Cognitive impairment in schizoaffective disorder: greater ...
Transcript of Cognitive impairment in schizoaffective disorder: greater ...
Cognitive impairment in schizoaffective disorder:greater or lesser impairment than schizophrenia or
bipolar disorder?
Carla TorrentBipolar Disorder ProgramHospital Clínic Barcelona
IRPB, Lisbon, 26th april 2015
Neurocognition and schizoaffectivedisorder (SAD)
One of the aims of research on neurocognition is tovalidate these diagnostic categories.
¢ The classical, kraepelinian classification of mental disordersmakes a distinction between dementia praecox and manic-depressive disorder.
¢ In clinical practice, some patients present a mixture ofschizophrenic and affective signs and symptoms.
¢ In more recent nosologic systems, a new diagnosticcategory: schizoaffective disorderØ A form of schizophrenia (SZ)Ø A form of bipolar disorder (BD)Ø An independent disorderØ A disorder intermediate between SZ and BD
Psychiatric disorders are associated withcomplex patterns of cognitive impairment
Adapted from Millan et al., Nature, 2012
• Attention
• Executive function
• Verbal learning and memory
• Speed of processing
• Social cognition
• Language
Genetic Epigenetic Developmental Environmental
Cognitive impairment by cognitive domains
Millanet al, 2012
Epidemiological, genetic, neuroimaging and neurocognitive studies show similaritiesbetween SZ and BD.
Cognitive impairment in SQZ and BD
¢ Prevalence 85-100%¢ Impairment across domains deficits 1-2
SD (verbal memory and processingspeed)
¢ Present at illness onset and remainrelatively stable over the course of theillness
¢ Do not change substantially withantipsychotic medications
¢ Account for much of the functionaldisability associated with the illness.
¢ Broad cognitive impairment is notattributable 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
Schizophrenia Bipolar disorder
Lewandowski et al, Psych Med, 2010
Cognitive development in subjects withschizophrenia, bipolar disorder and healthycontrols
A longitudinal study of cognitive functioning inschizophrenia
Dickerson et al, Schiz Res, 2014
N=132Mean age: 43.7 years
The results showed an absence ofcognitive decline for most measuresand modest gains in some measures
over a period of up to 10 years
Reichenberg et al, Am J Psychiatry, 2002
Premorbid intellectual, behavioral and languagefunctioning in schizophrenic, schizoaffective andnonpsychotic 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 andcomprehension tests.
Reichenberg et al, Schizophr Bull, 2009
Prevalence of NP normality ranged between:16% and 45% in schizophrenia,
20% and 33% in schizoaffective disorder,42% and 64% in bipolar disorder,and 42% and 77% in depression
Neuropsychological function and dysfunctionin schizophrenia and psychotic affectivedisorders
N=235
All groups demonstrated impairments inall cognitive domains. However, SZ
patients were more impaired than theother groups.
¢ Cognitive deficits in SAD do not differ significantlyfrom those of SZ.
¢ In the absence of comparisons with BD, noconclusions can be drawn with regard to SAD as aform of SZ or an intermediate disorder betweenBD and SZ.
¢ In some studies SZ and SAD patients were pooledtogether.
Studies comparing SAD with SZ
¢ In other studies, patients with psychotic disorders andthose with affective disorders presenting psychoticsymptoms were pooled together.Beatty et al, 1993; Bornstein et al, 1990; Evans et al, 1999; Glahn etal, 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 SZon neuropsychological measuresHeinrichs et al, 2008; Stip et al, 2005; Szoke et al, 2008
Studies comparing SAD with SZ
Study Characteristics Findings
Evans et al, 1999 N=154 SZN=29 SADN=27 non psychotic mooddisorder
SAD and SZ more impaired that non psychoticmood disorder patients,No significant differences between SZ and SADPsychotic spectrum
Glahn et al, 2006 N=15 SZN=15 SADN=15 BD non psychotic
Lack of significant differences between the groupsPsychotic spectrum
Szoke et al, 2008 N=26 SADN=52 BP with psychosisN=51 BDN=65 controls
Executive functions: non significant differences in aexecutive measure (TMT)SZ<SAD<BP with psychosis<BD<C on theWCST perseverative errorsContinuum in psychosis
Reichenberg et al, 2009 N=94 SZN= 15 SADN=78 psychotic BDN=48 psychotic MD
Greater impairment in SZ and SAD incomparison to both psychotic mood disorders,no differences between SZ and SAD
Neuropsychological studies comparing SAD withBD
Cognitive deficits are common to the psychotic spectrum regardless of specificdiagnostic
N= 28 SAD
N= 32 BP
A worse cognitive outcome of SAD compared to BP patients in remissionStudentkowski et al., 2010
Schizoaffective patients showed more impairment thanbipolar patients on tests of attention, psychomotor speedand memory, but there were not significant differences on
measures of cognitive flexibility
N=34 SAD N=41 BD without psychosis N=35 healthy controls
¢ SAD showed greater impairment than controls and BDin verbal memory, executive functions and attentionalmeasures.
¢ BD performed similar to the controls except for verbalfluency.
¢ SAD carries more neurocognitive impairment thannonpsychotic BD and more occupational difficulties.
¢ Lithium and antipsychotics did not seem to influenceresults.
¢ History of psychosis was the best predictor of verbalmemory impairment.
Cognitive functioning in SAD and nonpsychotic BD
N=102 SZN=27 SADN=75 psychotic BDN=61 non psychotic BDN=280 heatlhy controls
N=545
Simonsen et al, 2011
Simonsen et al. Schizophr Res, 2011
¢ 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 ofpsychosis than by DSM-IV diagnostic category orsubtype.
