Jeste, Dilip V

Nguyen, Tanya T

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UC San DiegoUC San Diego Previously Published WorksTitlePositive light on schizophrenia and aging: Commentary on course and predictors of symptomatic remission in schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area, by Lange et al.Permalinkhttps://escholarship.org/uc/item/7hb6x3cjAuthorsNguyen, Tanya TJeste, Dilip VPublication Date2019-09-01DOI10.1016/j.schres.2019.07.037 Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaThis article appeared in a journal published by Elsevier. The attachedcopy is furnished to the author for internal non-commercial researchand education use, including for instruction at the author'sinstitution and sharing with colleagues.Other uses, including reproduction and distribution, or selling orlicensing copies, or posting to personal, institutional or third partywebsites are prohibited.In most cases authors are permitted to post their version of thearticle (e.g. in Word or Tex form) to their personal website orinstitutional repository. Authors requiring further informationregarding Elsevier's archiving and manuscript policies areencouraged to visit:http://www.elsevier.com/authorsrightsSchizophrenia Research 211 (2019) 32–33Contents lists available at ScienceDirectSchizophrenia Researchj ourna l homepage: www.e lsev ie r .com/ locate /schresAuthor's Personal CopyPositive light on schizophrenia and aging: Commentary on course andpredictors of symptomatic remission in schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area, by Lange et al.Tanya T. Nguyen a,b, Dilip V. Jeste a,b,c,⁎a Department of Psychiatry, University of California San Diego, CA, United States of Americab Sam and Rose Stein Institute for Research on Aging, University of California San Diego, CA, United States of Americac Department of Neurosciences, University of California San Diego, CA, United States of AmericaWhen Kraepelin, a neuropsychiatrist colleague of Alzheimer's, firstcoined the term dementia praecox more than a century ago to describeschizophrenia, he conceptualized this psychotic disorder as a progressivedementing illness or a neurodegenerative disease (Kraepelin, 1971). De-terioration was an integral part of Kraepelin's description and diagnosis:“if no essential improvement intervenes, in at most 2 or 3 years after theappearance of the more striking morbid phenomena, a state of weak-mindedness will be developed, which usually changes only slowly andinsignificantly” (p. 210). Since then, it has been a common perspectivethat the long-termoutcomeof chronic schizophrenia is dismal,with clin-ical deterioration most often leading to a terminal demented state. Thisnegative view has continued to persist despite empirical evidence thatschizophrenia is a heterogeneous disorder and a number of patientscan experience more favorable outcomes. Manfred Bleuler, son of Eu-gene Bleuler who first introduced the term schizophrenia to renameKraepelin's dementia praecox, was perhaps the first researcher to iden-tify that remission could occur in schizophrenia over a period of time.He presented a view that schizophrenia was not necessarily a progres-sive condition, and that individual patients' coursemightmanifest differ-ent outcomes, including remission. In his long-term follow-up, Bleulerfound that 20% of patients with schizophrenia remained stable andwere “cured” over a period of many years (Bleuler, 1983). Subsequentstudies byHarding in the 1980s and 1990s also challenged the prevailingmisconception of a progressively worsening clinical trajectory in schizo-phrenia and emphasized instead the considerable heterogeneity in thelong-term outcome of this illness, with deteriorated states not being in-evitable (Harding et al., 1987; Harding et al., 1992).However, despite the publication of these facts and figures, the notionstill persists that schizophrenia is necessarily a lifelong illness – a life sen-tence of sorts, and the nature of sustained remission is often questioned.Our earlier study of aging in schizophrenia reported that 8% of middle-aged and older adults living in the community, suffering from chronicschizophrenia with duration of several decades, met strict researchcriteria for sustained remission (Auslander and Jeste, 2004). These criteriaincluded “normal” psychosocial functioning as reported by others, no⁎ Corresponding author at: Sam and Rose Stein Institute for Research on Aging,University of California San Diego, 9500 Gilman Drive #0664, La Jolla, CA 92093, UnitedStates of America.E-mail address: djeste@ucsd.edu (D.V. Jeste).https://doi.org/10.1016/j.schres.2019.07.0370920-9964/© 2019 Elsevier B.V. All rights reserved.psychiatric hospitalization for at least previous five years, and either notbeing on antipsychotic medications or not taking more than half of thehighest daily dose since enrollment. These finding indicated thatsustained remission could occur even in patients with very chronic ill-ness. Predictors of sustained remission include social support, early initi-ation of treatment, greater cognitive and/or personality reserve, andhaving a partner or spouse. Interestingly, neither age nor duration oftreatment was predictors, suggesting that it is never too late to interveneor hold the possibility of remission. Such observations offer hope and sug-gest that remission rates could bemuch higher if peoplewith schizophre-nia received optimal care, which includes not only pharmacologicaltreatment of psychiatric symptoms from an early stage but also generalmedical care and psychosocial and vocational support and resources.The article by (Lange et al. 2019) further builds on the growing area ofresearch suggesting that aging in schizophrenia is frequently associatedwith a potential for lasting symptomatic remission. This study is an ex-tension of the authors' previous work investigating the longitudinalcourse of symptomatic remission in older patients with schizophreniaover a 5-year period (Meesters et al., 2011). These Dutch researchersfound that the rate of remission substantially increased from 27.3% atbaseline to 49.4% at follow-up. Notably, 26% of patients converted fromnon-remission to remission status over the follow-up period, with only3.9% converting from remission to non-remission. Reduced positivesymptom severity and having a partner at baseline were significant pre-dictors of conversion to remission over the 5-year period. This is this firstknown longitudinal study of recovery and remission in older patientswith schizophrenia employing a catchment area-based design. The au-thors appropriately acknowledged limitations of their investigationsuch as a small sample size, somewhat biased sample, and a lack of infor-mation about the life events or changes that might have occurred be-tween the two assessments. At the same time, a noteworthy strength ofthis study is its inclusion of both community-living and institutionalizedpatients and of all patients regardless of the age of onset of the disorder.These findings further support what has been reported in severalother studies that even older adults with schizophrenia have the capac-ity to experience remission of symptoms and progress toward recovery.There is an important distinction between the models of remission andrecovery in chronic mental illness compared to those for physical dis-eases. Unlike some cancers, remission does not entail a cure or implythat patients are free from the underlying etiopathology. Instead,33T.T. Nguyen, D.V. Jeste / Schizophrenia Research 211 (2019) 32–33Author's Personal Copyrecovery in schizophrenia should be conceptualized as the ability to liveameaningful, satisfying, and hopeful life despite the limitations imposedby symptoms, rather than resulting from elimination of symptoms(Bellack, 2006). Advocacy organizations, especially theNational Allianceon Mental Illness (NAMI) and the National Empowerment Center, havebeen central to the recoverymovement in seriousmental illnesses. Theyhave argued that the nature of recoverymay be different from the tradi-tional disease-oriented scientific-clinical concept centered on completedisappearance of symptoms and return to premorbid levels of function.This new perspective is consistent with improvement in mental healthin later life despite worsening physical health in the general populationas well as in people with serious physical illnesses, like cancer and HIV-AIDS (Jeste, 2018). Of particular relevance to older patients with schizo-phrenia, remission and recovery are akin to the definitions “successfulaging” based on subjectively experiencedwell-being rather