Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium.
Ivanov I., Boedhoe PSW., Abe Y., Alonso P., Ameis SH., Arnold PD., Balachander S., Baker JT., Banaj N., Bargalló N., Batistuzzo MC., Benedetti F., Beucke JC., Bollettini I., Brem S., Brennan BP., Buitelaar J., Calvo R., Cheng Y., Cho KIK., Dallaspezia S., Denys D., Diniz JB., Ely BA., Feusner JD., Ferreira S., Fitzgerald KD., Fontaine M., Gruner P., Hanna GL., Hirano Y., Hoexter MQ., Huyser C., Ikari K., James A., Jaspers-Fayer F., Jiang H., Kathmann N., Kaufmann C., Kim M., Koch K., Kwon JS., Lázaro L., Liu Y., Lochner C., Marsh R., Martínez-Zalacaín I., Mataix-Cols D., Menchón JM., Minuzzi L., Morer A., Morgado P., Nakagawa A., Nakamae T., Nakao T., Narayanaswamy JC., Nurmi EL., Oh S., Perriello C., Piacentini JC., Picó-Pérez M., Piras F., Piras F., Reddy YCJ., Manrique DR., Sakai Y., Shimizu E., Simpson HB., Soreni N., Soriano-Mas C., Spalletta G., Stern ER., Stevens MC., Stewart SE., Szeszko PR., Tolin DF., van Rooij D., Veltman DJ., van der Werf YD., van Wingen GA., Venkatasubramanian G., Walitza S., Wang Z., Watanabe A., Wolters LH., Xu X., Yun J-Y., Zarei M., Zhang F., Zhao Q., Jahanshad N., Thomopoulos SI., Thompson PM., Stein DJ., van den Heuvel OA., O'Neill J., ENIGMA-OCD Working Group None.
BACKGROUND: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. METHODS: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. RESULTS: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31). CONCLUSIONS: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.