1 Mount Sinai School of Medicine, Dept. of Psychiatry, New York, NY VA Hudson Valley Health Care System, Rese

1. Decreased functional status in outpatients with chronic schizophreniaKushik Jaga, MBBS, MPH1,2, Cecile Sison, PhD2, Edward R. Allan, MD2, Christopher R. Bowie, PhD1, Philip D. Harvey, PhD1 1Mount Sinai School of Medicine, Dept. of Psychiatry, New York, NY VA Hudson Valley Health Care System, Research and Development, Montrose, NY

2. Abstract • Introduction: The course of illness in chronic schizophrenics is known to affect the functional status of patients over time. Psychotic symptoms also vary with age and determine the health outcome of patients such as; well being and physical functioning. In this study, functional status of outpatients with chronic schizophrenia was compared across age groups. • Methods: Outpatients aged 50 and above diagnosed with schizophrenia or schizoaffective disorder were included (196). Symptom severity was measured by the positive and negative syndrome scale (PANSS). Functional status was assessed with both a performance-based (UPSA) and observer rated Specific Level of Functioning (SLOF) measures. Mean scores of the PANSS, UPSA and SLOF were compared between 4 age groups; 50-54, 55-59, 60-64, >= 65, using Analysis of variance (ANOVA). Correlation analysis examined relationships between PANSS, UPSA and SLOF categories. • Results: Functional performance declined significantly with increasing age – UPSA (p = 0.001), SLOF (p=0.04). The PANSS general psychopathology symptoms improved significantly in ages 65 and above (p=0.05). Increasing age correlated with declining UPSA and SLOF scores (p < 0.01). The PANSS negative scale correlated with lower SLOF scores (p < 0.01). The mini-mental status (MMSE) mainly predicted performance on the UPSA and SLOF (p < 0.01). Negative symptoms predicted outcome of SLOF more than age. • Conclusion: With increasing age schizophrenic patients are more likely to demonstrate poorer functional abilities and have increasingly impaired functional ("real world") performance. Older schizophrenia patients might have different community-based and home care needs.

3. Course of Cognitive and Functional Deficits in Older Schizophrenic Patients Supported by: National Institute of Mental Health (NIMH) Grant MH 63116 Principal Investigator: Philip D. Harvey Co-Investigator: Cecile Sison, PhD Study Manager: Christopher R. Bowie, PhD. Clinical Research Coordinator: Kushik Jaga, MBBS, MPH

4. Introduction • Schizophrenia: Severe psychiatric disorder, Psychotic symptoms; hallucinations and delusions Cognitive and functional impairment – major cause of disability1,2 Affects more than 2 million people in the US 98,000 veterans received care for schizophrenia in the VA in 20033. • Figure 1: Longitudinal Course of Schizophrenia (Lieberman)4 Premorbid Stage Prodromal Onset/ Clinical Chronic/ Residual Progression Deterioration Stage Psychotic symptoms Birth Puberty -20 yrs 30 yrs 40 yrs and above Functional Decline (Cognitive Impairment)1,5

5. Outcome of Illness: Functional impairment - Social, occupational, independent living, rehabilitation skills1,2 " Not able to manage their way in the world" " Not able to function in a gainful way"4 Quality of life Measurement of Functional Status Standardized neurocognitive tests – neuropsychological performance Functional capacity – "real world outcome" What the person can doWhat the person does1 Objective: To compare the functional status across age groups in outpatients with chronic schizophrenia.

6. Methods • Study population: Outpatients with chronic schizophrenia; aging population in community dwelling or care, or independent living (changed environment from in-patients) On active treatment with antipsychotic medications Inclusions: schizophrenia or schizoaffective disorder age 50 years and above Exclusions: Other Axis I psychotic disorders; bipolar, psychosis NOS, Major Depressive Disorder (MDD) with psychotic features Medical illness known to affect cognitive functioning (dementia, head trauma) Mini-mental score < 17. • Selection: 196 patients were selected from VA, New York State, or academic research sites.

7. Measurements Mini-Mental Status Exam (MMSE) Positive and Negative Symptom Scale (PANSS) Functional Skills Assessment; USCD performance based (UPSA) comprehension and planning, finance, communication, mobility Specific Level of Functioning (SLOF) (observer rated) physical functioning, interpersonal relationships, social acceptability, activities, work skills • Statistical Analysis Comparison of mean scores of PANSS, UPSA, and SLOF between 4 age groups; 50-54, 55-59, 60-64, >=65 years - One Way Analysis of Variance (ANOVA) Correlation analysis between; age and UPSA, SLOF, PANSS and UPSA, SLOF. (Pearson's Correlation) Regression of MMSE, negative symptoms, and age to determine how well they predict variability on the UPSA and SLOF.

8. Results N=196; veterans 91 (46.4%) males 143 (73%), females 52 (27%) Table 1 Demographics of schizophrenic patients CharacteristicMean + SD Age (years) 59.1 + 9.4 MMSE 26.9 + 3.1 Education (years) 12.2 + 3.8 Age distribution: 50-54 yrs 73 (37.2%) 55-59 yrs 57 (29.1%) 60-64 yrs 28 (14.3%) >= 65 yrs 38 (19.4%)

9. Figure 2 Comparison of PANSS scores across Age groups • PANSS positive and negative symptoms did not change across age groups • The PANSS general psychopathology symptoms improved significantly • in older patients, 65 years and above (F=2.53, p=0.05).

10. Figure 3 Comparison of UPSA scores across age groups • Significant decline in UPSA scores in patients 65 years and older • - comprehension and planning, communication, mobility (F=5.67, p=0.001)

11. Figure 4 Comparison of SLOF scores across age groups • Patients 65 years and above had a significant decline in the SLOF • – physical functioning, activity, work skills (F=4.64, p=0.04)

12. Correlations • Increasing age correlated with declining scores of UPSA and SLOF respectively (r = -0.29, p < 0.001; r = -0.27, p < 0.001). • Correlation between PANSS negative symptoms and decreasing SLOF scores (r = -0.307, p < 0.001). Regression Analysis • Lower MMSE scores was a predictor of the decline in functional status; 21% of the variance on UPSA (p < 0.01, 95%CI: 1.23 – 2.19) 20% of the variance on SLOF (p < 0.01, 95%CI: 1.8-3.6) • Negative symptoms accounted for 4.0% of the variance on the SLOF (p=0.06). • Older age accounted for 3.0% of the variance on UPSA (p < 0.01), and 3.2% on the SLOF (p < 0.01).

13. Conclusions • Community dwelling patients with chronic schizophrenia are more likely to demonstrate poorer functional abilities with increasing age – impaired functional "real world" performance. • The level of impairment in older schizophrenics is related to cognitive impairment and negative symptoms. • Older schizophrenics might have different community-based and home care needs, requiring treatment targeted at cognitive and functional improvement.

14. References • Bowie CR. Reichenberg A, Patterson TL, Heaton R, Harvey P. Determinants of real-world functional performance in schizophrenia: Correlations with cognition, functional capacity, and symptoms. Am J Psychiatry 2006; 163: 418-425. • Green GF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 2006; 67 (suppl 9): 3-7. • Management Decision and Research Center. VA Health Services Research and Development Service (HSR&D). Effective treatment for schizophrenia. VA Practice Matters 2002; 7: 1-6. • Lieberman JA, Jarskog LF, Malaspina D. Preventing clinical deterioration in the course of schizophrenia: The potential for neuroprotection. J Clin Psychiatry 2006;67:983-985. • Bowie CR. Harvey D. Treatment of cognitive deficits in schizophrenia. Curr Opin Investig Drugs 2006; 7: 608-613.