This study expands upon previous work comparing volume of amygdala in patients with bipolar disorder and schizophrenia. In this context, studying psychotic bipolar disorder is of special interest as it has symptomatic overlap with schizophrenia (Coryell et al., 2001
) as well as potentially a shared genetic etiology (Potash et al., 2003
). We examined whether volume of amygdala was different or similar in psychotic bipolar disorder and schizophrenia.
Our finding of a significant effect of diagnosis on size of amygdala is consistent with previous studies. Specifically, we found that amygdala was smaller in our schizophrenia group than in the psychotic bipolar disorder group. Velakoulis et al (2006)
found that first-episode psychosis subjects with schizophrenia had larger right amygdala than subjects with first-episode psychotic affective disorders. Frazier et al (2008)
reported a sex-specific effect where a smaller left amygdala volume was seen in males with first-episode schizophrenia as compared to males with first-episode bipolar disorder and the difference was more pronounced in bipolar disorder without psychosis than in bipolar disorder with psychosis. Differences in methodology used contribute to the difficulty in directly comparing our results to previous studies. Importantly, the definition of phenotype used and the delineation of the boundaries of amygdala differed across studies. Velakoulis et al (2006)
examined morphological differences between first-episode schizophrenia and first-episode psychotic affective disorders, not limited to bipolar disorder. In contrast, Frazier et al (2008)
limited their analysis to the early-onset forms of schizophrenia, bipolar disorder with psychosis and bipolar disorder without psychosis. In our study, we compared patients with schizophrenia to those with psychotic bipolar disorder. For segmentation of amygdala, we utilized a semi-automated method based on the JHU-MNI-SS Type II atlas boundaries, while other studies utilized the method of Convit et al (1999)
or Filipek et al (1994)
We also observed that females had smaller amygdala bilaterally than males, independent of diagnosis. Evidence of a sex effect on volume of amygdala from previous studies is conflicting. Some studies have found that the volume of the amygdala was smaller in women compared with men after controlling for ICV (Fjell et al., 2009
; Goldstein et al., 2001
), while other studies have not (Kim et al., 2012
; Gur et al., 2002
; Pruessner et al., 2000
). Larger amygdala in men than in women may underlie well established sex differences in emotional regulation (Gur et al, 2002
A limitation of the current study is that we did not have available a bipolar without psychosis group and so we were not able to make any comparisons to this group. Also, we did not have available to us information about potential confounders such as global cognitive ability. Further studies including a bipolar without psychosis comparison group and assessing additional potential confounding variables would shed further light on the relationship between psychosis and amygdala size.
Patients with bipolar disorder and schizophrenia are necessarily treated with different classes of medications. Notably, patients with bipolar disorder are commonly treated with mood stabilizers such as lithium, which has been shown to increase volume of amygdala over time (Lyoo et al., 2010). Many of our bipolar patients were treated with lithium, while none of the patients with schizophrenia were taking mood stabilizers. Antipsychotics, a standard treatment for schizophrenia, have not been shown to affect size of amygdala (Szeszko et al., 2003
;Velakoulis et al., 2006
). Thus, we cannot rule out the possibility that the larger amygdala in psychotic bipolar disorder may be a treatment effect rather than a disease effect. However, there are important clinical implications to either of these explanations. In the case of a disease effect, these data suggest further studies in which the disease state is better characterized than in our study. In the case of a treatment effect, these results are consistent with previous studies suggesting the possibility that treatment with lithium might lead to neurotrophic or neuroprotective effects (Bowley et al., 2002
;Machado-Vieira et al., 2009
). It will be important for future studies to attempt to disentangle potential medication effects from effects of disorder.
Taken together, these results suggest that change in volume of amygdala may represent a morphologic feature distinguishing bipolar disorder subjects from subjects with schizophrenia, even though psychotic symptoms can be found in both. Potential mechanisms whereby size of amygdala may change include response to chronic stress, response to medication, changes in intercellular fluid, changes in number or size of neurons and glia or changes in connective tissue (Altshuler et al., 2000
;Vyas et al., 2002
). While the nature of abnormalities of the amygdala in bipolar disorder and schizophrenia differ, this brain region might still be the locus of a partially shared pathophysiology between these disorders.