We show for the first time that the neuroanatomical correlates of depressive symptoms in patients with epilepsy differ from those in controls without epilepsy, and include opposite findings in OFC, a limbic component of prefrontal cortex involved in the subjective experience of emotional and social stimuli [24
Within-group comparison showed that in controls, higher levels of self-reported depressive symptoms were associated with thinning of left lateral OFC. These results are consistent with prior studies demonstrating OFC abnormalities in major depression [16
], and extend the association between OFC abnormality and depression to subjects with subclinical depressive symptoms (since no enrolled subjects had a current or past diagnosis of depression). In contrast, patients with TLE had thickening
of left lateral OFC in association with greater self-reported depressive symptoms. See supplemental materials
for discussion of brain regions other than OFC which showed significant BDI-thickness correlations in either TLE patients or controls.
Between-group comparison confirmed that BDI-thickness correlations in left OFC differed significantly between TLE patients and controls. In addition, this analysis revealed similar between-group differences in right OFC, suggesting bilateral OFC involvement in TLE-related depressive symptoms. However, conclusions about laterality effects are limited by the underrepresentation of patients with right TLE in our sample (12/35), precluding separate analyses of right and left TLE patients [25
OFC has bidirectional connections with sensory association cortices and temporal lobe regions [24
]. In particular, lateral OFC has robust, direct connections with the amygdala [26
], suggesting a mechanism by which mesial temporal epileptic activity could affect lateral OFC structure. In depressed patients with TLE, FDG PET studies found OFC hypometabolism [27
]. Together with our demonstration of OFC thickening in association with depression, this suggests that the cellular components contributing to OFC thickening are unlikely to be normally-functioning neurons or glia. Future studies, perhaps using MR spectroscopy, may better define the nature of this thickening.
While a potential limitation of this study is the use of two different MRI scanners, prior multi-site studies of cortical thickness have shown negligible impact of initial scan acquisition [29
]. In addition, we scanned roughly equal numbers of patients and controls on each scanner, and included site as a covariate in analyses, making it unlikely that findings relate to local hardware or other factors.
It is a limitation of this study that we did not perform structured diagnostic interviews to diagnose major depression. Our findings can be considered relevant to understanding the neural basis only of depressive symptoms, not major depression. However, it is important to note that DSM-IV [5
] was not designed for the diagnosis of psychiatric disorders in neurologic patients, and we believe use of a symptom measure such as the BDI-II is appropriate in patients with epilepsy who often do not meet DSM criteria for major depression [1
]. Use of the BDI-II, an instrument validated in people both with and without epilepsy [21
], facilitates comparison between these two group. Our use of a symptom measure rather than an all-or-none diagnosis is also in accord with the idea that depression may be best investigated using a dimensional rather than a categorical approach [30
]. Still, it will be important for future studies to utilize a measure of symptom severity like the BDI-II as well as a structured clinical interview to fully assess depression, and to include subjects both with and without a formal diagnosis of major depression and with and without epilepsy. It will also be important to investigate different components of depression (e.g. affective, somatic and cognitive) to learn if they have specific neural correlates in subjects with and without epilepsy; while the BDI-II has been used for this purpose[31
], it has not been independently validated[32
Our findings support the idea that depression associated with temporal lobe epilepsy is not only phenomenologically distinct from depression unassociated with epilepsy, but is also neurobiologically distinct, thus highlighting the need for specifically-designed diagnostic instruments [4
], and perhaps, specific antidepressant treatments different from those used in patients without epilepsy.