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Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study

Published online by Cambridge University Press:  07 May 2009

E. Paulesu*
Affiliation:
Psychology Department, University of Milano Bicocca, Milano, Italy
E. Sambugaro
Affiliation:
Psychology Department, University of Milano Bicocca, Milano, Italy
T. Torti
Affiliation:
Psychology Department, University of Milano Bicocca, Milano, Italy
L. Danelli
Affiliation:
Psychology Department, University of Milano Bicocca, Milano, Italy
F. Ferri
Affiliation:
Psychology Department, University of Milano Bicocca, Milano, Italy
G. Scialfa
Affiliation:
Neuroradiology Department, Niguarda Cà Granda Hospital, Milano, Italy
M. Sberna
Affiliation:
Neuroradiology Department, Niguarda Cà Granda Hospital, Milano, Italy
G. M. Ruggiero
Affiliation:
‘Psicoterapia Cognitiva e Ricerca’ and ‘Studi Cognitivi’, Postgraduate Cognitive Psychotherapy Schools and Research Centres, Milano, Italy
G. Bottini
Affiliation:
Psychology Department, University of Pavia, Pavia, Italy Cognitive Neuropsychology Department, Niguarda Cà Granda Hospital, Milano, Italy
S. Sassaroli
Affiliation:
‘Psicoterapia Cognitiva e Ricerca’ and ‘Studi Cognitivi’, Postgraduate Cognitive Psychotherapy Schools and Research Centres, Milano, Italy
*
*Address for correspondence: Professor E. Paulesu, Psychology Department, University of Milano Bicocca, Piazza Ateneo Nuovo 1, 20126 Milan, Italy. (Email: eraldo.paulesu@unimib.it)

Abstract

Background

Worry is considered a key feature of generalized anxiety disorder (GAD), whose neural correlates are poorly understood. It is not known whether the brain regions involved in pathological worry are similar to those involved in worry-like mental activity in normal subjects or whether brain areas associated with worry are the same for different triggers such as verbal stimuli or faces. This study was designed to clarify these issues.

Method

Eight subjects with GAD and 12 normal controls underwent functional magnetic resonance imaging (fMRI) mood induction paradigms based on spoken sentences or faces. Sentences were either neutral or designed to induce worry. Faces conveyed a sad or a neutral mood and subjects were instructed to empathize with those moods.

Results

We found that the anterior cingulate and dorsal medial prefrontal cortex [Brodmann area (BA) 32/23 and BA 10/11] were associated with worry triggered by sentences in both subjects with GAD and normal controls. However, GAD subjects showed a persistent activation of these areas even during resting state scans that followed the worrying phase, activation that correlated with scores on the Penn State Worry Questionnaire (PSWQ). This region was activated during the empathy experiment for sad faces.

Conclusions

The results show that worry in normal subjects and in subjects with GAD is based on activation of the medial prefrontal and anterior cingulate regions, known to be involved in mentalization and introspective thinking. A dysregulation of the activity of this region and its circuitry may underpin the inability of GAD patients to stop worrying.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2009

