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The ‘organic’ basis of Late-Onset Schizophrenia
P Poster Presentations
62 Assessments of safety included AIMS (both studies), Simpson-Angus and Bame s-Akarhisia scales (M92-795 only) as well as adverse advent monitoring, routine laboratory tests and ECGs. Efficacy was assessed by means of CG!. Evaluations took place at approximately weekly intervals during the four-wee k titration period, then monthly during the maintenance phase. The CGI rating scale confirmed sertindole to be an effective treatment for the manifestations of psychosis. All parameters measured showed sertindole to have minimal adverse effects on extrapyramidal motor signs and symptom s. This was confirmed by the lack of need for anti-EPS medication in these patients. These findings are consistent with those from placebo-controlled studies. Sertindole appears to be both effective and well-tolerated in the treatment of the manifestations of psychosis without the extrapyramidal side effects seen with traditional neuroleptics.
I P-7-171
The 'Organic' Basis of Late-Onset Schizophrenia
P. Sachdev, H. Brodaty, N. Rose, N. Haindl, C. Frayter, P. Kitchener.
School of Psychiatry. University of New South Wales; and The Prince Henry and Prince of Wales Hospitals, Sydney, Australia Aim; The Late-Onset Schizophrenia (LOS) Study is an intensive clinical, neuropsychological, and neuroimaging investigation of LOS, comparing it with early-onset schizophrenia (EOS) and healthy control (C) subjects. The major hypothesi s is that unlike EOS subjects who manifest indicators of neurodeve1opmental abnormality, LOS subjects demonstrate significant acquired brain disease. Subjects: The sample comprised 30 LOS, 30 EOS and 34 C subjects, matched. as far as possible, for age, gender and parental social class. The LOS and EOS subjects met DSM-IIIR criteria for schizophrenia, and differed in ages of onset (after 50 years for LOS and before 35 years for EOS). The presence of coarse brain disease at baseline excluded publication. Assessment: This comprised: sociodernographic data; illness and treatment history ; family history using a structured interview; personality assessment using Standard ised Assessment of Personality and self- and informant-rating; psychiatric assessment using the CIOI and SAPS and SANS; a neurological examination ; examination for ' soft' neurological signs; EEG ; assessment of hearing and vision; MRI scans for Tl-weighted 1.5 mm contiguous coronal cuts and T2-weighted 5 mm axial cuts; HMPAO SPECf scans; and a detailed neuropsychological assessment. The subjects were followed up at 1-3 years after index assessment. Results: The clinical profile of LOS was consistent with the published literature except that our subjects did not have greater sensory deficits than the control populations. The LOS group had greater neuropsychological deficits than C subjects, but did not differ from the EOS group. The EOS group had more MRI abnormalties, in particular hyperintensities on TI-weighted images. The results support our hypothesis that LOS subjects have greater acquired brain impairments that may underpin the psychopathological process.
MAORS while EPS were evaluated with the Simpson, Barnes, and AIMS scales. 1047 or 53% of subjects had a baseline MAORS total score 2: 16. Analyses demonstrated a positive correlation between change in DSS and BPRS total, BPRS depression. PANSS positive and PANSS negative scores. There were no significant EPS correlate s. The novel antipsychotic OLZ was statistically significantly superior to HAL in baseline 10 endpoint change in MADRS total score, MADRS item I, and BPRS depression subscale. Significant treatment difference s favoring OLZ were evident by week 1. Reduced DA function in mesofrontal reward pathways have been implicated in DSS accompanying schizophren ia. The predominant 5-HT2 over 02 antagonism of OLZ, coupled with a relative D41D3 affinity, may explain its superior efficacy. Comparable positive symptom and superior negative symptom effects of OLZ versus HAL suggest this effect was mediated by negative symptom change and/or a direct antidepressant effect. Subjects with greater endpoint improvement in DSS are likely 10 have superior overall outcomes.
IP-7-191
Anhedonia and Depression in Chronic Schizophrenia: Distinct or Overlapping Constructs?
G. Loas, P. Boyer, C. Noisette, A. Legrand. University Department of
Psychiatry, Pinel Hospital. Amiens, France. EU The prevalence of depression in schizophrenia ranges from 30 to 60 percent. Anhedonia is a common feature of schizophrenia and depress ion. Moreover anhedonia is a negative symptom for several authors. In a follow-up study in schizophrenia, Harrow et al [ I I have shown first a strong link between neuroleptic use and anhedonia and secondly that the interference by neuroleptics with the dopamine reward system is one factor involved in the depressive-like symptoms found in schizophren ia. The aim of the present study is to examine the independency of the anhedonia and depression constructs in chronic schizophrenia, as measured by the Fawcett Clark Capacity Scale-Physical Pleasure (FCPCS-PP) and the abridged form of the Beck Depression Inventory (BOI), using factor analysis. 150 schizophrenics meeting the RDC criteria for chronic schizophrenia filled out the FCPCS-PP and the BDI. The 12 items from the FCPCS-PP and the 13 items from the BOI were intercorrelated and the matrix was then subjected to principal components analysis followed by a varimax rotation. The results have shown a two-factor solution with no overlap of the significant factor loadings for the items from each scale, and with the factors corresponding closely with their respective construct (depression, hedonic capacity). The finding support the view that anhedonia is a construct that is distinct and separate from depression in chronic schizophrenia. (I] Harrow M, Yonan C, Sands J, Marengo J. SchizoBull, 20, 2, (1994), 327- 328.
