S216 Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384

reward processing is linked to the genetic vulnerability for schizophrenia.

We plan to follow these groups longitudinally, so that we can identify

how the familial risk for schizophrenia impacts individual developmental

trajectories.

Poster #M73

THOUGHT DISORDER IN FIRST-EPISODE PSYCHOSIS

Ahmet Ayer1, Esra Aydınlı1, Silay Sevilmis2, Berna Yalınçetin2, Berna

Binnur Akdede3, Köksal Alptekin4

1Manisa Psychiatric Hospital; 2Dokuz Eylul University School of Medicine,

Department of Neuroscience; 3Dokuz Eylül University, School of Medicine,

Department of Psychiatry; 4Psychiatry Department at Medical School of Dokuz

Eylul University

Background: Thought disorder is one of the main symptom clusters in

schizophrenia. Few studies have investigated thought disorder in the sam-

ple of first-episode schizophrenia patients. However in these insufficient

number of studies examining thought disorder in first-episode psychosis,

thought disorder was evaluated indirectly using the subscales of the other

scales, such as BPRS, SAPS, SANS, SADS, in order to evaluate psychotic

symptoms. An assessment device which is primarily developed to evaluate

thought and language disorder in patients with schizophrenia hasn’t been

used in previous research. The aim of this study was to examine thought

disorder in first episode psychosis by using thought disorder language

index.

Methods: Fifty six patients aged between 15-45 and who had a first episode

psychosis over the last 2 years were included into the study. All the patients

were drug naive or using medicine less than 6 weeks. First episode patients

who had been treated with electroconvulsive treatment were excluded. All

the patients were diagnosed as DSM-IV criteria using SCID-I (Structured

Clinical Interview for DSM Axis I). 45 normal subjects who had no previous

history of mental and neurological disorders were also included as the

control group. PANSS was used to rate severity of psychotic symptoms

and thought disorder was evaluated by using the Thought and Language

Index (TLI) which comprises of impoverishment of thought and disorgani-

zation of thought subscales. Impoverishment of thought category includes:

poverty of speech, weakening of goal and perseveration. Disorganization of

thought category includes: looseness, peculiar word use, peculiar sentence

construction, peculiar logic and distractibility.

Results: There were no differences between patient and normal control

groups regarding age, gender and education level. First episode patients

had significant higher total TLI scores that show worse thought functions

(F=30.65 p=0.001) compared to normal controls. There were significant

differences between first episode psychosis patients and normal controls

regarding poverty of speech (F=3.191 p=0.001), weakening of goal (F=33.071

p=0.0010), perseveration (F=21.239 p=0.001), peculiar word use (F=33.061

p=0.001), peculiar sentence construction (F=50.55 p=0.001), peculiar logic

(F=48.937 p=0.001), thought distractibility (F=36.525 p=0.001).

Discussion: First episode patients had significantly thought and language

abnormalities compared to normal controls. Thought disorder may be eval-

uated as one of the important symptom domains of schizophrenia requiring

further research.

Poster #M74

PROBLEM-SOLVING BASED BIBLIOTHERAPY FOR FIRST-TIME PRIMARY

CAREGIVERS OF FAMILY MEMBERS WITH A FIRST EPISODE OF

PSYCHOSIS: RANDOMIZED CONTROLLED TRIAL

Terence McCann1,2, Susan Cotton3, John Gleeson4, Kingsley Crisp5,

Brendan Murphy6, Dan Lubman7

1College of Health and Biomedicine, Victoria University; 2Centre for Chronic

Disease Prevention and Management; 3Centre for Youth Mental Health, The

University of Melbourne; 4Australian Catholic University; 5Orygen Youth

Health; 6Private Psychiatrist; 7Turning Point Alcohol and Drug Centre &

Monash University

Background: First-time primary caregivers of young people with a first

episode of psychosis frequently experience significant physical, psychologi-

cal, social and financial problems as a consequence of their caregiving role.

In this study, we evaluated if caregivers who completed a problem-solving

based bibliotherapy intervention (PSBI) manual were able to deal with

everyday problems more so than a control group who received treatment

as usual (TAU).

