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Left Hippocampal Volume as a Vulnerability Indicator for Schizophrenia
A Magnetic Resonance Imaging Morphometric Study of Nonpsychotic First-Degree Relatives
Larry J. Seidman, PhD;
Stephen V. Faraone, PhD;
Jill M. Goldstein, PhD;
William S. Kremen, PhD;
Nicholas J. Horton, ScD;
Nikos Makris, MD, PhD;
Rosemary Toomey, PhD;
David Kennedy, PhD;
Verne S. Caviness, MD, DPhil;
Ming T. Tsuang, MD, PhD
Arch Gen Psychiatry. 2002;59:839-849.
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.
From the Department of Psychiatry, Massachusetts Mental Health Center,
Boston (Drs Seidman, Faraone, Goldstein, Toomey, and Tsuang), the Department
of Psychiatry, Brockton/West Roxbury Veterans Affairs Medical Center, Brockton,
Mass (Drs Seidman, Faraone, Goldstein, Toomey, and Tsuang), the Department
of Psychiatry at Massachusetts General Hospital, Boston (Drs Seidman, Faraone,
Goldstein, and Tsuang), Harvard Institute of Psychiatric Epidemiology and
Genetics, Cambridge, Mass (Drs Seidman, Faraone, Goldstein, Toomey, and Tsuang);
Department of Psychiatry, Davis School of Medicine, University of California–
Davis Napa Psychiatric Research Center, Sacramento, Calif (Dr Kremen); Department
of Epidemiology and Biostatistics, Boston University School of Public Health,
Boston (Dr Horton), Department of Medicine, Boston University School of Medicine,
Boston (Dr Horton), the Departments of Neurology and Radiology Services, Harvard
Medical School, and the Center for Morphometric Analysis, Massachusetts General
Hospital, Boston (Drs Makris, Kennedy and Caviness), and the Department of
Epidemiology, Harvard School of Public Health, Boston (Dr Tsuang).
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