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Forum Discussion: Neurocognitive Dysfunction in Schizophrenia and Bipolar Disorder


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In our Forum discussion “journal club” series, the editors of Schizophrenia Bulletin provide access to the full text of a recent article. A short introduction by a journal editor gets us started, and then it's up to our readers to share their ideas and insights, questions, and reactions to the selected paper. So read on….

Simonsen C, Sundet K, Vaskinn A, Birkenaes AB, Engh JA, Færden A, Jónsdóttir H, Ringen PA, Opjordsmoen S, Melle I, Friis S, Andreassen OA. Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group. Schizophr Bull . 2009 May 14. Abstract

View Comments By:
SK Hill — Posted 30 October 2009
Eduard Vieta — Posted 2 November 2009


Background Text
By Gunvant Thaker, Professor and Chief, Schizophrenia Related Disorders Program, Maryland Psychiatric Research Center and Deputy Editor, Schizophrenia Bulletin

Historically, there has been an interest in understanding the commonality and differences between the clinical manifestations of schizophrenia and bipolar disorder. With the field focusing on the next iteration of the Diagnostic and Statistical Manual of Mental Disorders, DSM-V, this interest has intensified. Recent genetic findings that implicate sharing of several vulnerability chromosomal loci and genes by the two disorders add further fuel (Berrettini, 2003; Craddock et al., 2006). If some of the etiological factors are shared between the disorders, one of the important questions is to what extent the phenotypic expressions overlap, and where the two disorders diverge.

In this context, the recent paper by Simonsen and colleagues provides interesting data on neurocognitive dysfunction in the two disorders. In a sample of over 500 subjects, Simonsen and colleagues administered a comprehensive cognitive battery. They found that bipolar patients with a history of psychosis showed similar cognitive dysfunction as observed in schizophrenia and schizoaffective disorder, while bipolar patients without a history of psychosis showed poor performance only in processing speed. Impairments in several of the cognitive functions assessed in the study are also observed in non-ill, first-degree relatives of schizophrenia probands and are moderately heritable. This raises an interesting question: does the shared cognitive dysfunction among schizophrenia and bipolar disorder patients mark the shared genetic effects that are associated with vulnerability to psychosis?

References:
Simonsen C, Sundet K, Vaskinn A, Birkenaes AB, Engh JA, Færden A, Jónsdóttir H, Ringen PA, Opjordsmoen S, Melle I, Friis S, Andreassen OA. Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group. Schizophr Bull . 2009 May 14. Abstract

Berrettini W. Evidence for shared susceptibility in bipolar disorder and schizophrenia. Am J Med Genet C Semin Med Genet . 2003 Nov 15 ; 123C(1):59-64. Abstract

Craddock N, O'Donovan MC, Owen MJ. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr Bull . 2006 Jan 1 ; 32(1):9-16. Abstract

Comments on Online Discussion
Comment by:  SK Hill
Submitted 30 October 2009
Posted 30 October 2009

This is a challenging question. Guidelines from genetics research indicate that much larger studies with samples exceeding 10,000 are needed to identify meaningful associations. This is complicated by the low incidence rate of psychosis and high likelihood that multiple genes of small effects contribute to vulnerability. Although several risk genes have been implicated, it will be challenging to determine the effect of each risk gene, particularly in light of the many possible interactions. Improved understanding of shared genetic effects associated with psychosis is further complicated by the lack of clear boundaries between schizophrenia and psychotic mood disorders. Too many studies evaluating cognition in mood disorders are confounded by combining psychotic and non-psychotic samples. It will be important to start by separating these groups until the existing nosological distinction among psychotic disorders can be updated.

View all comments by SK HillComment by:  Eduard Vieta
Submitted 2 November 2009
Posted 2 November 2009

This study by Simonsen and colleagues brings back an old, unsolved question: Is psychosis a core symptom of schizophrenia and bipolar disorder, or just an epiphenomenon? The study correctly points out that psychosis is a major driver of most of the effects that we may be able to detect when comparing patients with schizophrenia and bipolar disorder with healthy controls or with non-psychotic bipolar subjects, but the question that remains is whether psychosis is just reflecting an underlying increased vulnerability for neurocognitive impairment or, rather, direct, neurotoxic effects of psychosis and increased dopamine turnover. Studies by the same Norwegian group (Simonsen et al., 2008) and our group (Torrent et al., 2006) indicate that even "mild" forms of bipolar disorder may carry some cognitive impairment, and therefore psychosis is not the only variable influencing cognition in bipolar illness. Other factors, such as genetics, obstetric complications, sub-threshold depression, number of episodes, substance abuse, treatment adherence, and medication (Vieta, in press) may have some effects.

This new study by Simonsen et al. clearly demonstrates that psychosis is a major player in the neurocognitive overlap between schizophrenia and bipolar illness. Further research is needed to ascertain whether psychosis is actually the cause or the consequence of cognitive impairment.

References:

Simonsen C, Sundet K, Vaskinn A, Birkenaes AB, Engh JA, Hansen CF, Jónsdóttir H, Ringen PA, Opjordsmoen S, Friis S, Andreassen OA. Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction. Bipolar Disord. 2008 Mar;10(2):245-55. Abstract

Torrent C, Martínez-Arán A, Daban C, Sánchez-Moreno J, Comes M, Goikolea JM, Salamero M, Vieta E. Cognitive impairment in bipolar II disorder. Br J Psychiatry. 2006 Sep;189:254-9. Abstract

Vieta E. The influence of medications on neurocognition in bipolar disorder. Acta Psychiatrica Scand. In press.

View all comments by Eduard Vieta