Hippocampal volume and cognitive function in anorexia nervosa
Introduction
In women with anorexia nervosa (AN), an enlarged ventricular volume and dilated sulci have been consistently found (Dolan et al., 1988, Krieg et al., 1988, Krieg et al., 1989, Kingston et al., 1996, Swayze et al., 1996, Swayze et al., 2003). Reductions in both white and gray matter have also been observed (Katzman et al., 1996, Swayze et al., 2003). Brain metabolism studies parallel the structural findings, showing global reductions in brain metabolism (Delvenne et al., 1995) and perfusion (Krieg et al., 1989). Regional perfusion studies of children and adolescents with AN demonstrated unilateral reduced perfusion in the temporal lobe (in which the hippocampus is located) in the majority of those studied (Gordon et al., 1997, Chowdhury et al., 2003). In contrast, one unreplicated study reported relative hyperperfusion of the thalamus and the amygdala–hippocampal complex in adults with active AN (Takano et al., 2001). Structural deficits tend to improve with weight gain (Dolan et al., 1988, Krieg et al., 1988, Krieg et al., 1989, Kingston et al., 1996, Swayze et al., 1996, Golden et al., 1996), although gray and white matter volume may remain significantly reduced following recovery (Lambe et al., 1997, Katzman et al., 1997, Swayze et al., 2003) and temporal lobe hypoperfusion may also persist (Rastam et al., 2001). Significant reductions in the volume of the hippocampal–amygdala formation have also been reported (Giordano et al., 2001). It is unclear whether these various persisting abnormalities reflect premorbid vulnerability factors for AN or scars of the illness. One possible pathogenic mechanism is hypercortisolaemia, which along with other factors related to malnutrition may contribute to the differential recovery rates of the various structural abnormalities in AN (Naruo, 2002, Swayze et al., 2003). Cortisol is known to specifically endanger hippocampal neurones (Sapolsky et al., 1986), and is associated with both global hypometabolism (Brunetti et al., 1998) and significant hippocampal atrophy in Cushing's disease (Starkman et al., 1992).
The hippocampus is involved in learning and memory (Zola-Morgan and Squire, 1990), and discrete hippocampal lesions give rise to impaired recall with relative sparing of recognition (Baddeley et al., 2001, Mayes et al., 2002). An association between reduced hippocampal volume and impaired verbal recall has been observed in Cushing's disease (Starkman et al., 1992), depressive disorder (Sheline et al., 1999), posttraumatic stress disorder (PTSD) (Bremner et al., 1995) and normal aging (Lupien et al., 1998). Significant deficits of learning and memory have been demonstrated in AN (Jones et al., 1991, Mathias and Kent, 1998, Kingston et al., 1996), with some weak evidence of an association between memory impairment and structural brain abnormalities (Kingston et al., 1996).
The aim of the study was to test the hypothesis that hippocampal volume would be reduced in underweight AN and that it would be associated with impaired hippocampus-dependent cognitive function. Furthermore, hippocampal volume would be inversely related to the duration of the disorder, supporting the hypothesis that structural deficits are a scar of the illness.
Section snippets
Participants
Sixteen female inpatients with AN were recruited from the specialist eating disorders (ED) inpatient unit at the Bethlem Royal Hospital, London. All had no significant medical or psychiatric history, other than that associated with AN. The study took place during the weight-restoration phase of treatment.
Sixteen healthy comparison women, with no history of an ED or psychiatric illness, were recruited by advertisement from the staff and students of the Bethlem and Maudsley NHS Trust and
Clinical assessment
Clinical diagnoses (DSM-IV) and characteristics were obtained from routine clinical assessment. Age of onset was defined as the age at which an individual first fulfilled standard diagnostic criteria for AN (DSM-IV). Duration of amenorrhoea was estimated as an objective index of duration of disorder and of oestrogen deficiency. Lowest ever BMI was used as an index of severity of illness. Weight and BMI on the day of scanning were measured for all participants.
Neuropsychological assessment
Cognitive functioning was assessed
Participant characteristics
Participant characteristics are presented in Table 1. The patient group was slightly younger than the control group and, although statistically significant, the size of the difference is not clinically significant. As would be expected, average BMI was significantly lower in the patient group. Mean duration of amenorrhoea was 86.6 months (62.6) and mean lowest ever BMI (kg/m2) was 11.9 (1.1). These clinical indices are consistent with severe illness in the AN group. Mean age of onset of AN was
Discussion
We have observed a significant bilateral reduction in hippocampal volume in women with AN, but no evidence of impaired hippocampus-dependent cognitive function. There was no evidence of a significant relationship between hippocampal volume and age of onset, indices of illness duration or severity in the AN group.
There are several possible limitations to the study. Participants with AN were inpatients and at the severe end of the spectrum and may not be representative of AN. Depressive illness
Acknowledgments
Frances Connan was supported by a Medical Research Council Clinic Training Fellowship. This study was supported by a grant QLK1-1999-916 from the European Commission Framework V program (http://www.cordis.lu/life/home.html) and the Nina Jackson Eating Disorders Research Charity.
Many thanks are due to the staff and patients of the Bethlem and Maudsley Hospital Eating Disorders Unit and the Institute of Psychiatry (IOP) Neuroimaging Department for help and participation. Thanks are also owed to
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