¢ Neurocognition as an endophenotypic marker for thesedisorders.
Results
ü SAD schizomanic = 26
ü BD manic =51
(psychotic/ non-psychotic)
üAcute Schizophrenic =45
ü Controls=65
üWAIS-III / TAP
üPsychopathological assessment
(Young, PANSS)
üWechsler Memory Scale-III (WMS)
üAssessment Dysexecutive
Syndrome (BADS)
The aim of the study was to examine whether there is a pattern ofdecreasing cognitive impairment from SZ to SAD to BD.
Amann et al, 2011
Executive dysfunction and memory impairmentin schizoaffective disorder
Controls SADschizomanic
SchizophrenicBD manic
SADschizomanic
Controls BDmanic
Schizophrenic
Memory (WMS-III)
No differences between patient groups oncomposite score, verbal memory and
working memory.
Visual memory differences between SZ and HC.
Executive functions (BADS)
All 3 patient groups were moreimpaired in the BADS than controls.
Differences in Action program test:SZ < Bip= SAD
Amann et al, 2011
Executive dysfunction and memory impairmentin schizoaffective disorder
¢ Out of 10 tests, there was only one significant difference:SAD and BD patients peformed better than the SZpatients on the Action Program Test of the BADS, whichtests problem-solving skills.
¢ SZ, SAD and manic patients show a similar degree ofexecutive and memory deficits in the acute phase of theillness.
¢ No significant differences were found between psychotic(n=22) and nonpsychotic (n=29) bipolar patients.
¢ These findings do not support a categorical differentiationacross different psychotic categories with regard toneuropsychological deficits.
Executive dysfunction and memory impairmentin schizoaffective disorder
¢ Cognitive functioning in affectivepsychosis and schizoaffective disorder ismuch less studied compared withschizophrenia.
¢ 31 studies that compared theperformances of people with SZ(n=1979) with that of those withaffective psychosis or schizoaffectivedisorder (n=1314) were included.
¢ In 6 of 12 cognitive domains, peoplewith SZ performed worse than peoplewith schizoaffective disorder oraffective psychosis.
Bora et al, BJP 2009
Cognitive functioning in schizoaffectivedisorders
¢ Between-group differences were driven by a higherpercentage of males, more severe negativesymptoms and younger age at onset of illness in SZ.
¢ Neuropsychological data do not provide evidencefor categorical differences between SZ and othergroups.
¢ However, a subgroup of individuals with SZ withmore severe negative symptoms may be cognitivelymore impaired than those with affectivepsychosis/schizoaffective disorder.
Bora et al, BJP 2009
Cognitive functioning 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 quantitativechange in the degree of cognitive dysfuntion along thecontinuum from SZ and psychotic mood disorders.
¢ Only people with SZ with more severe negative symptomsare more impaired in certain domains (‘deficit’ SZ):categorical distinction between a subgroup with pooroutcome SZ and other psychotic disorders includingpeople with SZ with a good prognosis.
Cognitive functioning in schizoaffectivedisorders
Bora et al, BJP 2009
Cross-diagnostic cognitive study
Hill et al. AJP, 2013
SZ: 293
SAD: 165
Psychotic BD: 227
Healthy Controls: 295
Robust neuropsychologicalimpairment are present in SZ
and psychotic BD. Theseverity of cognitive across
psychotic disorders wasconsistent with a continuum .
with SZ having greaterimpairment than SAD and
SAD greater than BD
¢ Available evidence strongly supports that a generalized deficit ispresent across psychotic disorders that differs in severity moreso than form.
¢ Cognitive performance in groups of psychotic patients may beinfluenced by the degree to which they are symptomatic at thetime of testing (8-12 weeks of remission before testing).
¢ SAD vs. BD: One possible reason for the divergent findings maybe the presence or absence of psychotic symptoms in BD.
¢ Findings suggest that SZ, SAD and BDP are on a neurobiologicalcontinuum.
Conclusions
¢ Cognitive testing as well as functional assessment may be usefulin clinical practice to determine the extent of difficulties,beyond diagnosis or subtypes.
¢ A more complex, mixed, dimensional-categorical model couldbetter explain the available data.
¢ Early detection and intervention of cognitive deficits areessential to reduce disability in SZ, SAD and BD (optimizingindividualized pharmacological treatment + CR). Cognitiveremediation has at least equivalent benefits in affective andschizoaffective disorder as demonstrated in schizophrenia.
Conclusions
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
Pro-cognitive drugs?ü Neurotrophic and neuroprotective effects of lithium, valproateand new antipsychotic drugs counteracting possibleneurodegenerative effects of the illness.
üAtypical antipsychotics may improve cognition increasingprefrontal dopaminergic transmission (procholinergic effects):some evidence in SZ, limited or null in BD.
üOther procholinergic agents may be useful (rivastigmine,galantamine, nicotinic agonists).
üPotential use of psychoestimulants (methylphenidate, modafinil)in comorbid ADHD patients.
üOngoing studies focused on dopaminergic agonists(pramipexole) and antiglutamatergic agents (memantine) as newpharmacological strategies.
Solé y cols, , Eur Neuropsychopharm, en prensa
Posibles tratamientos para las disfuncionescognitivas en depresión unipolar
Modafinil (TDAH y SQZ)MemantinaGalantaminaDonepeciloEscopolaminaVortioxetinaDesvenlafaxinaEritropoietina (EPO)LisdexamfetaminaOxitocina intranasal
Omega-3S-adenosil-metioninaRehabilitación cognitivaEjercicio físicoTécnicas no invasivas deestimulación cerebralKetaminaEsketaminaLaniceminaGlyx-13