Hostname: page-component-7c8c6479df-8mjnm Total loading time: 0 Render date: 2024-03-28T22:12:36.071Z Has data issue: false hasContentIssue false

White-matter abnormalities in the right posterior hemisphere in generalized anxiety disorder: a diffusion imaging study

Published online by Cambridge University Press:  25 July 2011

P. Brambilla*
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy Scientific Institute IRCCS ‘E. Medea’, Udine, Italy
G. Como
Affiliation:
Department of Medical and Biological Sciences, University of Udine, Udine, Italy
M. Isola
Affiliation:
Department of Medical and Biological Sciences, University of Udine, Udine, Italy
F. Taboga
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
R. Zuliani
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
S. Goljevscek
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
M. Ragogna
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
G. Brondani
Affiliation:
Department of Medical and Biological Sciences, University of Udine, Udine, Italy
M. Baiano
Affiliation:
Centre for Weight and Eating Disorders, Portogruaro, Venice, Italy
L. Perini
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
A. Ferro
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
M. Bazzocchi
Affiliation:
Department of Medical and Biological Sciences, University of Udine, Udine, Italy
C. Zuiani
Affiliation:
Department of Medical and Biological Sciences, University of Udine, Udine, Italy
M. Balestrieri
Affiliation:
Department of Experimental Clinical Medical Sciences, Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy
*
*Address for correspondence: P. Brambilla, Dipartimento di Scienze Mediche Sperimentali e Cliniche, Università di Udine, P.Le Kolbe N.3, 33110 Udine, Italy. (Email: paolo.brambilla@uniud.it)

Abstract

Background

Prior imaging studies have shown structural, functional and biochemical impairments in patients with generalized anxiety disorder (GAD), particularly in the right hemisphere. In this study we investigated, for the first time to the best of our knowledge, the white-matter microstructure organization in GAD.

Method

A total of 12 patients with DSM-IV GAD and 15 matched healthy controls underwent a magnetic resonance imaging session of diffusion weighted imaging, exploring white-matter water molecules by the means of apparent diffusion coefficients (ADCs). Regions of interests were placed in the frontal, parietal, temporal and occipital lobes and in the splenium and genu of the corpus callosum, bilaterally.

Results

ADC measures were significantly greater in patients with GAD in the right splenium and right parietal cortex compared with healthy controls (p⩽0.002). No significant correlations between ADCs and age or clinical variables were found.

