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Cognitive reserve attenuates age-related cognitive decline in the context of putatively accelerated brain ageing in schizophrenia-spectrum disorders

Published online by Cambridge University Press:  09 July 2019

Tamsyn E. Van Rheenen*
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia
Vanessa Cropley
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia
Birgitte Fagerlund
Affiliation:
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center, Glostrup, Denmark Department of Psychology, University of Copenhagen, Copenhagen, Denmark
Cassandra Wannan
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia
Jason Bruggemann
Affiliation:
School of Psychiatry, University of New South Wales, New South Wales, Australia Neuroscience Research Australia, New South Wales, Australia
Rhoshel K. Lenroot
Affiliation:
School of Psychiatry, University of New South Wales, New South Wales, Australia Neuroscience Research Australia, New South Wales, Australia
Suresh Sundram
Affiliation:
Florey Institute of Neuroscience and Mental Health, Melbourne, Australia Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Australia Mental Health Program, Monash Health, Clayton, Victoria, Australia
Cynthia Shannon Weickert
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia School of Psychiatry, University of New South Wales, New South Wales, Australia Neuroscience Research Australia, New South Wales, Australia Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, New York13210, USA
Thomas W. Weickert
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia School of Psychiatry, University of New South Wales, New South Wales, Australia Neuroscience Research Australia, New South Wales, Australia
Andrew Zalesky
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia Department of Electrical and Electronic Engineering, University of Melbourne, VIC, Australia
Chad A. Bousman
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia Florey Institute of Neuroscience and Mental Health, Melbourne, Australia Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada
Christos Pantelis
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia Florey Institute of Neuroscience and Mental Health, Melbourne, Australia Department of Electrical and Electronic Engineering, University of Melbourne, VIC, Australia
*
Author for correspondence: Tamsyn E. Van Rheenen, E-mail: tamsyn.van@unimelb.edu.au

Abstract

Background

In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain–cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness.

Methods

Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR.

Results

Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients.

Conclusions

In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure – cognition outcomes in the extant literature.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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References