on objectivepresence and severity of physical illness. Aging in schizophrenia is asso-ciated with a paradoxical clinical profile of worse physical health butimproved psychosocial functioning, including decreased level of psy-chotic symptoms, reduction in psychotic relapses requiring hospitaliza-tion, and better self-management (Jeste et al., 2011). The better mentalhealth in later life centers on well-being, adaptation, attainment ormaintenance of goals, positive attitudes toward the self and future,and social milestones and connectedness. Multi-component interven-tions that include lifestyle and other behavioral interventions, in addi-tion to pharmacotherapy, are critical in optimizing successful aging inpeople with schizophrenia. Psychosocial interventions for schizophre-nia have been shown to be associated with altered brain structure andfunction. For instance, cognitive enhancement therapy led to signifi-cantly increased brain-derived neurotrophic factor (BDNF) in theblood (Vinogradov et al., 2009), greater preservation of graymatter vol-ume in the temporal lobes, and increased gray matter in the amygdalaonMRI (Eack et al., 2010). Thus, although the underlying pathophysiol-ogy may continue to be present, these studies suggest that behavioralinterventions can produce neurobiological changes, suggesting a possi-ble biological basis for improved functioning observed in schizophreniapatients who achieve remission.Where dowe go from here? Despite growing empirical evidence thatschizophrenia is heterogeneous in its presentation and course, a negativeview of schizophrenia still persists. To change this bias, we advocate forpositive psychiatry in conceptualizing schizophrenia and other seriousmental illnesses. Positive psychiatry focuses on the promotion of mentalhealth andwell-being through enhancement of positive psychosocial fac-tors relevant tomental and physical illnesses (Jeste et al., 2017). Focusingon the negative outcomes and disability associated with schizophrenia,most research attention has been directed in the past toward reducingpsychopathology. However, mental health is characterized not only byan absence of symptoms but also by the presence of mental well-beingand other positive outcomes, such as life satisfaction and happiness. Pos-itive psychiatry offers an alternative and more empowering perspectivefrom which scientists and clinicians should approach treatment forschizophrenia. Mental well-being and positive psychological traits canbe and are present in schizophrenia, if we look for them. Although pa-tients with schizophrenia tend to have lower mean levels of resilience,optimism, wisdom, happiness, and low perceived stress, there is consid-erable heterogeneity among patients, with one-third having levels com-parable to those in healthy comparison subjects (Edmonds et al., 2018;Palmer et al., 2014). Furthermore, greater presence of such positive fac-tors is significantly associated with improved physical well-being andeven healthier levels of biomarkers of inflammation and insulin resis-tance (Edmonds et al., 2018; Lee et al., 2018). These findings suggestthatmentalwell-being should be a treatment goal in schizophrenia to op-timize a likelihood of remission. Although individuals with schizophreniamay report higher prevalence of adverse life events and generally worsephysical health, these positive psychological traits are potentially modifi-able and could promote both mental and physical well-being andpossibly curtail accelerated biological aging trajectories. Positive psychia-try provides a light at the end of the tunnel and gives hope to patients,their families, clinicians, and the public at large, thereby helping the pro-cess of eliminating the stigma associated with serious mental illnesses.Increasing the focus in mental healthcare on positive psychological fac-tors such as resilience, optimism, hope, wisdom, and social support, iscritical for promoting overall wellness in people with schizophrenia. Apositive change in attitude about the chronicity of schizophrenia is neces-sary among scientists and clinicians, which in turn will effect a similarchange among people with schizophrenia and their families. While wewait for the biological means of curing and preventing schizophrenia,we must strive to change the societal attitude