IP-7-20 IThe Relationship between Negative Symptoms and Depression in Schizophrenia
D. Addington, J. Addington. Department of Psychiatry. University of
IP-7-18 1Comorbid Mood Disturbance in Schizophrenia Gary D. Tollefson, Yili Lu. Lilly Research Laboratories. Eli Lilly and
Company, Indianapolis. IN USA Depressive signs and symptoms (DSS) frequently appear as part of the core psychopathology in schizophrenia (7 to 70%). They may impart a less favorable outcome. including a heightened risk of relapse/suicide. DSS most often emerge during an acute psychotic episode and correlate with both positive and negative symptom severity. In this abstract the relationship of DSS to other core features of schizophrenia and various elements of the acute treatment outcome were assessed. In addition we hypothesize that the differential pharmacology of the novel atypical antipsychotic oJanzapine (OLZ) would have DSS treatment benefits over the conventional 0 2 antagonist, haloperidol (HAL). The investigation was an international double-bl ind parallel trial conducted in 1996 subjects with OSM-III-R schizophrenia or a closely related condition . Individuals were randomized (2:1) to either OLZ or HAL (5- 20 mg per day) for 6 weeks. Efficacy assessments were done with the BPRS, PANSS, CG!, and the
Calgary, Calgary, Canada Objective: In this study the relationship between negative symptoms and depression was explored using both categorical and dimensional measures of negative symptoms. Method: A cohort of 112 subjects with schizophrenia was followed for one year and assessed at three points on measures of negative, depressive and positive symptoms. The first assess ment occurred at a time of relapse, the second was three months later at a lime of relative remission and the third was one year after the initial assessment. Measures included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depre ssion Scale for Schizophrenia (CDSS) and the proxy Deficit Syndrome Scale. Results: An examination of the relationship between dimensional measures revealed no correlation between levels of negative symptom s and depression at either follow-up. Twenty-four of 34 subjects who met the proxy deficit syndrome criteria at three months continued to meet these criteria at one year follow-up. This group of24 was considered to have an enduring deficit syndrome. The deficit group differed from the non-deficit group on levels of depression but not on levels of negative or positive symptoms.
62 Assessments of safety included AIMS (both studies), Simpson-Angus and Bame s-Akarhisia scales (M92-795 only) as well as adverse advent monitoring, routine laboratory tests and ECGs. Efficacy was assessed by means of CG!. Evaluations took place at approximately weekly intervals during the four-wee k titration period, then monthly during the maintenance phase. The CGI rating scale confirmed sertindole to be an effective treatment for the manifestations of psychosis. All parameters measured showed sertindole to have minimal adverse effects on extrapyramidal motor signs and symptom s. This was confirmed by the lack of need for anti-EPS medication in these patients. These findings are consistent with those from placebo-controlled studies. Sertindole appears to be both effective and well-tolerated in the treatment of the manifestations of psychosis without the extrapyramidal side effects seen with traditional neuroleptics.
I P-7-171
The 'Organic' Basis of Late-Onset Schizophrenia
P. Sachdev, H. Brodaty, N. Rose, N. Haindl, C. Frayter, P. Kitchener.
School of Psychiatry. University of New South Wales; and The Prince Henry and Prince of Wales Hospitals, Sydney, Australia Aim; The Late-Onset Schizophrenia (LOS) Study is an intensive clinical, neuropsychological, and neuroimaging investigation of LOS, comparing it with early-onset schizophrenia (EOS) and healthy control (C) subjects. The major hypothesi s is that unlike EOS subjects who manifest indicators of neurodeve1opmental abnormality, LOS subjects demonstrate significant acquired brain disease. Subjects: The sample comprised 30 LOS, 30 EOS and 34 C subjects, matched. as far as possible, for age, gender and parental social class. The LOS and EOS subjects met DSM-IIIR criteria for schizophrenia, and differed in ages of onset (after 50 years for LOS and before 35 years for EOS). The presence of coarse brain disease at baseline excluded publication. Assessment: This comprised: sociodernographic data; illness and treatment history ; family history using a structured interview; personality assessment using Standard ised Assessment of Personality and self- and informant-rating; psychiatric assessment using the CIOI and SAPS and SANS; a neurological examination ; examination for ' soft' neurological signs; EEG ; assessment of hearing and vision; MRI scans for Tl-weighted 1.5 mm contiguous coronal cuts and T2-weighted 5 mm axial cuts; HMPAO SPECf scans; and a detailed neuropsychological assessment. The subjects were followed up at 1-3 years after index assessment. Results: The clinical profile of LOS was consistent with the published literature except that our subjects did not have greater sensory deficits than the control populations. The LOS group had greater neuropsychological deficits than C subjects, but did not differ from the EOS group. The EOS group had more MRI abnormalties, in particular hyperintensities on TI-weighted images. The results support our hypothesis that LOS subjects have greater acquired brain impairments that may underpin the psychopathological process.