Andreasen, NA (1983) Scale for the Assessment of Negative Symptoms. Iowa City, Iowa: University of Iowa.Google Scholar
Barbey, AK, Colom, R, Paul, EJ and Grafman, J (2014) Architecture of fluid intelligence and working memory revealed by lesion mapping. Brain Structure and Function 219, 485494.CrossRefGoogle ScholarPubMed
Barnett, J, Salmond, C, Jones, P and Sahakian, B (2006) Cognitive reserve in neuropsychiatry. Psychological Medicine 36, 10531064.CrossRefGoogle ScholarPubMed
Bartrés-Faz, D and Arenaza-Urquijo, EM (2011) Structural and functional imaging correlates of cognitive and brain reserve hypotheses in healthy and pathological aging. Brain Topography 24, 340357.CrossRefGoogle ScholarPubMed
Ben-David, BM, Erel, H, Goy, H and Schneider, BA (2015) ‘Older is always better’: age-related differences in vocabulary scores across 16 years. Psychology and Aging 30, 856.CrossRefGoogle Scholar
Brooks, BL, Sherman, EM, Iverson, GL, Slick, DJ and Strauss, E (2011) Psychometric foundations for the interpretation of neuropsychological test results. In Smelser, NJ and Baltes, PB (eds), The Little Black Book of Neuropsychology. New York: Springer, pp. 893922.CrossRefGoogle Scholar
Castle, DJ, Jablensky, A, McGrath, JJ, Carr, V, Morgan, V, Watereus, A, Valuri, G, Stain, H, McGuffin, P and Farmer, A (2006) The diagnostic interview for psychoses (DIP): development, reliability and applications. Psychological Medicine 36, 6980.CrossRefGoogle ScholarPubMed
Christensen, H, Anstey, KJ, Parslow, RA, Maller, J, Mackinnon, A and Sachdev, P (2007) The brain reserve hypothesis, brain atrophy and aging. Gerontology 53, 8295.CrossRefGoogle ScholarPubMed
Christoff, K, Prabhakaran, V, Dorfman, J, Zhao, Z, Kroger, JK, Holyoak, KJ and Gabrieli, JD (2001) Rostrolateral prefrontal cortex involvement in relational integration during reasoning. Neuroimage 14, 11361149.CrossRefGoogle ScholarPubMed
Crawford, JR and Garthwaite, PH (2009) Percentiles please: the case for expressing neuropsychological test scores and accompanying confidence limits as percentile ranks. The Clinical Neuropsychologist 23, 193204.CrossRefGoogle ScholarPubMed
Cropley, VL, Klauser, P, Lenroot, R, Bruggemann, J, Sundram, S, Bousman, C, Pereira, A, Di Biase, M, Weickert, TW, Shannon Weickert, C, Pantelis, C and Zalesky, A (2017) Accelerated gray and white matter deterioration with age in schizophrenia. The American Journal of Psychiatry 174, 286295.CrossRefGoogle Scholar
Czepielewski, LS, Wang, L, Gama, CS and Barch, DM (2016) The relationship of intellectual functioning and cognitive performance to brain structure in schizophrenia. Schizophrenia Bulletin 43, 355364.Google Scholar
Dale, AM, Fischl, B and Sereno, MI (1999) Cortical surface-based analysis: I. Segmentation and surface reconstruction. Neuroimage 9, 179194.CrossRefGoogle ScholarPubMed
de Zeeuw, P, Weusten, J, van Dijk, S, van Belle, J and Durston, S (2012) Deficits in cognitive control, timing and reward sensitivity appear to be dissociable in ADHD. PLoS ONE 7, e51416.CrossRefGoogle ScholarPubMed
Desikan, RS, Ségonne, F, Fischl, B, Quinn, BT, Dickerson, BC, Blacker, D, Buckner, RL, Dale, AM, Maguire, RP and Hyman, BT (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31, 968980.CrossRefGoogle ScholarPubMed
Fischl, B and Dale, AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences 97, 1105011055.CrossRefGoogle ScholarPubMed
Fischl, B, Sereno, MI and Dale, AM (1999) Cortical surface-based analysis: II: inflation, flattening, and a surface-based coordinate system. Neuroimage 9, 195207.CrossRefGoogle Scholar
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, Van Der Kouwe, A, Killiany, R, Kennedy, D and Klaveness, S (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341355.CrossRefGoogle ScholarPubMed
Fiszdon, J, Choi, J, Bryson, G and Bell, M (2006) Impact of intellectual status on response to cognitive task training in patients with schizophrenia. Schizophrenia Research 87, 261269.CrossRefGoogle ScholarPubMed
