Comparative Cognitive Impairment in Schizoaffective Disorder

1. Cognitive impairment in schizoaffective disorder: greater or lesser impairment than schizophrenia or bipolar disorder? Carla Torrent Bipolar Disorder Program Hospital Clínic Barcelona IRPB, Lisbon, 26th april 2015

2. Neurocognition and schizoaffectivedisorder (SAD) • The classical, kraepelinian classification of mental disorders makes a distinction between dementia praecox and manic-depressive disorder. • In clinical practice, some patients present a mixture of schizophrenic and affective signs and symptoms. • In more recent nosologic systems, a new diagnostic category: schizoaffective disorder • A form of schizophrenia (SZ) • A form of bipolar disorder (BD) • An independent disorder • A disorder intermediate between SZ and BD One of the aims of research on neurocognition is to validate these diagnostic categories.

3. Psychiatric disorders are associated with complex patterns of cognitive impairment • Attention • Executive function • Verbal learning and memory • Speed of processing • Social cognition • Language Environmental Genetic Epigenetic Developmental Adapted from Millan et al., Nature, 2012

4. Cognitive impairment by cognitive domains Millanet al, 2012

5. Epidemiological, genetic, neuroimaging and neurocognitive studies show similarities between SZ and BD.

6. Cognitive impairment in SQZ and BD Schizophrenia Bipolar disorder • Prevalence 85-100% • Impairment across domains deficits 1-2 SD (verbal memory and processing speed) • Present at illness onset and remain relatively stable over the course of the illness • Do not change substantially with antipsychotic medications • Account for much of the functional disability associated with the illness. • Broad cognitive impairment is not attributable to reduced general intellect • Prevalence 40-60% • Cognitive impairment during remission • Impairments present early in the course of illness • Do not change substantially with available treatments • Bipolar I > Bipolar II • Higher number of manic episodes • Related to functional dysfunction • Increased in patients with history of psychotic symptoms

7. Cognitive development in subjects with schizophrenia, bipolar disorder and healthy controls Lewandowski et al, Psych Med, 2010

8. A longitudinal study of cognitive functioning in schizophrenia N=132 Mean age: 43.7 years The results showed an absence of cognitive decline for most measures and modest gains in some measures over a period of up to 10 years Dickerson et al, Schiz Res, 2014

9. Premorbid intellectual, behavioral and language functioning in schizophrenic, schizoaffective and nonpsychotic bipolar patients SAD showed premorbid deficits on 3 of 4 intellectual measures, as well as on four of 5 behavioral measures. Future SAD scored worse than future BD on all four premorbid intellectual measures and on the reading and comprehension tests. Reichenberg et al, Am J Psychiatry, 2002

10. Neuropsychologicalfunction and dysfunction in schizophrenia and psychoticaffectivedisorders N=235 Prevalence of NP normalityrangedbetween:16% and 45% in schizophrenia, 20% and 33% in schizoaffectivedisorder, 42% and 64% in bipolar disorder, and 42% and 77% in depression Allgroupsdemonstratedimpairments in allcognitivedomains. However, SZ patientswere more impairedthantheothergroups. Reichenberg et al, Schizophr Bull, 2009

11. Studiescomparing SAD with SZ Cognitive deficits in SAD do not differ significantly from those of SZ. In the absence of comparisons with BD, no conclusions can be drawn with regard to SAD as a form of SZ or an intermediate disorder between BD and SZ. In some studies SZ and SAD patients were pooled together.

12. Studiescomparing SAD with SZ • In other studies, patients with psychotic disorders and those with affective disorders presenting psychotic symptoms were pooled together. Beatty et al, 1993; Bornstein et al, 1990; Evans et al, 1999; Glahn et al, 2006; Goldstein et al, 2005; Gooding et al, 2002; Jeste et al, 1996; Miller et al, 1996; Stip et al, 2005, Simonsen et al, 2009 • Other studies show that SAD perform better than SZ on neuropsychological measures Heinrichs et al, 2008; Stip et al, 2005; Szoke et al, 2008

13. Neuropsychological studies comparing SAD with BD Cognitive deficits are common to the psychotic spectrum regardless of specific diagnostic

14. Schizoaffective patients showed more impairment than bipolar patients on tests of attention, psychomotor speed and memory, but there were not significant differences on measures of cognitive flexibility N= 28 SAD N= 32 BP A worsecognitiveoutcome of SAD comparedto BP patients in remission Studentkowski et al., 2010

15. N=34 SAD N=41 BD without psychosis N=35 healthy controls

16. Cognitive functioning in SAD and nonpsychotic BD SAD showed greater impairment than controls and BD in verbal memory, executive functions and attentional measures. BD performed similar to the controls except for verbal fluency. SAD carries more neurocognitive impairment than nonpsychotic BD and more occupational difficulties. Lithium and antipsychotics did not seem to influence results. History of psychosis was the best predictor of verbal memory impairment.

