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Anxiety and Traumatic Stress Disorders Laboratory

Director: Isabelle M. Rosso, PhD

The Anxiety and Traumatic Stress Disorders Laboratory conducts research on the neurobiological basis of posttraumatic stress disorder (PTSD) and anxiety disorders, which may help inform diagnosis and lead to new treatment development for these serious and often debilitating conditions.

The lab uses brain imaging technologies to study the function, structure, and chemistry of the brain in both healthy people and patients suffering from PTSD, anxiety, and depression. We also use behavioral paradigms, including tasks that assess learning and memory, so that we can study brain-behavior relationships.

Research questions of interest to our laboratory include:

* What are the cognitive and brain mechanisms underlying the development of persistent trauma-related mental disorders such as PTSD?

* What are the shared versus distinct brain changes across different anxiety and emotional disorders?

* What are the neural mechanisms underlying risk and resilience for emotional disorders? For example, why do some people develop PTSD after experiencing trauma while other people do not?

* Are there brain “markers” of risk and resilience to trauma?

* What are the brain changes that occur during successful treatment of emotional disorders?

Ongoing Research Projects at McLean Hospital

The primary focus of the Anxiety and Traumatic Stress Disorders Laboratory is understanding the neurobiological basis of posttraumatic stress disorder (PTSD), and anxiety disorders.

Cerebral GABA and fear conditioning in PTSD (PI: Rosso)
This study uses a type of imaging called magnetic resonance spectroscopy (MRS) to examine whether PTSD patients compared with healthy subjects have abnormal levels of certain neurotransmitters in brain regions that mediate fear, and whether these neurochemical alterations are correlated with patients’ performance on a behavioral task of fear learning and extinction. This will allow the lab to determine whether brain chemicals measured with MRS may hold promise as neurobiological markers of PTSD’s core behavioral features, whether they may inform biologically-based definitions of the disorder, or be used as targets for developing new treatments.

Hippocampus neurochemistry in PTSD (PI: Rosso)
This study is investigating levels of the neurotransmitter glutamate in the hippocampus of adults with PTSD, using MRS. There is evidence from animal research that chronic stress and trauma can lead to neuronal atrophy and death in the hippocampus, mediated by excess levels of the glutamate in this brain region. The study examines whether in vivo glutamate, as detected with MRS, might be a biological marker of PTSD, and whether it is associated with certain types of clinical symptoms as well as measures of stress and anxiety.

Internet-based cognitive behavioral therapy effects on depressive cognitions and brain function (PI: Rauch)
This study strives to understand the effectiveness of Internet-based cognitive behavioral therapy (iCBT) treatment on improving depressive symptoms, coping and resilience skills, and cognitive processing. In this study, adults with major depressive disorder are assessed before and after a 10-week course of iCBT. Identifying and mapping the brain systems before and after treatment may help researchers guide future attempts to implement iCBT as a large-scale option for treating individuals with depression.

External Collaborative Projects

Neural Mechanisms of Fear Extinction Across Anxiety Disorders (PI: Milad)
This study is in collaboration with Mohammed Milad, Ph.D. of Massachusetts General Hospital. 
The aim of the study is to investigate the neural substrates of fear extinction learning and extinction recall in healthy individuals and in patients with anxiety disorders. In this study, healthy human subjects and patients with anxiety disorders undergo a visual fear conditioning and extinction protocol using functional neuroimaging while measuring psychophysiological responses. We are interested in elucidating neural correlates of fear conditioning and extinction across different anxiety and stress-related disorders, including PTSD, generalized anxiety disorder, social anxiety disorder, specific phobia and obsessive compulsive disorder.

Neurobiological Basis of Emotional Intelligence (PI: Killgore)
This study is in collaboration with Scott Killgore, Ph.D. of the University of Arizona.
This study uses functional and structural brain imaging techniques to isolate the brain networks that are critical to adaptive coping, resilience, and emotional intelligence (EQ).  EQ is the ability to accurately perceive and identify emotions in oneself and others, and to understand, use, and manage these emotions to enhance cognitive processes, decision-making, mental health, and social functioning.  It has been suggested that in some cases, these emotional skills and attributes may contribute as much or more to an individual’s ultimate success at work, school, or social pursuits than the more commonly known aspects of cognitive intelligence or “IQ.”  Despite growing appreciation for the importance that emotional intelligence plays in mental health, resilience, and general life success, there is little known about the underlying brain processes associated with these abilities.

