Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-23T00:27:35.308Z Has data issue: false hasContentIssue false
  • English
  • Français

Reduced cortical thickness and increased gyrification in generalized anxiety disorder: a 3 T MRI study

Published online by Cambridge University Press:  14 December 2017

Cinzia Molent ,
Eleonora Maggioni ,
Filippo Cecchetto ,
Marco Garzitto ,
Sara Piccin ,
Carolina Bonivento ,
Marta Maieron ,
Serena D'Agostini ,
Matteo Balestrieri  and
Giampaolo Perna
...Show all authors
Cinzia Molent
Affiliation:
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Eleonora Maggioni
Affiliation:
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
Filippo Cecchetto
Affiliation:
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy Department of Clinical Neurosciences, Villa San Benedetto Menni, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Como, Italy
Marco Garzitto
Affiliation:
Scientific Institute IRCCS ‘Eugenio Medea’, Polo FVG, San Vito al Tagliamento, Pordenone, Italy
Sara Piccin
Affiliation:
Scientific Institute IRCCS ‘Eugenio Medea’, Polo FVG, San Vito al Tagliamento, Pordenone, Italy
Carolina Bonivento
Affiliation:
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Marta Maieron
Affiliation:
Department of Physics, Azienda Ospedaliero Universitaria ‘S.Maria della Misericordia’, Udine, Italy
Serena D'Agostini
Affiliation:
Department of Neuroradiology, Azienda Ospedaliero Universitaria ‘S.Maria della Misericordia’, Udine, Italy
Matteo Balestrieri
Affiliation:
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Giampaolo Perna
Affiliation:
Department of Clinical Neurosciences, Villa San Benedetto Menni, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Como, Italy Research Institute of Mental Health and Neuroscience and Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, Netherlands Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami, USA
A. Carlo Altamura
Affiliation:
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
Paolo Brambilla*
Affiliation:
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA
*
Author for correspondence: Prof. Paolo Brambilla, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD.

Methods

A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs.

Results

Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed.

Conclusions

Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Keywords

Cortical surface areafrontal gyrusfusiform gyrusgray matterMRIparietal gyrustemporal gyrus
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 12 , September 2018 , pp. 2001 - 2010
Copyright
Copyright © Cambridge University Press 2017 

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.)

Footnotes

*

The two authors contributed equally to the study.

