In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group

Haukvik UK, Gurholt TP, Nerland S, Elvsåshagen T, Akudjedu TN, Alda M, Alnaes D, Alonso-Lana S, Bauer J, Baune BT, Benedetti F, Berk M, Bettella F, Bøen E, Bonnín CM, Brambilla P, Canales-Rodríguez EJ, Cannon DM, Caseras X, Dandash O, Dannlowski U, Delvecchio G, Díaz-Zuluaga AM, van Erp TGM, Fatjó-Vilas M, Foley SF, Förster K, Fullerton JM, Goikolea JM, Grotegerd D, Gruber O, Haarman BCM, Haatveit B, Hajek T, Hallahan B, Harris M, Hawkins EL, Howells FM, Hülsmann C, Jahanshad N, Jørgensen KN, Kircher T, Krämer B, Krug A, Kuplicki R, Lagerberg TV, Lancaster TM, Lenroot RK, Lonning V, López-Jaramillo C, Malt UF, McDonald C, McIntosh AM, McPhilemy G, van der Meer D, Melle I, Melloni EMT, Mitchell PB, Nabulsi L, Nenadić I, Oertel V, Oldani L, Opel N, Otaduy MCG, Overs BJ, Pineda-Zapata JA, Pomarol-Clotet E, Radua J, Rauer L, Redlich R, Repple J, Rive MM, Roberts G, Ruhe HG, Salminen LE, Salvador R, Sarró S, Savitz J, Schene AH, Sim K, Soeiro-de-Souza MG, Stäblein M, Stein DJ, Stein F, Tamnes CK, Temmingh HS, Thomopoulos SI, Veltman DJ, Vieta E, Waltemate L, Westlye LT, Whalley HC, Sämann PG, Thompson PM, Ching CRK, Andreassen OA, Agartz I; ENIGMA Bipolar Disorder Working Group

Zusammenfassung

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.