S212 Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384

tricles were assessed using manual tracing and spherical harmonics applied

for shape description. Linear regression was used to determine the effect

of group on brain change (volume, thickness or shape) correcting for age

(ICV was controlled for in the case of the volume measures only) and using

a false discovery rate (FDR, p=0.05) to correct for multiple comparisons.

Linear regression was then utilised to determine if identified structural

changes were related to Negative Symptom Scale (PANSS) and Global As-

sessment of Functioning (GAF) at follow-up, a diagnosis of an affective or

non-affective disorder, cumulative antipsychotic medication use and illicit

psychoactive drug use. Age and ICV (for volume measures) were added as

covariates.

Results: A significant increase in caudate volume, left lateral ventricle

volume and a decrease in cerebral white matter volume over time in

FEP patients was identified when compared to HC. Surface based anal-

ysis revealed regional volume increases in the bilateral caudate in FEP.

Although superior temporal gyrus (STG) thinning was observed at baseline,

this abnormality did not appear to be progressive in FEP compared to

HC. Changes in left lateral ventricle volume (F=2.1, p=0.05) and right STG

thickness (F=−2.2, p=0.04) were predictive of Negative PANSS at follow-up.

An increase in caudate volume was associated with FEP patients with no

previous psychoactive drug use (F=5.3, p<0.001). The caudate volume of

patients with a history of drug use did not significantly differ from healthy

controls at baseline, whereas patients without a drug history had signif-

icantly smaller caudate volume at baseline, which then normalised over

time. No brain structure change was related to the other clinical measures.

Discussion: The results support the hypothesis that longitudinal brain

changes are better predictors of clinical outcome than baseline brain

changes alone. This study supports the growing literature that progres-

sive brain structure volume loss is associated with a poorer outcome and

more recent research that suggests patients with and without a history

of psychoactive drug use may represent distinct subgroups of psychosis

patients.

Poster #M64

CONTINUING GREY MATTER CHANGES IN FIRST-EPISODE

SCHIZOPHRENIA AND AFFECTIVE PSYCHOSIS

Maristela S. Schaufelberger1,2, Pedro Rosa3, Marcus Zanetti3, Fabio Duran3,

Luciana Santos3, Paulo Menezes3, Marcia Scazfuca3, Robin M. Murray4,

Geraldo Busatto3

1Department of Neuroscience and Behaviour, School of Medicine of Ribeirão

Preto, University of Sao Paulo, Brazil; 2Laboratory of Psychiatric Neuroimaging,

Department of Psychiatry, Faculty of Medicine of São Paulo, University of São

Paulo, Brazil; 3Faculty of Medicine of the University of São Paulo; 4Institute of

Psychiatry, King’s College London

Background: Magnetic Resonance Imaging (MRI) studies have shown that

brain abnormalities in psychosis might be progressive during the first years

of illness. We sought to determine whether first-episode psychosis subjects

show progressive regional grey matter changes compared with controls,

and whether those changes are associated with diagnosis, illness course or

antipsychotic use.

Methods: The cases for the present study were selected from a sample of

200 first episode psychosis subjects who took part in a population-based

incidence and case-control study conducted in São Paulo, Brazil. Inclusion

criteria for patients at baseline were age 18-50 years and a diagnosis

of psychotic disorders according to DSM-IV criteria. Thirty-two subjects

with first-episode schizophrenia-spectrum disorders (including schizophre-

nia, schizophreniform disorder and schizoaffective disorder), 24 patients

with first-episode affective psychoses (16 with bipolar disorder and 08

with psychotic depression) and 34 controls recruited using a population-

based design underwent structural MRI scanning at baseline and at 5-year

follow-up. Seventeen schizophrenia-spectrum subjects and 11 affective

psychosis patients were categorized as fully remitted. Patients were treated

at community settings, and thirty-six percent of them remained mainly

untreated during follow-up. Regional grey matter volumes were assessed

with voxel-based morphometry. Images were processed and analyzed using

the statistical parametric mapping (SPM). Repeated-measures analysis of

covariance (ANCOVA) was employed for group comparisons and post hoc

evaluation of significant between-groups differences was then performed

with secondary two-tailed t-tests. We reported significant clusters of voxels

that survived family-wise error (FWE) correction for multiple comparisons

(p<0.05).

