Upload
outi
View
213
Download
1
Embed Size (px)
Citation preview
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S57
from both sets of findings were similar, implying that sample selection bias
was unlikely to have influenced study findings.
Discussion: Persistent and incident internalising and externalising prob-
lems from mid-childhood into adolescence are associated with later PLEs
in the general population, whereas childhood-limited psychopathology (re-
mitting problems) are not. Interventions that target the persistence or
incidence of internalising or externalising psychopathology from childhood
to adolescence may impact on the expression of PLEs. Further research is
needed to elucidate whether common or distinct mechanisms influence the
associations of internalising and externalising psychopathology with PLEs.
4:30 PM
INFLAMMATORY RESPONSE IN FIRST-EPISODE PSYCHOSIS
Jaana Suvisaari1, Teemu J.S. Mäntylä1,2, Tuukka Raij3, Tuula Kieseppä1,
Minna Torniainen1, Outi Vaarala1
1National Institute for Health and Welfare; 2National Institute for Health and
Welfare, Helsinki, Finland and Brain Research Unit in Aalto University School
of Science, Espoo, Finland; 3Aalto University
Background: Cytokines, and chemokines as their subgroup, are a large
group of proteins that regulate all aspects of innate and adaptive immu-
nity. Several first-episode psychosis studies have observed elevations in
proinflammatory cytokines in first-episode psychosis, while chemokines
have received much less attention. Therefore, we set out to investigate
changes in cyto- and chemokines in patients with first-episode psychosis
and matched general population controls.
Methods: First episode psychosis patients with a median of 27 days of
antipsychotic medication and matched controls were recruited from the
capital area of Finland. Serum levels of 38 cytokines and chemokines were
analyzed using the Milliplex MAP Kit (HCYTMAG-60K-PX38, Millipore Corp.,
Billerica, MA). In addition, cardiovascular risk markers were measured. The
analyses were done at baseline and for patients also 2 months later.
Results: The study group consisted of 37 (21 males) first-episode patients
and 19 (10 males) controls, with a mean age of 26.1 and 28.6 years,
respectively. At baseline, patients and controls did not differ significantly in
terms of BMI or waist circumference. FEP patients as compared to healthy
controls had higher CCL22 and lower TGFα, CXCL1, CCL7, IFNα2, ApoA-I and
HDL-C levels. The findings remained significant after adjusting for BMI, age
and sex. Duration of antipsychotic treatment did not correlate significantly
with cytokine levels. CCL22 level had decreased significantly at 2 month
follow-up, but was still higher than in controls.
Discussion: Inflammatory response is dynamic, and our findings reflect
the situation in a subacute phase of first-episode psychosis. The observed
profile of systemic chemokines in first-episode psychosis, such as increased
CCL22 and decreased CXCL1, CCL7 and IFN-α, could reflect up-regulation
of STAT6 signaling. The classical proinflammatory state characterized by
elevated IL-1, IL-6 and TNF-α may be a relatively short-lived phenomenon
associated with acute psychosis, and was not observed in this study. The
earliest metabolic alteration in first-episode psychosis was decreased HDL-
C and ApoA-I, suggesting a vulnerability to metabolic syndrome from the
onset of psychosis.
4:45 PM
PREMORBID AND CURRENT COGNITIVE FUNCTION IN SCHIZOPHRENIA
ASSOCIATE WITH TREATMENT RESISTANCE AND EGF 61 AA GENOTYPE
Vaidy Swaminathan1,2, Avril M. Pereira3, Cynthia Shannon-Weickert4,
Thomas Weickert4, Suresh Sundram3
1University of Melbourne; 2The Florey Institute of Neuroscience and Mental
Health; 3The Florey Institute; 4Neuroscience Research Australia
Background: Disaggregating clinical clusters within schizophrenia (SCZ)
such as cognitive impairment (CI) and treatment resistance will assist in
identifying pathological mechanisms and possible biomarkers. Others’ and
our data have elucidated involvement of the epidermal growth factor (EGF)
system in both these clinical processes in SCZ and other neuropsychiatric
disorders. We have proposed that deficient EGF signalling is ameliorated
by clozapine through EGF receptor transactivation in treatment resistant
SCZ (TRS) and low EGF function is associated with cognitive impairment
in Parkinson’s disorder, dementias and mouse models of psychosis. A func-
tional single nucleotide polymorphism in the EGF gene (61A>G) provides
a model where the 61AA homozygote produces less EGF than the AG
heterozygote and GG homozygote. We therefore, postulated that cogni-
tive impairment is associated with TRS and that the EGF 61A>G SNP is
associated with impaired cognitive processes.
