title: A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings.
abstract: OBJECTIVE
  In this report, we seek to (i) identify a potential neuroimaging endophenotype for bipolar disorder (BD) in emotion regulatory and autonomic circuitry in young first-degree relatives of persons with BD; and (ii) replicate our previous work identifying the functional neuroanatomy of working memory (WM) in an older sample of relatives of persons with BD.
  
  
  METHODS
  Ten adolescent and young adult (age 13-24) unmedicated, non-ill, first-degree relatives of persons with BD (RELS) and 10 demographically comparable healthy controls performed a 2-back WM task and a 0-back control task during functional magnetic resonance imaging (fMRI). fMRI data were collected on a 1.5 Tesla scanner and analyzed using SPM-2. Mood was assessed on the day of scanning.
  
  
  RESULTS
  The groups did not differ on any demographic, neuropsychological, or in-scanner task performance variables. In contrast to controls, RELS showed (i) weak task-dependent modulation activity in the cerebellar vermis (CV), insula, and amygdala/parahippocampal region, and (ii) exaggerated modulation of activity in the frontopolar cortex and brainstem, even after controlling for potential confounders. Many of the group differences were driven by differences in activity in the low-level (0-back) baseline task.
  
  
  CONCLUSIONS
  Young, unmedicated RELS exhibited altered task-dependent modulation of frontopolar, CV, and insula activity during WM, especially during the low-level (0-back) baseline task. Results are largely consistent with our initial study of older adult RELS, suggesting these alterations may represent biomarkers of genetic risk for BD.
authors.affiliation: Division of Public Psychiatry, Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston, USA. hthermen@bidmc.harvard.edu
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Thermenos
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Brown
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Giuliano
authors.forename: Erica H
authors.initials: EH
authors.lastname: Lee
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000339:Affect / Q000502:physiology; D001143:Arousal / Q000502:physiology; D001714:Bipolar Disorder / Q000150:complications* / Q000235:genetics; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology*; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D010100:Oxygen