Results: No significant progressive changes in grey matter regional vol-

umes were observed in either schizophrenia-spectrum patients or affective

patients compared to controls. However, schizophrenia-spectrum subjects

with a non-remitting course showed grey matter decrements in the left

superior temporal gyrus and in the left insula relative to remitted patients.

Non-remitted affective subjects exhibited grey matter decrease in the dor-

solateral prefrontal cortex bilaterally in comparison to remitted subjects.

Among schizophrenia-spectrum subjects, antipsychotic use was associated

with regional grey matter decrements in the right insula and in the left

superior temporal gyrus. We did not analyze the effects of medication on

grey matter volumes in the affective psychosis group due to the highly

heterogeneous use of medication use in such a relative small sample size.

Discussion: Our results suggest that the progression of brain abnormali-

ties in first episode psychosis subjects is restricted to those with a poor

outcome. Moreover, the pattern of grey matter reductions over time differs

according to diagnosis of affective or non-affective psychosis. Our findings

are also in accordance with previous MRI studies that showed longitudinal

effects of antipsychotics on grey matter in patients with schizophrenia.

Poster #M65

ZNF804A AND CORTICAL STRUCTURE IN SCHIZOPHRENIA – IN VIVO AND

POSTMORTEM STUDIES

Carl C. Schultz1, Igor Nenadic2, Brien Riley3, Vladimir Vladimirov4,

Gerd Wagner5, Thomas Mühleisen6, Markus Nöthen7, Sven Cichon8,

Kathrin Koch9, Ralf Schlösser10, Heinrich Sauer5

1Jena University Hospital, Department of Psychiatry and Psychotherapy;2Department of Psychiatry, Jena University Hospital, Philosophenweg 3,

D-07743 Jena, Germany; 3VIrginia Commonwealth University; 4Virginia

Commonwealth University, Richmond, USA; 5Jena University Hospital;6Research Center Juelich; 7Department of Genomics, Life and Brain Center,

University of Bonn; 8Division of Medical Genetics; 9Department of

Neuroradiology, Klinikum rechts der Isar, Technische Universität München;10AHG Klinik Römhild

Background: Recent evidence indicated that the ZNF804A (rs1344706) risk

allele A is associated with better cognitive performance in patients with

schizophrenia. Moreover, it has been demonstrated that ZNF804A may also

be related to relatively intact gray matter volume in patients. To further

explore these putatively protective effects the impact of ZNF804A on corti-

cal thickness and folding was examined in this study. To elucidate potential

molecular mechanisms an allelic-specific gene expression study was also

carried out.

Methods: MRI cortical thickness and folding were computed in 55 geno-

typed patients with schizophrenia and 40 healthy controls. Homozygous

risk allele carriers (AA) were compared with AC/CC carriers. ZNF804A gene

expression was analyzed in a prefrontal region using postmortem tissue

from another cohort of 35 patients.

Results: In patients, AA carriers exhibited significantly thicker cortex in

prefrontal and temporal regions and less disturbed superior temporal cor-

tical folding, whereas the opposite effect was observed in controls, i.e. AA

carrier status was associated with thinner cortex and more severe altered

cortical folding. Along with this, our expression analysis revealed that

the risk allele is associated with lower prefrontal ZNF804A expression in

patients, whereas the opposite effect in controls has been observed by prior

analyses.

Discussion: In conclusion, our analyses provide convergent support for

the hypothesis that the schizophrenia-associated ZNF804A variant medi-

ates protective effects on cortex structure in patients. In particular, the

allele-specific expression profile in patients might constitute a molecular

mechanism for the observed protective influence of ZNF804A on cortical

thickness and folding and potentially other intermediate phenotypes.

Reference:[1] Schultz, CC. et al.; Schizophr Bull. 2013 Sep 27.