumes (3) and metabolic dysregulation (4), begging the question what the actual status is of the prediction offered by Murray et al. more than 5 years ago. These issues are particularly important given the upcoming revisions of diagnostic systems in psychiatry: how should bipolar disorder and schizophrenia be classified in DSM-V and ICD-11? A review was conducted of studies focussing on this issue, with a special focus on work published in the last 10 years; results are displayed in Table 1 below. Both Sz and BPD have onset in adolescence and young adulthood, with an earlier onset in men. The incidence of both disorders is low and associated with a high prevalence:incidence ratio, indicative of a high rate of chronicity. Schizophrenia patients have high rates of affective symptoms, although lower than in BPD, and bipolar patients have negative symptoms and cognitive impairment, although lower than in Sz. The diagnostic contrast between Sz and BPD is high for affective symptoms, but this is mostly due to artificial diagnostic exclusion criteria. Sz and BPD have correlated genetic liabilities, some of which is becoming substantiated in recent genome-wide molecular genetic association studies. Of interest, however, is the fact that genetic risk for Sz is strongly expressed as neurocognitive impairment whereas genetic risk for BPD is only weakly expressed in the neurocognitive domain. Danish studies have shown that BPD and Sz have a high population comorbidity index; general population studies have shown that both BPD and Sz phenotypes are associated with psychometric risk states in healthy individuals, and that BPD and Sz psychometric risk states are similarly highly comorbid with each other. Risk factors representing social stress and defeat as well as early emotional alterations are associated with both BPD and Sz whereas risk factors reflecting early motor and cognitive alterations appear specific for schizophrenia. Interesting is the differential association with growing up in an urban environment (not associated with bipolar disorder), suggesting that this exposure impacts on specific developmental alterations associated with schizophrenia. The literature on neuroimaging, biological variables and prenatal life suggests differences and similarities as regards their prevalences in Sz and BPD; firm conclusions, however, cannot be drawn because of many methodological constraints and the lack of direct comparisons. In conclusion, science is catching up with century-old diagnostic traditions in psychiatry. It is becoming apparent that due to the strict separation imposed by DSM and ICD on the domains of affective and non-affective psychotic disorder, major opportunities have been missed to study the causes and treatment of psychiatric disorders. Psychotic disorders appear to be originating from (partly) overlapping areas of risk, one more developmental associated with cognitive impairment, and one more associated with affective dysregulation. It has been suggested that where these areas of risk overlap and interact with environmental risks, delusions and hallucinations may ensue through a final common pathway of dopamine dysregulation and affective cognitive biases (5). Therefore an elegant way of adapting the revisions of DSM and ICD diagnostic manuals to the scientific reality is to keep diagnostic categories more or less as they were and add cross-disorder dimensions of psychopathology, as depicted in Fig. 1. The simple addition of dimensions would finally clear the way for an official cross-diagnostic approach in psychiatry, ending a dysfunctional and rigid system of artificial partitioning. A combined dimensional and categorical system of diagnosis of psychotic disorders. Categorical diagnoses of schizophrenia (yellow), bipolar disorder (brown), and schizoaffective disorder (pink) are accompanied by a patient’s quantitative scores (connected by red lines) on five main dimensions of psychopathology. Nil Kaymaz is supported by the Netherlands Organisation for Scientific Research (NWO) under project number: 017.002.048.