References

Abdallah, CG, Coplan, JD, Jackowski, A, Sato, JR, Mao, X, Shungu, DC et al. (2012) Riluzole effect on occipital cortex: a structural and spectroscopy pilot study. Neuroscience Letters 530, 103–107.Google Scholar
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: Author.Google Scholar
Andreescu, C, Sheu, LK, Tudorascu, D, Walker, S and Aizenstein, H (2014) The ages of anxiety--differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder. International Journal of Geriatric Psychiatry 29, 704–712.Google Scholar
Blair, K, Shaywitz, J, Smith, BW, Rhodes, R, Geraci, M, Jones, M et al. (2008) Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. American Journal of Psychiatry 165, 1193–1202.Google Scholar
Bourgeois, JP and Rakic, P (1993) Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage. Journal of Neuroscience 13, 2801–2820.Google Scholar
Brambilla, P, Como, G, Isola, M, Taboga, F, Zuliani, R, Goljevscek, S et al. (2012) White-matter abnormalities in the right posterior hemisphere in generalized anxiety disorder: a diffusion imaging study. Psychological Medicine 42, 427–434.Google Scholar
Canu, E, Kostic, M, Agosta, F, Munjiza, A, Ferraro, PM, Pesic, D et al. (2015) Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity. Journal of Neurology 262, 1255–1265.Google Scholar
Cha, J, Greenberg, T, Carlson, JM, Dedora, DJ, Hajcak, G and Mujica-Parodi, LR (2014) Circuit-wide structural and functional measures predict ventromedial prefrontal cortex fear generalization: implications for generalized anxiety disorder. Journal of Neuroscience 34, 4043–4053.Google Scholar
D'urso, G, Brunoni, AR, Mazzaferro, MP, Anastasia, A, De Bartolomeis, A and Mantovani, A (2016) Transcranial direct current stimulation for obsessive-compulsive disorder: a randomized, controlled, partial crossover trial. Depression and Anxiety 33, 1132–1140.Google Scholar
Davidson, RJ and Irwin, W (1999) The functional neuroanatomy of emotion and affective style. Trends in Cognitive Sciences 3, 11–21.Google Scholar
De Bellis, MD, Keshavan, MS, Shifflett, H, Iyengar, S, Dahl, RE, Axelson, DA et al. (2002) Superior temporal gyrus volumes in pediatric generalized anxiety disorder. Biological Psychiatry 51, 553–562.Google Scholar
Desikan, RS, Segonne, F, Fischl, B, Quinn, BT, Dickerson, BC, Blacker, D et al. (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31, 968–980.Google Scholar
Dosenbach, NU, Fair, DA, Cohen, AL, Schlaggar, BL and Petersen, SE (2008) A dual-networks architecture of top-down control. Trends in Cognitive Sciences 12, 99–105.Google Scholar
Ducharme, S, Albaugh, MD, Hudziak, JJ, Botteron, KN, Nguyen, TV, Truong, C et al. Brain Development Cooperative G (2014) Anxious/depressed symptoms are linked to right ventromedial prefrontal cortical thickness maturation in healthy children and young adults. Cerebral Cortex 24, 2941–2950.Google Scholar
Endicott, J, Spitzer, RL, Fleiss, JL and Cohen, J (1976) The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766–771.Google Scholar
Etkin, A, Prater, KE, Schatzberg, AF, Menon, V and Greicius, MD (2009) Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Archives of General Psychiatry 66, 1361–1372.Google Scholar
Fischl, B (2012) Freesurfer. NeuroImage 62, 774–781.Google Scholar
Fonzo, GA, Ramsawh, HJ, Flagan, TM, Simmons, AN, Sullivan, SG, Allard, CB et al. (2016) Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood. Psychological Medicine 46, 1037–1054.Google Scholar
Fonzo, GA, Ramsawh, HJ, Flagan, TM, Sullivan, SG, Letamendi, A, Simmons, AN et al. (2015) Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders. British Journal of Psychiatry 206, 206–215.Google Scholar
Frick, A, Howner, K, Fischer, H, Eskildsen, SF, Kristiansson, M and Furmark, T (2013) Cortical thickness alterations in social anxiety disorder. Neuroscience Letters 536, 52–55.Google Scholar
Gerrits, NJ, Van Loenhoud, AC, Van Den Berg, SF, Berendse, HW, Foncke, EM, Klein, M et al. (2016) Cortical thickness, surface area and subcortical volume differentially contribute to cognitive heterogeneity in parkinson's disease. PLoS ONE 11, e0148852.Google Scholar
Greenberg, T, Carlson, JM, Cha, J, Hajcak, G and Mujica-Parodi, LR (2013) Ventromedial prefrontal cortex reactivity is altered in generalized anxiety disorder during fear generalization. Depression and Anxiety 30, 242–250.Google Scholar
Greicius, MD, Krasnow, B, Reiss, AL and Menon, V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences USA 100, 253–258.Google Scholar
Hamilton, M (1959) The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 50–55.Google Scholar
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 56–62.Google Scholar
Heller, W, Nitschke, JB, Etienne, MA and Miller, GA (1997) Patterns of regional brain activity differentiate types of anxiety. Journal of Abnormal Psychology 106, 376–385.Google Scholar