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References

Alex, KD, Pehek, EA (2007). Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacology and Therapeutics 113, 296320.Google Scholar
APA (1994). Diagnostic and Statistic Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Beck, AT, Emery, G, Greenberg, RL (1985). Anxiety Disorders and Phobias: A Cognitive Perspective. Basic Books: New York.Google Scholar
Behar, E, Alcaine, O, Zuellig, AR, Borkovec, TD (2003). Screening for generalized anxiety disorder using the Penn State Worry Questionnaire: a receiver operating characteristic analysis. Journal of Behavior Therapy and Experimental Psychiatry 34, 2543.Google Scholar
Borkovec, TD (1994). The nature, functions, and origins of worry. In Worrying: Perspectives on Theory, Assessment and Treatment (ed. Davey, G. and Tallis, F.), pp. 533. Wiley: Chichester, UK.Google Scholar
Borkovec, TD, Inz, J (1990). The nature of worry in generalized anxiety disorder: a predominance of thought activity. Behaviour Research and Therapy 28, 153158.Google Scholar
Borkovec, TD, Ray, WJ, Stober, J (1998). Worry: a cognitive phenomenon intimately linked to affective, physiological, and interpersonal behavioral processes. Cognitive Therapy and Research 22, 561576.Google Scholar
Brown, TA, O'Leary, TA, Barlow, DH (2001). Generalised anxiety disorder. In Clinical Handbook of Psychological Disorders: A Step-by-Step Treatment Manual (ed. Barlow, I. D. H.), pp. 154208. Guilford Press: New York.Google Scholar
Dinstein, I, Thomas, C, Behrmann, M, Heeger, DJ (2008). A mirror up to nature. Current Biology 18, R13R18.Google Scholar
Frankle, WG, Laruelle, M, Haber, SN (2006). Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection. Neuropsychopharmacology 31, 16271636.Google Scholar
Fresco, DM, Frankel, AN, Mennin, DS, Turk, CL, Heimberg, RG (2002). Distinct and overlapping features of rumination and worry: the relationship of cognitive production to negative affective states. Cognitive Therapy and Research 26, 179188.Google Scholar
Fresco, DM, Mennin, DS, Heimberg, RG, Turk, CL (2003). Using the Penn State Worry Questionnaire to identify individuals with generalized anxiety disorder: a receiver operating characteristic analysis. Journal of Behavior Therapy and Experimental Psychiatry 34, 283291.Google Scholar
Frison, L, Pocock, SJ (1992). Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Statistics in Medicine 11, 16851704.Google Scholar
Friston, KJ, Frith, CD, Turner, R, Frackowiak, RS (1995). Characterizing evoked hemodynamics with fMRI. Neuroimage 2, 157165.Google Scholar
Friston, KJ, Holmes, AP, Worsley, KJ (1999). How many subjects constitute a study? Neuroimage 10, 15.Google Scholar
Frith, CD, Frith, U (1999). Interacting minds: a biological basis. Science 286, 16921695.Google Scholar
Frith, CD, Frith, U (2006). The neural basis of mentalizing. Neuron 50, 531534.Google Scholar
Gallese, V, Fadiga, L, Fogassi, L, Rizzolatti, G (1996). Action recognition in the premotor cortex. Brain 119, 593609.Google Scholar
Hoehn-Saric, R, McLeod, DR, Zimmerli, WD (1988). Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms. Journal of Clinical Psychiatry 49, 293301.Google Scholar
Hoehn-Saric, R, Schlund, MW, Wong, SH (2004). Effects of citalopram on worry and brain activation in patients with generalized anxiety disorder. Psychiatry Research 131, 1121.Google Scholar
Iacoboni, M, Woods, RP, Brass, M, Bekkering, H, Mazziotta, JC, Rizzolatti, G (1999). Cortical mechanisms of human imitation. Science 286, 25262528.Google Scholar
Meyer, TJ, Miller, ML, Metzger, RL, Borkovec, TD (1990). Development and validation of the Penn State Worry Questionnaire. Behaviour Research and Therapy 28, 487495.Google Scholar
Newman, MG, Zuellig, AR, Kachin, KE, Constantino, MJ, Przeworski, A, Erickson, T, Cashman-McGrath, L (2002). Preliminary reliability and validity of the Generalized Anxiety Disorder Questionnaire-IV: a revised self-report diagnostic measure of generalized anxiety disorder. Behavior Therapy 33, 215233.Google Scholar
Pollack, MH, Zaninelli, R, Goddard, A, McCafferty, JP, Bellew, KM, Burnham, DB, Iyengar, MK (2001). Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. Journal of Clinical Psychiatry 62, 350357.Google Scholar
Pratt, P, Tallis, F, Eysenck, M (1997). Information-processing, storage characteristics and worry. Behaviour Research and Therapy 35, 10151023.Google Scholar
Ramnani, N, Owen, AM (2004). Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nature Reviews Neuroscience 5, 184194.Google Scholar
Schönpflug, W (1989). Anxiety, worry, prospective orientation, and prevention. In Stress and Anxiety (ed. Spielberger, C. D. and Sarason, I. G.), pp. 245258. Hemisphere: Washington, DC.Google Scholar
Segerstrom, SC, Tsao, JCI, Alden, LE, Craske, MG (2000). Worry and rumination: repetitive thought as a concomitant and predictor of negative mood. Cognitive Therapy and Research 24, 671688.Google Scholar
Watkins, E, Moulds, M, Mackintosh, B (2005). Comparisons between rumination and worry in a non-clinical population. Behaviour Research and Therapy 43, 15771585.Google Scholar
Williams, SM, Goldman-Rakic, PS (1998). Widespread origin of the primate mesofrontal dopamine system. Cerebral Cortex 8, 321345.Google Scholar