Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives.
BACKGROUND
Clues to the causes of schizophrenia can be derived from studying first-degree relatives because they are genetically related to an ill family member. Abnormalities observed in nonpsychotic relatives are indicators of possible genetic vulnerability to illness, independent of psychosis. We tested 4 hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than in controls, particularly in the left hemisphere; (2) that hippocampi will be smaller in multiplex relatives as compared with simplex relatives, and both will be smaller than in controls; (3) that hippocampal volumes and verbal declarative memory function will be positively correlated; and (4) that hippocampi will be smaller in patients with schizophrenia than in their nonpsychotic relatives or in controls.


METHODS
Subjects were 45 nonpsychotic adult first-degree relatives from families with either 2 people ("multiplex," n = 17) or 1 person ("simplex," n = 28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the total cerebrum and the hippocampus were measured.


RESULTS
Compared with controls, relatives, particularly from multiplex families, had significantly smaller left hippocampi. Verbal memory and left hippocampal volumes were significantly and positively correlated. Within families, hippocampal volumes did not differ between schizophrenic patients and their nonpsychotic relatives.


CONCLUSIONS
Results support the hypothesis that the vulnerability to schizophrenia includes smaller left hippocampi and verbal memory deficits. Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia.
Seidman
Larry J
LJ
Neuropsychology Laboratory, Massachusetts Mental Health Center, 74 Fenwood Rd, Boston, MA 02115, USA. larry_seidman@hms.harvard.edu
Faraone
Stephen V
SV
Goldstein
Jill M
JM
Kremen
William S
WS
Horton
Nicholas J
NJ
Makris
Nikos
N
Toomey
Rosemary
R
Kennedy
David
D
Caviness
Verne S
VS
Tsuang
Ming T
MT
D000328:Adult; D005190:Family; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D012565:Schizophrenic Psychology; D014706:Verbal Learning