Vol.:(0123456789) 1 3 European Archives of Psychiatry and Clinical Neuroscience https://doi.org/10.1007/s00406-018-0887-1 ORIGINAL PAPER Cingulate abnormalities in bipolar disorder relate to gender and outcome: a voxel-based morphometry study Giuseppe Delvecchio 1  · Valentina Ciappolino 2  · Cinzia Perlini 3,4  · Marco Barillari 5  · Mirella Ruggeri 4,6  · A. Carlo Altamura 2  · Marcella Bellani 4,6  · Paolo Brambilla 2,7 Received: 12 September 2017 / Accepted: 16 March 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigat- ing the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a signifcant gender efect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a signifcant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = − 0.51, p = 0.04) and in male BD patients (r = − 0.88, p = 0.04). Finally, no statistically signifcant correlations were observed in female BD patients. Our fndings further confrm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender- specifc GM volume reductions in ACC in BD, which may also be associated to poor outcome. Keywords Mood disorders · Outcome · Gray matter · Illness severity · Hospitalizations Introduction Bipolar disorder (BD) is defned as a chronic disease afect- ing around 3% of the population worldwide [1] with the peak age of onset in adolescence and early adult life [2]. Its neurobiology has been widely investigated by several magnetic resonance imaging (MRI) studies, which identifed selective structural and functional abnormalities in specifc brain areas involved in emotional and cognitive processing [3–8], with specifc regards to the cingulate cortex [9–11]. The cingulate cortex is part of the limbic system, which can be divided into an anterior and a posterior region, subserv- ing cognitive and afective processing, respectively [9, 12, 13]. Interestingly, although the majority of the MRI studies Giuseppe Delvecchio and Valentina Ciappolino contributed equally to the study. * Paolo Brambilla paolo.brambilla1@unimi.it 1 IRCCS “E. Medea” Scientifc Institute, San Vito al Tagliamento, PN, Italy 2 Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, via F. Sforza 35, 20122 Milan, Italy 3 Section of Clinical Psychology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy 4 Interuniversity Centre for Behavioural Neurosciences, AOUI Verona, Verona, Italy 5 Section of Radiology, Department of Neurological and Movement Sciences, University Hospital of Verona, Verona, Italy 6 Section of Psychiatry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy 7 Department of Psychiatry and Behavioural Neurosciences, University of Texas at Houston, Houston, TX, USA