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      Neuroimaging predictors of treatment response in anxiety disorders

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          Abstract

          Although several psychological and pharmacological treatment options are available for anxiety disorders, not all patients respond well to each option. Furthermore, given the relatively long duration of adequate treatment trials, finding a good treatment fit can take many months or longer. Thus, both clinicians and patients would benefit from the identification of objective pre-treatment measures that predict which patients will best respond to a given treatment. Recent studies have begun to use biological measures to help predict symptomatic change after treatment in anxiety disorders. In this review, we summarize studies that have used structural and functional neuroimaging measures to predict treatment response in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). We note the limitations of the current studies and offer suggestions for future research. Although the literature is currently small, we conclude that pre-treatment neuroimaging measures do appear to predict treatment response in anxiety disorders, and future research will be needed to determine the relative predictive power of neuroimaging measures as compared to clinical and demographic measures.

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          Most cited references81

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          Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

          The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.
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            A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

            Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. Case-control study. Academic medical center. Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions. The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.
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              A meta-analysis of structural brain abnormalities in PTSD.

              This series of meta-analyses examined structural abnormalities of the hippocampus and other brain regions in persons with PTSD compared to trauma-exposed and non-exposed control groups. The findings were significantly smaller hippocampal volumes in persons with PTSD compared to controls with and without trauma exposure, but group differences were moderated by MRI methodology, PTSD severity, medication, age and gender. Trauma-exposed persons without PTSD also showed significantly smaller bilateral hippocampal compared to non-exposed controls. Meta-analyses also found significantly smaller left amygdala volumes in adults with PTSD compared to both healthy and trauma-exposed controls, and significantly smaller anterior cingulate cortex compared to trauma-exposed controls. Pediatric samples with PTSD exhibited significantly smaller corpus callosum and frontal lobe volumes compared to controls, but there were no group differences in hippocampal volume. The overall findings suggested a dimensional, developmental psychopathology systems model in which: (1) hippocampal volumetric differences covary with PTSD severity; (2) hippocampal volumetric differences do not become apparent until adulthood; and (3) PTSD is associated with abnormalities in multiple frontal-limbic system structures.
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                Author and article information

                Contributors
                Journal
                Biol Mood Anxiety Disord
                Biol Mood Anxiety Disord
                Biology of Mood & Anxiety Disorders
                BioMed Central
                2045-5380
                2013
                2 August 2013
                : 3
                : 15
                Affiliations
                [1 ]Department of Psychology, Tufts University, Medford, MA, USA
                [2 ]Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA
                Article
                2045-5380-3-15
                10.1186/2045-5380-3-15
                3750275
                23915782
                ceb68a59-5f45-4232-8686-796e0e229249
                Copyright © 2013 Shin et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons 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.

                History
                : 22 April 2013
                : 19 June 2013
                Categories
                Review

                Neurology
                social anxiety disorder,obsessive-compulsive disorder,posttraumatic stress disorder,generalized anxiety disorder,amygdala,medial prefrontal cortex,anterior cingulate cortex,orbitofrontal cortex,fmri,pet

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