Anxiety Disorders: Price JL

Drevets WC, Price JL, Furey ML. · Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health (NIH/NIMH DIRP), 15K North Dr., Room 210, Bethesda, MD 20892, USA. · Brain Struct Funct. · Pubmed #18704495 links to  free full text

Abstract: The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The MPFC is part of a larger "default system" of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions. Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans. Further, because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders. This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies.

Monson CM, Gradus JL, Young-Xu Y, Schnurr PP, Price JL, Schumm JA. · Women's Health Sciences Division, National Center for PTSD, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA. · Psychol Assess. · Pubmed #18557690 No free full text.

Abstract: This study assessed the longitudinal association between clinician and patient ratings of posttraumatic stress disorder (PTSD) symptoms over the course of 2 different randomized clinical trials of veterans with chronic PTSD. One trial, the Department of Veterans Affairs Cooperative Study 420 (CSP 420; N = 360) compared trauma-focused and present-centered group therapies, and the 2nd trial compared cognitive processing theory and a waitlist control condition (N = 60). Linear mixed effects modeling revealed significant associations between clinician ratings (Clinician-Administered PTSD Scale; CAPS; D. D. Blake et al., 1990) and patient ratings (Posttraumatic Stress Disorder Checklist; PCL; F. W. Weathers, B. T. Litz, J. A. Herman, J. A. Huska, & T. M. Keane, 1993) in total and symptom clusters of PTSD. Contrary to hypothesis, the amount of change on the CAPS ranged from .75 to .82 standard deviations for every 1 standard deviation change on the PCL. The CAPS and PCL were more closely associated in the trauma-focused vs. present-centered treatment condition in CSP 420, and especially regarding hyperarousal symptoms. When comparing categorization of clinically significant change on the CAPS and PCL, the authors found no differences in the percentages of agreement between clinicians and patients in improvement and exacerbation. The value of multimodal assessment of PTSD treatment outcomes is discussed.

Nugent AC, Milham MP, Bain EE, Mah L, Cannon DM, Marrett S, Zarate CA, Pine DS, Price JL, Drevets WC. · Section on Neuroimaging in Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, 1 Center Drive, MSC 0135, Bethesda, MD 20892-0135, USA. · Neuroimage. · Pubmed #16256376 No free full text.

Abstract: Bipolar disorder (BD) has been associated with abnormalities of brain structure. Specifically, in vivo volumetric MRI and/or post mortem studies of BD have reported abnormalities of gray matter (GM) volume in the medial prefrontal cortex (PFC), amygdala, hippocampal subiculum and ventral striatum. These structures share anatomical connections with each other and form part of a "visceromotor" network modulating emotional behavior. Areas of the lateral orbital, superior temporal and posterior cingulate cortices project to this network, but morphometric abnormalities in these areas have not been established in BD. The current study assessed tissue volumes within these areas in BD using MRI and voxel-based morphometry (VBM). MRI images were obtained from 36 BD subjects and 65 healthy controls. To account for possible neurotrophic and neuroprotective effects of psychotropic medications, BD subjects were divided into medicated and unmedicated groups. Images were segmented into tissue compartments, which were examined on a voxel-wise basis to determine the location and extent of morphometric changes. The GM was reduced in the posterior cingulate/retrosplenial cortex and superior temporal gyrus of unmedicated BD subjects relative to medicated BD subjects and in the lateral orbital cortex of medicated BD subjects relative to controls. White matter (WM) was increased in the orbital and posterior cingulate cortices, which most likely reflected alterations in gyral morphology resulting from the reductions in the associated GM. The morphometric abnormalities in the posterior cingulate, superior temporal and lateral orbital cortices in BD support the hypothesis that the extended network of neuroanatomical structures subserving visceromotor regulation contains structural alterations in BD. Additionally, localization of morphometric abnormalities to areas known to exhibit increased metabolism in depression supports the hypothesis that repeated stress and elevated glucocorticoid secretion may result in neuroplastic changes in BD.

Price JL, Monson CM, Callahan K, Rodriguez BF. · VA National Center for PTSD, Executive Division, White River Junction, VT, USA. · J Anxiety Disord. · Pubmed #16139471 No free full text.

Abstract: This two-part study investigated the cross-sectional and across-treatment relationships among measures of emotional functioning and posttraumatic stress disorder (PTSD) symptomatology for veterans receiving specialized treatment for military-related PTSD. Cross-sectional analyses revealed overlap among emotion regulation, affective control, depressive symptoms, and PTSD symptoms at pre-treatment. In regression analyses, fear of losing affective control was most predictive of PTSD symptoms. Bivariate analyses of residualized change scores showed that changes in emotion regulation and fear of losing affective control were associated with changes in PTSD and depressive symptoms across treatment. Regression analyses revealed that changes in fear of losing affective control most strongly predicted changes in PTSD and depressive symptoms. Theoretical and clinical implications are discussed, including an understanding of the differences between emotion regulation and affective control processes. Future research directions are offered, including improved measurement of emotional functioning and longitudinal research delineating the likely bi-directional relationship between emotional functioning and PTSD.

Monson CM, Price JL, Rodriguez BF, Ripley MP, Warner RA. · VA National Center for PTSD, Executive Division, 215 N. Main, White River Junction, Vermont 05009, USA. · J Trauma Stress. · Pubmed #15253100 No free full text.

Abstract: To expound on the nature of emotional deficits in PTSD, the current study investigated the relationships among emotion content and process variables and PTSD symptomatology in a sample of 85 veterans with military-related trauma. Alexithymic externally oriented thinking and negative affectivity emerged as the most consistent predictors of PTSD symptoms; however, depression was the only variable associated with emotional numbing. Theoretical and clinical implications of these findings are discussed, as well as future research directions including the collateral and clinician assessment of emotional functioning, use of other process measures, and inclusion of various control groups.

Black KJ, Hershey T, Koller JM, Videen TO, Mintun MA, Price JL, Perlmutter JS. · Departments of Psychiatry, School of Medicine, Washington University, 660 South Euclid Avenue, St. Louis, MO 63110, USA. · Proc Natl Acad Sci U S A. · Pubmed #12482941 links to  free full text

Abstract: Dopamine can induce fascinating, complex human behavioral states, including disinhibition, euphoria, or elaborate stereotypies, whereas dopamine deficiency can cause anxiety or sadness. Limited data suggest that these phenomena may involve dysfunction of orbital frontal cortex, cingulate cortex, or ventral striatum. The dopamine D3 receptor (D3R) has an anatomic distribution that suggests it could mediate these effects, but almost no data directly demonstrate the regional functional effects of D3R activation. We used quantitative positron emission tomography (PET), [15O]water, and the D3-preferring dopamine agonist pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. We studied seven normal baboons ventilated with 70% nitrous oxide, and analyzed results voxelwise in a common atlas space. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. The dose-response curve and duration of pramipexole's effects suggest that these rCBF responses indicate functional effects of a D3-preferring agonist. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. We conclude that a dopamine D3 receptor agonist preferentially affects brain activity in prefrontal and limbic cortex, and speculate that dopamine's effects on these regions via D3Rs may mediate some of the known psychiatric complications of dopamine deficiency or excess.

Drevets WC, Price JL, Bardgett ME, Reich T, Todd RD, Raichle ME. · Section on Neuroimaging of Mood and Anxiety Disorders, Molecular Imaging Branch, NIH/National Institute of Mental Health, Building 1, Room B3-10, 1 Center Drive, MSC-0135, Bethesda, MD 20892-0135, USA. · Pharmacol Biochem Behav. · Pubmed #11830178 No free full text.

Abstract: In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1<P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.