Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S319

Poster #T84

SEMAPHORINS AND PLEXINS GENE EXPRESSION IS ALTERED IN THE

PREFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS WITH AND

WITHOUT AUDITORY HALLUCINATIONS

Rocío González-Martínez1, Javier Gilabert-Juan2,3, Ana Rosa Saez4,

Guillermo Lopez-Campos5, Noelia Sebastiá4, Juan Nacher6, Julio Sanjuán7,

María Dolores Moltó2

1University of Valencia; Department of Genetics; 2Genetics Department,

University of Valencia. CIBERSAM, INCLIVA; 3Universidad de Valencia, INCLIVA;4Genetics Department, University of Valencia; 5Health and Biomedical Centre,

University of Melbourne; 6Department of Cell Biology, University of Valencia,

CIBERSAM, INCLIVA; 7CIBERSAM, INCLIVA

Background: A focused brain area of study in schizophrenia is the PFC, a

complex structure with altered connectivity, cell populations and functions

in patients with schizophrenia. The PFC has been associated with auditory

hallucinations, a positive symptom of this disease that means a clear en-

dophenotype among the total schizophrenic spectrum. The endophenotype

study facilitates the detection of specific alterations associated with this

trait of the disease. The main aim of this project is to study the gene

expression in the human PFC between schizophrenic patients with and

without auditory hallucinations compared to healthy controls.

Methods: In this study we have analyzed the gene expression of fourteen

postmortem brains of schizophrenic patients with and without auditory

hallucinations in relation to brains of control individuals. Firstly, we have

study the complete transcriptome of the PFC of three individuals of each

group, to identify altered pathways or genes. After the identification of

the Axon Guidance pathway as one of the most differentially expressed

pathways we have performed, in the total brain sample, a qRT-PCR of

several genes involved in Axon Guidance, such as semaphorin family and

the semaphorin receptors, the plexin family, in order to fathom differences

in gene expression.

Results: Microarray results indicated the Axon Guidance pathway as po-

tentially altered network between the three groups. The quantitative gene

study pointed several differences in the expression of PLXNB1, SEMA3A,

SEMA3C and SEMA4D genes between schizophrenic patients with and

without auditory hallucinations. Furthermore, different gene expression of

PLXNA1, SEMA3D, SEMA3E, SEMA6C and SEMA7Awas seen in schizophrenic

patients without auditory hallucinations compared to healthy controls.

Discussion: The plexin-semaphorin signaling system is widely involved in

neural development and brain plasticity and has been previously impli-

cated in the etiology of schizophrenia. In our study of prefrontocortical

postmortem brains we have found several alterations in Axon Guidance

pathway and concretely the expression of some semaphorin and plexin

genes in schizophrenic patients without auditory hallucinations and other

in common with patients with auditory hallucinations.

Poster #T85

THE EFFECTS OF MOTIVATIONAL INCENTIVES ON COGNITION IN

PATIENTS WITH SCHIZOPHRENIA AND NEGATIVE SYMPTOMS –

A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY

Oliver M. Hager1,2, Matthias Kirschner1, Matthias N. Hartmann1,

Agne Kluge1, Martin Bischof1, Philippe N. Tobler2, Stefan Kaiser1

1Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric

Hospital, University of Zurich; 2Laboratory for Social and Neural Systems

Research, Department of Economics, University of Zurich

Background: Patients with schizophrenia suffering from negative symp-

toms show a persistent reduction of goal-directed behavior. A putative

mechanism for this apathetic behavior is a dysfunctional integration of ab-

stract representations of motivationally salient events (e.g., future rewards)

with higher order cognitive operations (e.g., goal maintenance/updating).

The goal of the current study is to examine the relationship between cogni-

tive and motivational deficits in patients with schizophrenia and negative

symptoms in a functional magnetic resonance imaging (fMRI) study using

a n-back working memory task with monetary incentives dependent on

performance.

Methods: Thus far, 19 medicated patients with schizophrenia and 14

healthy control subjects were included in the study. At the conference, data

from the full sample of 30 participants in each group will be presented.

