S266 Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384

pessimistic description of the illness course into later life. Evidence base

for interventions needs improvement and future trials must include older

participants.

Poster #M209

THE LONGITUDINAL COURSE OF SCHIZOPHRENIA: A SYSTEMATIC REVIEW

Adrian Preda1, Robert Bota2, Steven Potkin1

1University of California Irvine; 2Kaiser Permanente

Background: Naturalistic studies of schizophrenia have been completed

prior to the emergence of neuroleptics in the last part of the last century.

Since the advent of neuroleptics longitudinal studies of schizophrenia have

mostly followed medicated patients. In addition to changes in the medica-

tion background of schizophrenia, a number of changes in the diagnostic

criteria over time brings an additional layer of complexity to any attempt to

systematically organize data about the longitudinal course of schizophrenia.

In this context a systematic review of the literature is essential to prop-

erly understand the longitudinal course of schizophrenia, with important

implications for early diagnosis and intervention, prophylaxis, diagnostic

validity, and prognosis. Further, properly charting the longitudinal course

of schizophrenia is essential to improve our definition of concepts such as

partial response, remission and recovery.

Methods: We completed a systematic literature search for longitudinal,

both retrospective and prospective studies of schizophrenia. To decrease

the heterogeneity of studies span using different diagnostic criteria and

important confounders in the study population (e.g. non-medicated vs.

medicated patients, institutionalization status) we organized our review

based on historical periods which were deemed “homogeneous” in rapport

to important variables of interest (e.g. institutionalization and deinstitu-

tionalization, pre and post neuroleptic periods).

Results: The majority of the longitudinal studies of schizophrenia report

that up to 30-50% of patients present with a stable or favorable course.

Gender, age of onset, duration of illness, core symptoms (positive, negative,

cognitive) can putatively affect prognosis and course.

Discussion: The literature indicated that the course of schizophrenia is one

of stability of symptoms over time for the majority of patients. Stability is

maintained at a lower level of functioning than pre-diagnosis - and as such

is not the optimal outcome - at the same time stability also implies that

gradually deterioration is unlikely for the majority of patients. Of note, the

literature tends to emphasize the less favorable outcome of the minority of

the patients (less than 50%) who show a gradual and progressive deterio-

ration during the course of illness. A “bleaker” interpretation of course and

prognosis dat while justified from a public health perspective might not

be as informative to the clinician aiming to have an objective and, if not

unjustified, appropriately hopeful discussion of course and prognosis with

individual patients.

Poster #M210

THE UCSD PERFORMANCE-BASED SKILLS ASSESSMENT-BRIEF JAPANESE

VERSION (UPSA-B_J): DISCRIMINATIVE VALIDITY FOR SCHIZOPHRENIA

Chika Sumiyoshi1,2, Manabu Takaki3, Yuko Okahisa3, Thomas Patterson4,

Philip D. Harvey5, Tomiki Sumiyoshi6

1Faculty of Human Development and Culture, Fukushima University;2Fukushima University; 3Dept. of Neuropsychiatry, Okayama University

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; 4Dept. of

Psychiatry, School of Medicine, University of California San Diego; 5Dept. of

Psychiatry and Behavioral Sciences, University of Miami Miller School of

Medicine; 6National Center of Neurology and Psychiatry, Clinical Research Unit

Background: The UCSD Performance-based Skills Assessment (UPSA) has

been developed to assess daily living skills related to neurocognition in

people with psychiatric disorders (Patterson et al, 2001). Specifically, its

brief version (UPSA-B; Mausbach et al, 2007) has been widely used for eval-

uating functional capacity in patients with schizophrenia (Harvey, 2009).

To enhance the clinical utility of this battery, its sensitivity, i.e. an optimal

cut-off point discriminating between normal subjects and patients, needs

to be clarified. The current study investigated the issue using the Japanese

version of UPSA-B (UPSA-B_J; Sumiyoshi et al., 2011).

Methods: Sixty-four Japanese patients meeting DSM-IV-TR criteria for

schizophrenia (M/F=34/30; mean age=35.2) and 113 normal controls

(university students=9/21, mean age=20.6; office workers=71/12, mean

age=34.6) entered the study. The UPSA-B_J and MATRICS Cognitive Consen-

sus Battery Japanese version (MCCB_J) was administered to all participants.