Methods: Family caregivers were recruited through case managers at Ory-

gen Youth Health and the Recovery and Prevention of Psychosis Service,

both in Melbourne, Australia. Participants were assigned randomly to PSBI

or TAU groups. The Social Problem-Solving Inventory-Revised Short Form

(SPSI-R:S) (D’Zurilla, Nezu, & Maydeu-Olivares, 2002), a 25 item measure,

was used to assess individual’s ability to deal with everyday problems. Five

standardised scale scores (positive problem orientation, negative problem

orientation, rational problem solving, impulsivity/carelessness, avoidance)

are derived along with a total score, each of which is measured on a scale

with a mean of 100 and a SD of 15 points, with higher scores suggesting

“good” social problem solving ability. Intent-to-treat principles were used

for the main analyses.

Results: Participant Flow and Sample Characteristics 216 family carers were

assessed for eligibility and 57.41% (n=124) met inclusion/exclusion criteria

and consented to take part in the study. 61 were randomised to the PSBI

and 63 to TAU groups. The majority of carers were female, a parent of,

and living with, the client. The majority of clients were in the recovery

phase. The carers indicated that their support role had adversely influenced

their mental (76.4%, n=94), physical (59.3%, n=73) and social (59.3%, n=73)

well-being, and employment (62.7%, n=69). A significantly longer time

had elapsed since diagnosis in the PSBI in comparison to the TAU group,

t(120)=2.15, p=0.033. No other between group differences were detected,

at baseline, on any of the demographic variables. 19 participants dropped

out of the study (15.3%); 8 from the PSBI group (13.1%) and 11 from the

TAU group (17.5%). The dropout rate did not differ significantly between

both groups, χ2(1)=0.45, p=0.502. No significant differences in demographic

variables were detected between study completers and non-completers.

Social Problem-Solving For the SPSI, there was a significant group by

time interaction for the impulsivity/carelessness subscale, F(2,136.6) = 5.76,

p=0.004. The rate of improvement in impulsivity/carelessness, from base-

line to 6 weeks (t(157.9) = −3.22, p=0.002) and baseline to 12 weeks

(t(110.1) = −2.65, p=0.009), was greater in the PSBI than the TAU group.

Although the two groups appear to differ at baseline, this difference was

not significant (p=0.053). For the remaining SPSI subscales there were no

significant interactions between group and time, between the PSBI and

TAU groups, from baseline to 6 weeks and from baseline to 12 weeks.

The main effect for time for the rational problem-solving subscale was

significant, F(2,124.3) = 3.74, p=0.027, with significant reductions seen from

baseline to 6 weeks (p=0.018), and baseline to 12 weeks (p=0.012) in both

groups.

Discussion: The PSBI group showed significant improvements in their so-

cial problem solving in impulsivity/carelessness in comparison to the TAU

group, and significant reductions in rational problem-solving. However,

there were no significant differences between the groups in social problem

solving in positive problem orientation, negative problem orientation, and

avoidance. The implications of the findings for caregivers, clinicians and

futher research are also outlined.

Poster #M75

THE EFFECTS OF MODAFINIL ON COGNITIVE TRAINING: A PROOF-OF-

CONCEPT TRIAL IN PATIENTS WITH SCHIZOPHRENIA

Panayiota Michalopoulou1, Shon Lewis2, Richard Drake2,

Abraham Reichenberg3, Richard Emsley2, Anastasia Kalpakidou1,

Jane Lees2, Eve Applegate2,4, Til Wykes5, Shitij Kapur1

1Institute of Psychiatry, King’s College London; 2University of Manchester;3Mount Sinai School of Medicine; 4Institute of Brain, Behaviour and Mental

Health, University of Manchester; 5Department of Psychology, Institute of

Psychiatry, Kings College London

Background: The optimal therapeutic approach for cognitive impairment

in schizophrenia may require a combination of cognitive remediation with

pharmacological compounds that enhance learning. Our goal was to test

the feasibility and cognitive effects of such a combined intervention in

patients with schizophrenia.

