Age and treatment related local hippocampal changes in schizophrenia explained by a novel shape anal

1
Age and treatment related local hippocampal
changes in schizophrenia explained by a novel
shape analysis method 1,2G Gerig, 3K Muller, 3E
Kistner, 3Y Chi, 1M Chakos, 2M Styner,1JA
Lieberman Departments of 1Psychiatry, 2Computer
Science, 3Biostatistics University of North
Carolina, Chapel Hill,NC 27614,
USA gerig_at_cs.unc.edu / http//www.cs.unc.edu/geri
g
RESULTS
SUMMARY
Volume reduction of the hippocampus observed with
MRI is one of the most consistently described
structural abnormalities in patients with
schizophrenia. However, the timing, the
association with treatment, and an intuitive
explanation of morphologic changes are not known.
This study analyzed subtle changes of the
hippocampal structure in schizophrenics (N57) as
compared to matched controls (N26). The effect
of age, duration of illness and drug type to
local shape changes was studied with a new shape
representation technique and an exploratory
statistical analysis. The M-rep shape
representation model allows a separate analysis
of shape deformation and of local atrophy. The
exploratory statistical model was a repeated
measures ANOVA, cast as a general linear
multivariate model. The exploratory nature of
the analysis means that the promising results
must be replicated in order to provide full
confidence in the conclusions.
Shape Deformation between Schizophrenics and
Controls
Patient-Control Euclidean distance differences
(shape deformation or bending) at age 20, 30 and
40, left to right. Height indicates the
deformation difference between patients and
controls in mm. The graph characterizes time
slices of the continuous age range. The
differences between patients and controls
increase over time and are located mostly in the
tail and to a lesser extent in the head of the
hippocampus.
SUBJECTS
L/R Asymmetry of Radius Difference
Quantitative 1.5 Tesla MRI examinations of the
brain were utilized to examine a young patient
group in the early illness stage of illness
(N34) and an older group of schizophrenic
patients who were chronically ill (N22). MRI
examinations of the brain were also acquired for
26 right-handed male controls matched to both
patient groups for age and handedness (young
controls N14, older controls N12). Patients
were characterized with regards to duration of
illness and illness severity utilizing PANSS
assessments. At the time of scan, 17 early
illness patients were on typical antipsychotic
medication (haloperidol), and 17 were on atypical
antipsychotic medications (13 olanzapine, 4 on
risperidone). For chronic patients, only 5 were
on typical medications (3 haloperidol, 1 tri
u-perazine and 1 thiothixene), and 18 were on
atypical medications (6 olanzapine, 8 clozapine
and 4 risperidone).
Drug-type versus Control group differences of
left to right radius difference log2(L/R), which
can be interpreted as L to R local width
asymmetry. Left Typical Drug - Control radius
asymmetry difference at age 20, 30 and 40. Right
Atypical Drug Control radius asymmetry
difference. the graphs characterize time slices
of the continuous age range and show decreasing
asymmetry of local width with age, particularly
in the tail and head regions.
Comparison Longitudinal Shape Change of Controls
Deformation and width asymmetry changes due to
aging within controls for 10 years. Left
Distance model representing shape deformation,
scale in mm. Right Radius model representing
left/right asymmetry of local radius change
(local width), log-scaled in mm.
METHODS
Shape representation by sampled medial mesh
(M-rep). Mesh represents shape with over 99
overlap.
Summary of Results
Features for Shape Analysis
Statistical analysis of 3x8 mesh. Height
represents difference.
Statistical analysis
M-rep 3x8 mesh
M-rep 3x8 mesh
Head
Tail
Radius Local width attribute (atrophy, growth).
CONCLUSIONS
Deformation Bending, curvature change.

• New analysis scheme overcomes problem of feature
  reduction/selection from high-dimensional shape
  representation.
• Analysis does not require correction for multiple
  tests as in schemes using a high number of
  surface-based statistical tests.
• Systematic integration of shape with clinical
  variables (age, duration of illness and drug
  effect) ? Leads to intuitive answers in regard to
  treatment effects and longitudinal changes.
• Significant hippocampal deformation difference
  between schizophrenics and controls (plt0.0091).
  Deformation increases with age (tail/head)
• Drug treatment groups (Atypical, Typical) show
  significant differences of Width Asymmetry
  measure. Decreasing asymmetry of width with age
  is found.
• Deformation and width asymmetry changes in
  controls analyzed over a ten years interval are
  not significant.
• Conclusions w.r.t. age changes from
  cross-sectional study Longitudinal study.
• Exploratory analysis Requires confirmatory
  analysis in independent study.

Statistical Model
Supported by NCI grant P01 CA47982 and the
UNC-MHNCRC (MH33127).
MICCAI Nov. 2003