Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

David R Cotter, MD, PhD, Department of Psychiatry, Education and Research Centre, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Fax: +353 1 8093741;
e-mail: drcotter@rcsi.ie


Background:  The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in subjects with major depressive disorder (MDD).

Aims:  Stereologically based investigation of caudal orbitofrontal cortex (cOFC), in 60 postmortem brains from four groups of 14 subjects each with bipolar disorder (BPD), schizophrenia and MDD.

Methods:  Glial cell and neuronal size and density were examined in all subjects using stereological probes such as the nucleator and the optical disector.

Results:  We found statistical evidence for a neuronal size reduction in BPD in layer 1 (21%, p = 0.007) and a trend for a reduction in layer 5 (20%, p = 0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p = 0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p < 0.001). We found no evidence for group differences in glial cell size nor for differences in glial or neuronal density.

Conclusions:  These findings provide preliminary evidence that neuronal size reduction in cOFC is a component of the pathology of BPD. Overall, the data implicate this cortical region in affective disorders, but provide no evidence for neuronal or glial pathology in this region in schizophrenia.