Major depressive disorder and bone mass in adolescents and young adults

Abstract

Depression has been associated with reduced bone mass in adults, but the mechanisms remain unclear. In addition, little is known about the association between depression and bone health during growth and development. To address this knowledge gap, we examined bone density and structure in 222 adolescents and young adults (69% females, mean ± SD age: 19.0 ± 1.5 years), enrolled within 1 month of starting a selective serotonin reuptake inhibitor (SSRI) or unmedicated. Psychiatric functioning was assessed with self-report and researcher-administered instruments, including the Longitudinal Interval Follow-up Evaluation for Adolescents (A-LIFE). Anthropometric and laboratory measures included dual-energy x-ray absorptiometry and peripheral quantitative computed tomography scans. Linear multivariable regression analysis tested the association between depression and bone mass, after accounting for relevant confounders. The presence of current depression was associated with a significant reduction in age-sex-height-race-specific bone mineral density (BMD) and content (BMC) of total body less head and lumbar spine. The findings varied by assessment method with self-report scales, capturing symptom severity over the prior week or two, yielding the weakest associations. Depression was also associated with reduced cortical thickness and a trend for increased endosteal circumference. In contrast, generalized anxiety disorder was not associated with bone deficits. In sum, depressive illness is associated with significantly lower bone mass in youths. Future investigations must examine whether bone recovery is possible following depression remission or whether remedial interventions are warranted to optimize bone mass in order to minimize the long-term risk of osteoporosis.

Keywords: BONE QCT/microCT; BONE-BRAIN-NERVOUS SYSTEM INTERACTIONS; DXA.

Figure 1

Cohen’s d effect size comparing the association of major depressive disorder (MDD) group status and generalized anxiety disorder (GAD) with age-sex-height-race-specific total body less head (TBLH) bone mineral content Z-score and lumbar spine (LS) areal bone mineral density Z-score. These were generated from multivariable linear regression analyses adjusting for GAD, age, sex-age-specific lean body mass index Z-score, and 25-OH-vitamin D concentration. The presence of MDD was based on the DSM-IV (top three), the Longitudinal Interval Follow-up Evaluation for Adolescents (A-LIFE), the Beck Depression Inventory (BDI), and the Inventory of Depressive Symptomatology (IDS). One asterisk denotes marginally significant results (p<0.10) and two denote significant results (p<0.05).

Figure 2

Cohen’s d effect size comparing the association of major depressive disorder (MDD) group status and generalized anxiety disorder (GAD) with volumetric bone mineral density (vBMD) at the 4% and 20% radius sites and other cortical bone parameters at the 20% site. The analysis modeling trabecular vBMD adjusted for sex, height, BMI, and 25-OH-vitamin D concentration. The analysis modeling cortical vBMD adjusted for age, sex, and physical activity. The analysis modeling cortical thickness adjusted for age, sex, height, BMI, and forearm length. The analyses modeling periosteal circumference and polar section modulus adjusted for sex, BMI, grip strength, and forearm length. The analyses modeling endosteal circumference adjusted for age, sex, BMI, grip strength, and forearm length. In addition, the models that examined the association between categorically-defined MDD and bone outcomes also adjusted for the presence of GAD. One asterisk denotes marginally significant results (p<0.10) and two denote significant results (p<0.05).