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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
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Eleonora Maggioni
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
Filippo Cecchetto
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
Scientific Institute IRCCS ‘Eugenio Medea’, Polo FVG, San Vito al Tagliamento, Pordenone, Italy
Sara Piccin
Scientific Institute IRCCS ‘Eugenio Medea’, Polo FVG, San Vito al Tagliamento, Pordenone, Italy
Carolina Bonivento
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Marta Maieron
Department of Physics, Azienda Ospedaliero Universitaria ‘S.Maria della Misericordia’, Udine, Italy
Serena D'Agostini
Department of Neuroradiology, Azienda Ospedaliero Universitaria ‘S.Maria della Misericordia’, Udine, Italy
Matteo Balestrieri
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
Giampaolo Perna
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
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
Paolo Brambilla*
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:



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.


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.


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.


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.

Original Articles
Copyright © Cambridge University Press 2017 

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The two authors contributed equally to the study.


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