Generalized anxiety modulates frontal and limbic activation in major depression Page: 1

                                
Schlund et al. Behavioral and Brain Functions 2012, 8:8
http://www.behavioralandbrainfunctions.com/content/8

( BF BEHAVIORAL AND
BRAIN FUNCTIONS

Generalized anxiety modulates frontal and limbic
activation in major depression
Michael W Schlund'2,3 , Guillermo Verduzco, Michael F Cataldoi 2 and Rudolf Hoehn-Saric
Abstract
Background: Anxiety is relatively common in depression and capable of modifying the severity and course of
depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.
Methods: We used functional magnetic resonance imaging and two emotional information processing tasks to
examine frontal and limbic activation in ten patients with major depression and comorbid with preceding
generalized anxiety (MDD/GAD) and ten non-depressed controls.
Results: Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and
middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in
MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the
effects varied with the type of emotional information presented.
Conclusions: Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid
anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional
context. One implication of this finding is that divergent findings reported in the imaging literature on depression
could reflect modulation of activation by anxiety level in response to different types of emotional information.

Background
Depression is characterized by reductions in brain acti-
vation in the dorsal lateral and medial frontal cortex,
the anterior cingulate and limbic structures [1-4].
Recent reports suggest that up to 12% of patients with
major depressive disorder (MDD) are also comorbid
with generalized anxiety disorder (GAD) [5]. Some
hypothesize the early onset of GAD may confer vulner-
ability to later-developing disorders, including depres-
sion [6]. Comorbid anxiety may also modify the
psychopathology and course of depression, with patients
with agitated depression showing exacerbated bodily
responses while patients with non-anxious depression
manifest inhibitory autonomic responses [7]. Evidence
also shows anxious arousal and anxious apprehension
modulate activation differently in depression [1]. How-
ever, few neuroimaging investigations have examined
brain activation in patients with depression and comor-
bid with preceding generalized anxiety (MDD/GAD).
* Correspondence: rhoehn@jhmi.edu
1Department of Psychiatry, Johns Hopkins School of Medicine, 600 N. Wolfe
St., Meyer 4-109, Baltimore MD 21287
Full list of author information is available at the end of the article

Such investigations are needed to ascertain whether
frontal-limbic dysfunction common in depression is pre-
sent and advance our understanding of the brain regions
impacted by anxiety level.
Accordingly, we employed functional magnetic reso-
nance imaging (fMRI) to examine the hypothesis that
frontal-limbic dysfunction is present in a MDD/GAD
group and anxiety level modulates regional brain activa-
tion, highlighting its importance as an individual differ-
ence variable. Frontal and limbic regions often
associated with dysfunctional processing of emotional
stimuli in depression were targeted. During imaging,
subjects completed two affective challenges: one task
that involved viewing facial expressions exhibiting anger,
happiness or sadness and a second task involved hearing
autobiographic sentences describing situations of
ongoing significance that elicit anger, happiness or sad-
ness. Brain activation was contrasted between the
MDD/GAD group and a non-depressed control group
and regions exhibiting hypoactivation in the MDD/GAD
group were correlated with anxiety level. Importantly,
this investigation specifically chose patients with major
depression in whom chronic GAD preceded the first

S2012 Schlund et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
BioMed Central Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.