Working memory networks and activation patterns in schizophrenia and bipolar disorder: comparison with healthy controls

Background Schizophrenia and bipolar disorder are severe mental disorders with overlapping genetic and clinical characteristics, including cognitive impairments. An important question is whether these disorders also have overlapping neuronal deficits. Aims To determine whether large-scale brain networks associated with working memory, as measured with functional magnetic resonance imaging (fMRI), are the same in both schizophrenia and bipolar disorder, and how they differ from those in healthy individuals. Method Patients with schizophrenia (n = 100) and bipolar disorder (n = 100) and a healthy control group (n = 100) performed a 2-back working memory task while fMRI data were acquired. The imaging data were analysed using independent component analysis to extract large-scale networks of task-related activations. Results Similar working memory networks were activated in all groups. However, in three out of nine networks related to the experimental task there was a graded response difference in fMRI signal amplitudes, where patients with schizophrenia showed greater activation than those with bipolar disorder, who in turn showed more activation than healthy controls. Secondary analysis of the patient groups showed that these activation patterns were associated with history of psychosis and current elevated mood in bipolar disorder. Conclusions The same brain networks were related to working memory in schizophrenia, bipolar disorder and controls. However, some key networks showed a graded hyperactivation in the two patient groups, in line with a continuum of neuronal abnormalities across psychotic disorders.

[1]  Nick Craddock,et al.  Psychosis genetics: modeling the relationship between schizophrenia, bipolar disorder, and mixed (or "schizoaffective") psychoses. , 2009, Schizophrenia bulletin.

[2]  I. Melle,et al.  The validity of d prime as a working memory index: Results from the “Bergen n-back task” , 2010, Journal of clinical and experimental neuropsychology.

[3]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[4]  I. Melle,et al.  Neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends on history of psychosis rather than diagnostic group. , 2011, Schizophrenia bulletin.

[5]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[6]  S. Borgwardt,et al.  Parietal Lobes in Schizophrenia: Do They Matter? , 2011, Schizophrenia research and treatment.

[7]  James McKirdy,et al.  Prefrontal function and activation in bipolar disorder and schizophrenia. , 2008, The American journal of psychiatry.

[8]  Stephen M. Smith,et al.  Advances and Pitfalls in the Analysis and Interpretation of Resting-State FMRI Data , 2010, Front. Syst. Neurosci..

[9]  K Kroenke,et al.  Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. , 1994, JAMA.

[10]  J. Stockman,et al.  Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study , 2010 .

[11]  Theo G. M. van Erp,et al.  Re-evaluating dorsolateral prefrontal cortex activation during working memory in schizophrenia , 2009, Schizophrenia Research.

[12]  I. Melle,et al.  Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder , 2007, Psychological Medicine.

[13]  W. Carpenter,et al.  Will The Kraepelinian Dichotomy Survive DSM-V? , 2009, Neuropsychopharmacology.

[14]  Heather C Whalley,et al.  Review of functional magnetic resonance imaging studies comparing bipolar disorder and schizophrenia , 2012, Bipolar disorders.

[15]  F. M. van der Veen,et al.  FMRI, antipsychotics and schizophrenia. Influence of different antipsychotics on BOLD-signal. , 2010, Current pharmaceutical design.

[16]  Liberty S. Hamilton,et al.  Alterations in functional activation in euthymic bipolar disorder and schizophrenia during a working memory task , 2009, Human brain mapping.

[17]  M. Egan,et al.  Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. , 2003, The American journal of psychiatry.

[18]  Medial prefrontal cortical activation during working memory differentiates schizophrenia and bipolar psychotic patients: A pilot FMRI study , 2010, Schizophrenia Research.

[19]  I. Melle,et al.  Decreased self-reported arousal in schizophrenia during aversive picture viewing compared to bipolar disorder and healthy controls , 2011, Psychiatry Research.

[20]  R. Coppola,et al.  Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. , 2000, Cerebral cortex.

[21]  V. Calhoun,et al.  Exploring the Psychosis Functional Connectome: Aberrant Intrinsic Networks in Schizophrenia and Bipolar Disorder , 2012, Front. Psychiatry.

[22]  A M McIntosh,et al.  Hippocampal function in schizophrenia and bipolar disorder , 2009, Psychological Medicine.

[23]  Jared X. Van Snellenberg,et al.  Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. , 2009, Archives of general psychiatry.

[24]  M. D’Esposito,et al.  Estrogen Shapes Dopamine-Dependent Cognitive Processes: Implications for Women's Health , 2011, The Journal of Neuroscience.

[25]  H. Möller.  Is the Overlap of Neurobiological and Psychopathological Parameters Large Enough to Give up the Dichotomic Classification , 2010 .

[26]  H. Möller.  Bipolar disorder and schizophrenia: distinct illnesses or a continuum? , 2003, The Journal of clinical psychiatry.

[27]  Michael F. Green,et al.  Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. , 2006, The Journal of clinical psychiatry.

[28]  S. Marder.  Initiatives to promote the discovery of drugs to improve cognitive function in severe mental illness. , 2006, The Journal of clinical psychiatry.

[29]  U. Habel,et al.  Neural correlates of working memory dysfunction in first-episode schizophrenia patients: An fMRI multi-center study , 2007, Schizophrenia Research.

[30]  Aapo Hyvärinen,et al.  Validating the independent components of neuroimaging time series via clustering and visualization , 2004, NeuroImage.

[31]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[32]  D. Glahn,et al.  Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia , 2005, Human brain mapping.

[33]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[34]  V. Schmithorst,et al.  Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task. , 2004, Bipolar disorders.

[35]  R. Spitzer.  Utility of new procedure for diagnosing mental disorders in primary care , 1994 .

[36]  K. Hugdahl,et al.  Brain activation measured with fMRI during a mental arithmetic task in schizophrenia and major depression. , 2004, The American journal of psychiatry.

[37]  Kathryn M. McMillan,et al.  N‐back working memory paradigm: A meta‐analysis of normative functional neuroimaging studies , 2005, Human brain mapping.

[38]  M. Phillips,et al.  Effects of medication on neuroimaging findings in bipolar disorder: an updated review , 2012, Bipolar disorders.

[39]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[40]  Mary L. Phillips,et al.  Deconstructing Bipolar Disorder: A Critical Review of its Diagnostic Validity and a Proposal for DSM-V and ICD-11 , 2007, Schizophrenia bulletin.

[41]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.