Osteocalcin levels decrease during the treatment of an acute depressive episode

Abstract

ObjectivesOsteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role—stress response, monoamine synthesis, and cognitive functioning—are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode.MethodsThe study included female inpatients with at least moderate depressive episode. In these patients, depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), and osteocalcin levels were assessed before the stabilization of antidepressive treatment and after 6 weeks. Relationships between osteocalcin levels and symptoms were analyzed with mixed-effect and linear models, taking into account age, menopausal status, and body mass index.ResultsIn 11 out of 13 enrolled inpatients, osteocalcin levels decreased during the first 6 weeks of treatment; this decrease was significant according to the mixed-effects model (t = −2.345, p = 0.019). According to the linear model, this decrease was significantly associated with reduction in depressive symptom severity (t = 2.673, p = 0.028). Osteocalcin was not associated with initial depressive symptom severity, and initial osteocalcin levels did not predict response to treatment. Limitations of the study include low sample size and inclusion of both pre- and postmenopausal women of various ages.ConclusionsThis preliminary study suggests that osteocalcin may be a candidate biomarker of antidepressive treatment response and that this topic warrants further investigation.

Lithium use and bone health in women with bipolar disorder: A cross‐sectional study

“…Supporting this hypothesis, lithium use has been associated with decreased osteocalcin levels in bipolar patients compared to the general population while treatment‐naive bipolar patients display higher levels of osteocalcin 14,26 . Osteocalcin seems to be elevated in depressed older adults and decreases significantly after successful treatment of depression 27,28 . We propose that lithium's effects on osteocalcin signaling cascades can explain some of lithium's effects on mood and other stress and age‐related processes including lithium's neuroprotective, osteoprotective, anti‐cancer and anti‐aging properties 5,29–33 .…”

“…14,26 Osteocalcin seems to be elevated in depressed older adults and decreases significantly after successful treatment of depression. 27,28 We propose that lithium's effects on osteocalcin signaling cascades can explain some of lithium's effects on mood and other stress and age-related processes including lithium's neuroprotective, osteoprotective, anti-cancer and anti-aging properties. 5,[29][30][31][32][33] Lithium has also been associated with weight gain, which theoretically should be associated with a positive effect on BMD.…”

Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression

“…OC, a bone-derived protein, is recognized as a marker of bone turnover related to low BMD [ 9 ]. Apart from its impact on bone, the beneficial effects of OC on improving neurological performance were reported, such as cognition impairment, neuromotor dysfunction, and anxiety and depression [ 36 ]. However, there are inconsistent results in the relationship between OC and depressive symptoms, as well as treatment response.…”

“…For example, a previous study also demonstrated that peripheral OC level was correlated with depressive severity in premenopausal women with major depression, and escitalopram (one of SSRIs) treatment increased serum OC levels [ 37 ], which might be a risk factor of osteoporosis. A recent longitudinal study conducted by Bartecku E et al also enrolled female patients with depression and demonstrated that OC was not related to baseline depressive symptom severity, and pre-treatment OC levels did not predict response to treatment, but the decrease of OC level was associated with the improvements of depressive symptoms after 6 weeks of anti-depressive treatment [ 36 ], suggesting OC may be a candidate biomarker of antidepressant response in female patients. Nevertheless, since most studies on bone health and depression have focused on female patients, no studies have examined the relationship between OC and antidepressant response in male patients with depression.…”

GPR158 in pyramidal neurons mediates social novelty behavior via modulating synaptic transmission in mice

“…The copyright holder for this preprint this version posted April 9, 2023. ; https://doi.org/10.1101/2023.04.09.536148 doi: bioRxiv preprint osteocalcin (OCN) may modulate GPR158 to alleviate the symptoms of depression, anxiety and memory loss in rodents [55][56][57][58] . OCN can activate the brain-derived neurotrophic factor (BDNF) signaling pathway by connecting GPR158 and RbAp48 in the hippocampus 58,59 .…”