Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents

青少年血清素再摄取抑制剂和骨矿化

• 批准号: 8663307
• 负责人: Chadi A. Calarge
• 金额: $ 62.8万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8663307
• 关键词: 17 year old; 20 year old; Accounting; Adolescent; Adolescent and Young Adult; Adult; Adverse effects; Affect; Age Distribution; Alkaline Phosphatase; Animals; Architecture; Award; Bone Density; Bone Resorption; Boxing; Cell Differentiation process; Child; Childhood; Clinical Trials; Collagen Type I; Complement; Cyclophosphamide; Development; Elderly; Enrollment; Epidemiologic Studies; Exhibits; Failure; Female; Fracture; Future; Genes; Genetic; Genetic Variation; Genetic screening method; Genotype; Growth; Individual; Intervention; Knowledge; Laboratories; Life; Life Expectancy; Light; Link; Measures; Medicine; Mental disorders; Minerals; Minisatellite Repeats; Mission; Morbidity - disease rate; Mus; National Institute of Mental Health; Observational Study; Osteocalcin; Osteogenesis; Osteoporosis; Participant; Patients; Peripheral; Pharmaceutical Preparations; Pharmacogenetics; Physiologic calcification; Play; Population; Preventive Intervention; Process; Psychiatric therapeutic procedure; Psychopathology; Quality of life; Radial; Recruitment Activity; Research Priority; Risk; Role; Safety; Sampling; Selective Serotonin Reuptake Inhibitor; Serotonin; Sex Distribution; Site; Staging; Sum; System; Testing; Variant; Vertebral column; Vulnerable Populations; Weight-Bearing state; Work; X-Ray Computed Tomography; Youth; age group; bone; bone cell; bone health; bone loss; bone mass; bone metabolism; bone turnover; emerging adult; follow-up; genetic variant; high risk; improved; lifetime risk; male; mortality; pre-clinical; preclinical study; prevent; prospective; receptor; research study; restoration; senescence; serotonin receptor; serotonin transporter; skeletal; treatment duration; young adult

DESCRIPTION (provided by applicant): Bone mass achieved by early adulthood is a major determinant of lifetime risk for osteoporosis. Therefore, optimizing peak bone mass is crucial to avoiding bone fracture with its associated morbidity and mortality. Emerging evidence suggests that serotonin plays a central role in bone metabolism. For example, preclinical experiments have shown that bone cells express the serotonin transporter and a variety of functional serotonin receptors whose activity modulates bone turnover. Epidemiologic studies have linked selective serotonin reuptake inhibitors (SSRIs) to reduced bone mineral density and increased fracture risk in the elderly. SSRIs are widely used in youths to treat a number of psychiatric disorders. However, while their short-term efficacy and safety have been established, their long-term safety remains little investigated. We, here, propose to recruit, in a 2-year prospective observational study, 15 to 20 year-old participants upon the initiation of SSRI treatment. During the period of the Award, bone mineral density of the lumbar spine and whole body will be measured using dual x-ray absorptiometry and of the radius using peripheral quantitative computerized tomography. A detailed psychiatric assessment will be conducted to control for psychopathology, as a potential confounding factor affecting bone mineralization. Changes in psychiatric treatment during the follow up period will also be documented and accounted for. By using a group of healthy controls, of comparable age and sex distribution, we aim to evaluate 1) whether psychopathology, at baseline, is associated with low bone mass, 2) if treatment with SSRIs suppresses bone mineralization, and 3) if the discontinuation of the SSRI is followed by a restoration of bone mineral accrual. 4) Furthermore, genetic testing will investigate whether variants of the serotonin system genes moderate the effect of SSRI treatment on bone mineral density. In sum, this work aims to improve the long-term safety of psychiatric treatments in order to optimize functioning and the quality of life of those who suffer from psychiatric disorders. This is consistent with the mission of the National Institute of Mental Health.

描述（由申请人提供）：成年早期实现的骨质量是骨质疏松症的终生风险的主要决定因素。因此，优化峰值骨量对于避免骨断裂及其相关的发病率和死亡率至关重要。 新兴的证据表明5-羟色胺在骨代谢中起着核心作用。例如，临床前实验表明，骨细胞表达5-羟色胺转运蛋白和各种功能性5-羟色胺受体，它们的活性调节骨骼更新。流行病学研究已将选择性5-羟色胺再摄取抑制剂（SSRI）联系起来，以降低骨矿物质密度并增加老年人的断裂风险。 SSRI被广泛用于年轻人治疗多种精神疾病。但是，尽管已经确定了它们的短期疗效和安全性，但他们的长期安全仍未得到调查。 我们在这里提议在一项为期两年的前瞻性观察研究中招募，在开始SSRI治疗后，有15至20岁的参与者。在奖励期间，使用双X射线吸收仪和半径使用外围定量计算机断层扫描来测量腰椎和整个身体的骨矿物质密度。将进行详细的精神病评估以控制精神病理学，这是影响骨矿化的潜在混杂因素。在后续期间，精神病治疗的变化也将记录并记录下来。通过使用一组健康对照，具有可比的年龄和性别分布，我们旨在评估1）在基线时心理病理学是否与低骨骼质量相关，2）如果用SSRIS治疗抑制骨矿化，而3） SSRI之后是骨骼矿物质应计的恢复。 4）此外，基因检测将研究5-羟色胺系统基因的变体是否适应SSRI处理对骨矿物质密度的影响。 总而言之，这项工作旨在提高精神疗法的长期安全性，以优化患有精神疾病的人的功能和生活质量。这与国家心理健康研究所的使命是一致的。

项目成果

Sexual Functioning in Adolescents With Major Depressive Disorder.

• DOI: 10.4088/jcp.15m09840
• 发表时间: 2016-07
• 期刊: The Journal of clinical psychiatry
• 作者: Deumic E;Butcher BD;Clayton AD;Dindo LN;Burns TL;Calarge CA
• 通讯作者: Calarge CA

Sexual Functioning in Adolescents With Major Depressive Disorder: A Prospective Study.

患有重度抑郁症的青少年的性功能：一项前瞻性研究。

• DOI: 10.4088/jcp.21m13892
• 发表时间: 2021
• 期刊: The Journal of clinical psychiatry
• 作者: DeumicShultz,Emira;Mills,JamesA;Ellingrod,VickiL;Bishop,JeffreyR;Calarge,ChadiA
• 通讯作者: Calarge,ChadiA

The Effect of Depression, Generalized Anxiety, and Selective Serotonin Reuptake Inhibitors on Change in Bone Metabolism in Adolescents and Emerging Adults.

• DOI: 10.1002/jbmr.3238
• 发表时间: 2017-12
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Calarge CA;Mills JA;Janz KF;Burns TL;Schlechte JA;Coryell WH;Zemel BS
• 通讯作者: Zemel BS

Gut microbiome in adolescent depression.

• DOI: 10.1016/j.jad.2021.05.107
• 发表时间: 2021-09-01
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Thapa S;Sheu JC;Venkatachalam A;Runge JK;Luna RA;Calarge CA
• 通讯作者: Calarge CA

Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating SSRI Treatment.

• DOI: 10.1080/13811118.2016.1158677
• 发表时间: 2016-10
• 期刊: Archives of suicide research : official journal of the International Academy for Suicide Research
• 作者: Coryell W;Yolken R;Butcher B;Burns T;Dindo L;Schlechte J;Calarge C
• 通讯作者: Calarge C