Brief reportRegional cerebral metabolism associated with anxiety symptoms in affective disorder patients
Introduction
Patients with primary affective disorders often have prominent comorbid anxiety symptoms that impact behavior and response to treatment (McElroy et al, in press). Previous functional brain imaging studies in affective disorders have not always addressed the contribution of anxiety symptoms to the patterns of regional brain activity observed.
Several investigators have studied a variety of primary anxiety disorders as well as anxiety induced in normal subjects. The right, compared with the left, parahippocampal gyrus has been found to have increased regional cerebral blood flow and metabolism in subjects with primary anxiety disorders, i.e., panic disorder Nordahl et al 1990, Reiman et al 1984, Reiman et al 1986. Increases in regional cerebral glucose metabolism (rCMRglu) in the insular cortex, right frontal and posterior medial orbitofrontal cortices, and lenticular nucleus have been found to be associated with symptom provocation in three anxiety disorders, including obsessive-compulsive disorder (OCD), simple phobia, and posttraumatic stress disorder (PTSD) (Rauch et al 1997). Other brain areas associated with anxiety include the left inferior parietal lobe in panic disorder (Nordahl et al 1990) and secondary visual cortex, hippocampus, prefrontal and orbitofrontal cortices, temporal poles, and posterior cingulate gyrus in simple phobias (Fredrikson et al 1995). Lucey et al (1997) found decreased regional cerebral blood flow in superior frontal cortices and right caudate in both OCD and PTSD patients compared to healthy control subjects.
Studies of anxiety provoked in healthy control subjects have demonstrated increased rCMRglu in the left anterior cingulate gyrus (Chua et al 1999; Kimbrell et al 1999) left inferior frontal, temporal, and cuneus gyri (Kimbrell et al 1999), and orbitofrontal, inferior frontal, and left insula (Chua et al 1999). Kimbrell et al (1999) also showed decreased rCMRglu in right posteriotemporoparietal cortex, right superior frontal, and right medial frontal cortices with anxiety induction in these same subjects.
These findings in diverse anxiety patient populations and healthy volunteers with induction of anxiety indicate several regions of general overlap, such as frontal and temporal cortices and insula. The purpose of this study was to identify changes in rCMRglu associated with the severity of anxiety symptoms (controlling for depression severity) in patients diagnosed with an affective disorder and to differentiate these from rCMRglu associated with severity of depression. We expected to find associations between anxiety and rCMRglu in frontal, insular, and temporal areas.
Section snippets
Methods and materials
Fifty-two patients (mean age 39.8 years, SD = 12.7, range = 20–65; 23 male), with a primary affective disorder (25 unipolar, 27 bipolar), who were free of medication for at least two weeks, underwent positron emission tomography (PET) studies using [18F]-fluorodeoxyglucose (FDG) after being given a complete description of the study and giving their written informed consent. Subjects were participants in studies of treatment interventions and underwent assessments and PET scans as part of those
Results
Mean SAnx was 47.1 ± 12.7 (range = 21–74) and HAMD was 22.2 ± 9.7 (range = 3–42). There was no significant difference in SAnx or HAMD scores between unipolar and bipolar groups. SAnx and HAMD were highly correlated (r = .62, p < .0001, n = 52).
SAnx correlated directly with rCMRglu in right parahippocampal gyrus and the left anterior cingulate gyrus bordering the callosum (from Talairach coordinate Z = +16 to Z = +32) after covarying for age, gender, and HAMD scores. In the same analysis, SAnx
Discussion
Severity of anxiety symptoms in affective disorder patients was positively correlated with rCMRglu in the right parahippocampal and left anterior cingulate regions. The increase in the right parahippocampal gyrus is consistant with findings in other subject populations, such as those with panic disorder Nordahl et al 1990, Reiman et al 1984, Reiman et al 1986. Increases in rCMRglu in the left anterior cingulate gyrus converge with findings in healthy control subjects with self-induced anxiety
Acknowledgements
The support of the Theodore and Vada Stanley Foundation to T.A. Kimbrell and M.W. Willis is gratefully acknowledged.
References (18)
- et al.
A functional anatomy of anticipatory anxiety
Neuroimage
(1999) - et al.
Regional brain activity during transient self-induced anxiety and anger in healthy adults
Biol Psychiatry
(1999) - et al.
The functional neuroanatomy of anxietyA study of three disorders using positron emission tomography and symptom provocation
Biol Psychiatry
(1997) - et al.
Regional cerebral blood flow in depression measured by positron emission tomographyThe relationship with clinical dimensions
Psychol Med
(1993) Prefrontal cortical-amygdalar metabolism in major depression
Ann N Y Acad Sci
(1999)- et al.
Functional anatomical differences between major depressive subtypes
J Cereb Blood Flow Metab
(1995) - et al.
Functional neuroanatomy of visually elicited simple phobic fearAdditional data and theoretical analysis
Psychophysiology
(1995) - et al.
Comparing functional (PET) imagesThe assessment of significant change
J Cereb Blood Flow Metab
(1991) - et al.
Assessing the significance of focal activation using their spatial extent
Hum Brain Mapp
(1994)
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