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7. White matter microstructure and its relation to clinical features of obsessive–compulsive disorder: findings from the ENIGMA OCD Working Group

Author

Piras F., Abe Y., Agarwal S. M., Anticevic A., Ameis S., Arnold P., Banaj N., Bargallo N., Batistuzzo M. C., Benedetti F., Beucke J. -C., Boedhoe P. S. W., Bollettini I., Brem S., Calvo A., Cho K. I. K., Ciullo V., Dallaspezia S., Dickie E., Ely B. A., Fan S., Fouche J. -P., Gruner P., Gursel D. A., Hauser T., Hirano Y., Hoexter M. Q., Iorio M., James A., Reddy Y. C. J., Kaufmann C., Koch K., Kochunov P., Kwon J. S., Lazaro L., Lochner C., Marsh R., Nakagawa A., Nakamae T., Narayanaswamy J. C., Sakai Y., Shimizu E., Simon D., Simpson H. B., Soreni N., Stampfli P., Stern E. R., Szeszko P., Takahashi J., Venkatasubramanian G., Wang Z., Yun J. -Y., Assogna F., Calvo R., Wit S. J., Hough M., Kuno M., Miguel E. C., Morer A., Pittenger C., Poletti S., Smeraldi E., Sato J. R., Tsuchiyagaito A., Walitza S., van der Werf Y. D., Vecchio D., Zarei M., Stein D. J., Jahanshad N., Thompson P. M., van den Heuvel O. A., Spalletta G., Piras, F., Abe, Y., Agarwal, S. M., Anticevic, A., Ameis, S., Arnold, P., Banaj, N., Bargallo, N., Batistuzzo, M. C., Benedetti, F., Beucke, J. -C., Boedhoe, P. S. W., Bollettini, I., Brem, S., Calvo, A., Cho, K. I. K., Ciullo, V., Dallaspezia, S., Dickie, E., Ely, B. A., Fan, S., Fouche, J. -P., Gruner, P., Gursel, D. A., Hauser, T., Hirano, Y., Hoexter, M. Q., Iorio, M., James, A., Reddy, Y. C. J., Kaufmann, C., Koch, K., Kochunov, P., Kwon, J. S., Lazaro, L., Lochner, C., Marsh, R., Nakagawa, A., Nakamae, T., Narayanaswamy, J. C., Sakai, Y., Shimizu, E., Simon, D., Simpson, H. B., Soreni, N., Stampfli, P., Stern, E. R., Szeszko, P., Takahashi, J., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Assogna, F., Calvo, R., Wit, S. J., Hough, M., Kuno, M., Miguel, E. C., Morer, A., Pittenger, C., Poletti, S., Smeraldi, E., Sato, J. R., Tsuchiyagaito, A., Walitza, S., van der Werf, Y. D., Vecchio, D., Zarei, M., Stein, D. J., Jahanshad, N., Thompson, P. M., van den Heuvel, O. A., Spalletta, G., Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Neurodegeneration

Subjects
Adult, Obsessive-Compulsive Disorder, medicine.medical_specialty, Younger age, Cross-sectional study, Article, lcsh:RC321-571, White matter, neuroscience, Cellular and Molecular Neuroscience, Group differences, Obsessive compulsive, Internal medicine, Fractional anisotropy, medicine, Humans, 100 Philosophie und Psychologie::150 Psychologie::150 Psychologie, Child, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, Brain, White Matter, White matter microstructure, obsessive-compulsive disorder, Psychiatry and Mental health, Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, medicine.anatomical_structure, psychiatric disorders, Anisotropy, business, Diffusion MRI
Abstract

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Published
2021
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49. White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5-HTTLPR

Author

Benedetti F, Bollettini I, Poletti S, Locatelli C, Lorenzi C, Pirovano A, Smeraldi E, Colombo C, Benedetti, F, Bollettini, I, Poletti, S, Locatelli, C, Lorenzi, C, Pirovano, A, Smeraldi, E, and Colombo, C

Subjects
Adult, Male, Serotonin Plasma Membrane Transport Proteins, Bipolar Disorder, Diffusion Tensor Imaging, Genotype, Humans, Female, Middle Aged, Polymorphism, Single Nucleotide, White Matter
Abstract

Bipolar disorder (BD) is associated with signs of widespread disruption of white matter (WM) integrity. A polymorphism in the promoter of the serotonin transporter (5-HTTLPR) influenced functional cortico-limbic connectivity in healthy subjects and course of illness in BD, with the short (s) allele being associated with lower functional connectivity, and with earlier onset of illness and poor response to treatment. We tested the effects of 5-HTTLPR on diffusion tensor imaging (DTI) measures of WM microstructure in 140 inpatients, affected by a major depressive episode in course of BD, of Italian descent. We used whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity and fractional anisotropy. Compared with l/l homozygotes, 5-HTTLPR * s carriers showed significantly increased radial and mean diffusivity in several brain WM tracts, including corpus callosum, cingulum bundle, uncinate fasciculus, corona radiata, thalamic radiation, inferior and superior longitudinal fasciculus and inferior fronto-occipital fasciculus. An increase of mean and radial diffusivity, perpendicular to the main axis of the WM tract, is thought to signify increased space between fibers, thus suggesting demyelination or dysmyelination, or loss of bundle coherence. The effects of 5-HTTLPR on the anomalous emotional processing in BD might be mediated by changes of WM microstructure in key WM tracts contributing to the functional integrity of the brain.

Published
2014

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