Differential time courses and specificity of amygdala activity in posttraumatic stress disorder subjects and normal control subjects

Protopopescu, Xenia; Pan, Hong; Tuescher, Oliver; Cloitre, Marylène; Goldstein, Martin; Engelien, Wolfgang; Epstein, Jennifer A.; Yang, Yihong; Gorman, Jack M.; LeDoux, Joseph E.; Silbersweig, David; Stern, Emily

doi:10.1016/j.biopsych.2004.12.026

Cited by 253 publications

(176 citation statements)

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“…So far, there is no explanation as to why these FKBP5 effects were lateralized, as findings of lateralization of amygdala activation and volume remain inconclusive. For example, PTSD patients were found to show more pronounced hyperactivity in the left than in the right amygdala when confronted with trauma-related words (Protopopescu et al 2005) or masked fearful faces (Rauch et al 2000). However, this lateralized effect was not confirmed in a meta-analysis (Etkin and Wager 2007).…”

Section: Discussionmentioning

confidence: 98%

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

et al. 2014

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Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective selfreport (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. Abstract Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stresssensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxelbased morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective selfreport (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-env...

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Section: Discussionmentioning

confidence: 98%

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

et al. 2014

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“…All correlations are reported for po0.05, two-tailed. ANOVAs examining amygdala volume and function were conducted both including and excluding the subjects meeting PTSD, as PTSD has been associated with both increased (Protopopescu et al, 2005;Shin et al, 2004), and decreased amygdala activity (Britton et al, 2005); amygdala volume in PTSD has been shown not to be different from controls (Bremner, 2002;Wignall et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Amygdala–Prefrontal Disconnection in Borderline Personality Disorder

New

Hazlett

Buchsbaum

et al. 2007

Neuropsychopharmacol

259

160

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Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with 18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

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“…Emotion recognition difficulties have been noted in persons with PTSD (Shin et al, 2005). One study showed increased initial amygdala response to trauma-related negative stimuli (Protopopescu et al, 2005), and another study showed exaggerated amygdala activation, and diminished medial prefrontal cortex activation, in response to fearful versus happy facial expressions (Shin et al, 2005).Collectively, results of numerous studies have demonstrated that within neural systems involved in affective functioning, different neuroanatomical loci or circuitry contributes to the recognition of different emotions and, further, that various neuropathological changes and conditions can result in distinct disruptions of these circuits leading to specific patterns of deficits. Accordingly, an examination of affect recognition abilities across multiple patient populations is likely to prove beneficial in the identification of the underlying neural regions that give rise to these deficits in alcoholic individuals.…”

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confidence: 99%

Alcoholism and judgments of affective stimuli.

Clark¹,

Oscar‐Berman²,

Shagrin³

et al. 2007

Neuropsychology

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This study sought to differentiate alcoholism-related changes in judgments of emotional stimuli from those of other populations in which such changes have been documented. Two sets of visual stimuli, one containing words and the other containing drawings of faces (representing a range of emotional content), were presented to abstinent alcoholic adults with and without Korsakoff's syndrome, as well as to a healthy control group and four groups of patients with other neurobehavioral disorders: Parkinson's disease, schizophrenia, depression, and posttraumatic stress disorder. Participants rated the stimuli according to emotional valence and intensity of emotion. Results implicated bi-hemispheric frontal and subcortical involvement in the abnormalities of emotion identification associated with alcoholism, and they also support the notion of age-related vulnerabilities in conjunction with alcoholism. Keywords alcoholism; aging; Korsakoff's syndrome; emotion; neurobehavioral disorders Emotional changes that accompany long-term chronic alcoholism cover a broad spectrum (National Institute of Alcohol Abuse and Alcoholism, 1997) and have significant social and interpersonal significance (Kornreich et al., 2002). Among the abnormalities are affective processing deficits such as a diminished ability to recognize facial expressions of emotion (Howard, Oscar-Berman, Marinkovic, O'Reilly, & Harris, 2003;Kornreich et al., 2002;Philippot et al., 1999;Townshend & Duka, 2003) and reduced ability to decipher affective prosody in spoken language (Monnot, Nixon, Lovallo, & Ross, 2001). The abnormalities in Correspondence concerning this article should be addressed to Marlene Oscar-Berman, Boston University School of Medicine L-815, 715 Albany Street, Boston, MA 02118. oscar@bu.edu. Uraina S. Clark, Department of Psychology, Boston University; Marlene Oscar-Berman, Departments of Anatomy and Neurobiology, Psychiatry, and Neurology, Boston University School of Medicine, and Psychology Research Service, U.S. Department of Veterans Affairs Healthcare System, Boston Campus; Barbara Shagrin, U.S. Department of Veterans Affairs Healthcare System, Boston Campus; Michael Pencina, Department of Mathematics, Boston University. NIH Public Access Author ManuscriptNeuropsychology. Author manuscript; available in PMC 2014 July 08. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript emotional perception have been attributed to a combination of underlying factors, for example, visuospatial deficits, abnormal processing of social information, poor inhibitory control, and interpersonal stress (Moselhy, Georgiou, & Kahn, 2001;Philippot et al., 1999). Brain changes associated with these deficits include pathology of frontosubcortical and limbic systems or disturbances in the functioning of the right hemisphere (Bowirrat & Oscar-Berman, 2005;. For example, it has been suggested that alcoholic individuals' tendencies to overestimate facial emotions could be related to interference with frontally mediated disinhibition proces...

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Differential time courses and specificity of amygdala activity in posttraumatic stress disorder subjects and normal control subjects

Cited by 253 publications

References 65 publications

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

Amygdala–Prefrontal Disconnection in Borderline Personality Disorder

Alcoholism and judgments of affective stimuli.

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