Conclusions

We provide evidence that GAD is associated with disrupted white-matter coherence of posterior right hemisphere regions, which may partly sustain the impaired cognitive regulation of anxiety. Future diffusion imaging investigations are expected to better elucidate the communication between the parietal cortex and other right hemisphere regions in sustaining the cognitive processing of social and emotional stimuli in patients with GAD.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aboitiz, F, Scheibel, AB, Fisher, RS, Zaidel, E (1992). Fiber composition of the human corpus callosum. Brain Research 598, 143153.Google Scholar
Aikins, DE, Craske, MG (2001). Cognitive theories of generalized anxiety disorder. Psychiatric Clinics of North America 24, 5774, vi.Google Scholar
Alexander, AL, Lee, JE, Lazar, M, Field, AS (2007). Diffusion tensor imaging of the brain. Neurotherapeutics 4, 316329.Google Scholar
Andreone, N, Tansella, M, Cerini, R, Versace, A, Rambaldelli, G, Perlini, C, Dusi, N, Pelizza, L, Balestrieri, M, Barbui, C, Nose, M, Gasparini, A, Brambilla, P (2007). Cortical white-matter microstructure in schizophrenia. Diffusion imaging study. British Journal of Psychiatry 191, 113119.Google Scholar
Antonius, D, Prudent, V, Rebani, Y, D'Angelo, D, Ardekani, BA, Malaspina, D, Hoptman, MJ (2011). White matter integrity and lack of insight in schizophrenia and schizoaffective disorder. Schizophrenia Research 128, 7682.Google Scholar
Assaf, Y, Pasternak, O (2008). Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. Journal of Molecular Neuroscience 34, 5161.Google Scholar
Baloch, HA, Brambilla, P, Soares, JC (2009). Corpus callosum abnormalities in pediatric bipolar disorder. Expert Review in Neurotherapeutics 9, 949955.Google Scholar
Basser, PJ (2002). Diffusion and diffusion tensor MR imaging. In Magnetic Resonance Imaging of the Brain and Spine, 3rd edn (ed. Atlas, S. W.), pp. 197214. Lippincott Williams & Wilkins: Philadelphia.Google Scholar
Beaulieu, C, Allen, PS (1994). Determinants of anisotropic water diffusion in nerves. Magnetic Resonance Medicine 31, 394400.Google Scholar
Bellani, M, Ferro, A, Brambilla, P (2010 a). The potential role of the parietal lobe in schizophrenia. Epidemiology and Psychiatric Sciences 19, 118119.Google Scholar
Bellani, M, Marzi, CA, Brambilla, P (2009). Interhemispheric communication in schizophrenia. Epidemiology and Psychiatric Sciences 18, 1922.Google Scholar
Bellani, M, Marzi, CA, Savazzi, S, Perlini, C, Cerruti, S, Ferro, A, Marinelli, V, Sponda, S, Rambaldelli, G, Tansella, M, Brambilla, P (2010 b). Laterality effects in schizophrenia and bipolar disorder. Experimental Brain Research 201, 339344.Google Scholar
Bogels, SM, Zigterman, D (2000). Dysfunctional cognitions in children with social phobia, separation anxiety disorder, and generalized anxiety disorder. Journal of Abnormal Child Psychology 28, 205211.Google Scholar
Bradley, BP, Mogg, K, Millar, N, White, J (1995). Selective processing of negative information: effects of clinical anxiety, concurrent depression, and awareness. Journal of Abnormal Psychology 104, 532536.Google Scholar
Brambilla, P, Bellani, M, Yeh, PH, Soares, JC, Tansella, M (2009). White matter connectivity in bipolar disorder. International Review of Psychiatry 21, 380386.Google Scholar
Brambilla, P, Cerini, R, Gasparini, A, Versace, A, Andreone, N, Vittorini, E, Barbui, C, Pelizza, L, Nose, M, Barlocco, L, Marrella, G, Gregis, M, Tournikioti, K, David, AS, Keshavan, MS, Tansella, M (2005). Investigation of corpus callosum in schizophrenia with diffusion imaging. Schizophrenia Research 79, 201210.Google Scholar
Brambilla, P, Nicoletti, M, Sassi, RB, Mallinger, AG, Frank, E, Keshavan, MS, Soares, JC (2004). Corpus callosum signal intensity in patients with bipolar and unipolar disorder. Journal of Neurology, Neurosurgery and Psychiatry 75, 221225.Google Scholar
Brambilla, P, Nicoletti, MA, Sassi, RB, Mallinger, AG, Frank, E, Kupfer, DJ, Keshavan, MS, Soares, JC (2003). Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder. Biological Psychiatry 54, 12941297.Google Scholar
Brambilla, P, Tansella, M (2007). The role of white matter for the pathophysiology of schizophrenia. International Review of Psychiatry 19, 459468.Google Scholar
