TY - JOUR
T1 - Bone mineral density as a marker of cumulative endogenous estrogen exposure
T2 - Relationship to background genetic risk of psychotic disorder
AU - van der Leeuw, C.
AU - Habets, P.
AU - Domen, P.
AU - van Kroonenburgh, M.
AU - van Os, J.
AU - Marcelis, M.
N1 - Funding Information:
This work was sponsored by the Dutch organization for scientific research NWO (Genetic Risk and Outcome of Psychosis [G.R.O.U.P.]) and the European Community's Seventh Framework Programme under Grant Agreement No. HEALTH-F2-2009-241909 (European Network of National Schizophrenia Networks Studying Gene–Environment Interactions Consortium). The sponsors had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Funding Information:
Jim van Os is or has been an unrestricted research grant holder with, or has received financial compensation as an independent symposium speaker from, Eli Lilly, BMS, Lundbeck, Organon, Janssen-Cilag, GlaxoSmithKline, AstraZeneca, Pfizer, and Servier. Machteld Marcelis has received financial compensation as an independent symposium speaker from Eli Lilly and Janssen-Cilag. All other authors report no biomedical financial interests or potential conflicts of interest.
PY - 2013/1
Y1 - 2013/1
N2 - Background: Alterations in bone mineral density (BMD) in patients with psychotic disorder may reflect the effect of treatment (disease effect observed in patients but not their siblings) or, as an intermediate marker of cumulative endogenous estrogen exposure, alterations in the neuroprotective effect of estrogen in the brain (vulnerability effect observed in patients and siblings). Methods: Dual X-ray absorptiometry (DEXA) scans were acquired in 62 patients with a psychotic disorder, 67 non-psychotic siblings of patients with a psychotic disorder, and 48 controls. BMD (g/cm2), Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and BMD were investigated with multilevel random regression analyses. Group×sex interactions and effects of antipsychotic medication (AP) on BMD were examined. Results: Group was not associated with BMD outcome measures, although patients had consistently lower BMD measures compared to both siblings and controls. There were no significant group × sex interactions, but stratified analyses showed that BMD measures in female patients were significantly lower in comparison to female controls and siblings (e.g. total femoral BMD, P vs. C: B = - 0.100, p = 0.010; P vs. S: B = - 0.104, p = 0.008). After excluding female patients who used prolactin-raising AP, the effect was attenuated (e.g. total femoral BMD, P vs. C: B = - 0.073, p = 0.072; P vs. S: B = - 0.085, p = 0.051). In men, there were no significant BMD differences between patients and controls. Conclusion: Familial risk of psychotic disorder was not associated with BMD. Instead, decreased BMD in the femur may reflect treatment effects or non-familial risk associated with low cumulative endogenous estrogen levels in women.
AB - Background: Alterations in bone mineral density (BMD) in patients with psychotic disorder may reflect the effect of treatment (disease effect observed in patients but not their siblings) or, as an intermediate marker of cumulative endogenous estrogen exposure, alterations in the neuroprotective effect of estrogen in the brain (vulnerability effect observed in patients and siblings). Methods: Dual X-ray absorptiometry (DEXA) scans were acquired in 62 patients with a psychotic disorder, 67 non-psychotic siblings of patients with a psychotic disorder, and 48 controls. BMD (g/cm2), Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and BMD were investigated with multilevel random regression analyses. Group×sex interactions and effects of antipsychotic medication (AP) on BMD were examined. Results: Group was not associated with BMD outcome measures, although patients had consistently lower BMD measures compared to both siblings and controls. There were no significant group × sex interactions, but stratified analyses showed that BMD measures in female patients were significantly lower in comparison to female controls and siblings (e.g. total femoral BMD, P vs. C: B = - 0.100, p = 0.010; P vs. S: B = - 0.104, p = 0.008). After excluding female patients who used prolactin-raising AP, the effect was attenuated (e.g. total femoral BMD, P vs. C: B = - 0.073, p = 0.072; P vs. S: B = - 0.085, p = 0.051). In men, there were no significant BMD differences between patients and controls. Conclusion: Familial risk of psychotic disorder was not associated with BMD. Instead, decreased BMD in the femur may reflect treatment effects or non-familial risk associated with low cumulative endogenous estrogen levels in women.
KW - Bone mineral density
KW - Endophenotype
KW - Estrogen
KW - Genetics
KW - Psychotic disorder
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84871930990&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2012.10.031
DO - 10.1016/j.schres.2012.10.031
M3 - Article
C2 - 23194650
AN - SCOPUS:84871930990
SN - 0920-9964
VL - 143
SP - 25
EP - 31
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1
ER -