Trait or state? A longitudinal neuropsychological evaluation and fMRI study in schizoaffective disorder

Schizoaffective patients can have neurocognitive deficits and default mode network dysfunction while being acutely ill. It remains unclear to what extent these abnormalities persist when they go into clinical remission. Memory and executive function were tested in 22 acutely ill schizoaffective patients; they also underwent fMRI scanning during performance of the n-back working memory test. The same measures were obtained after they had been in remission for ≥ 2 months. Twenty-two matched healthy individuals were also examined. In clinical remission, schizomanic patients showed an improvement of memory but not of executive function, while schizodepressive patients did not change in either domain. All schizoaffective patients in clinical remission showed memory and executive impairment compared to the controls. On fMRI, acutely ill schizomanic patients had reversible frontal hypo-activation when compared to clinical remission, while activation patterns in ill and remitted schizodepressive patients were similar. The whole group of schizoaffective patients in clinical remission showed a failure of de-activation in the medial frontal gyrus compared to the healthy controls. There was evidence for memory improvement and state dependent changes in activation in schizomanic patients across relapse and remission. Medial frontal failure of de-activation in remitted schizoaffective patients, which probably reflects default mode network dysfunction, appears to be a state independent feature of the illness.

[1]  A. Gevins,et al.  Spatiotemporal dynamics of component processes in human working memory. , 1993, Electroencephalography and clinical neurophysiology.

[2]  R. Salvador,et al.  Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls , 2012, Psychological Medicine.

[3]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[4]  T. Suppes,et al.  Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia , 2013, BMC Medicine.

[5]  F. Schneider,et al.  Modulation of the default mode network is task-dependant in chronic schizophrenia patients , 2011, Schizophrenia Research.

[6]  Robin M. Murray,et al.  A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder , 2004, Schizophrenia Research.

[7]  Kangguang Lin,et al.  Neuropsychological performance in bipolar I, bipolar II and unipolar depression patients: a longitudinal, naturalistic study. , 2012, Journal of affective disorders.

[8]  E. Robins,et al.  Research diagnostic criteria: rationale and reliability. , 1978, Archives of general psychiatry.

[9]  J. Gabrieli,et al.  Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia , 2009, Proceedings of the National Academy of Sciences.

[10]  Peter Gallagher,et al.  A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. , 2006, Journal of affective disorders.

[11]  John Suckling,et al.  A longitudinal fMRI study of the manic and euthymic states of bipolar disorder. , 2010, Bipolar disorders.

[12]  R. Salvador,et al.  Validation of the Word Accentuation Test (TAP) as a means of estimating premorbid IQ in Spanish speakers , 2011, Schizophrenia Research.

[13]  G. Juckel,et al.  Cognitive impairment in patients with a schizoaffective disorder: a comparison with bipolar patients in euthymia , 2010, European journal of medical research.

[14]  Christos Pantelis,et al.  Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study , 2009, British Journal of Psychiatry.

[15]  P. J. McKenna,et al.  Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients , 2011, Schizophrenia Research.

[16]  R. Murray,et al.  A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. , 2004, Bipolar disorders.

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

[18]  J. Lagopoulos,et al.  An event-related functional MRI study of working memory in euthymic bipolar disorder. , 2007, Journal of psychiatry & neuroscience : JPN.

[19]  R. Salvador,et al.  Brain functional changes across the different phases of bipolar disorder. , 2015, The British journal of psychiatry : the journal of mental science.

[20]  J. Kasanin THE ACUTE SCHIZOAFFECTIVE PSYCHOSES , 1933 .

[21]  I. Nimmo-Smith,et al.  Hypofrontality in schizophrenia: a meta‐analysis of functional imaging studies , 2004, Acta psychiatrica Scandinavica.

[22]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[23]  Sophia Frangou,et al.  New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[24]  B. Cohen,et al.  "Schizoaffective disorder": an invalid diagnosis? A comparison of schizoaffective disorder, schizophrenia, and affective disorder. , 1980, The American journal of psychiatry.

[25]  Eduard Vieta,et al.  Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. , 2004, The American journal of psychiatry.

[26]  R. Heaton,et al.  What Do We Know About Neuropsychological Aspects Of Schizophrenia? , 2009, Neuropsychology Review.

[27]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[28]  V. Calhoun,et al.  Temporal lobe and “default” hemodynamic brain modes discriminate between schizophrenia and bipolar disorder , 2008, Human brain mapping.

[29]  J. Sanz,et al.  Behavioral Assessment of the Dysexecutive Syndrome Battery (BADS) in Schizophrenia: A Pilot Study in the Spanish Population , 2009, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[30]  Kang Sim,et al.  Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: Review of the evidence , 2013, Neuroscience & Biobehavioral Reviews.

[31]  Stephen M Smith,et al.  Applying FSL to the FIAC data: Model‐based and model‐free analysis of voice and sentence repetition priming , 2006, Human brain mapping.

[32]  R. Saan,et al.  Behavioural assessment of the dysexecutive syndrome (BADS) , 2012 .

[33]  T. Becker,et al.  Schizoaffective disorder–an ongoing challenge for psychiatric nosology , 2010, European Psychiatry.

[34]  Stephan Heckers,et al.  Is schizoaffective disorder a useful diagnosis? , 2009, Current psychiatry reports.

[35]  P. McKenna,et al.  Cognitive impairment in schizoaffective disorder: a comparison with non‐psychotic bipolar and healthy subjects , 2007, Acta psychiatrica Scandinavica.

[36]  M. Walshe,et al.  A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives , 2010, Psychological Medicine.

[37]  J A Swets,et al.  Signal detection and identification at successive stages of observation , 1978, Perception & psychophysics.

[38]  E. Pomarol-Clotet,et al.  Brain functional abnormality in schizo-affective disorder: an fMRI study , 2012, Psychological Medicine.

[39]  R. Salvador,et al.  Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network? , 2008, Psychological Medicine.

[40]  Ron Dumont,et al.  Wechsler Memory Scale–Third Edition , 2008 .

[41]  F. Bermejo,et al.  Estimation of Premorbid Intelligence in Spanish People with the Word Accentuation Test and Its Application to the Diagnosis of Dementia , 1997, Brain and Cognition.

[42]  R. Salvador,et al.  Bipolar depressed patients show both failure to activate and failure to de-activate during performance of a working memory task. , 2013, Journal of affective disorders.

[43]  A. Marneros Schizoaffective disorder: clinical aspects, differential diagnosis, and treatment , 2003, Current psychiatry reports.

[44]  Lori L. Altshuler,et al.  fMRI abnormalities in dorsolateral prefrontal cortex during a working memory task in manic, euthymic and depressed bipolar subjects , 2010, Psychiatry Research: Neuroimaging.

[45]  R. Salvador,et al.  Failure of de-activation in the medial frontal cortex in mania: evidence for default mode network dysfunction in the disorder , 2012, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

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

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

[48]  Vince D Calhoun,et al.  Resting state and task‐induced deactivation: A methodological comparison in patients with schizophrenia and healthy controls , 2009, Human brain mapping.

[49]  D. Weinberger,et al.  Common and Differential Pathophysiological Features Accompany Comparable Cognitive Impairments in Medication-Free Patients with Schizophrenia and in Healthy Aging Subjects , 2012, Biological Psychiatry.

[50]  M. Minzenberg,et al.  Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. , 2009, Archives of general psychiatry.