Resting state corticolimbic connectivityabnormalities in unmedicated bipolar disorder and unipolar d

Resting state corticolimbic connectivity abnormalities inunmedicated bipolar disorder and unipolar depression✩

Amit Ananda,b,*, Yu Lia, Yang Wangb, Mark J. Lowec, and Mario DzemidzicdaDepartment of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States

bDepartment of Radiology, Indiana University School of Medicine, Indianapolis, IN, United States

cDivision of Radiology, The Cleveland Clinic Foundation, Cleveland, OH, United States

dDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States

AbstractThis study for the first time investigated resting state corticolimbic connectivity abnormalities inunmedicated bipolar disorder (BD) and compared them with findings in healthy controls andunipolar major depressive disorder (MDD) patient groups. Resting state correlations of lowfrequency BOLD fluctuations (LFBF) in echoplanar functional magnetic resonance (fMRI) datawere acquired from a priori defined regions of interests (ROIs) in the pregenual anterior cingulatecortex (pgACC), dorsomedial thalamus (DMTHAL), pallidostriatum (PST) and amygdala(AMYG), to investigate corticolimbic functional connectivity in unmedicated BD patients incomparison to healthy subjects and MDD patients. Data were acquired from 11 unmedicated BDpatients [six manic (BDM) and five depressed (BDD)], and compared with data available from 15unmedicated MDD and 15 healthy subjects. BD patients had significantly decreased pgACCconnectivity to the left and right DMTHAL, similar to findings seen in MDD. Additionally, BDpatients had decreased pgACC connectivity with the left and right AMYG as well as the left PST.An exploratory analysis revealed that both BDD and BDM patients had decreased connectivitybetween the pgACC and DMTHAL. The results of the study indicate a common finding ofdecreased corticolimbic functional connectivity in different types of mood disorders.

KeywordsfMRI; Resting state connectivity; Bipolar disorder; Depression; Brain imaging

1. IntroductionConverging findings from animal and human studies point to the anterior cingulate–pallidostriatal–thalamic– amygdala circuit as a putative corticolimbic mood-regulatingcircuit (MRC) that may be dysfunctional in mood disorders (Drevets, 1998;Anand andCharney, 2000; Mayberg, 2003). Brain-imaging techniques such as functional magneticresonance imaging (fMRI) and positron emission tomography have shown increasedactivation in major depressive disorder (MDD) of mood-generating limbic areas such as theamygdala (AMYG) (Ketter et al., 2001; Sheline et al., 2001; Drevets et al., 2002; Siegle et

✩The results of this study have been previously presented at the Society of Biological Psychiatry meeting in San Diego (2007).

© 2008 Elsevier Ireland Ltd. All rights reserved.*Corresponding author. Outpatient Psychiatry Clinic, University Hospital Suite #3124, 550 N. University Boulevard, Indianapolis, IN

46202, United States. Tel.: +1 317 274 7424; fax: +1 317 274 1497. aanand@iupui.edu (A. Anand).

NIH Public AccessAuthor ManuscriptPsychiatry Res. Author manuscript; available in PMC 2010 December 13.Published in final edited form as:Psychiatry Res. 2009 March 31; 171(3): 189–198. doi:10.1016/j.pscychresns.2008.03.012.

NIH-PA Author Manuscript

NIH-PA Author ManuscriptNIH-PA Author Manuscriptal., 2002; Anand et al 2005a), ventral striatum (VST), and dorsomedial thalamus(DMTHAL) (Drevets, 1998; Taber et al., 2004). Other areas of the brain that are alsoimplicated are the insula, hippocampus and parahippocampal areas (Mayberg et al., 1999;Phillips et al., 2003; Anand et al., 2005a). Conversely, decreased activation of certaincortical areas have been reported in MDD — in particular, the pregenual and ventralsubdivisions of the anterior cingulate cortex (pgACC and vACC) (Drevets et al., 1997;Mayberg et al., 1999), the anteromedial prefrontal cortex, the orbitofrontal cortex (OFC),and the dorsolateral prefrontal cortex (DLPFC) (Mayberg et al., 1999; Ketter et al., 2001).

Compared with the literature on MDD, considerably fewer studies have investigatedregional brain activation in bipolar disorder (BD). In studies in which phase of illness hasbeen characterized, most have been conducted in BD depression (BDD), which has also hasbeen reported to be associated with increased limbic activation and decreased activation ofcortical regions such as the DLPFC and ACC (Buchsbaum et al., 1986; Baxter et al., 1989;Drevets et al., 1997; Yurgelun-Todd et al., 2000; Ketter et al., 2001; Blumberg et al., 2003;Phillips et al., 2003; Chang et al., 2004). In mania (BDM), increased metabolism of theventral and dorsal ACC, the striatum (Drevets et al., 1997; Blumberg et al., 2000), and theamygdala (Altshuler et al., 2005) [another study reported decreased amygdala activation(Lennox et al., 2004)], and decreased activity of the OFC (Blumberg et al., 1999), have beenreported. Strakowski et al. (2004) have reported an abnormality in the anterior limbicnetwork in BD in response to cognitive stimuli. Compared with healthy subjects,unmedicated euthymic BP patients showed increased activation in the limbic and paralimbicareas (parahippocampus, amygdala and insula) as well as ventral prefrontal regions whenperforming attentional tasks (Strakowski et al., 2004). Therefore, in BD, abnormalitieswithin the prefrontal cortex, subcortical structures such as the striatum and thalamus, andmedial temporal structures such as the amygdala and the parahippocampus, are likely to bepresent (Strakowski et al., 2005; Adler et al., 2006).