Trait or state? A longitudinal neuropsychological evaluation and fMRI study in schizoaffective disorder
Introduction
Since the first description of schizoaffective disorder in 1933 (Kasanin, 1933), its nosological status has been debated repeatedly (Pope et al., 1980, Marneros, 2003, Heckers, 2009, Jager et al., 2011). This uncertainty remains until today, with DSM-V considering removing it as a separate category and instead adding mood symptoms as a dimension to schizophrenia and schizophreniform disorder. However, the category was ultimately maintained; it was felt that there was not enough neurobiological data to support this motion (Allin et al., 2010, Cosgrove and Suppes, 2013).
From a neuropsychological point of view, cognitive impairment, mainly attention and memory deficits and executive dysfunction, is well documented in patients with schizoaffective disorder (e.g. Torrent et al., 2007, Bora et al., 2009, Studentkowski et al., 2010, Amann et al., 2012). Conversely, there exists less functional neuroimaging data: Our group recently published results of 32 acutely ill schizoaffective patients who, using a working memory task, activated prefrontal, parietal and temporal regions significantly less than healthy subjects (Madre et al., 2013). They also showed failure of de-activation in the medial frontal cortex which was more pronounced in the schizodepressed than in the schizomanic group. The finding of failure of deactivation was interpreted as evidence of dysfunction in the so-called default mode network, a series of interconnected brain regions which are metabolically active at rest but whose activity diminishes while the brain performs a wide range of cognitive tasks (Gusnard and Raichle, 2001, Raichle et al., 2001). Similar failure of de-activation during cognitive task performance has also been found in schizophrenia (Pomarol-Clotet et al., 2008, Whitfield-Gabrieli et al., 2009, Milanovic et al., 2011, Salgado-Pineda et al., 2011, Schneider et al., 2011) and bipolar disorder (Allin et al., 2010, Fernandez-Corcuera et al., 2013, Pomarol-Clotet et al., 2012).
A question that has not yet been addressed in the literature is whether and to what extent neuropsychological and functional imaging changes seen in schizoaffective disorder persist into remission or in other words: Are detected abnormalities a state or trait phenomenon of the disease? This is pertinent to the relationship of the disorder to schizophrenia and bipolar disorder, since neuropsychological deficits in the former disorder are widely considered to be static and unchanging, whereas those in bipolar disorder are presumed to resolve with clinical remission (e.g. Murray et al., 2004), even if the phenomenon of euthymic cognitive impairment indicates that this is not complete in all cases (e.g. Martinez-Aran et al., 2004, Robinson et al., 2006). Similarly, while functional imaging changes in schizophrenia are usually considered to be persistent, studies comparing patients in different phases of bipolar disorder, together with a small number of longitudinal studies, clearly point to changes between phases of illness and euthymia (Chen et al., 2010, Lim et al., 2013).
The present study was undertaken to examine the neuropsychological and functional neuroimaging features of schizoaffective disorder from a longitudinal perspective. We used a sample that contained roughly equal numbers of schizomanic and schizodepressive patients. Participants were studied when they were ill, and again when they were in clinical remission. We hypothesized that brain function, measured with cognitive tests and fMRI, differed in the two states.
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Participants
The patient sample consisted of 22 patients with schizoaffective disorder, bipolar type and were part of the sample of a previously published study of our group (Madre et al., 2013). They all met Research Diagnostic Criteria (RDC) (Spitzer et al., 1978) for schizoaffective disorder, based on a psychiatrist interview and the review of case-notes. We used these criteria because they are the most detailed of all available criteria for schizoaffective disorder. They posit that patients show
Demographic and clinical data
Demographic and clinical data for the schizoaffective patients and controls are shown in Table 1.
