total intracranial contents through linear regression, were examined in relationship to 2 neuropsychological domains that tapped executive and memory functions. Statistical analyses were conducted using Spearman Rank order correlations. Results indicated significant (p⬍.05) positive correlations between anterior hippocampus and amygdala volumes and functioning on the memory domain. Investigation of the tests comprising the memory domain revealed that smaller anterior hippocampus and amygdala volumes correlated significantly with worse WMS-R Logical Memory I and Logical Memory II performance. These findings suggest that mesiotemporal lobe volumes may be a significant predictor of neuropsychological functioning in schizophrenia.
95. SMOOTH PURSUIT EYE MOVEMENT
DYSFUNCTION IN PATIENTS AT CLINICAL
RISK FOR SCHIZOPHRENIA
M. Obuchowski (1), T.C. Chan (1),
E. Pappadopulos (1), T. Lencz (1), D. Coscia (1),
K. Ditkowsky (2), J. Becker (1), J.A. Sweeney (3),
B. Cornblatt (1)
(1) Psychiatry Research, Hillside Hospital, Glen Oaks, NY 11004, USA (2) Schneider Children’s Hospital, Glen Oaks, NY 11004, USA (3) Western Psychiatric Institute & Clinic, Pittsburgh, PA 15213, USA Research involving individuals at risk for schizophrenia has traditionally focused on the identification of early biobehavioral indicators of schizo-phrenia. Biobehavioral indicators are subtle neurocognitive deficits that can be accurately detected before onset of psychotic illness. Of the many neurocognitive domains that have been studied, eye-movement dysfunc-tions have been found to be among the most promising candidate indicators.
Early studies of the at-risk offspring and siblings of schizophrenia probands suggest the presence of eye movement impairments in at least a subgroup of subjects. However, more recently, detection of indicator deficits has focused on a new high risk population—subjects at clinical risk for schizophrenia. These subjects are characterized by symptoms that have been retrospectively identified with the schizophrenia prodrome.
In this study, we evaluated smooth pursuit eye movement performance in 29 adolescents at clinical risk for schizophrenia recruited from the RAPP (Recognition and Prevention of Psychological Problems) clinic (Barbara Cornblatt, Ph.D., Director) at Hillside Hospital/Schneider Chil-dren’s Hospital, which is a recently opened program specializing in the treatment and assessment of adolescents with early prodromal symptoms of schizophrenia. These at-risk subjects were compared with 25 adoles-cent patients diagnosed with schizophrenia, recruited from an adolesadoles-cent inpatient unit at Hillside Hospital.
Preliminary results suggest that 28% of the adolescents at clinical risk for schizophrenia display impaired smooth pursuit eye tracking perfor-mance similar to that of patients with schizophrenia. These results provide early evidence of the presence of a well-established schizophre-nia-specific neurocognitive deficit in subjects at clinical risk for schizophrenia.
96. AWARENESS OF MEMORY
DYSFUNCTION IN FIRST-EPISODE
SCHIZOPHRENIA
R.S. Goldman, J. Conley, R. Miller, J. Bates,
G. Reiter, D. Robinson, N.R. Schooler
Hillside Hospital; Psychiatry Research; Glen Oaks, NY 11004 Patients with schizophrenia manifest a high degree of generalized neurocognitive dysfunction, with particularly severe impairment in memory. There is growing interest in patient awareness of clinical and cognitive symptoms, since this has implications for treatment compliance and outcome. The present study reports preliminary data addressing awareness of memory dysfunction and its impact on daily activities in a cohort of prospectively ascertained first-episode patients with schizo-phrenia. Fourteen patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder rated their daily memory function in a number of real-life contexts and received formal neurocognitive tests of memory. Family members independently rated patient memory function, using the same item content that were performed in patient self-ratings. The results revealed a surprising concordance between patient and observer ratings of daily memory function; absolute scores of patients ratings did not differ significantly from observer ratings, though the correlation between patients and observers was less consistent. Both patients and informants agreed on ratings of the quality of recent episodic memory. Patient ratings of daily memory function correlated modestly with test based assessment of memory (range of correlations: .33 to 45). Informant ratings of recent episodic memory were more consistently associated with actual patient performance, particularly on measures of working memory and explicit recall. The findings indicate that patients have partial awareness of memory function as it impacts on recall of daily episodes. Test based assessment of memory provides an indirect indica-tion of global memory capability in real-world situaindica-tions, but is less directly associated with more specific daily functions.
97. THE HILLSIDE RAPP CLINIC: WHY
THE SUDDEN INTEREST IN THE
SCHIZOPHRENIA PRODROME?
B. Cornblatt (1), K. Ditkowsky (2), J. Becker (1),
E. Pappadopulos (1), T. Lencz (1), D. Coscia (1),
M. Obuchowski (1)
(1) Psychiatry Research, Hillside Hospital, Glen Oaks, NY 11004, USA (2) Schneider Children’s Hospital, Glen Oaks, NY 11004, USA The RAPP (Recognition and Prevention of Psychological Problems) Clinic of Hillside Hospital is a research/early intervention center focusing on adolescents thought to be in the pre-psychotic or prodromal stages of schizophrenia. A major research goal of the RAPP clinic is to prospec-tively establish risk factors that predict future illness, since the current definition of the prodrome has been derived from retrospective research. Clinical assessments, neurocognitive data and treatment outcome will be presented for 50 adolescents who have received at least one year of treatment. To date, four major non-specific disturbances have accounted for most referrals: a sudden decline in school functioning, increasing social withdrawal, emergence of odd behaviors and the presence of depression. Self reports by the RAPP adolescents indicate the presence of a range of schizophrenia-like symptoms, including schizotypal, schizoid, paranoid and avoidant features and elevated levels of social isolation. Parental reports further corroborate the presence of these characteristics. In addition, performance on measures of attention, working memory and
Thursday Abstracts BIOL PSYCHIATRY 29S
executive functioning indicate that the RAPP patients display neurocog-nitive deficits that are comparable to those characterizing adolescents at genetic risk.
