Læknablaðið : fylgirit - 01.08.2003, Page 37

ABSTRACTS / 27TH NORDIC PSYCHIATRIC CONGRESS I
References
T Stefánsson et al. Ant J Hum Genet 2002; 71: 877-92.
2- Straub et al. Am J Hum Genet 2002; 71: 337-48.
3- Chumakov et al. Proc Natl Acad Sci USA 1999; 96:13675-80.
4- Detera-Wadleigh et al Proc Natl Acad Sci USA 1999; 96: 5604-9.
5. Hattori et al. Am J Hum Genet 2003; 72:1131-40.
S-XII/3 Friday 15/8,11:00-12:30
Conditional analyses in a genome-wide scan of bipolar
disorder: Evidence for gene-gene interaction
Mclnnis MG, Associate Professor of Psychiatry, Johns Hopkins University, 600 N Wolfe
Street, Baltimore MD, 21287-7381, USA. DePaulo, JR, Numberger J, Reich T, Foroud T.
Mmcinnis@jhmi.edu
In 1989 the NIMH began an extensive collaborative effort to identify
susceptibility genes for bipolar (BP) disorder. This collaboration has
identified several hundred multiplex BP disorder families and we
now describe results of genetic analyses performed in the combined
sample of 153 pedigrees. Three hierarchical affection status models
Were employed in analyses performed with 513 highly polymorphic
simple sequence repeat markers distributed throughout the genome.
Under the broadest affection status model there were 641 affected
subjects creating 909 affected relative pairs. Both parametric and
nonparametric genetic analyses were performed. We identified 15
chromosomal regions with nominally significant linkage findings
(p<0.05), 11 of which have been previously implicated in indepen-
dent studies of either bipolar disorder or schizophrenia. The most
significant linkage results were on chromosomes 16pl3,20pl2,6q24,
10pl2, and llpl5. We performed conditional analyses based on epi-
stasis or heterogeneity for these five loci. There was a significant
•ncrease for evidence of linkage at four chromosomal regions under
the epistasis model and three under the heterogeneity model of inter-
action. Conditional on non-linkage to 10pl2 there was a significant
increase in the linkage on lp22 and 4q35, a region on 19ql3 was iden-
tified based on heterogeneity with llpl5. Families linked to 6q24
showed asignificant increase in NPLsat 5qll and7q21. Epistasis was
observed between 20pl2 and 13q21, and between 16pl3 and 9q21.
Application of conditional analyses is potentially useful in larger
sample collections to identify susceptibility genes of modest influence
lhat may not be identified in a genome-wide scan aimed to identify
single gene effects.
S - XII / 4 Friday 15/8,11:00-12:30
The brain structural phenotypes of schizophrenia and
bipolar disorder
Colni McDonald1, Div. of Psychological Medicine, Box No 63, Institute of Psychiatry, de
Crespjgny Park, Camberwell, London Se5 8 AF. Ed Bullmore-, Pak Shami, Xavier
Chitnisi, Robin Murray'.
Division of Psychological Medicine, Institute of Psychiatry, de Crespigny Park, London
~L5 8AF, U.K, ^Brain Mapping Unit, University of Cambridge, Department of Psy-
chiatry, Addenbrookes Hospital, Cambridge CB2 2GO, UK
sPhacdm@iop. kcl.ac.uk
There is considerable uncertainty about whether the same genetic
aetiology and pathophysiology underlies the major functional psy-
chotic disorders of schizophrenia and bipolar disorder. We ex-
P'ored the structural MRI phenotype of these illnesses using com-
putational morphometry to detect regional grey and white matter
volume changes in multiply affected families. MRI scans were
obtained from 25 patients with schizophrenia, 36 of their unaffected
first-degree relatives, 37 patients with psychotic bipolar 1 disorder
and 50 of their unaffected first-degree relatives. A measure of
‘genetic loading’ was calculated for each subject based on the
density of illness within their family and this score was used to pre-
dict regional tissue volume in each set of families.
Genetic risk for schizophrenia was associated with distributed
grey matter volume deficit in frontal-subcortical and left lateral
temporal regions (p=0.004), but for bipolar disorder with deficit
only in the right medial frontal lobe and ventral striatum (p=0.004).
Increasing genetic liabilities for schizophrenia (p=0.010) and bi-
polar disorder (p=0.011) were associated with white matter volume
deficit, which included overlapping left fronto-temporal regions.
Our data indicates that distributed grey matter volume deficit re-
presents a distinctive morphometric phenotype of schizophrenia
and that the overlapping impact of susceptibility genes for the
major psychoses upon brain structure is expressed as anatomical
dysconnectivity in frontal and temporal lobes.
S-XIII/1 Friday 15/8,11:00-12:30
DSM-IV disorders, comorbidity and completed suicide
after discharge from inpatient psychiatric care
Walby FA, Research Fellow, Suicide Research and Prevention Unit, University of Oslo,
Sognsvannsveien 21, building 20, Norway. 0degaard E, Mehlum L.
fredrik. walby@psykiatri. uio.no
Background: Psychiatric disorders are well known risk factors for
suicide and the time following discharge from psychiatric inpatienl
care is an extreme high-risk period. Few, if any, studies have looked
at the impact of different disorders and comorbidity in this
population using structured diagnostic procedures.
Aims: To investigate whether some psychiatric disorders imply in-
creased risk over others, and whether comorbidity predicts suicide
in a sample of discharged inpatients.
Method: A total of 108 suicides were compared to matched con-
trols (1:1). Raters were blind to outcome and clinical diagnoses.
DSM-IV Axis-I diagnoses were made on the basis of case notes by
using the SCID-CV and divided into 6 groups. Axis-II diagnoses
were rated as present/absent using the general criteria in DSM-IV.
Data were analyzed using conditional logistic regression.
Results: Independent of previous suicidal behaviour, depressive
disorders implied increased risk whereas schizophrenia implied
reduced risk for suicide after discharge. Neither Axis-I nor Axis-II
comorbidity was significant when adjusted for main diagnoses and
other factors.
Conclusions: A psychiatric diagnosis of depression or schizophre-
nia was related to completed suicide in a sample of consecutive dis-
charged patients whereas comorbidity was not.
LÆKNABLAÐIÐ / FYLGIRIT 48 2003/89 37