Giorgio, A, Santelli, L, Tomassini, V, Bosnell, R, Smith, S, De Stefano, N and Johansen-Berg, H (2010) Age-related changes in grey and white matter structure throughout adulthood. NeuroImage 51, 943951.CrossRefGoogle ScholarPubMed
Harvey, PD and Rosenthal, JB (2018) Cognitive and functional deficits in people with schizophrenia: evidence for accelerated or exaggerated aging? Schizophrenia Research 196, 1421.CrossRefGoogle ScholarPubMed
Heaton, R, Paulsen, JS, McAdams, LA, Kuck, J, Zisook, S, Braff, D, Harris, MJ and Jeste, DV (1994) Neuropsychological deficits in schizophrenics: relationship to age, chronicity, and dementia. Archives of General Psychiatry 51, 469476.CrossRefGoogle ScholarPubMed
Heaton, RK, Gladsjo, JA, Palmer, BW, Kuck, J, Marcotte, TD and Jeste, DV (2001) Stability and course of neuropsychological deficits in schizophrenia. Archives of General Psychiatry 58, 2432.CrossRefGoogle Scholar
Heinrichs, RW, Pinnock, F, Parlar, M, Hawco, C, Hanford, L and Hall, GB (2017) Cortical thinning in network-associated regions in cognitively normal and below-normal range schizophrenia. Schizophrenia Research and Treatment 2017, 9760905.CrossRefGoogle ScholarPubMed
Holdnack, JA (2001) Wechsler Test of Adult Reading. San Antonio, Texas: The Psychological Corporation.Google Scholar
Holthausen, EAE, Wiersma, D, Sitskoorn, MM, Hijman, R, Dingemans, PM, Schene, AH and van den Bosch, RJ (2002) Schizophrenic patients without neuropsychological deficits: subgroup, disease severity or cognitive compensation? Psychiatry Research 112, 111.CrossRefGoogle ScholarPubMed
Hulshoff Pol, HE, Schnack, HG, Bertens, MG, van Haren, NE, van der Tweel, I, Staal, WG, Baaré, WF and Kahn, RS (2002) Volume changes in gray matter in patients with schizophrenia. American Journal of Psychiatry 159, 244250.CrossRefGoogle ScholarPubMed
Hutton, C, Draganski, B, Ashburner, J and Weiskopf, N (2009) A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging. NeuroImage 48, 371380.CrossRefGoogle ScholarPubMed
Karantonis, J, Hughes, M, Rossell, SL, Wannan, C, Pantelis, C, Cropley, V and Rheenen, TEV (In preparation) A review of brain morphology-cognition relationships on the schizophrenia-bipolar disorder spectrum.Google Scholar
Kievit, RA, Davis, SW, Mitchell, DJ, Taylor, JR, Duncan, J, Tyler, LK, Brayne, C, Bullmore, E, Calder, A and Cusack, R (2014) Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking. Nature Communications 5, 5658.CrossRefGoogle ScholarPubMed
Kontis, D, Huddy, V, Reeder, C, Landau, S and Wykes, T (2013) Effects of age and cognitive reserve on cognitive remediation therapy outcome in patients with schizophrenia. The American Journal of Geriatric Psychiatry 21, 218230.CrossRefGoogle ScholarPubMed
Leeson, VC, Sharma, P, Harrison, M, Ron, MA, Barnes, TRE and Joyce, EM (2011) IQ trajectory, cognitive reserve, and clinical outcome following a first episode of psychosis: a 3-year longitudinal study. Schizophrenia Bulletin 37, 768777.CrossRefGoogle ScholarPubMed
Lemaitre, H, Goldman, AL, Sambataro, F, Verchinski, BA, Meyer-Lindenberg, A, Weinberger, DR and Mattay, VS (2012) Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiology of Aging 33, 617, e1-617. e9.CrossRefGoogle ScholarPubMed
Lewandowski, KE, McCarthy, JM, Öngür, D, Norris, LA, Liu, GZ, Juelich, RJ and Baker, JT (2019) Functional connectivity in distinct cognitive subtypes in psychosis. Schizophrenia Research 204, 120126.CrossRefGoogle ScholarPubMed
Lindenberger, U (2001) Lifespan theories of cognitive development. In Smelser, NJ and Baltes, PB (eds), International Encyclopedia of the Social and Behavioral Sciences. Elsevier Science, pp. 88488854.CrossRefGoogle Scholar
Loewenstein, DA, Czaja, SJ, Bowie, CR and Harvey, PD (2012) Age-associated differences in cognitive performance in older patients with schizophrenia: a comparison with healthy older adults. The American Journal of Geriatric Psychiatry 20, 2940.CrossRefGoogle ScholarPubMed
Loughland, C, Draganic, D, McCabe, K, Richards, J, Nasir, A, Allen, J, Catts, S, Jablensky, A, Henskens, F and Michie, P (2010) Australian Schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia. Australian and New Zealand Journal of Psychiatry 44, 10291035.Google Scholar