The potential of intervention during the prodrome to prevent schizo-phrenia is a complex and often controversial issue. Ratings obtained from clinicians indicate that the majority of adolescents treated with atypical anti-psychotics (either Olanzapine or Risperidone) in the RAPP clinic have either been stabilized or have shown substantial improvement. The question of whether such clinical benefits are sufficient to outweigh side effects, stigma and the high rate of false positives will also be discussed.
98. A SELF-REPORT QUESTIONNAIRE TO
SCREEN FOR PRODROMAL
SCHIZOPHRENIA
T. Lencz (1), E. Pappadopulos (1,2),
M. Obuchowski (1), K. Ditkowsky (2),
J. Becker (1), M. Lenzenweger (3),
B. Cornblatt (1)
(1) Research Dept., Hillside Hospital/North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004 (2) Psychiatry Dept., Schneider Children’s Hospital//NS-LIJ Health System, New Hyde Park, NY 11004 (3) Psychology Dept., Harvard University, Cambridge, MA 02138
The RAPP (Recognition and Prevention of Psychological Problems) Clinic, opened two years ago at Hillside and Schneider Children’s Hospitals (Barbara Cornblatt, Director), is dedicated to the identification, characterization, and treatment of adolescents and young adults with prodromal symptoms of schizophrenia. One major goal of the RAPP Clinic is to develop a brief assessment that will screen for teenagers reporting symptoms thought to characterize the schizophrenia prodrome. As the first step, a self-report instrument including items drawn from the International Personality Disorders Examination Screen (IPDE), a true/ false questionnaire that measures each of the ten DSM-IV personality disorders, was routinely administered to all adolescents undergoing intake in Schneider’s outpatient department. Data were collected from two groups of patients: (a) 33 patients later enrolled (blind to IPDE scores) in the RAPP clinic, identified as prodromal based on other clinical information; and (b) 60 patients with other mental disorders (OMD). RAPP patients endorsed significantly more symptoms than OMD patients for odd cluster personality disorders (schizotypal p⬍.01; paranoid and schizoid, p⬍.05) and for avoidant personality disorder (p⬍.05). The RAPP patients did not differ from OMD on any other subscales, indicating specificity of symptom profile. Additionally, a novel index of social isolation was constructed from seven IPDE items; RAPP patients had significantly higher scores than the OMD patients (p⫽.001). These preliminary findings suggest that a brief self-report assessment has considerable potential for prodromal screening.
99. SAFETY AND EFFECTIVENESS OF
OLANZAPINE VERSUS OTHER
ANTIPSYCHOTIC DRUGS IN THE
TREATMENT OF OUTPATIENTS WITH
SCHIZOPHRENIA
J.C. Gomez (1), J.A. Sacristan (1),
P.R. Carrasco (2), C.A. Saiz (3), E.F. Carbonell (4)
(1) Department of Clinical Research, Eli Lilly and Company, Madrid, Spain. (2) Psychiatrist, Sevilla, Spain. (3) Psychiatrist, Hospital Son Dureta, Palma de Mallorca, Spain. (4) Psychiatrist, Barcelona, Spain Prospective, comparative, non-randomized, open, observational study, including 2949 outpatients with schizophrenia who were followed up for 6 months after receiving a new prescription of an antipsychotic. Safety was evaluated collecting adverse events and global clinical status was measured through CGI and GAF Scales. A total of 2128 patients received olanzapine, as monotherapy or in combination (Olanzapine group), and 821 received other antipsychotics (Control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, severity of symptoms, and EPS. Incidence of adverse events and specifically extrapyramidal symptoms was signif-icantly lower in the olanzapine group compared to the control group (p⬍ 0.001). Mean change in the CGI and the GAF was significantly higher in the olanzapine group compared to the control group (p⬍0.001). Despite the limitations of an observational study, these results shows that olanzapine is safe and effective in non-selected schizophrenic outpa-tients, and are consistent with results of previous controlled trials.
100. COMPARATIVE EFFICACY OF
OLANZAPINE AND HALOPERIDOL FOR
PATIENTS WITH TREATMENT-RESISTANT
SCHIZOPHRENIA
A. Breier, S.H. Hamilton
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana
There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted. A sub-population of patients (N ⫽ 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, six-week study assessing the efficacy and safety of olanzapine and haloperidol was examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted. Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, co-morbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale and extrapyramidal symptoms as measured by Simpson-Angus Extrapyrami-dal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale (BPRS) total (p⫽.006), PANSS total (p ⫽.005), and PANSS positive symptoms (p ⫽.017) in completers of the six-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-olanzapine-treated (35%) patients in the LOCF analysis (p⫽.008), but significance was not reached in the completers analysis (p⫽.093). Mean doses (⫾SD) of olanzapine and haloperidol were 11.1⫾3.4 mg/day and 10.0⫾3.6 mg/day, respectively.
Olanza-30S BIOL PSYCHIATRY Thursday Abstracts