17. N=102 SZ N=27 SAD N=75 psychotic BD N=61 non psychotic BD N=280 heatlhy controls N=545 Simonsen et al, 2011

18. Results • SZ, SAD, psychotic BD < nonpsychotic BD, HC • Nonpsychotic BD < HC (only on processing speed) • Psychotic BD < nonpsychotic BD (verbal fluency and interference control). • Neurocognitive dysfunction in bipolar and SZ spectrum disorders seems to be determined more by history of psychosis than by DSM-IV diagnostic category or subtype. • Neurocognition as an endophenotypic marker for these disorders. Simonsen et al. Schizophr Res, 2011

19. Executivedysfunction and memoryimpairment in schizoaffectivedisorder • WAIS-III / TAP • Psychopathological assessment (Young, PANSS) • Wechsler Memory Scale-III (WMS) • Assessment Dysexecutive Syndrome (BADS) • SAD schizomanic = 26 • BD manic =51 (psychotic/ non-psychotic) • Acute Schizophrenic =45 • Controls=65 The aim of the study was to examine whether there is a pattern of decreasing cognitive impairment from SZ to SAD to BD. Amann et al, 2011

20. Executivedysfunction and memoryimpairment in schizoaffectivedisorder Memory (WMS-III) No differences between patient groups on composite score, verbal memory and working memory. Visual memory differences between SZ and HC. SAD schizomanic Controls BD manic Schizophrenic Executive functions (BADS) All 3 patient groups were more impaired in the BADS than controls. Differences in Action program test: SZ < Bip= SAD SAD schizomanic Controls BD manic Schizophrenic Amann et al, 2011

21. Out of 10 tests, there was only one significant difference: SAD and BD patients peformed better than the SZ patients on the Action Program Test of the BADS, which tests problem-solving skills. SZ, SAD and manic patients show a similar degree of executive and memory deficits in the acute phase of the illness. No significant differences were found between psychotic (n=22) and nonpsychotic (n=29) bipolar patients. These findings do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits. Executivedysfunction and memoryimpairment in schizoaffectivedisorder

22. Cognitivefunctioning in schizoaffectivedisorders Cognitive functioning in affective psychosis and schizoaffective disorder is much less studied compared with schizophrenia. 31 studies that compared the performances of people with SZ (n=1979) with that of those with affective psychosis or schizoaffective disorder (n=1314) were included. In 6 of 12 cognitive domains, people with SZ performed worse than people with schizoaffective disorder or affective psychosis. Bora et al, BJP 2009

23. Cognitivefunctioning in schizoaffectivedisorders Between-group differences were driven by a higher percentage of males, more severe negative symptoms and younger age at onset of illness in SZ. Neuropsychological data do not provide evidence for categorical differences between SZ and other groups. However, a subgroup of individuals with SZ with more severe negative symptoms may be cognitively more impaired than those with affective psychosis/schizoaffective disorder. Bora et al, BJP 2009

24. Cognitivefunctioning in schizoaffectivedisorders Two different alternatives of the Kraepelinian dichotomy: The most severe SZ and psychotic BD may lie on the opposite ends of a continuum, with only a quantitative change in the degree of cognitive dysfuntion along the continuum from SZ and psychotic mood disorders. Only people with SZ with more severe negative symptoms are more impaired in certain domains (‘deficit’ SZ): categorical distinction between a subgroup with poor outcome SZ and other psychotic disorders including people with SZ with a good prognosis. Bora et al, BJP 2009

25. Cross-diagnostic cognitive study SZ: 293 SAD: 165 Psychotic BD: 227 Healthy Controls: 295 Robust neuropsychological impairment are present in SZ and psychotic BD. The severity of cognitive across psychotic disorders was consistent with a continuum . with SZ having greater impairment than SAD and SAD greater than BD Hill et al. AJP, 2013

26. Available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. Cognitive performance in groups of psychotic patients may be influenced by the degree to which they are symptomatic at the time of testing (8-12 weeks of remission before testing). SAD vs. BD: One possible reason for the divergent findings may be the presence or absence of psychotic symptoms in BD. Findings suggest that SZ, SAD and BDP are on a neurobiological continuum. Conclusions

27. Cognitive testing as well as functional assessment may be useful in clinical practice to determine the extent of difficulties, beyond diagnosis or subtypes. A more complex, mixed, dimensional-categorical model could better explain the available data. Early detection and intervention of cognitive deficits are essential to reduce disability in SZ, SAD and BD (optimizing individualized pharmacological treatment + CR). Cognitive remediation has at least equivalent benefits in affective and schizoaffective disorder as demonstrated in schizophrenia. Conclusions

28. Antoni Benabarre Mar Bonnín Francesc Colom Mercè Comes Marina Garriga Jose M Goikolea Iria Grande Diego Hidalgo Esther Jiménez Anabel Martinez-Arán Andrea Murru Isabella Pacchiarotti Rosa Palaus Dina Popovic María Reinares Jose Sánchez-Moreno Brisa Solé Carla Torrent Imma Torres Marc Valentí Èlia Valls Cristina Varo Eduard Vieta Ackowledgements