Nelson, HE, Pantelis, C, Carruthers, K, Speller, J, Baxendale, S and Barnes, TR (1990) Cognitive functioning and symptomatology in chronic schizophrenia. Psychological Medicine 20, 357365.CrossRefGoogle ScholarPubMed
Nguyen, TT, Eyler, LT and Jeste, DV (2018) Systemic biomarkers of accelerated aging in schizophrenia: a critical review and future directions. Schizophrenia Bulletin 44, 398408.CrossRefGoogle ScholarPubMed
Opdebeeck, C, Martyr, A and Clare, L (2016) Cognitive reserve and cognitive function in healthy older people: a meta-analysis. Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition 23, 4060.CrossRefGoogle ScholarPubMed
Pantelis, C, Barnes, T, Nelson, HE, Tanner, S, Weatherley, L, Owen, AM and Robbins, TW (1997) Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain: A Journal of Neurology 120, 18231843.CrossRefGoogle ScholarPubMed
Petrides, M, Alivisatos, B, Meyer, E and Evans, AC (1993) Functional activation of the human frontal cortex during the performance of verbal working memory tasks. Proceedings of the National Academy of Sciences 90, 878882.CrossRefGoogle ScholarPubMed
Plomin, R and Deary, IJ (2015) Genetics and intelligence differences: five special findings. Molecular Psychiatry 20, 98108.CrossRefGoogle ScholarPubMed
Pol, HEH and Kahn, RS (2008) What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophrenia Bulletin 34, 354366.Google Scholar
Prabhakaran, V, Smith, JA, Desmond, JE, Glover, GH and Gabrieli, JD (1997) Neural substrates of fluid reasoning: an fMRI study of neocortical activation during performance of the Raven's Progressive Matrices Test. Cognitive Psychology 33, 4363.CrossRefGoogle ScholarPubMed
Ramsden, S, Richardson, FM, Josse, G, Shakeshaft, C, Seghier, ML and Price, CJ (2013) The influence of reading ability on subsequent changes in verbal IQ in the teenage years. Developmental Cognitive Neuroscience 6, 3039.CrossRefGoogle ScholarPubMed
Randolph, C, Tierney, MC, Mohr, E and Chase, TN (1998) The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. Journal of Clinical and Experimental Neuropsychology 20, 310319.CrossRefGoogle ScholarPubMed
Raz, N and Rodrigue, KM (2006) Differential aging of the brain: patterns, cognitive correlates and modifiers. Neuroscience & Biobehavioral Reviews 30, 730748.CrossRefGoogle ScholarPubMed
Raz, N and Lindenberger, U (2011) Only time will tell: cross-sectional studies offer no solution to the age–brain–cognition triangle: Comment on Salthouse (2011). Psychological Bulletin 137, 790795.CrossRefGoogle Scholar
Raz, N, Lindenberger, U, Rodrigue, KM, Kennedy, KM, Head, D, Williamson, A, Dahle, C, Gerstorf, D and Acker, JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cerebral Cortex 15, 16761689.CrossRefGoogle ScholarPubMed
Ritchie, SJ and Tucker-Drob, EM (2018) How much does education improve intelligence? A meta-analysis. Psychological Science 29, 13581369.CrossRefGoogle ScholarPubMed
Ritchie, SJ, Bates, TC and Plomin, R (2015) Does learning to read improve intelligence? A longitudinal multivariate analysis in identical twins from age 7 to 16. Child Development 86, 2336.CrossRefGoogle ScholarPubMed
Rodríguez-Aranda, C and Martinussen, M (2006) Age-related differences in performance of phonemic verbal fluency measured by Controlled Oral Word Association Task (COWAT): a meta-analytic study. Developmental Neuropsychology 30, 697717.CrossRefGoogle ScholarPubMed
Ryan, JJ, Sattler, JM and Lopez, SJ (2000) Age effects on Wechsler adult intelligence scale-III subtests. Archives of Clinical Neuropsychology 15, 311317.CrossRefGoogle ScholarPubMed
Schnack, HG, van Haren, NE, Nieuwenhuis, M, Pol, HEH, Cahn, W and Kahn, RS (2016) Accelerated brain aging in schizophrenia: a longitudinal pattern recognition study. American Journal of Psychiatry 173, 607616.CrossRefGoogle ScholarPubMed
Solé-Padullés, C, Bartrés-Faz, D, Junqué, C, Vendrell, P, Rami, L, Clemente, IC, Bosch, B, Villar, A, Bargalló, N and Jurado, MA (2009) Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease. Neurobiology of Aging 30, 11141124.CrossRefGoogle ScholarPubMed
