Abstract
Decreased volumes of subgenual cingulate (SGC) have been reported primarily among familial bipolar patients, which is one of the hallmarks of an endophenotype. In order to investigate specificity of SGC volume abnormalities to familial mood disorders and to test whether SGC volumes represent an endophenotype for BD, we measured SGC volumes in young affected and unaffected relatives of bipolar patients (high-risk design) and in sporadic bipolar patients. We included 20 unaffected, 15 affected offspring of bipolar I or bipolar II parents, 18 controls, and 19 sporadic bipolar patients between 15 and 30 years of age. SGC volumes were measured on 1.5 T 3D anatomical MRI images using standard methods. We also combined the effect sizes from all published studies of sporadic patients with mood disorders (N = 61) and controls (N = 84) using random-effect models. We found comparable SGC volumes among unaffected, affected offspring of BD parents and controls (F = 0.7, df = 2; 50, P = 0.47). Likewise no SGC abnormalities were found between sporadic bipolar and control subjects (F = 2.31, df = 1; 34, P = 0.14). When combining all available data from sporadic patients, there were no differences in left (SDM 0.19, 95% CI −0.13 to 0.51) or right (SDM −0.11, 95% CI −0.47 to 0.26) SGC volumes between sporadic bipolar patients and controls. The limitations of the study are cross-sectional design and inclusion of both bipolar I and bipolar II probands. In conclusion, SGC volume abnormalities were absent in unaffected, affected relatives of bipolar patients as well as sporadic bipolar patients and thus did not meet criteria for endophenotype.
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References
Blacker D, Tsuang MT (1993) Unipolar relatives of bipolar pedigrees: are they bipolar? Psychiatr Genet 3:5–16
Brambilla P, Nicoletti MA, Harenski K, Sassi RB, Mallinger AG, Frank E et al (2002) Anatomical MRI study of subgenual prefrontal cortex in bipolar and unipolar subjects. Neuropsychopharmacology 27:792–799
Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29:162–173
Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M et al (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386:824–827
Duffy A, Alda M, Crawford L, Milin R, Grof P (2007) The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents. Bipolar Disord 9:828–838
Duffy A, Alda M, Kutcher S, Cavazzoni P, Robertson C, Grof E et al (2002) A prospective study of the offspring of bipolar parents responsive and nonresponsive to lithium treatment. J Clin Psychiatry 63:1171–1178
Duffy A, Hajek T, Alda M, Grof P, Milin R, MacQueen G (2009) Neurocognitive functioning in early stages of bipolar disorder: visual backward masking performance in high risk subjects. Eur Arch Psychiatry Clin Neurosci 259(5):263–269
Endicott J, Spitzer RL (1978) A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 35:837–844
Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S et al (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41
Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645
Hajek T, Carrey N, Alda M (2005) Neuroanatomical abnormalities as risk factors for bipolar disorder. Bipolar Disord 7:393–403
Hajek T, Gunde E, Bernier D, Slaney C, Propper L, Grof P et al (2007) Subgenual cingulate volumes in affected and unaffected offspring of bipolar parents. J Affect Disord
Hajek T, Gunde E, Bernier D, Slaney C, Propper L, MacQueen G et al (2008) Pituitary volumes in relatives of bipolar patients: high-risk study. Eur Arch Psychiatry Clin Neurosci 258:357–362
Hajek T, Gunde E, Slaney C, Propper L, MacQueen G, Duffy A et al (2008) Striatal volumes in affected and unaffected relatives of bipolar patients—high-risk study. J Psychiatr Res 43(7):724–729
Hajek T, Kozeny J, Kopecek M, Alda M, Hoschl C (2008) Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. J Psychiatry Neurosci 33:91–99
Hillegers MH, Reichart CG, Wals M, Verhulst FC, Ormel J, Nolen WA (2005) Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents. Bipolar Disord 7:344–350
Hirayasu Y, Shenton ME, Salisbury DF, Kwon JS, Wible CG, Fischer IA et al (1999) Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiatry 156:1091–1093
Kempton MJ, Geddes JR, Ettinger U, Williams SC, Grasby PM (2008) Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry 65:1017–1032
Keri S, Kelemen O, Benedek G, Janka Z (2001) Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach. Psychol Med 31:915–922
Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S et al (2000) Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48:830–843
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA et al (1999) Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 156:675–682
Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C et al (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660
McDonald C, Marshall N, Sham PC, Bullmore ET, Schulze K, Chapple B et al (2006) Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry 163:478–487
Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 95:13290–13295
Phillips ML, Drevets WC, Rauch SL, Lane R (2003) Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry 54:504–514
Sanches M, Sassi RB, Axelson D, Nicoletti M, Brambilla P, Hatch JP et al (2005) Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study. Psychiatry Res 138:43–49
Sharma V, Menon R, Carr TJ, Densmore M, Mazmanian D, Williamson PC (2003) An MRI study of subgenual prefrontal cortex in patients with familial and non-familial bipolar I disorder. J Affect Disord 77:167–171
Acknowledgments
This study was supported by grant NR8786, from the Internal Grant Agency of Ministry of Health, Czech Republic. The authors thank Pavla Stopkova, M.D., Ph.D. for help with proband enrollment and Ms. Jolana Sediva for administrative and technical support.
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Hajek, T., Novak, T., Kopecek, M. et al. Subgenual cingulate volumes in offspring of bipolar parents and in sporadic bipolar patients. Eur Arch Psychiatry Clin Neurosci 260, 297–304 (2010). https://doi.org/10.1007/s00406-009-0077-2
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DOI: https://doi.org/10.1007/s00406-009-0077-2