Memory and executive test performance
When compared to clinical remission, the schizomanic group showed a significant improvement in memory (WMS: 29 ± 5 vs. 36 ± 9, p = 0.036) but not in executive function (BADS: 76 ± 21 vs. 80 ± 20, p = 0.67). In contrast, there were no changes on either measure in the schizodepressive patients in comparison to clinical remission (WMS: 30 ± 6 vs. 31 ± 9, p = 1; BADS: 67 ± 27 vs. 78 ± 28, p = 0.55). The whole group of
Discussion
To the best of our knowledge, this study is the first to examine changes in neuropsychological performance and brain activation patterns in schizoaffective disorder longitudinally, comparing illness and remission. We found some evidence of improvement in memory in the schizomanic sample once in clinical remission but no changes in executive function in this group and no changes in either cognitive domain in the schizodepressive group. Furthermore, changes in brain activation were observed,
Role of Funding Source
The study received support by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and grant support from the Instituto de Salud Carlos III (Spanish Ministry of Health) by a Miguel Servet Research Contract to B. L. Amann (CP06/0359) and two specific research projects to B.L. Amann (PI07/1278 and PI10/02622).
Contributors
MM, EPC, and BLA designed the study and wrote the protocol. MM and BLA managed the literature searches. BLA, FP and MM recruited patients and followed them up. JR, MM, SA and RL undertook the statistical and neuroimaging analysis. MM and BLA wrote the first draft of the manuscript which was revised by EPC. All authors contributed to and have approved the final manuscript.
Conflict of interest
All authors exclude any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could have inappropriately influenced, or be perceived to influence, their work.
Acknowledgements
We acknowledge the generous support by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and grant support from the Instituto de Salud Carlos III (Spanish Ministry of Health): Miguel Servet Research Contract to B. L. Amann (CP06/0359), R. Salvador (CP07/00048), and E. Pomarol-Clotet (CP10/00596); Río Hortega research contract to J. Radua (CM11/00024); Research Projects to B.L. Amann (PI07/1278 and PI10/02622), E. Pomarol-Clotet (PI10/01058) and R. Salvador (PI05/1874). We
References (51)
- et al.
Estimation of premorbid intelligence in Spanish people with the Word Accentuation Test and its application to the diagnosis of dementia
Brain Cogn.
(1997) - et al.
Common and differential pathophysiological features accompany comparable cognitive impairments in medication-free patients with schizophrenia and in healthy aging subjects
Biol. Psychiatry
(2012) - et al.
Bipolar depressed patients show both failure to activate and failure to de-activate during performance of a working memory task
J. Affect. Disord.
(2013) - et al.
Spatiotemporal dynamics of component processes in human working memory
Electroencephalogr. Clin. Neurophysiol.
(1993) - et al.
Validation of the Word Accentuation Test (TAP) as a means of estimating premorbid IQ in Spanish speakers
Schizophr. Res.
(2011) - et al.
New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2004) - et al.
Schizoaffective disorder—an ongoing challenge for psychiatric nosology
Eur. Psychiatry
(2011) - et al.
Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: review of the evidence
Neurosci. Biobehav. Rev.
(2013) - et al.
Medial prefrontal cortical activation during working memory differentiates schizophrenia and bipolar psychotic patients: a pilot FMRI study
Schizophr. Res.
(2011) - et al.
A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder
Schizophr. Res.
(2004)
A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder
J. Affect. Disord.
Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients
Schizophr. Res.
Modulation of the default mode network is task-dependant in chronic schizophrenia patients
Schizophr. Res.
Advances in functional and structural MR image analysis and implementation as FSL
Neuroimage
fMRI abnormalities in dorsolateral prefrontal cortex during a working memory task in manic, euthymic and depressed bipolar subjects
Psychiatry Res.
Neuropsychological performance in bipolar I, bipolar II and unipolar depression patients: a longitudinal, naturalistic study
J. Affect. Disord.
A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives
Psychol. Med.
Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls
Psychol. Med.
Applying FSL to the FIAC data: model-based and model-free analysis of voice and sentence repetition priming
Hum. Brain Mapp.
Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study
Br. J. Psychiatry
Temporal lobe and "default" hemodynamic brain modes discriminate between schizophrenia and bipolar disorder
Hum. Brain Mapp.
A longitudinal fMRI study of the manic and euthymic states of bipolar disorder
Bipolar Disord.
Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia
BMC Med.
Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia
Hum. Brain Mapp.
Searching for a baseline: functional imaging and the resting human brain
Nat. Rev. Neurosci.
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