Methods: Clinical and cognitive data and DNA from participants with a
diagnosis of SCZ (n=664) were accessed from the Australian Schizophrenia
Research Bank. TRS was defined as current or past treatment with clozapine.
Cognitive data were the Wechsler Test of Adult Reading (WTAR) standard
score as a measure of premorbid cognitive ability and Letter Number
Sequencing (LNS), Controlled Oral Word Association Test (COWAT) and Re-
peatable Battery for the Assessment of Neuropsychological Status (RBANS)
as measures of current cognitive ability. These scores were z transformed
(based on a cohort including healthy controls n=634) and composite scores
were computed for the domains of Executive Functioning, Memory and
Attention. Genotyping for EGF 61 A>G SNP (rs4444903) was performed
using a TaqMan® assay and allele frequencies for AA, AG and GG genotypes
were obtained. The groups were compared using standard statistical tests.
Results: TRS patients had significantly lower premorbid intellectual func-
tion when compared to non-TRS patients (WTAR score – TRS=−0.55±1.2,
non TRS=−0.23±1.1, mean±σ; p=0.004). TRS patients had significantly lower
current performance when compared to non-TRS patients in working
memory and executive functioning tests (LNS score – TRS=−0.72±0.86,
non-TRS=−0.33±0.92; p<0.001; RBANS Memory composite score –
TRS=−1.11±0.91, non-TRS=−0.43±0.90; p<0.001; RBANS Attention compos-
ite score – TRS=−0.83±0.80, non-TRS=−0.46±0.87; p<0.001; but not COWAT
score; p=0.79, and RBANS Language composite score; p=0.17).
The EGF genotypes were in Hardy-Weinberg Equilibrium. Patients with
the 61AA genotype had significantly lower premorbid cognitive ability
(WTAR score – AA participant s=−0.40±1.12), than non-AA participants
(−0.21±1.1; p=0.031). AA patients had significantly lower current cogni-
tive abilities characterised by working memory (LNS; AA=−0.55±0.84, non
AA=−0.38±0.93; p=0.018), Executive Functioning (COWAT; AA=−0.50±0.91,
non AA=−0.31±0.96; p=0.014) and RBANS Attention domain composite
score (AA=−0.64±0.82, non AA=−0.49±0.89; p=0.033) but not RBANS Lan-
guage composite score (p=0.21) and Memory composite score (p=0.19).
Discussion: These data demonstrate in a large cohort that people with TRS
have significantly poorer pre-morbid intellectual function than people with
treatment responsive schizophrenia and that impairment persists through
the illness. Moreover, cognitive impairment is associated with the 61AA
genotype suggesting that lower EGF levels may contribute to this symptom
domain. Together these data support a model where a hypofunctioning EGF
system may predispose and link to both treatment resistance and cognitive
impairment in schizophrenia. This provides genetic and molecular targets
to investigate as plausible biomarkers for treatment planning and early
intervention in schizophrenia.
5:00 PM
REAL-TIME DETECTION OF COGNITIVE DECLINE IN CHILDREN AT HIGH
GENETIC RISK OF SCHIZOPHRENIA AND BIPOLAR DISORDER
Michel Maziade1, Thomas Paccalet2, Elsa Gilbert2, Nicolas Berthelot3,
Chantal Mérette4, Nancie Rouleau4
1Laval University; 2Centre de recherche Institut universitaire en santé mentale
de Québec; 3Université de Québec à Trois-Rivières; 4Université Laval
Background: There is an emerging consensus that schizophrenia is a
neurodevelopmental disorder characterized by a cognitive deterioration
beginning in childhood (1-3). We have already reported severe cognitive
impairments in children and adolescents (HR) descending from multi-
affected families of Eastern Quebec (4). We now report in a longitudinal
study of 40 high-risk offspring aged 6 to 26 that 10 of them presented
a global IQ decline of 10 points suggesting that they are going through a
developmental transition toward the disease.
Methods: We already reported that the phenotypic, endophenotypic and
genetic findings in the children, the non-affected adults and the patients
of this familial sample were strongly resembling the findings reported
in general or sporadic samples (5). In this high-risk sample, we used a
step by step sampling approach to narrow-down the early disease mech-
anisms. Upstream, we started with a 20-year follow-up of 48 densely