Brantley, PJ, Mehan, DJ Jr., Ames, SC, Jones, GN (1999). Minor stressors and generalized anxiety disorder among low-income patients attending primary care clinics. Journal of Nervous and Mental Disorders 187, 435440.Google Scholar
Cannistraro, PA, Rauch, SL (2003). Neural circuitry of anxiety: evidence from structural and functional neuroimaging studies. Psychopharmacology Bulletin 37, 8–25.Google Scholar
Comer, JS, Blanco, C, Hasin, DS, Liu, SM, Grant, BF, Turner, JB, Olfson, M (2011). Health-related quality of life across the anxiety disorders: results from the national epidemiologic survey on alcohol and related conditions (NESARC). Journal of Clinical Psychiatry 72, 4350.Google Scholar
Constantinidis, C, Steinmetz, MA (2005). Posterior parietal cortex automatically encodes the location of salient stimuli. Journal of Neuroscience 25, 233238.Google Scholar
Cunnington, R, Windischberger, C, Robinson, S, Moser, E (2006). The selection of intended actions and the observation of others' actions: a time-resolved fMRI study. Neuroimage 29, 12941302.Google Scholar
Davidson, RJ, Abercrombie, H, Nitschke, JB, Putnam, K (1999). Regional brain function, emotion and disorders of emotion. Current Opinion on Neurobiology 9, 228234.Google Scholar
De Bellis, MD, Casey, BJ, Dahl, RE, Birmaher, B, Williamson, DE, Thomas, KM, Axelson, DA, Frustaci, K, Boring, AM, Hall, J, Ryan, ND (2000). A pilot study of amygdala volumes in pediatric generalized anxiety disorder. Biological Psychiatry 48, 5157.Google Scholar
De Bellis, MD, Keshavan, MS, Shifflett, H, Iyengar, S, Dahl, RE, Axelson, DA, Birmaher, B, Hall, J, Moritz, G, Ryan, ND (2002). Superior temporal gyrus volumes in pediatric generalized anxiety disorder. Biological Psychiatry 51, 553562.Google Scholar
Duncan, GE, Knapp, DJ, Breese, GR (1996). Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety. Brain Research 713, 7991.Google Scholar
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J (1976). The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766771.Google Scholar
Engels, AS, Heller, W, Mohanty, A, Herrington, JD, Banich, MT, Webb, AG, Miller, GA (2007). Specificity of regional brain activity in anxiety types during emotion processing. Psychophysiology 44, 352363.Google Scholar
Etkin, A, Prater, KE, Schatzberg, AF, Menon, V, Greicius, MD (2009). Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Archives of General Psychiatry 66, 13611372.Google Scholar
Fabri, M, Polonara, G, Mascioli, G, Salvolini, U, Manzoni, T (2011). Topographical organization of human corpus callosum: an fMRI mapping study. Brain Research 25, 99–111.Google Scholar
Fogassi, L, Ferrari, PF, Gesierich, B, Rozzi, S, Chersi, F, Rizzolatti, G (2005). Parietal lobe: from action organization to intention understanding. Science 308, 662667.Google Scholar
Gorman, JM, Hirschfeld, RM, Ninan, PT (2002). New developments in the neurobiological basis of anxiety disorders. Psychopharmacol Bulletin 36 (Suppl. 2), 4967.Google Scholar
Hamilton, M (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology 12, 5055.Google Scholar
Heller, W, Etienne, MA, Miller, GA (1995). Patterns of perceptual asymmetry in depression and anxiety: implications for neuropsychological models of emotion and psychopathology. Journal of Abnormal Psychology 104, 327333.Google Scholar
Heller, W, Nitschke, JB, Etienne, MA, Miller, GA (1997). Patterns of regional brain activity differentiate types of anxiety. Journal of Abnormal Psychology 106, 376385.Google Scholar
Jackson, GD, Duncan, JS (1996). MRI Anatomy: A New Angle on the Brain. Churchill Livingstone: New York.Google Scholar
Kessler, RC (2000). The epidemiology of pure and comorbid generalized anxiety disorder: a review and evaluation of recent research. Acta Psychiatrica Scandinavica Supplementum 406, 7–13.Google Scholar
Kitamura, H, Matsuzawa, H, Shioiri, T, Someya, T, Kwee, IL, Nakada, T (2005). Diffusion tensor analysis in chronic schizophrenia. A preliminary study on a high-field (3.0T) system. European Archives of Psychiatry and Clinical Neuroscience 255, 313318.Google Scholar
Kret, ME, Denollet, J, Grezes, J, de Gelder, B (2011). The role of negative affectivity and social inhibition in perceiving social threat: an fMRI study. Neuropsychologia 49, 11871193.Google Scholar