Bright Light Therapy to Improve Sleep following Mild Traumatic Brain Injury (PI: Killgore)
This study is in collaboration with Scott Killgore, Ph.D. of the University of Arizona.
The present study examines the efficacy of Bright Light Therapy in improving cognitive functioning, mood and sleep in individuals who have experienced a traumatic brain injury. We employ functional magnetic resonance imaging as well as diffusion tensor imaging to evaluate brain function and structure before and after a six-week course of light therapy. The goal of this line of research is both to evaluate the effectiveness of this therapy as well as to understand the effects of axonal damage on cognitive and emotional functioning in traumatic brain injury.

Neuropredictors of cognitive resilience to sleep loss
This study is in collaboration with Scott Killgore, Ph.D. of the University of Arizona.
Our lab is the first to combine multimodal neuroimaging techniques such as functional MRI, diffusion tensor imaging, resting state functional connectivity and MR spectroscopy to attempt to clarify why some individuals are coping well with sleep loss, while others are vulnerable to insufficient sleep. This study will therefore clarify the role of brain regions such as the medial prefrontal cortex in sleep deprivation and cognitive resilience to sleep loss.  Findings from this study could be used to identify brain regions that using behavioral or pharmacological interventions may specifically be targeted to increase performance in the context of insufficient sleep (e.g., military operations).

Neurocorrelates of cognitive and emotional health following mild traumatic brain injury
This study is in collaboration with Scott Killgore, Ph.D. of the University of Arizona.
This study will combine the MR imaging techniques diffusion tensor imaging and resting state functional connectivity to investigate neurocorrelates of cognitive and psychological health in 150 individuals with mild traumatic brain injury at different recovery stages (i.e., two weeks, one month, two months, six months, 12 months) compared to 30 healthy controls. Findings from this study will be used to inform a preliminary model regarding the relationship between white matter integrity and neuropsychological functioning following mild traumatic brain injury.

Brain Function, and Structure, and Genes in Pediatric Obsessive Compulsive Disorder (PI: Stewart)
This study is in collaboration with Evelyn Stewart, Ph.D. of the University of British Columbia.
The objectives of this line of work are to combine functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and genotyping of risk genes in a cross-sectional study of youth with OCD. Specifically, the aims are: (1) To examine functional activation in the regions implicated in OCD (orbitofrontal cortex, striatum, insula), using three fMRI paradigms: a visuospatial priming task, a task-switching task, and an implicit facial affect recognition task, (2) To examine the relationship between brain structure and OCD-susceptibility genotypes in OCD subjects and healthy individuals. We are collecting anatomical and diffusion tensor imaging data, as well as specific allele and haplotype information in previously identified gene susceptibility regions. Individuals will be grouped based on risk genotypes and the risk groups will be compared in terms of regional brain structure.

PUBLICATIONS 2014 & 2013 (Selected)

Cui J, Olson EA, Weber M, Schwab ZJ, Rosso IM, Rauch SL, Killgore WD. Trait emotional suppression is associated with increased activation of the rostral anterior cingulate cortex in response to masked angry faces. Neuroreport. 2014 Jul 9;25(10):771-776. PMID: 24858795.

Silveri MM, Cohen-Gilbert J, Crowley DJ, Rosso IM, Jensen JE, Sneider JT. Altered anterior cingulate neurochemistry in emerging adult binge drinkers with a history of alcohol-induced blackouts. Alcohol Clin Exp Res. 2014 Apr;38(4):969-79. PMID: 24512596.

Dillon DG, Rosso IM, Pechtel P, Killgore WD, Rauch SL, Pizzagalli DA. Peril and pleasure: an rdoc-inspired examination of threat responses and reward processing in anxiety and depression. Depress Anxiety. 2014 Mar;31(3):233-49. PMID: 24151118; PMCID: PMC3951656.

