White matter abnormalities in adolescents with generalized anxiety disorder: a diffusion tensor imaging study

BackgroundPrevious neuroimaging studies have suggested an abnormal neural circuitry of emotion regulation including the amygdala and prefrontal cortex in both adult and adolescent generalized anxiety disorder (GAD) patients. Aberrant integrity of white matter in this neural circuitry has been verified in adult GAD patients. White matter abnormalities in adolescent GAD patients have not been detected.MethodsTwenty-five adolescents with GAD and 24 healthy controls underwent a diffusion tensor imaging scan. Fractional anisotropy (FA) was compared between groups with a voxel-wise Tract-Based Spatial Statistics (TBSS) analysis method.ResultsCompared with healthy controls, adolescents with GAD showed significantly reduced FA in bilateral uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and corona radiata.ConclusionsThe findings in the present study suggest a neural basis of emotion dysregulation in adolescent GAD patients.

[1]  B. J. Casey,et al.  Amygdala response to fearful faces in anxious and depressed children. , 2001, Archives of general psychiatry.

[2]  Monique Ernst,et al.  Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. , 2006, The American journal of psychiatry.

[3]  Neal D Ryan,et al.  A pilot study of amygdala volumes in pediatric generalized anxiety disorder , 2000, Biological Psychiatry.

[4]  Zhen Jin,et al.  Brain structural abnormalities in obsessive-compulsive disorder: converging evidence from white matter and grey matter. , 2012, Asian journal of psychiatry.

[5]  Tom Johnstone,et al.  Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. , 2009, The American journal of psychiatry.

[6]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[7]  Monique Ernst,et al.  Selective reduction in amygdala volume in pediatric anxiety disorders: A voxel-based morphometry investigation , 2005, Biological Psychiatry.

[8]  S. Strakowski,et al.  NEUROCIRCUITRY OF GENERALIZED ANXIETY DISORDER IN ADOLESCENTS: A PILOT FUNCTIONAL NEUROIMAGING AND FUNCTIONAL CONNECTIVITY STUDY , 2012, Depression and anxiety.

[9]  H. Wittchen,et al.  Human and economic burden of generalized anxiety disorder , 2008, Depression and anxiety.

[10]  Katherine E. Prater,et al.  Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. , 2010, The American journal of psychiatry.

[11]  Monique Ernst,et al.  Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. , 2007, Archives of general psychiatry.

[12]  Jun Liu,et al.  Neuroanatomical correlates of intellectual ability across the life span , 2011, Developmental Cognitive Neuroscience.

[13]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[15]  N. De Stefano,et al.  Longitudinal changes in grey and white matter during adolescence , 2010, NeuroImage.

[16]  Bumseok Jeong,et al.  Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood , 2012, NeuroImage.

[17]  B. Birmaher,et al.  Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[18]  Lingjiang Li,et al.  White matter integrity alterations in first episode, treatment-naive generalized anxiety disorder. , 2013, Journal of affective disorders.

[19]  Bruce W. Smith,et al.  Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. , 2008, The American journal of psychiatry.

[20]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[21]  S. Strakowski,et al.  ESTABLISHING THE NEUROBIOLOGIC BASIS OF TREATMENT IN CHILDREN AND ADOLESCENTS WITH GENERALIZED ANXIETY DISORDER , 2012, Depression and anxiety.

[22]  Monique Ernst,et al.  Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. , 2008, Archives of general psychiatry.

[23]  J M Gorman,et al.  Neuroanatomical hypothesis of panic disorder, revised. , 2000, The American journal of psychiatry.

[24]  I. Liberzon,et al.  The Neurocircuitry of Fear, Stress, and Anxiety Disorders , 2011, Neuropsychopharmacology.

[25]  M. Herrero,et al.  Functional anatomy of thalamus and basal ganglia , 2002, Child’s Nervous System.

[26]  Axel Schäfer,et al.  Localized gray matter volume abnormalities in generalized anxiety disorder , 2011, European Archives of Psychiatry and Clinical Neuroscience.

[27]  Yu-Te Wu,et al.  Fronto-occipital fasciculus, corpus callosum and superior longitudinal fasciculus tract alterations of first-episode, medication-naïve and late-onset panic disorder patients. , 2013, Journal of affective disorders.

[28]  Michael Davis,et al.  The amygdala: vigilance and emotion , 2001, Molecular Psychiatry.

[29]  Do P. M. Tromp,et al.  Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. , 2012, Archives of general psychiatry.

[30]  Joseph E LeDoux.  Emotion circuits in the brain. , 2009, Annual review of neuroscience.

[31]  J. Schmitt,et al.  Pilot multimodal twin imaging study of generalized anxiety disorder , 2012, Depression and anxiety.

[32]  P. Bandettini,et al.  What's New in Neuroimaging Methods? , 2009, Annals of the New York Academy of Sciences.

[33]  C. Stark,et al.  Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder. , 2012, Journal of psychiatric research.

[34]  L. Su,et al.  Reliability and validity of the screen for child anxiety related emotional disorders (SCARED) in Chinese children. , 2008, Journal of anxiety disorders.

[35]  Olga V. Demler,et al.  Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[36]  T J Meyer,et al.  Development and validation of the Penn State Worry Questionnaire. , 1990, Behaviour research and therapy.

[37]  Arthur W. Toga,et al.  Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template , 2008, NeuroImage.

[38]  Helen Barbas,et al.  Sensory Pathways and Emotional Context for Action in Primate Prefrontal Cortex , 2011, Biological Psychiatry.

[39]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[40]  M. Dugas,et al.  Generalized anxiety disorder publications: where do we stand a decade later? , 2010, Journal of anxiety disorders.

[41]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[42]  Katherine E. Prater,et al.  Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. , 2009, Archives of general psychiatry.

[43]  D. Pine,et al.  Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. , 2010, Archives of general psychiatry.