Stern, Y (2002) What is cognitive reserve? Theory and research application of the reserve concept. Journal of the International Neuropsychological Society 8, 448460.CrossRefGoogle ScholarPubMed
Stern, Y (2009) Cognitive reserve. Neuropsychologia 47, 20152028.CrossRefGoogle ScholarPubMed
Stern, Y (2012) Cognitive reserve in ageing and Alzheimer's disease. The Lancet Neurology 11, 10061012.CrossRefGoogle ScholarPubMed
Stine-Morrow, EA, Hussey, EK and Ng, S (2015) The potential for literacy to shape lifelong cognitive health. Policy Insights from the Behavioral and Brain Sciences 2, 92100.CrossRefGoogle Scholar
Storsve, AB, Fjell, AM, Tamnes, CK, Westlye, LT, Overbye, K, Aasland, HW and Walhovd, KB (2014) Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. The Journal of Neuroscience 34, 84888498.CrossRefGoogle ScholarPubMed
Sumowski, JF, Chiaravalloti, N and DeLuca, J (2009) Cognitive reserve protects against cognitive dysfunction in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology 31, 913926.CrossRefGoogle ScholarPubMed
Sumowski, JF, Wylie, GR, Chiaravalloti, N and DeLuca, J (2010 a) Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis. Neurology 74, 19421945.CrossRefGoogle ScholarPubMed
Sumowski, JF, Wylie, GR, DeLuca, J and Chiaravalloti, N (2010 b) Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain 133, 362374.CrossRefGoogle ScholarPubMed
Van Rheenen, TE, Lewandowski, KE, Ongur, D, Tan, EJ, Neill, E, Gurvich, C, Pantelis, C, Malhotra, A, Rossell, SL and Burdick, KE (2017) Characterizing cognitive heterogeneity on the schizophrenia – bipolar disorder spectrum. Psychological Medicine 47, 18481864.CrossRefGoogle ScholarPubMed
Van Rheenen, TE, Cropley, V, Wells, R, Bruggemann, J, Swaminathan, V, Sundram, S, Weinberg, W, Jacomb, I, Lenroot, R, Pereira, AM, Zalesky, A, Bousman, C, Shannon Weickert, C, Weickert, TW and Pantelis, C (2018) Widespread volumetric reductions in schizophrenia and schizoaffective patients displaying compromised cognitive abilities. Schizophrenia Bulletin 44, 560574.CrossRefGoogle ScholarPubMed
Vuoksimaa, E, Panizzon, MS, Chen, C-H, Eyler, LT, Fennema-Notestine, C, Fiecas, M, Fischl, B, Franz, CE, Grant, MD, Jak, A, Lyons, MJ, Neale, MC, Thompson, WK, Tsuang, MT, Xian, H, Dale, AM and Kremen, WS (2013) Cognitive reserve moderates the association between hippocampal volume and episodic memory in middle Age. Neuropsychologia 51, 11241131.CrossRefGoogle ScholarPubMed
Wechsler, D (1997 a) Wechsler Adult Intelligence Scale-Revised: Administration and Scoring Manual. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D (1997 b) Wechsler Memory Scale. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D (1999) Wechsler Abbreviated Scale of Intelligence. Psychological Corporation.Google Scholar
Weickert, TW, Goldberg, TE, Gold, JM, Bigelow, LB, Egan, MF and Weinberger, DR (2000) Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. Archives of General Psychiatry 57, 907913.CrossRefGoogle ScholarPubMed
Weinberg, D, Lenroot, R, Jacomb, I, Allen, K, Bruggemann, J, Wells, R, Balzan, R, Liu, D, Galletly, C, Catts, S, Shannon Weickert, C and Weickert, T (2016) Cognitive subtypes of schizophrenia characterized by differential brain volumetric reductions and cognitive decline. JAMA Psychiatry 73, 12511259.CrossRefGoogle ScholarPubMed
Wells, R, Swaminathan, V, Sundram, S, Weinberg, D, Bruggemann, J, Jacomb, I, Cropley, V, Lenroot, R, Pereira, AM and Zalesky, A (2015) The impact of premorbid and current intellect in schizophrenia: cognitive, symptom, and functional outcomes. npj Schizophrenia 1, 15043.CrossRefGoogle ScholarPubMed
Woodberry, KA, Giuliano, AJ and Seidman, LJ (2008) Premorbid IQ in schizophrenia: a meta-analytic review. American Journal of Psychiatry 165, 579587.CrossRefGoogle ScholarPubMed
Woodward, ND and Heckers, S (2015) Brain structure in neuropsychologically defined subgroups of schizophrenia and psychotic bipolar disorder. Schizophrenia Bulletin 41, 13491359.CrossRefGoogle ScholarPubMed
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