Killgore WD, Britton JC, Schwab ZJ, Price LM, Weiner MR, Gold AL, Rosso IM, Simon NM, Pollack MH, Rauch SL. Cortico-limbic responses to masked affective faces across PTSD, panic disorder, and specific phobia. Depress Anxiety. 2014 Epub 2013 Jul 16. PMID: 23861215.

Rosso IM, Weiner MR, Crowley DJ, Silveri MM, Rauch SL, Jensen JE. Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. Depress Anxiety. 2014 Feb;31(2):115-23. PMID: 23861191; PMCID: PMC3894264.

Weber M, Killgore WD, Rosso IM, Britton JC, Schwab ZJ, Weiner MR, Simon NM, Pollack MH, Rauch SL. Voxel-based morphometric gray matter correlates of posttraumatic stress disorder. J Anxiety Disord. 2013 May;27(4):413-9.  PMID: 23746489; PMCID: PMC3782384.

Silveri MM, Sneider JT, Crowley DJ, Covell MJ, Acharya D, Rosso IM, Jensen JE. Frontal lobe γ-aminobutyric acid levels during adolescence: associations with impulsivity and response inhibition. Biol Psychiatry. 2013 Aug 15;74(4):296-304. PMID: 23498139; PMCID: PMC3695052.

Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014 May 20;15(6):410-24. PMID: 24840803.

Peters AT, Peckham AD, Stange JP, Sylvia LG, Hansen NS, Salcedo S, Rauch SL, Nierenberg AA, Dougherty DD, Deckersbach T. Correlates of real world executive dysfunction in bipolar I disorder. J Psychiatr Res. 2014 Jun;53:87-93. PMID: 24655587; PMCID: PMC4045408.

Holt DJ, Cassidy BS, Yue X, Rauch SL, Boeke EA, Nasr S, Tootell RB, Coombs G 3rd. Neural correlates of personal space intrusion. J Neurosci. 2014 Mar 19;34(12):4123-34. PMID: 24647934; PMCID: PMC3960459.

Killgore WD, Schwab ZJ, Tkachenko O, Webb CA, DelDonno SR, Kipman M, Rauch SL, Weber M. Emotional intelligence correlates with functional responses to dynamic changes in facial trustworthiness. Soc Neurosci. 2013;8(4):334-46. PMID: 23802123.

Rauch SL, Carlezon WA Jr. Neuroscience. Illuminating the neural circuitry of compulsive behaviors. Science. 2013 Jun 7;340(6137):1174-5. PMID: 23744931.

Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, Jenike M, Rauch SL, Wilhelm S. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013 Jun;70(6):608-18; quiz 554. PMID: 23740049.

Savitz JB, Rauch SL, Drevets WC. Reproduced from Habenula volume in bipolar disorder and major depressive disorder: a high-resolution magnetic resonance imaging study. Mol Psychiatry. 2013 May;18(5):523. PMID: 23608961.

Savitz JB, Rauch SL, Drevets WC. Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play. Mol Psychiatry. 2013 May;18(5):528-39. PMID: 23546169; PubMed Central PMCID: PMC3633788.

Killgore WD, Schwab ZJ, Weber M, Kipman M, Deldonno SR, Weiner MR, Rauch SL. Daytime sleepiness affects prefrontal regulation of food intake. Neuroimage. 2013 May 1;71:216-23. PMID: 23353029.

Rosmarin DH, Bigda-Peyton JS, Kertz SJ, Smith N, Rauch SL, Björgvinsson T. A test of faith in God and treatment: the relationship of belief in God to psychiatric treatment outcomes. J Affect Disord. 2013 Apr 25;146(3):441-6. PMID: 23051729.

PUBLICATIONS 2012 and earlier (Selected)

Silveri MM, Jensen JE, Rosso IM, Sneider JT, Yurgelun-Todd DA. Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla. Psychiatry Res. 2011 Mar 31;191(3):201-11. PMID: 21334181; PMCID: PMC3065822.

Rosso IM, Makris N, Britton JC, Price LM, Gold AL, Zai D, Bruyere J, Deckersbach T, Killgore WD, Rauch SL. Anxiety sensitivity correlates with two indices of right anterior insula structure in specific animal phobia. Depress Anxiety. 2010 Dec;27(12):1104-10. PMID: 21132846; PMCID: PMC3010373.

