Schizophrenia: A neuro-developmental disorder of social and cognitive decline Demian Rose, MD, PhD

Take Home Point 1 Schizophrenia is associated with three primary symptom domains: positive symptoms, negative symptoms and cognitive symptoms. Of these, cognitive symptoms are most associated with functional impairment, followed by negative symptoms Despite this, we have traditionally focused our conceptualization based on positive symptoms

Components of the Illness attention concentration memory Cognitive Impairment Psychotic Symptoms hallucinations delusions Negative Symptoms anergia anhedonia amotivation

Percent of Patients Ever in Recovery (5 Follow-ups Over 15-Years) (Harrow et al., 2005, fig 2)

Take Home Point 2 Schizophrenia is a neuro-developmental disorder involving abnormal brain development during adolescence and young adulthood Multiple brain regions are affected in measurable ways

Dysfunction in multiple regions in brain areas implicated in schizophrenia Schobel, S. A. et al. Arch Gen Psychiatry 2009;66:938-946. Copyright restrictions may apply.

Iowa Longitudinal Study of First Episode Schizophrenia (Investigator: Nancy Andreasen, MD) Hundreds of subjects recruited over 20 years All adolescents or young adults Half of all subjects show significant brain tissue loss in the frontal lobes (at least 0.5% per year) One-third of all subjects lose average of 1% per year Normal loss is on the order of 0.1-0.2% per year Most loss in Schizophrenia occurs in the first few years after diagnosis

Take Home Point 3 The cognitive and social dysfunction associated with schizophrenia typically pre-dates the onset of the more easily identified “psychotic” symptoms

Potential neurodevelopmental stages of schizophrenia Insel, T. R. Arch Gen Psychiatry 2009;66:128-133. Copyright restrictions may apply.

Cognitive deficits predate psychotic symptoms FE = first episode schizophrenia, UHR = ultra high risk for developing schizophrenia BS/PCO = controls Simon (2007) Schizophrenia Bulletin, vol 33, pg 761-71

Take Home Point 4 By the time of first diagnosis, a crucial time for successful intervention, abnormal brain development and cognitive deficits are already significant, and many psychosocial supports are already in jeopardy

Survival graphs for suicide by psychiatric disorder in people admitted to hospital during 1973-82 for attempted suicide in Sweden and followed to 2003 Tidemalm, D. et al. BMJ 2008;337:a2205 Copyright ©2008 BMJ Publishing Group Ltd.

Duration of Untreated Psychosis Matters Finding is consistent across many studies Perkins (2005) AJP, 162:1785

Schizophrenia is defined as much by cognitive deficits as by psychotic symptoms People with schizophrenia have significant deficits in many measurable domains of cognition (1 to 2 standard deviations below the mean, i.e. as low as 5th percentile) 14

Schizophrenia memory impairments Forbes et al (2009) Psychological Medicine Vol 39, pg 889-905

Impairments affect “real world” activities of daily living When cooking a meal: “Sequencing errors, repetitions and omissions were significantly higher [in people with schizophrenia] compared to controls” Stip (2006) Encephale, vol 3, pg 341-50

Social deficits can be comparable to Autism in type People with schizophrenia have deficits in social cognition that are comparable to people with high-functioning autism Poor emotion perception Poor ability to accurately guess at the motives of others Couture (2009) Psychological Medicine vol 12, pg 1-11

Cognitive deficits can be comparable to Alzheimer’s in severity People with schizophrenia have a different pattern of cognitive deficits than people with Alzheimer’s Disease, but are equally or more impaired on measures of: Naming Object construction New learning (encoding) Davidson (1996) American Journal of Psychiatry vol 153, pg 1274-1279

Take Home Point 5 If we are to reduce the lifetime morbidity burden of schizophrenia and work towards functional recovery, we must provide a psychosocial framework that allows for evidence-based recovery strategies In this context, disability benefits can help ensure recovery, by allowing for a shift from necessary external decision-making to independent living and recovery

Cognitive Impairment and Recovery For persons so seriously impaired in their decision making capacity that they are incapable of determining what is in their best interest, a paternalistic externally reasoned treatment approach seems not only appropriate but also necessary … .However, as these impaired persons begin to benefit from externally initiated interventions the locus of control should increasingly shift from the treatment provider to the person who is recovering Frese et al (2001), Psychiatric Services, vol 52, pg 1462-1468

Supported Employment Works (Cook et al., 2005) Fig 1. Proportion of subjects employed competitively by month

Keeping families involved leads to better outcomes Average relapse rates across 11 RTC’s (N = 895) Mean length of treatment = 19.7 months McFarlane, W. R., Dixon, L., Lukens, E., Lucksted, A. (2003). Family psychoeducation and schizophrenia: a review of the literature. Journal of Marital and Family Therapy, 29(2), 223-245. A number of reviews of the research literature on family psychoeducation have been published, all of which support the efficacy of family psychoeducation. There are various ways to divide this research literature, such as comparing different formats of intervention, lengths of intervention. This particular graph represents a summary of relapse rates across 11 RTC’s that included some combination of standard treatment conditions, single family, and multiple family formats. The relapse rates represent total percentage of patients that relapsed during the study period, which ranged from 9 months to 4 years, with a mean length of treatment of 19.7 months. First, starting with the relapse rates in the “standard treatment” conditions, which typically included medication management and (usually) some form of individual psychosocial services, we see an average relapse rate of 63%. When a SF psychoeducation intervention is added to medication management, we see the relapse rate roughly cut in ½, to slightly below 30%. Mean relapse rates for multiple family groups fall in the same range, slightly below 30%. TAU = treatment as usual, SF = single family group, MF = multifamily group

Cognitive training can enhance back-to-work programs (McGurk et al

And all of these evidence-based interventions require: Adequate, sustained financial and social services support that begins as soon as possible after diagnosis and assumes a timeline of recovery that is from months to years