Hettema, JM, Neale, MC and Kendler, KS (2001 a). A review and meta-analysis of the genetic epidemiology of anxiety disorders. American Journal of Psychiatry 158, 1568–1578.Google Scholar
Hettema, JM, Prescott, CA and Kendler, KS (2001 b). A population-based twin study of generalized anxiety disorder in men and women. The Journal of Nervous and Mental Disease 189, 413–420.Google Scholar
Hilbert, K, Lueken, U and Beesdo-Baum, K (2014) Neural structures, functioning and connectivity in generalized anxiety disorder and interaction with neuroendocrine systems: a systematic review. Journal of Affective Disorders 158, 114–126.Google Scholar
Hilbert, K, Pine, DS, Muehlhan, M, Lueken, U, Steudte-Schmiedgen, S and Beesdo-Baum, K (2015) Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization. Psychiatry Research: Neuroimaging 234, 314–320.Google Scholar
Hogstrom, LJ, Westlye, LT, Walhovd, KB and Fjell, AM (2013) The structure of the cerebral cortex across adult life: age-related patterns of surface area, thickness, and gyrification. Cerebral Cortex 23, 2521–2530.Google Scholar
Holzel, BK, Hoge, EA, Greve, DN, Gard, T, Creswell, JD, Brown, KW et al. (2013) Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training. Neuroimage: Clinical 2, 448–458.Google Scholar
Kalu, UG, Sexton, CE, Loo, CK and Ebmeier, KP (2012) Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychological Medicine 42, 1791–1800.Google Scholar
Kessler, RC, Petukhova, M, Sampson, NA, Zaslavsky, AM and Wittchen, HU (2012) Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research 21, 169–184.Google Scholar
Kuhn, S, Schubert, F and Gallinat, J (2011) Structural correlates of trait anxiety: reduced thickness in medial orbitofrontal cortex accompanied by volume increase in nucleus accumbens. Journal of Affective Disorders 134, 315–319.Google Scholar
Ladouceur, R, Gosselin, P and Dugas, MJ (2000) Experimental manipulation of intolerance of uncertainty: a study of a theoretical model of worry. Behaviour Research and Therapy 38, 933–941.Google Scholar
Lueken, U, Leisse, M, Mattes, K, Naumann, D, Wittling, W and Schweiger, E (2009) Altered tonic and phasic cortisol secretion following unilateral stroke. Psychoneuroendocrinology 34, 402–412.Google Scholar
Mainio, A, Hakko, H, Niemela, A, Tuurinkoski, T, Koivukangas, J and Rasanen, P (2003) The effect of brain tumour laterality on anxiety levels among neurosurgical patients. Journal of Neurology, Neurosurgery & Psychiatry 74, 1278–1282.Google Scholar
Makovac, E, Meeten, F, Watson, DR, Garfinkel, SN, Critchley, HD and Ottaviani, C (2016 a). Neurostructural abnormalities associated with axes of emotion dysregulation in generalized anxiety. Neuroimage: Clinical 10, 172–181.Google Scholar
Makovac, E, Meeten, F, Watson, DR, Herman, A, Garfinkel, SN, DC, H et al. (2016 b). Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder. Biological Psychiatry 80, 786–795.Google Scholar
Mclean, CP, Asnaani, A, Litz, BT and Hofmann, SG (2011) Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. Journal of Psychiatric Research 45, 1027–1035.Google Scholar
Mennin, DS, Heimberg, RG, Fresco, DM and Ritter, MR (2008) Is generalized anxiety disorder an anxiety or mood disorder? Considering multiple factors as we ponder the fate of GAD. Depression and Anxiety 25, 289–299.Google Scholar
Mochcovitch, MD, Da Rocha Freire, RC, Garcia, RF and Nardi, AE (2014) A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis. Journal of Affective Disorders 167, 336–342.Google Scholar
Mohlman, J, Price, RB, Eldreth, DA, Chazin, D, Glover, DM and Kates, WR (2009) The relation of worry to prefrontal cortex volume in older adults with and without generalized anxiety disorder. Psychiatry Research: Neuroimaging 173, 121–127.Google Scholar
Moon, CM and Jeong, GW (2015) Functional neuroanatomy on the working memory under emotional distraction in patients with generalized anxiety disorder. Psychiatry and Clinical Neurosciences 69, 609–619.Google Scholar
Moon, CM and Jeong, GW (2016) Brain morphological alterations and cellular metabolic changes in patients with generalized anxiety disorder: a combined DARTEL-based VBM and (1)H-MRS study. Magnetic Resonance Imaging 34, 429–436.Google Scholar
Morrison, JH and Hof, PR (1997) Life and death of neurons in the aging brain. Science 278, 412–419.Google Scholar
Mutlu, AK, Schneider, M, Debbane, M, Badoud, D, Eliez, S, and Schaer, M (2013) Sex differences in thickness, and folding developments throughout the cortex. NeuroImage 82, 200–207.Google Scholar
Nixon, NL, Liddle, PF, Nixon, E, Worwood, G, Liotti, M and Palaniyappan, L (2014) Biological vulnerability to depression: linked structural and functional brain network findings. British Journal of Psychiatry 204, 283–289.Google Scholar
Noesselt, T, Driver, J, Heinze, HJ and Dolan, R (2005) Asymmetrical activation in the human brain during processing of fearful faces. Current Biology 15, 424–429.Google Scholar