The group differences (students vs. workers vs. patients) were analyzed by

one-way ANOVA for the UPSA-B_J Total score, and by ANCOVA (controlling

for education) for the MCCB T-score. The profiles UPSA-B_J were created

to show task-specific performance in each group. Receiver Operating Char-

acteristic (ROC) curve analysis was conducted for the UPSA Total score.

The optimal cut-off was determined in a manner to maximize the sum of

sensitivity (% of hit) and specificity (% of correct rejection) (Youden, 1950;

Mausbach, 2011).

Results: Overall results: Normal students and workers performed better

than patients both in the MCCB_J (Students > Workers > Patients; F=56.65,

df=2 170, p<0.5) and UPSA-B_J (Students=Workers > Patients: F=38.19

df=2 174, p<0.01). The profiles for UPSA-B_J revealed that scores of the

memory-oriented tasks in the Communication part for normal workers and

patients tended to be worse compared to those for normal students. ROC

analysis: The area under the ROC curve (0.80, CI: 0.73-0.87, p <0.001)

and d’ (1.46) indicated good discriminative power of the UPSA-B_J. The

optimal cut-off was estimated as 81.5 (MAX=100), at which sensitivity and

specificity were 81.3% and 65.5%, respectively.

Discussion: The UPSA-B_J Total score around 80 was found to distinguish

adequately between patients and control subjects. This cut-off seems to

be consistent with a previous study reporting “functional milestones (i.e.

residential of employment status)” in patients were to be around this

point (Mausbach, 2011). Result from MCCB_J and UPSA-B_J indicated that

daily-living skills (especially Communication), as measured by the UPSA-B,

depend on neuropsychological abilities.

References:[1] Sumiyoshi T, Sumiyoshi C, Hemmi C: UCSD Performance-Based Skills Assessment-

Brief (UPSA-B): Japanese version; Administration and Scoring Manual, 2011.

Poster #M211

THE THREE FACES OF SCHIZOPHRENIA: SUB-TYPING SCHIZOPHRENIA

BASED ON RESPONSE AND IMPLICATIONS FOR TREATMENT

Ofer Agid1, Gagan Fervaha1,2, George Foussias1, Cynthia Siu3,

Krysta McDonald2, Gary Remington1

1University of Toronto; 2Centre for Addiction and Mental Health; 3Data Powers

Background: Treatment and classification of schizophrenia continues to

present an enormous challenge, in part due to the disease’s heterogeneous

nature. Of note, response to a particular treatment, or lack thereof, is used

for diagnostic purposes in other areas of medicine (e.g., Insulin/Non-Insulin

Dependent Diabetes Mellitus, certain cancers). The present work set out

to establish if, in fact, antipsychotic treatment response can be used to

subtype distinguishable groups of schizophrenia that may, in turn, be used

to better elucidate differences in underlying pathophysiologic mechanisms.

Methods: Relevant literature was reviewed with specific reference to an-

tipsychotic treatment response. Where available, we focused on the early

stages of the illness and evidence that sequentially followed antipsychotic

trials, including use of clozapine in individuals identified as treatment resis-

tant. This approach aligns with evidence that early and effective treatment

favourably alters clinical and functional outcome measures.

Results: While the first-episode schizophrenia population has very high

symptom response rates, approximately 25-30% do not respond favourably.

For patients experiencing partial or non-response to first-line treatment,

current guidelines indicate a switch to another non-clozapine antipsychotic

before resorting to clozapine as a third (or later) line of treatment. Clini-

cians also often employ dose increase and/or polypharmacy in these cases,

although the benefit of these strategies has been called into question. These

early non-responders, or treatment-resistant patients (TRS), generally re-

spond exclusively to clozapine. While D2 blockade is identified as central

to the antipsychotic effect observed with standard antipsychotics, clozap-

ine’s mechanism(s) of action are currently unclear. In those demonstrating

suboptimal response to clozapine (i.e. URS) we currently have no effective

treatments, making it even more difficult to speculate regarding underlying

pathophysiological differences.

Discussion: Antipsychotic response patterns identify three subtypes of