Britton JC, Rauch SL, Rosso IM, Killgore WD, Price LM, Ragan J, Chosak A, Hezel DM, Pine DS, Leibenluft E, Pauls DL, Jenike MA, Stewart SE. Cognitive inflexibility and frontal-cortical activation in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):944-53. PMID: 20732630.

Rosso IM, Makris N, Thermenos HW, Hodge SM, Brown A, Kennedy D, Caviness VS, Faraone SV, Tsuang MT, Seidman LJ. Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study. Schizophr Res. 2010 Oct;123(1):15-21. PMID: 20705433; PMCID: PMC2939267.

Britton JC, Stewart SE, Killgore WD, Rosso IM, Price LM, Gold AL, Pine DS, Wilhelm S, Jenike MA, Rauch SL. Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder. Depress Anxiety. 2010 Jul;27(7):643-51. PMID: 20602430; PMCID: PMC2951127.

Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH. Paternal age as a risk factor for schizophrenia: how important is it? Schizophr Res. 2009 Oct;114(1-3):1-5. PMID: 19683417.

Killgore WD, Rosso IM, Gruber SA, Yurgelun-Todd DA. Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder. Cogn Behav Neurol. 2009 Mar;22(1):28-37. PMID: 19372768.

Gruber SA, Rosso IM, Yurgelun-Todd D. Neuropsychological performance predicts clinical recovery in bipolar patients. J Affect Disord. 2008 Jan;105(1-3):253-60. PMID: 17524493; PMCID: PMC3271707.

Rosso IM, Killgore WD, Cintron CM, Gruber SA, Tohen M, Yurgelun-Todd DA. Reduced amygdala volumes in first-episode bipolar disorder and correlation with cerebral white matter. Biol Psychiatry. 2007 Mar 15;61(6):743-9. PMID: 17123471.

Silveri MM, Rohan ML, Pimentel PJ, Gruber SA, Rosso IM, Yurgelun-Todd DA. Sex differences in the relationship between white matter microstructure and impulsivity in adolescents. Magn Reson Imaging. 2006 Sep;24(7):833-41. PMID: 16916700.

Rosso IM. Review: hippocampal volume is reduced in people with unipolar depression. Evid Based Ment Health. 2005 May;8(2):45. PMID: 15851808.

Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA. Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry. 2005 Jan 1;57(1):21-6. PMID: 15607296.

Rosso IM, Young AD, Femia LA, Yurgelun-Todd DA. Cognitive and emotional components of frontal lobe functioning in childhood and adolescence. Ann N Y Acad Sci. 2004 Jun;1021:355-62. PMID: 15251910.

Niendam TA, Bearden CE, Rosso IM, Sanchez LE, Hadley T, Nuechterlein KH, Cannon TD. A prospective study of childhood neurocognitive functioning in schizophrenic patients and their siblings. Am J Psychiatry. 2003 Nov;160(11):2060-2. PubMed PMID: 14594759.

Cannon TD, Rosso IM. Levels of analysis in etiological research on schizophrenia. Dev Psychopathol. 2002 Summer;14(3):653-66. Review. PMID: 12349878.

Van Erp TG, Saleh PA, Rosso IM, Huttunen M, Lönnqvist J, Pirkola T, Salonen O, Valanne L, Poutanen VP, Standertskjöld-Nordenstam CG, Cannon TD. Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder, their unaffected siblings, and healthy unrelated volunteers. Am J Psychiatry. 2002 Sep;159(9):1514-20. PMID: 12202271.

Cannon TD, van Erp TG, Rosso IM, Huttunen M, Lönnqvist J, Pirkola T, Salonen O, Valanne L, Poutanen VP, Standertskjöld-Nordenstam CG. Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry. 2002 Jan;59(1):35-41. PMID: 11779280.

Cannon TD, Gasperoni TL, van Erp TG, Rosso IM. Quantitative neural indicators of liability to schizophrenia: implications for molecular genetic studies. Am J Med Genet. 2001 Jan 8;105(1):16-9. PMID: 11424984.