Oldfield, RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.Google Scholar
Palm, ME, Elliott, R, Mckie, S, Deakin, JF and Anderson, IM (2011) Attenuated responses to emotional expressions in women with generalized anxiety disorder. Psychological Medicine 41, 1009–1018.Google Scholar
Park, JI, Kim, GW, Jeong, GW, Chung, GH and Yang, JC (2016) Brain activation patterns associated with the effects of emotional distracters during working memory maintenance in patients with generalized anxiety disorder. Psychiatry Investigation 13, 152–156.Google Scholar
Peng, D, Shi, F, Li, G, Fralick, D, Shen, T, Qiu, M et al. (2015) Surface vulnerability of cerebral cortex to major depressive disorder. PLoS ONE 10, e0120704.Google Scholar
Rakic, P (2009) Evolution of the neocortex: a perspective from developmental biology. Nature Reviews Neuroscience 10, 724–735.Google Scholar
Raven, J (2000) The raven's progressive matrices: change and stability over culture and time. Cognitive Psychology 41, 1–48.Google Scholar
Raznahan, A, Shaw, P, Lalonde, F, Stockman, M, Wallace, GL, Greenstein, D et al. (2011) How does your cortex grow? Journal of Neuroscience 31, 7174–7177.Google Scholar
Schaer, M, Ottet, MC, Scariati, E, Dukes, D, Franchini, M, Eliez, S et al. (2013) Decreased frontal gyrification correlates with altered connectivity in children with autism. Frontiers in Human Neuroscience 7, 750.Google Scholar
Schienle, A, Ebner, F and Schafer, A (2011) Localized gray matter volume abnormalities in generalized anxiety disorder. European Archives of Psychiatry and Clinical Neuroscience 261, 303–307.Google Scholar
Schlund, MW, Verduzco, G, Cataldo, MF and Hoehn-Saric, R (2012) Generalized anxiety modulates frontal and limbic activation in major depression. Behavioral and Brain Functions 8, 8.Google Scholar
Shaw, P, Kabani, NJ, Lerch, JP, Eckstrand, K, Lenroot, R, Gogtay, N et al. (2008) Neurodevelopmental trajectories of the human cerebral cortex. Journal of Neuroscience 28, 3586–3594.Google Scholar
Shiozawa, P, Leiva, AP, Castro, CD, Da Silva, ME, Cordeiro, Q, Fregni, F et al. (2014) Transcranial direct current stimulation for generalized anxiety disorder: a case study. Biological Psychiatry 75, e17–e18.Google Scholar
Sowell, ER, Thompson, PM, Leonard, CM, Welcome, SE, Kan, E and Toga, AW (2004) Longitudinal mapping of cortical thickness and brain growth in normal children. Journal of Neuroscience 24, 8223–8231.Google Scholar
Strawn, JR, Bitter, SM, Weber, WA, Chu, WJ, Whitsel, RM, Adler, C et al. (2012) Neurocircuitry of generalized anxiety disorder in adolescents: a pilot functional neuroimaging and functional connectivity study. Depression and Anxiety 29, 939–947.Google Scholar
Strawn, JR, John Wegman, C, Dominick, KC, Swartz, MS, Wehry, AM, Patino, LR et al. (2014) Cortical surface anatomy in pediatric patients with generalized anxiety disorder. Journal of Anxiety Disorders 28, 717–723.Google Scholar
Strawn, JR, Wehry, AM, Chu, WJ, Adler, CM, Eliassen, JC, Cerullo, MA et al. (2013) Neuroanatomic abnormalities in adolescents with generalized anxiety disorder: a voxel-based morphometry study. Depression and Anxiety 30, 842–848.Google Scholar
Su, S, White, T, Schmidt, M, Kao, CY and Sapiro, G (2013) Geometric computation of human gyrification indexes from magnetic resonance images. Human Brain Mapping 34, 1230–1244.Google Scholar
Syal, S, Hattingh, CJ, Fouche, JP, Spottiswoode, B, Carey, PD, Lochner, C et al. (2012) Grey matter abnormalities in social anxiety disorder: a pilot study. Metabolic Brain Disease 27, 299–309.Google Scholar
Sylvester, CM, Corbetta, M, Raichle, ME, Rodebaugh, TL, Schlaggar, BL, Sheline, YI et al. (2012) Functional network dysfunction in anxiety and anxiety disorders. Trends in Neurosciences 35, 527–535.Google Scholar
Vanderhaeghen, P and Cheng, HJ (2010) Guidance molecules in axon pruning and cell death. Cold Spring Harbor Perspectives in Biology 2, a001859.Google Scholar
Van Essen, DC (1997) A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385, 313–318.Google Scholar
Ventura, J, Nuechterlein, KH, Subotnik, KL, Gutkind, D and 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, 129–135.Google Scholar
Watson, D (2005) Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V. Journal of Abnormal Psychology 114, 522–536.Google Scholar
White, T, Su, S, Schmidt, M, Kao, CY and Sapiro, G (2010) The development of gyrification in childhood and adolescence. Brain and Cognition 72, 36–45.Google Scholar
Zhang, Y, Li, L, Yu, R, Liu, J, Tang, J, Tan, L et al. (2013) White matter integrity alterations in first episode, treatment-naive generalized anxiety disorder. Journal of Affective Disorders 148, 196–201.Google Scholar
Supplementary material: File

Molent et al. supplementary material

Molent et al. supplementary material 1

Download Molent et al. supplementary material(File)
File 95.1 KB