Methods: 49 participants with schizophrenia or schizoaffective disorder

were enrolled in a double-blind, placebo-controlled study across two sites

Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S217

and were randomised to either modafinil (200mg/day), a compound with

known effects on learning and cognition, or placebo. All participants en-

gaged in a broadly-targeted, computer-based cognitive training program

daily for 10 consecutive days. The primary outcome measure was the

performance on the cognitive training tasks and secondary outcome mea-

sures included neuropsychological measures (MATRICS Consensus Cognitive

Battery), proxy measures of everyday functioning and symptom measures.

Results: 84% of the participants enrolled in the trial completed all study

visits. The performance of all participants in all cognitive training tasks im-

proved over time irrespective of treatment arm assignment. Repeated doses

of modafinil did not induce differential enhancement in the performance

of the trained tasks nor on the neuropsychological, functional capacity and

symptom measures compared to placebo.

Discussion: Interventions combining pharmacological compounds with

cognitive training are feasible, though demanding, in schizophrenia. The

combination of the particular drug, modafinil, with the cognitive training

program used here did not result in differential cognitive enhancement.

Issues such as choice of drug, cognitive domains to be trained and cogni-

tive outcome measures remain open for future studies that will combine

cognitive training programs with pharmacological compounds for cognitive

impairment in schizophrenia.

Poster #M76

AN OPEN-LABEL, FLEXIBLE-DOSE STUDY OF PALIPERIDONE EXTENDED

RELEASE IN CHINESE PATIENTS WITH FIRST-ONSET PSYCHOSIS

Tianmei Si1, Wang Yang2, Rui Qing2, Tan QingRong3, Zhang KeRang4

1Peking University Intitute of Mental Health; 2Janssen Research &

Development, China; 3Fourth Military Medical University, 1st Hospital, Xi’an,

China; 4Shanxi Medical University, 1st hospital, China

Background: Antipsychotic medications facilitate improvement of positive

psychotic symptoms in patients with first episode psychosis (FEP). Paliperi-

done extended-release (pali-ER) is an atypical antipsychotic approved in

many countries, including China, for the treatment of schizophrenia in

adults. The efficacy and safety of pali-ER in Chinese patients with FEP was

examined.

Methods: In this 8-week, open-label, single-arm, multicenter prospective

study, patients (aged 18-65 years) with FEP (DSM-IV criteria), and with

Positive and Negative Syndrome Scale (PANSS) total score ≥70 were treated

with flexible-dose pali-ER tablets (3-12 mg/day). The primary efficacy end-

point was percentage of patients with ≥8 points increase in personal and

social performance (PSP) scale from baseline to day 56 (week 8). The PSP

scale scores and its four domains were assessed at baseline, day 28 (week

4) and day 56.

Results: Of the 313 enrolled patients, 308 were included in safety set and

306 in full analysis set. Total 35/308 (11.4%) patients discontinued the study.

The percentage of men and women (50%) was similar, with a mean (SD) age

of 30.88 (10.4) years; baseline PSP score of 41.39 (12.21) and PANSS total

score of 95.3 (18.50). The mean (SD) actual daily dose of pali-ER was 3.65

(2.14) mg at baseline, and 6.53 (1.82) mg at day 56±3. A total of 283/294

(96.3%) patients achieved a ≥8 point increase at endpoint in PSP score

(primary endpoint). Secondary efficacy endpoints: 284/306 (92.8%) patients

had ≥30% reduction in PANSS total score (P<0.0001); 266 (86.9%, 95%

CI: 83.2-90.7%) patients achieved a ≤3 Clinical Global Impression-Severity

(CGI-S) scale score and 218/294 (74.2%, 95% CI: 69.2-79.2%) patients had PSP

score ≥71. PANSS Marder factor scores significantly improved (P<0.0001)

after 8 weeks of pali-ER treatment, with greatest improvement occurring in

“positive symptoms”. The mean (SD) changes in PANSS total scores (51.80

[21.60]), CGI-S scores (3.20 [1.21]) and Neuroleptics Scale scores (21.97

[20.38]) from baseline to endpoint were also significant (P<0.0001). There

was a significant improvement on Subjective Well-being under Neuroleptics

(SWN) scale from (72.67 [16.95]) at baseline to (94.66 [16.70]) at day 56.