Bearden CE, Rosso IM, Hollister JM, Sanchez LE, Hadley T, Cannon TD. A prospective cohort study of childhood behavioral deviance and language abnormalities as predictors of adult schizophrenia. Schizophr Bull. 2000;26(2):395-410. PMID: 10885639.

Cannon TD, Bearden CE, Hollister JM, Rosso IM, Sanchez LE, Hadley T. Childhood cognitive functioning in schizophrenia patients and their unaffected siblings: a prospective cohort study. Schizophr Bull. 2000;26(2):379-93. PMID: 10885638.

Rosso IM, Bearden CE, Hollister JM, Gasperoni TL, Sanchez LE, Hadley T, Cannon TD. Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: a prospective cohort study. Schizophr Bull. 2000;26(2):367-78. PMID: 10885637.

Cannon TD, Rosso IM, Hollister JM, Bearden CE, Sanchez LE, Hadley T. A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia. Schizophr Bull. 2000;26(2):351-66. PMID: 10885636.

Rosso IM, Cannon TD, Huttunen T, Huttunen MO, Lönnqvist J, Gasperoni TL. Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort. Am J Psychiatry. 2000 May;157(5):801-7. PMID: 10784475.

Cannon TD, Rosso IM, Bearden CE, Sanchez LE, Hadley T. A prospective cohort study of neurodevelopmental processes in the genesis and epigenesis of schizophrenia. Dev Psychopathol. 1999 Summer;11(3):467-85. PMID: 10532620.

Killgore WD, Weber M, Schwab ZJ, Deldonno SR, Kipman M, Weiner MR, Rauch SL. Gray matter correlates of Trait and Ability models of emotional intelligence. Neuroreport. 2012 Jun 20;23(9):551-5. doi: 10.1097/WNR.0b013e32835446f7. PMID: 22546702.

Britton JC, Rauch SL. Attention bias modification and the serotonin transporter: personalized treatment implications of gene interactions with learning. Biol Psychiatry. 2011 Dec 1;70(11):1004-5. doi: 10.1016/j.biopsych.2011.09.028. PMID: 22045036.

Killgore WD, Britton JC, Price LM, Gold AL, Deckersbach T, Rauch SL. Neural correlates of anxiety sensitivity during masked presentation of affective faces. Depress Anxiety. 2011 Mar;28(3):243-9. doi: 10.1002/da.20788. PMID: 21308886; PubMed Central PMCID: PMC3079408.

Rauch SL, Britton JC. Developmental neuroimaging studies of OCD: the maturation of a field. J Am Acad Child Adolesc Psychiatry. 2010 Dec;49(12):1186-8. doi: 10.1016/j.jaac.2010.08.016. PubMed PMID: 21093768.

Britton JC, Stewart SE, Killgore WD, Rosso IM, Price LM, Gold AL, Pine DS, Wilhelm S, Jenike MA, Rauch SL. Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder. Depress Anxiety. 2010 Jul;27(7):643-51. doi: 10.1002/da.20718. PMID: 20602430; PMCID: PMC2951127.

Britton JC, Rauch SL, Rosso IM, Killgore WD, Price LM, Ragan J, Chosak A, Hezel DM, Pine DS, Leibenluft E, Pauls DL, Jenike MA, Stewart SE. Cognitive inflexibility and frontal-cortical activation in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):944-53. PMID: 20732630.

Haber SN, Rauch SL. Neurocircuitry: a window into the networks underlying neuropsychiatric disease. Neuropsychopharmacology. 2010 Jan;35(1):1-3. doi: 10.1038/npp.2009.146. PMID: 20010702; PMCID: PMC3055437.

Craske MG, Rauch SL, Ursano R, Prenoveau J, Pine DS, Zinbarg RE. What is an anxiety disorder? Depress Anxiety. 2009;26(12):1066-85. doi: 10.1002/da.20633. Review. PMID: 19957279.

Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, Zeidan MA, Handwerger K, Orr SP, Rauch SL. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009 Dec 15;66(12):1075-82. PMID: 19748076; PMCID: PMC2787650.

Britton JC, Gold AL, Deckersbach T, Rauch SL. Functional MRI study of specific animal phobia using an event-related emotional counting stroop paradigm. Depress Anxiety. 2009;26(9):796-805. PMID: 19434621; PMCID: PMC2792204.

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