Increased right amygdala volume in lithium‐treated patients with bipolar I disorder

Usher, Juliana; Menzel, Peter; Schneider‐Axmann, Thomas; Kemmer, C.; Reith, Wolfgang; Falkai, Peter; Gruber, Oliver; Scherk, Harald

doi:10.1111/j.1600-0447.2009.01428.x

Cited by 33 publications

(28 citation statements)

References 38 publications

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“…Our MRI data also pointed to the absence of an active neurodegenerative process in older BD cases. Consistent with recent observations (Delaloye et al, 2009a; Sarnicola et al, 2009;Usher et al, 2010), the VBM analysis yielded no significant differences in graymatter volume between euthymic older BD patients and controls at baseline. Interestingly, two studies indicated the presence of regional increases in brain volume in older BD compared to healthy controls raising the question of the association between neurodevelopmental and neurodegenerative deficits in this disorder (Beyer et al, 2004;Usher et al, 2010).…”

Section: Discussionsupporting

confidence: 93%

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Longitudinal analysis of cognitive performances and structural brain changes in late‐life bipolar disorder

Delaloye

Moy

Bilbao

et al. 2011

Int J Geriat Psychiatry

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Section: Discussionsupporting

confidence: 93%

“…In their meta-analysis Usher et al (2010) reported a positive correlation between mean age and amygdala volume in patients with BD and postulated that early neurodevelopmental abnormalities may be masked by the compensatory effect of medication. (Moore et al, 2000;Yucel et al, 2007;Savitz and Drevets, 2009).…”

Section: Discussionmentioning

confidence: 96%

Longitudinal analysis of cognitive performances and structural brain changes in late‐life bipolar disorder

Delaloye

Moy

Bilbao

et al. 2011

Int J Geriat Psychiatry

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“…These data were difficult to interpret, however, since the non-lithium-treated group was receiving treatment with a variety of other medications (including other mood stabilizers, benzodiazepines, anti-depressants, and/or anti-psychotic agents), no HC group was available for comparison with the two BD samples, and the BD samples were not matched for gender. (Usher et al , 2009) recently found that BD I patients treated with lithium, but not non-lithium treated BD I patients had larger right amygdala volumes than a healthy comparison group. However, the non lithium-treated BD group also displayed larger (but not significantly so) right amygdala volumes than the controls.…”

Section: Discussionmentioning

confidence: 99%

“…Previous MRI studies of the amygdala either failed to control for medication effects (Altshuler et al , 2000, Frangou, 2005, Lyoo et al , 2004, Strakowski et al , 1999b, Velakoulis et al , 2006), or attempted to address this confound by comparing subjects receiving medication at the time of scanning against subjects not currently taking such agents at scanning (Blumberg et al , 2003, Brambilla et al , 2003, Foland et al , 2008, Usher et al , 2009). The neuroprotection afforded by such agents would, however, be expected to persist for a few weeks following treatment discontinuation (while the drug clears from the brain and the drug effects on gene expression subside), and it is unclear when the pathological processes accounting for a primary abnormality in BD would reassert themselves—manifested by the reappearance of GM abnormalities—following treatment cessation.…”

Section: Introductionmentioning

confidence: 99%

Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: The impact of medication

et al. 2010

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MRI-based reports of both abnormally increased and decreased amygdala volume in bipolar disorder (BD) have surfaced in the literature. Two major methodological weaknesses characterizing extant studies are treatment with medication and inaccurate segmentation of the amygdala due to limitations in spatial and tissue contrast resolution. Here, we acquired high-resolution images (voxel size=0.55×0.55×0.60mm) using a GE 3T MRI scanner, and a pulse sequence optimized for tissue contrast resolution. The amygdala was manually segmented by one rater blind to diagnosis, using coronal images. Eighteen unmedicated (mean medication-free period 11±10 months) BD subjects were age and gender matched with 18 healthy controls, and 17 medicated (lithium or divalproex) subjects were matched to 17 different controls. The unmedicated BD patients displayed smaller left and right amygdala volumes than their matched control group (p<0.01). Conversely, the BD subjects undergoing medication treatment showed a trend towards greater amygdala volumes than their matched HC sample (p=0.051). Right and left amygdala volumes were larger (p<0.05) or trended larger, respectively, in the medicated BD sample compared with the unmedicated BD sample. The two control groups did not differ from each other in either left or right amygdala volume. BD patients treated with lithium have displayed increased gray matter volume of the cortex and hippocampus relative to untreated BD subjects in previous studies. Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications.

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“…Lithium treatment has been associated with increased gray matter volumes in general [Moore et al 2000], and in particular brain regions such as the hippocampus [Foland et al 2008;Yucel et al 2007], and the amygdala [Usher et al 2010;Foland et al 2008]. Recently, several studies have examined whether such gray matter changes correlate with lithium response rather than simply treatment.…”

Section: Bipolar Disordermentioning

confidence: 99%

Predictors of lithium response in bipolar disorder

Tighe

Mahon

Potash

2011

Therapeutic Advances in Chronic Disease

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While lithium is generally regarded as the first-line agent for patients with bipolar disorder, it does not work for everyone, which raises the question: can we predict who will be most likely to respond? In this paper, we review the most compelling clinical, biologic, and genetic predictors of lithium response in bipolar disorder. Among clinical factors, the strongest predictors of good response are fewer hospitalizations preceding treatment, an episodic course characterized by an illness pattern of mania followed by depression, and a later age at onset of bipolar disorder. While several biologic predictors have been studied, the results are preliminary and require replication with studies of larger patient samples over longer observation periods. Neuroimaging is a particularly promising method given that it might concurrently illuminate pathophysiologic underpinnings of bipolar disorder, the mechanism of action of lithium, and potential predictors of lithium response. The first genome-wide association study of lithium response was recently completed. No definitive results emerged, perhaps because the study was underpowered. With major new initiatives in progress aiming to identify genes and genetic variations associated with lithium response, there is much reason to be hopeful that clinically useful information might be generated within the next several years. This could ultimately translate into tests that could guide the choice of mood-stabilizing medication for patients. In addition, it might facilitate pharmacologic research aimed at developing newer, more effective medications that might act more quickly and yield fewer side effects.

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Increased right amygdala volume in lithium‐treated patients with bipolar I disorder

Abstract: Lithium appears to have a sustained effect on a central core region of emotional processing and should therefore be considered in studies examining BD.

Cited by 33 publications

References 38 publications

Longitudinal analysis of cognitive performances and structural brain changes in late‐life bipolar disorder

Longitudinal analysis of cognitive performances and structural brain changes in late‐life bipolar disorder

Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: The impact of medication

Predictors of lithium response in bipolar disorder

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