All subjects participated in three sessions, consisting of an extensive psy-

chopathological assessment, a neuropsychological test battery and the fMRI

session. Negative symptoms were assessed with the Brief Negative Symp-

tom Scale (BNSS) and the Scale for the Assessment of Negative Symptoms

(SANS). The incentivized verbal n-back task was presented in a 2×2 facto-

rial design with the factors reward (reward vs. no reward) and cognitive

load (2-back vs. 0-back).

Results: In the preliminary analysis we found no significant differences in

reaction time or performance between both groups. On the neural level, the

main effect of cognition showed a significant increase in the BOLD signal

in fronto-parietal regions across all subjects. As a main effect of reward,

we found significant activation in the bilateral thalamus. The interaction

cognition x reward yielded a significant increase in BOLD signal in the left

superior frontal and middle gyrus and the right anterior cingulate. With

the current sample size, no significant differences between groups were

found for any contrast. Furthermore, the interaction contrast values in the

left superior frontal gyrus and the left anterior cingulate were negatively

correlated with global negative symptoms, i.e. more negative symptoms

were associated with less activation.

Discussion: The incentivized version of the verbal n-back task differentiates

neural effects of cognition, reward and the cognition x reward interaction.

Thus, it seems to be a good operationalization for measuring motivation-

cognition interaction in a clinical sample. Until now, we found no significant

differences in the behavioral or neural measures between patients with

schizophrenia and healthy controls. This is a first hint that patients with

schizophrenia are able to use motivational goals to drive current behavior.

However, we found a negative association of negative symptoms with BOLD

related activity in prefrontal regions. This negative correlation suggests that

the neural “enhancement” of regions associated with goal-directed behavior

due to secondary rewards is reduced with increasing negative symptoms.

A dysfunctional coupling of motivation and cognition could be a promising

pathway for investigating the neural basis of negative symptoms.

Poster #T86

STRUCTURAL MRI IN FIRST EPISODE PSYCHOSIS: AN INTERNATIONAL

COLLABORATIVE MEGA-ANALYSIS OF INDIVIDUAL ADULT PATIENT DATA

Brian Hallahan1,2, Colm McDonald3, Anne Gallagher2, Cathy Scanlon1,

Aengus O’Conghaile2

1National University of Ireland Galway; 2Galway University Hospital;3University of Galway

Background: Meta-analysis is the most widely used method for averaging

statistical effect sizes from different studies and is usually based on com-

bining effect sizes from published literature rather than analysing pooled

individual patient data, however it is associated with several methodolog-

ical problems, the most significant of which are the frequent inclusion of

studies that are heterogenous in nature. In this international collaborative

mega-analysis examining regional brain structures in individuals with First

Episode Psychosis (FEP) compared to healthy controls, we pooled individ-

ual patient data and consequently were able to adjust for between-study

differences, enabling us to compare regional brain measurements of indi-

viduals with FEP to those of healthy controls, whilst co-varying for relevant

confounds, not possible in conventional meta-analysis.

Methods: Published brain volumetric studies were identified through sys-

tematic database searches for articles published between 1980 and 2012.

Consequently we invited 43 international research groups who had em-

ployed robust methodology in MRI data acquisition in relation to individuals

with FEP or healthy controls to participate in this study. MRI and clini-

cal data (e.g. age, gender, duration of untreated psychosis, psycho-active

substance use, age of onset of illness, diagnosis, medication usage) was

provided by 21 international research groups on 1068 individuals with

FEP and 941 controls. Linear mixed effects regression models were used

where research centre was incorporated as a random effect to account

for the correlation due to individuals within each research centre and

possible heterogeneity between research centre. Gender was included as a

fixed factor and age as a co-variates. We repeated the analysis including

intracranial volume as an additional co-variate.

Results: The most common FEP diagnosis was schizophrenia (n=730),

followed by schizophreniform psychosis (n=93), bipolar disorder (n=78),