Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders

David L. Perez, Department of Neurology, Functional Neurology Research Group, Cognitive Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nassim Matin, Department of Neurology, Functional Neurology Research Group, Cognitive Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.Follow
Arthur Barsky, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Victor Costumero-Ramos, Department of Methodology, University of Valencia, Valencia, Spain.
Sara J. Makaretz, Department of Neurology, Functional Neurology Research Group, Cognitive Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sigrid S. Young, Department of Neurology, Functional Neurology Research Group, Cognitive Behavioral Neurology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jorge Sepulcre, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
W Curt LaFrance, Neuropsychiatry and Behavioral Neurology Division, Departments of Psychiatry and Neurology, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Matcheri S. Keshavan, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Bradford C. Dickerson, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Document Type

Article

Abstract

OBJECTIVE: Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. METHODS: This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. RESULTS: Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. CONCLUSIONS: This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified.

Medical Subject Headings

Adult; Cerebral Cortex (diagnostic imaging, physiopathology); Child; Child Abuse (diagnosis, psychology); Conversion Disorder (diagnostic imaging, physiopathology, psychology); Dominance, Cerebral (physiology); Female; Gray Matter (diagnostic imaging); Gyrus Cinguli (diagnostic imaging, physiopathology); Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Life Change Events; Magnetic Resonance Imaging; Male; Middle Aged; Nervous System Diseases (diagnostic imaging, physiopathology, psychology); Organ Size (physiology); Psychophysiologic Disorders (diagnostic imaging, physiopathology, psychology); Statistics as Topic; Stress Disorders, Post-Traumatic (diagnosis, diagnostic imaging, physiopathology, psychology)

Publication Date

6-1-2017

Publication Title

Journal of neurology, neurosurgery, and psychiatry

E-ISSN

1468-330X

Volume

88

Issue

6

First Page

491

Last Page

497

PubMed ID

28416565

Digital Object Identifier (DOI)

10.1136/jnnp-2016-314998

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