Structural connectivity in late‐onset mania

The scientific approach to first-episode mania in late life lacks systematized data regarding etiology, differential diagnosis, prognosis, and treatment. As previously shown, the peaks of incidence for manic states appear between 15 and 30 years of age (1), and 90% of patients with a bipolar disorder diagnosis will become symptomatic by the time they are 50 years old (2). In regard to patients with a first-episode mania in late life, this appears to be a rare and heterogeneous disorder, frequently related to neurological comorbid conditions (3). Neurodegenerative disease [e.g., the behavioral variant of frontotemporal dementia (4)], as well as cerebrovascular disease (5), has been proposed as a possible etiological basis for late-onset manic episodes. These disorders may disrupt the functional and structural connectivity between cortical and limbic networks related to emotional and cognitive processing. Hence, the purpose of the present study was to explore differences in structural connectivity between a group of patients with late-onset mania and a control group of healthy subjects, by measuring the anisotropic diffusion of water in white matter tracts with the use of magnetic resonance diffusion tensor imaging. A case–control study was carried out at the National Institute of Neurology and Neurosurgery of Mexico (NINN), after approval from the Institutional Research Committee, in strict accordance with the Helsinki Declaration of 1975. We included patients with first-episode mania in late life (> 50 years old), who were treated from January 2010 to December 2011, by means of a consecutive sampling, if they fulfilled the ICD-10 (6) criteria for mania without psychotic symptoms (codified as F30.1), as well as mania with psychotic symptoms (codified as F30.2). According to the DSM-IV criteria (7), all patients were diagnosed as having bipolar I disorder, a single manic episode, and were recruited during or after developing their first manic episode. A sample of age-paired healthy controls was included for comparison. Magnetic resonance image acquisition was obtained using 3T General Electric equipment at the Neuroradiology Unit of NINN. Forty-three diffusion tensor data points were obtained in each patient or control using a spin echoplanar imaging sequence, with the following parameters: repetition time = 10,150 msec; echo time = 84.1 msec; 2.6-mm thick sections; matrix size = 128 9 128 voxels; diffusion sensitizing gradients were applied along 25 non-colinear directions uniformly distributed on a unit sphere, with a b-value = 800 sec/mm. All diffusion tensor data were analyzed using the FSL program (developed by Oxford University) (8). One of the main measures derived from diffusion data is fractional anisotropy, which quantifies how strongly directional the tract structure is. Voxelwise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics (TBSS) (9), which are part of the FSL program. TBSS projects all subjects’ fractional anisotropy data onto a mean tract skeleton, before applying voxelwise cross-subject statistics. Ten patients and ten controls were included, with no significant differences regarding age (56.9 6.4 years versus 55.8 6.2 years, respectively; p = 0.705, t-test), sex (40% female in each group), or scholastic level (10.0 3.3 years versus 10.1 5.2 years, respectively; p = 0.946, t-test). Figure 1 shows the main results obtained by means of the TBSS analysis of diffusion tensor data. We found significant differences (p < 0.05) in several tracts, including: (A) the right corpus callosum (minor forceps); (B) the left corpus callosum (minor forceps); (C) the right uncinate fasciculus (frontal portion); (D) the left uncinate fasciculus (frontal portion); (E) the right cingulum (posterior division); and (F) the left cingulum (anterior division). A previous study (3), found that 71% of the patients with first-episode mania in late life may