toward persons withschizophrenia and improve the rates of recovery in this long-neglectedgroup of people. A wise society is defined by how it cares for its mostdisenfranchised segments.ContributorsAll authorsmade substantial contributions to the work and intellectual content of thearticle. Authors TTN and DVJ participated in conceptualization and writing of the manu-script. The final version of the manuscript was read and approved by all authors.FundingThis work was supported, in part, by National Institute of MentalHealth (grant numbers 2R01 MH094151-06 to DVJ, and K23MH118435-01A1 to TTN), and UC San Diego, Sam and Rose Stein Insti-tute for Research on Aging.AcknowledgementsThe authors have declared that there are no conflicts of interest in relation to the sub-ject of this study.ReferencesAuslander, L.A., Jeste, D.V., 2004. Sustained remission of schizophrenia amongcommunity-dwelling older outpatients. Am. J. Psychiatry 161 (8), 1490–1493.Bellack, A.S., 2006. Scientific and consumer models of recovery in schizophrenia: concor-dance, contrasts, and implications. Schizophr. Bull. 32 (3), 432–442.Bleuler, M., 1983. Schizophrenic deterioration. Br. J. Psychiatry J. Ment. Sci. 143 (1), 78–79.Eack, S.M., Hogarty, G.E., Cho, R.Y., Prasad, K.M., Greenwald, D.P., Hogarty, S.S., Keshavan,M.S., 2010. Neuroprotective effects of cognitive enhancement therapy against graymatter loss in early schizophrenia: results from a 2-year randomized controlledtrial. Arch. Gen. Psychiatry 67 (7), 674–682.Edmonds, E.C., Martin, A.S., Palmer, B.W., Eyler, L.T., Rana, B.K., Jeste, D.V., 2018. Positivemental health in schizophrenia and healthy comparison groups: relationships withoverall health and biomarkers. Aging Ment. Health 22 (3), 354–362.Harding, C.M., Brooks, G.W., Ashikaga, T., Strauss, J.S., Breier, A., 1987. The Vermont longi-tudinal study of persons with severe mental illness, II: long-term outcome of subjectswho retrospectively met DSM-III criteria for schizophrenia. Am. J. Psychiatry 144 (6),727–735.Harding, C.M., Zubin, J., Strauss, J.S., 1992. Chronicity in schizophrenia: revisited. Br J Psy-chiatry Suppl (18), 27–37.Jeste, D.V., 2018. Positive psychiatry comes of age. Int. Psychogeriatr. 30 (12), 1735–1738.Jeste, D.V., Wolkowitz, O.M., Palmer, B.W., 2011. Divergent trajectories of physical, cogni-tive, and psychosocial aging in schizophrenia. Schizophr. Bull. 37 (3), 451–455.Jeste, D.V., Palmer, B.W., Saks, E.R., 2017.Whywe need positive psychiatry for schizophre-nia and other psychotic disorders. Schizophr. Bull. 43 (2), 227–229.Kraepelin, E., 1971. Dementia Praecox and Paraphrenia. Krieger Publishing Company,Huntington, NY.Lange, S.M.M., Meesters, P.D., Stek, M.L., Wunderink, L., Penninx, B.W.J.H., Rhebergen, D.,2019. Course and predictors of symptomatic remission in late-life schizophrenia: A5-year follow-up study in a Dutch psychiatric catchment area. Schizophr Res 209,179–184.Lee, E.E., Martin, A.S., Tu, X., Palmer, B.W., Jeste, D.V., 2018. Childhood adversity andschizophrenia: the protective role of resilience in mental and physical health andmetabolic markers. The Journal of clinical psychiatry 79 (3).Meesters, P.D., Comijs, H.C., de Haan, L., Smit, J.H., Eikelenboom, P., Beekman, A.T., Stek,M.L., 2011. Symptomatic remission and associated factors in a catchment areabased population of older patients with schizophrenia. Schizophr. Res. 126 (1–3),237–244.Palmer, B.W., Martin, A.S., Depp, C.A., Glorioso, D.K., Jeste, D.V., 2014. Wellness within ill-ness: happiness in schizophrenia. Schizophr. Res. 159 (1), 151–156.Vinogradov, S., Fisher, M., Holland, C., Shelly, W., Wolkowitz, O., Mellon, S.H., 2009. Isserum brain-derived neurotrophic factor a biomarker for cognitive enhancement inschizophrenia? Biol. Psychiatry 66 (6), 549–553.

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Positive light on schizophrenia and aging: Commentary on course and predictors of symptomatic remission in schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area, by Lange et al.

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Positive light on schizophrenia and aging: Commentary on course and predictors of symptomatic remission in schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area, by Lange et al.

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