MAORS while EPS were evaluated with the Simpson, Barnes, and AIMS scales. 1047 or 53% of subjects had a baseline MAORS total score 2: 16. Analyses demonstrated a positive correlation between change in DSS and BPRS total, BPRS depression. PANSS positive and PANSS negative scores. There were no significant EPS correlate s. The novel antipsychotic OLZ was statistically significantly superior to HAL in baseline 10 endpoint change in MADRS total score, MADRS item I, and BPRS depression subscale. Significant treatment difference s favoring OLZ were evident by week 1. Reduced DA function in mesofrontal reward pathways have been implicated in DSS accompanying schizophren ia. The predominant 5-HT2 over 02 antagonism of OLZ, coupled with a relative D41D3 affinity, may explain its superior efficacy. Comparable positive symptom and superior negative symptom effects of OLZ versus HAL suggest this effect was mediated by negative symptom change and/or a direct antidepressant effect. Subjects with greater endpoint improvement in DSS are likely 10 have superior overall outcomes.
IP-7-191
Anhedonia and Depression in Chronic Schizophrenia: Distinct or Overlapping Constructs?
G. Loas, P. Boyer, C. Noisette, A. Legrand. University Department of
Psychiatry, Pinel Hospital. Amiens, France. EU The prevalence of depression in schizophrenia ranges from 30 to 60 percent. Anhedonia is a common feature of schizophrenia and depress ion. Moreover anhedonia is a negative symptom for several authors. In a follow-up study in schizophrenia, Harrow et al [ I I have shown first a strong link between neuroleptic use and anhedonia and secondly that the interference by neuroleptics with the dopamine reward system is one factor involved in the depressive-like symptoms found in schizophren ia. The aim of the present study is to examine the independency of the anhedonia and depression constructs in chronic schizophrenia, as measured by the Fawcett Clark Capacity Scale-Physical Pleasure (FCPCS-PP) and the abridged form of the Beck Depression Inventory (BOI), using factor analysis. 150 schizophrenics meeting the RDC criteria for chronic schizophrenia filled out the FCPCS-PP and the BDI. The 12 items from the FCPCS-PP and the 13 items from the BOI were intercorrelated and the matrix was then subjected to principal components analysis followed by a varimax rotation. The results have shown a two-factor solution with no overlap of the significant factor loadings for the items from each scale, and with the factors corresponding closely with their respective construct (depression, hedonic capacity). The finding support the view that anhedonia is a construct that is distinct and separate from depression in chronic schizophrenia. (I] Harrow M, Yonan C, Sands J, Marengo J. SchizoBull, 20, 2, (1994), 327- 328.
IP-7-20 IThe Relationship between Negative Symptoms and Depression in Schizophrenia
D. Addington, J. Addington. Department of Psychiatry. University of
IP-7-18 1Comorbid Mood Disturbance in Schizophrenia Gary D. Tollefson, Yili Lu. Lilly Research Laboratories. Eli Lilly and
Company, Indianapolis. IN USA Depressive signs and symptoms (DSS) frequently appear as part of the core psychopathology in schizophrenia (7 to 70%). They may impart a less favorable outcome. including a heightened risk of relapse/suicide. DSS most often emerge during an acute psychotic episode and correlate with both positive and negative symptom severity. In this abstract the relationship of DSS to other core features of schizophrenia and various elements of the acute treatment outcome were assessed. In addition we hypothesize that the differential pharmacology of the novel atypical antipsychotic oJanzapine (OLZ) would have DSS treatment benefits over the conventional 0 2 antagonist, haloperidol (HAL). The investigation was an international double-bl ind parallel trial conducted in 1996 subjects with OSM-III-R schizophrenia or a closely related condition . Individuals were randomized (2:1) to either OLZ or HAL (5- 20 mg per day) for 6 weeks. Efficacy assessments were done with the BPRS, PANSS, CG!, and the
Calgary, Calgary, Canada Objective: In this study the relationship between negative symptoms and depression was explored using both categorical and dimensional measures of negative symptoms. Method: A cohort of 112 subjects with schizophrenia was followed for one year and assessed at three points on measures of negative, depressive and positive symptoms. The first assess ment occurred at a time of relapse, the second was three months later at a lime of relative remission and the third was one year after the initial assessment. Measures included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depre ssion Scale for Schizophrenia (CDSS) and the proxy Deficit Syndrome Scale. Results: An examination of the relationship between dimensional measures revealed no correlation between levels of negative symptom s and depression at either follow-up. Twenty-four of 34 subjects who met the proxy deficit syndrome criteria at three months continued to meet these criteria at one year follow-up. This group of24 was considered to have an enduring deficit syndrome. The deficit group differed from the non-deficit group on levels of depression but not on levels of negative or positive symptoms.