Kubicki, M, Styner, M, Bouix, S, Gerig, G, Markant, D, Smith, K, Kikinis, R, McCarley, RW, Shenton, ME (2008). Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum. Schizophrenia Research 106, 125131.Google Scholar
Kumra, S, Ashtari, M, McMeniman, M, Vogel, J, Augustin, R, Becker, DE, Nakayama, E, Gyato, K, Kane, JM, Lim, K, Szeszko, P (2004). Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study. Biological Psychiatry 55, 11381145.Google Scholar
Kyriakopoulos, M, Perez-Iglesias, R, Woolley, JB, Kanaan, RA, Vyas, NS, Barker, GJ, Frangou, S, McGuire, PK (2009). Effect of age at onset of schizophrenia on white matter abnormalities. British Journal of Psychiatry 195, 346353.Google Scholar
LaBar, KS, Gatenby, JC, Gore, JC, LeDoux, JE, Phelps, EA (1998). Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 20, 937945.Google Scholar
Lazar, M, Lee, JH, Alexander, AL (2005). Axial asymmetry of water diffusion in brain white matter. Magnetic Resonance Medicine 54, 860867.Google Scholar
Le Bihan, D, Mangin, JF, Poupon, C, Clark, CA, Pappata, S, Molko, N, Chabriat, H (2001). Diffusion tensor imaging: concepts and applications. Journal of Magnetic Resonance Imaging 13, 534546.Google Scholar
Legerstee, JS, Garnefski, N, Verhulst, FC, Utens, EM (2011). Cognitive coping in anxiety-disordered adolescents. Journal of Adolescence 34, 319326.Google Scholar
Lieb, R, Becker, E, Altamura, C (2005). The epidemiology of generalized anxiety disorder in Europe. European Neuropsychopharmacology 15, 445452.Google Scholar
Lim, L, Ng, TP, Chua, HC, Chiam, PC, Won, V, Lee, T, Fones, C, Kua, EH (2005). Generalised anxiety disorder in Singapore: prevalence, co-morbidity and risk factors in a multi-ethnic population. Social Psychiatry and Psychiatric Epidemiology 40, 972979.Google Scholar
Mathew, SJ, Mao, X, Coplan, JD, Smith, EL, Sackeim, HA, Gorman, JM, Shungu, DC (2004). Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 11191121.Google Scholar
Mathew, SJ, Price, RB, Mao, X, Smith, EL, Coplan, JD, Charney, DS, Shungu, DC (2008). Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder. Biological Psychiatry 63, 891898.Google Scholar
Mathew, SJ, Price, RB, Shungu, DC, Mao, X, Smith, EL, Amiel, JM, Coplan, JD (2010). A pilot study of the effects of chronic paroxetine administration on hippocampal N-acetylaspartate in generalized anxiety disorder. Journal of Psychopharmacology 24, 11751181.Google Scholar
McClure, EB, Monk, CS, Nelson, EE, Parrish, JM, Adler, A, Blair, RJ, Fromm, S, Charney, DS, Leibenluft, E, Ernst, M, Pine, DS (2007). Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Archives of General Psychiatry 64, 97–106.Google Scholar
Mengotti, P, D'Agostini, S, Terlevic, R, De Colle, C, Biasizzo, E, Londero, D, Ferro, A, Rambaldelli, G, Balestrieri, M, Zanini, S, Fabbro, F, Molteni, M, Brambilla, P (2011). Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study. Brain Research Bulletin 1, 189195.Google Scholar
Mohlman, J, Price, RB, Eldreth, DA, Chazin, D, Glover, DM, Kates, WR (2009). The relation of worry to prefrontal cortex volume in older adults with and without generalized anxiety disorder. Psychiatry Research 173, 121127.Google Scholar
Monk, CS, Nelson, EE, McClure, EB, Mogg, K, Bradley, BP, Leibenluft, E, Blair, RJ, Chen, G, Charney, DS, Ernst, M, Pine, DS (2006). Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. American Journal of Psychiatry 163, 10911097.Google Scholar
Monk, CS, Telzer, EH, Mogg, K, Bradley, BP, Mai, X, Louro, HM, Chen, G, McClure-Tone, EB, Ernst, M, Pine, DS (2008). Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Archives of General Psychiatry 65, 568576.Google Scholar
Nusbaum, AO, Tang, CY, Wei, T, Buchsbaum, MS, Atlas, SW (2000). Whole-brain diffusion MR histograms differ between MS subtypes. Neurology 54, 14211427.Google Scholar
Nutt, D, Argyropoulos, S, Hood, S, Potokar, J (2006). Generalized anxiety disorder: a comorbid disease. European Neuropsychopharmacology 16 (Suppl. 2), S109S118.Google Scholar
Nutt, DJ, Ballenger, JC, Sheehan, D, Wittchen, HU (2002). Generalized anxiety disorder: comorbidity, comparative biology and treatment. Internationl Journal of Neuropsychopharmacology 5, 315325.Google Scholar