There was a negative correlation between duration of untreated period and

posttreatment PSP score (r=−0.2019, P=0.0006) and positive correlation with

posttreatment PANSS total score (r=0.1952, P=0.0007). Most common treat-

ment emergent adverse events (TEAEs) were extrapyramidal symptoms

(12%), agitation, and somnolence (4% each). Three patients (1%) experienced

serious TEAEs: depression, excitement, and extrapyramidal symptoms, of

which excitement and extrapyramidal symptoms led to permanent study

discontinuation.

Discussion: An 8-week flexible dose (3-12 mg/day) treatment with pali-ER

resulted in significant improvement in psychotic symptoms and social

functions in Chinese patients with FEP and was generally tolerable. Results

were consistent with previous placebo-controlled studies conducted in

non-Chinese and Chinese population. The study is limited by the open-label

study design and lack of placebo-control, but the flexible-dose treatment

simulates current clinical treatment practice.

Poster #M77

HOW DOES THE NSA-4 COMPARE TO THE NSA-16?

Janet B.W. Williams, Lori Garzio, Douglas Osman

MedAvante

Background: The 16-item Negative Symptom Assessment (NSA-16) is in-

creasingly used as a validated measure to track response to treatment of

negative symptoms in clinical trials of schizophrenia. The NSA-16, although

reliable, takes up to 30 minutes to administer. As clinical trials have become

more complex, a briefer assessment tool would be useful. Alphs et al have

proposed a four-item version, the NSA-4, as a reliable and valid alternative

to the NSA-16. Four of the 16 NSA items are included: restricted speech

quantity, emotion: reduced range, reduced social drive, and reduced inter-

ests; in addition, both versions of the scale include an overall global rating

of negative symptoms. Alphs et al examined the psychometric properties of

the NSA-4 in two randomized clinical trials. The current study is an effort

to replicate their findings in two other large schizophrenia trials.

Methods: Data are from two Phase 2 randomized double-blind studies

comparing an antipsychotic medication with placebo in the treatment of

subjects with DSM-IV-TR schizophrenia with prominent negative symp-

toms. Subjects were interviewed by live two-way videoconferencing at

screen, baseline, and 11 more visits, including end point. Raters were from

a centralized independent and blinded cohort who were uniformly trained

via initial didactic and applied training, and were monitored throughout

the studies to ensure calibration and prevent drift. At each visit, raters

administered the PANSS immediately followed by the NSA-16. Correlation

coefficients between the NSA-16 and the NSA-4 were calculated for the

NSA global rating, the PANSS negative and positive subscales, and the

Marder factors for PANSS negative symptoms, anxiety/depression, hostil-

ity/excitement, disorganized thought, and positive symptoms. Cronbach’s

alpha and interrater reliability (calculated as an ICC) were determined for

the NSA-16 and NSA-4.

Results: The NSA-16 was administered a total of 2804 times by 29 Central

Raters, to a total of 483 subjects enrolled in two clinical trials. Overall,

the correlation between the total scores of the NSA-4 and NSA-16 was

high (0.86). Good convergent validity of the NSA-4 was demonstrated by

correlations between the NSA-4 and the NSA global rating (r=0.67), as well

as the PANSS negative subscale (r=0.73) and the PANSS negative symptoms

Marder factor (r=0.73). Divergent validity in our sample was demonstrated

by low correlations between the NSA-4 and the following PANSS Marder

factors: anxiety/depression (r=−0.11), disorganized thought (r=0.29), hostil-

ity/excitement (r=0.03), and PANSS positive symptoms (r=0.13). Cronbach’s

alpha was lower for the NSA-4 (α=0.65) compared to the NSA-16 (α=0.87).

Finally, the interrater reliability estimates for the NSA-4 and NSA-16 were

0.94 and 0.97, respectively.

Discussion: The PANSS and NSA-16 in this study were not administered

independently of one another, so the usefulness of the NSA-4 alone can

only be evaluated in the context of its pairing with the PANSS. Overall,

these results were very similar to those obtained by Alphs et al. In the

hands of highly trained and calibrated Central Raters, the NSA-4 had very

good overall agreement with the NSA-16, and even higher convergent

and divergent validity with the selected PANSS subscales and interrater

reliability than was demonstrated by Alphs et al.