Structural and Diffusion Tensor Imaging of the Fornix in Childhood- and Adolescent-Onset Schizophrenia

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Abstract

Objective

There is emerging evidence that aberrations in the integrity of cerebral white matter tracts, especially those connected to limbic structures, play a role in the pathophysiology of schizophrenia. The fornix is the primary efferent neural pathway of the hippocampus and has been shown to be abnormal in adults with schizophrenia.

Method

High-resolution structural magnetic resonance imaging and diffusion tensor images were obtained on 15 patients with childhood- and adolescent-onset schizophrenia and 15 age- and sex-matched controls. Measures of cross-sectional area and water diffusion properties were obtained on regions of interest of the fornix performed by a trained radiologist.

Results

The volume of the fornix was significantly smaller (10.9%) in children and adolescents with schizophrenia compared to controls (Cohen d = 0.87, p = .025). There were no significant differences between the fractional anisotropy or mean diffusivity between the groups.

Conclusions

These findings suggest that the early stages of schizophrenia are associated with a decrease in fornix volume without microstructural white matter changes. The volume differences may reflect an early insult to neighboring brain regions (i.e., hippocampus), that could decrease the number of efferent fibers without necessarily disrupting fiber integrity. J. Am. Acad. Child Adolesc. Psychiatry, 2008; 47(7):826–832.

Section snippets

Subjects

The participants included 15 patients (seven males and eight females) with a diagnosis of schizophrenia (n = 14) and schizoaffective disorder (n = 1). The control group consisted of 15 healthy volunteers (eight males and seven females). Each participant, including the healthy volunteers, underwent a diagnostic evaluation using the Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version.29 Additional clinical measures included the Scale for the

Demographics

There were no statistical differences in either age or sex between the two groups (Table 1). As would be expected, the children and adolescents with schizophrenia had a significantly lower IQ (t = 2.93, df = 26, p < .01). Two subjects (one patient and one control) did not return for a subsequent session, which included IQ testing, and so no IQ information was available on these two subjects. There was a significant difference in socioeconomic status (SES) between the two groups (t = 3.09, df =

Discussion

We found a decrease in the volume of the fornix without a decrease in FA in children and adolescents with schizophrenia. The volume decrease may represent a decrease in the number of white matter fibers connecting the hippocampus to anterior limbic and frontal regions. No differences between the patients and controls in FA implies that the white matter microstructure of the fornix is relatively intact. The latter finding is in contrast to a recent study in adult males with schizophrenia that

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    This work was funded by NIMH MH068540, the Essel Foundation support of a NARSAD Young Investigator Award, and the Mental Illness and Neuroscience Discovery (MIND) Institute. The authors acknowledge MRI infrastructure grants: P30NS057091 and P41 RR00807. Finally, they thank the anonymous peer reviewers for their helpful suggestions.

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