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.Google Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.Google Scholar
Pasternak, O, Sochen, N, Gur, Y, Intrator, N, Assaf, Y (2009). Free water elimination and mapping from diffusion MRI. Magnetic Resonance Medicine 62, 717730.Google Scholar
Patel, VH, Friedman, L (1997). MRI of the Brain: Normal Anatomy and Normal Variants. W. B. Saunders Co.: Philadelphia.Google Scholar
Paulesu, E, Sambugaro, E, Torti, T, Danelli, L, Ferri, F, Scialfa, G, Sberna, M, Ruggiero, GM, Bottini, G, Sassaroli, S (2010). Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychological Medicine 40, 117124.Google Scholar
Pfefferbaum, A, Sullivan, EV, Carmelli, D (2001). Genetic regulation of regional microstructure of the corpus callosum in late life. Neuroreport 12, 16771681.Google Scholar
Saxe, R, Xiao, DK, Kovacs, G, Perrett, DI, Kanwisher, N (2004). A region of right posterior superior temporal sulcus responds to observed intentional actions. Neuropsychologia 42, 14351446.Google Scholar
Stapleton, JM, Morgan, MJ, Liu, X, Yung, BC, Phillips, RL, Wong, DF, Shaya, EK, Dannals, RF, London, ED (1997). Cerebral glucose utilization is reduced in second test session. Journal of Cerebral Blood Flow and Metabolism 17, 704712.Google Scholar
Sun, Z, Wang, F, Cui, L, Breeze, J, Du, X, Wang, X, Cong, Z, Zhang, H, Li, B, Hong, N, Zhang, D (2003). Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study. Neuroreport 14, 18331836.Google Scholar
Taylor, WD, Kuchibhatla, M, Payne, ME, Macfall, JR, Sheline, YI, Krishnan, KR, Doraiswamy, PM (2008). Frontal white matter anisotropy and antidepressant remission in late-life depression. PLoS One 3, e3267.Google Scholar
Thomas, KM, Drevets, WC, Dahl, RE, Ryan, ND, Birmaher, B, Eccard, CH, Axelson, D, Whalen, PJ, Casey, BJ (2001). Amygdala response to fearful faces in anxious and depressed children. Archives of General Psychiatry 58, 10571063.Google Scholar
Ventura, J, Nuechterlein, KH, Subotnik, KL, Gutkind, D, Gilbert, EA (2000). Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale. Psychiatry Research 97, 129135.Google Scholar
Vistoli, D, Brunet-Gouet, E, Lemoalle, A, Hardy-Bayle, MC, Passerieux, C (2011). Abnormal temporal and parietal magnetic activations during the early stages of theory of mind in schizophrenic patients. Social Neuroscience 6, 316326.Google Scholar
Wells, A (1999). A cognitive model of generalized anxiety disorder. Behavioral Modifications 23, 526555.Google Scholar
Whalen, PJ, Johnstone, T, Somerville, LH, Nitschke, JB, Polis, S, Alexander, AL, Davidson, RJ, Kalin, NH (2008). A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biological Psychiatry 63, 858863.Google Scholar
White, T, Magnotta, VA, Bockholt, HJ, Williams, S, Wallace, S, Ehrlich, S, Mueller, BA, Ho, BC, Jung, RE, Clark, VP, Lauriello, J, Bustillo, JR, Schulz, SC, Gollub, RL, Andreasen, NC, Calhoun, VD, Lim, KO (2011). Global white matter abnormalities in schizophrenia: a multisite diffusion tensor imaging study. Schizophrenia Bulletin 37, 222232.Google Scholar
Whitford, TJ, Kubicki, M, Schneiderman, JS, O'Donnell, LJ, King, R, Alvarado, JL, Khan, U, Markant, D, Nestor, PG, Niznikiewicz, M, McCarley, RW, Westin, CF, Shenton, ME (2010). Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia. Biological Psychiatry 68, 7077.Google Scholar
Witelson, SF (1989). Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. Brain 112, 799835.Google Scholar
Witte, EA, Villareal, M, Marrocco, RT (1996). Visual orienting and alerting in rhesus monkeys: comparison with humans. Behavioral Brain Research 82, 103112.Google Scholar
Wolkin, A, Choi, SJ, Szilagyi, S, Sanfilipo, M, Rotrosen, JP, Lim, KO (2003). Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. American Journal of Psychiatry 160, 572574.Google Scholar
Wu, JC, Buchsbaum, MS, Hershey, TG, Hazlett, E, Sicotte, N, Johnson, JC (1991). PET in generalized anxiety disorder. Biological Psychiatry 29, 11811199.Google Scholar
Wu, YC, Field, AS, Chung, MK, Badie, B, Alexander, AL (2004). Quantitative analysis of diffusion tensor orientation: theoretical framework. Magnetic Resonance Medicine 52, 11461155.Google Scholar