Functional TSPO polymorphism predicts variance in the diurnal cortisol rhythm in bipolar disorder

PSYCHONEUROENDOCRINOLOGY

卷:89

Article

Prossin, Alan R.^1,2  Chandler, Matthew¹  Ryan, Kelly A.³  Saunders, Erika F.^3,5,6  Kamali, Masoud^3,4  Papadopoulos, Vassilios⁷  Zollner, Sebastian³  Dantzer, Robert⁸  McInnis, Melvin G.³ 

[1] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Psychiat, 1941 East Rd,2308, Houston, TX 77054 USA

[2] Houston Methodist Res Inst, Houston, TX USA

[3] Univ Michigan, Med Sch, Dept Psychiat, Ann Arbor, MI USA

[4] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[5] Penn State Coll Med, Med Sch, Dept Psychiat, Hershey, PA USA

[6] Milton S Hershey Med Ctr, Hershey, PA USA

[7] Univ Southern Calif, Sch Pharm, Los Angeles, CA USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Div Internal Med, Houston, TX 77030 USA

关键词: Bipolar disorder;    Biomarker;    Stress;    Cortisol;    Immune;    Genetics;    TSPO;    rs6971;    Alcohol use disorder;    Variance factor;    Diurnal rhythm;    HPA axis;    Precision medicine;   

DOI  :  10.1016/j.psyneuen.2018.01.013

来源: Elsevier

【 摘 要 】

Introduction: Psychosocial stress contributes to onset/exacerbation of mood episodes and alcohol use, suggesting dysregulated diurnal cortisol rhythms underlie episodic exacerbations in Bipolar Disorder (BD). However, mechanisms underlying dysregulated HPA rhythms in BD and alcohol use disorders (AUD) are understudied. Knowledge of associated variance factors have great clinical translational potential by facilitating development of strategies to reduce stress-related relapse in BD and AUD. Evidence suggests structural changes to mitochondria) translocator protein (TSPO) (a regulator of steroid synthesis) due to the single nucleotide polymorphism rs6971, may explain much of this variance. However, whether rs6971 is associated with abnormal HPA rhythms and clinical exacerbation in humans is unknown. Methods: To show this common TSPO polymorphism impacts HPA rhythms in BD, we tested whether rs6971 (dichotomized: presence/absence of polymorphism) predicted variance in diurnal cortisol rhythm (saliva: morning and evening for 3 days) in 107 BD (50 with and 57 without AUD) and 28 healthy volunteers of similar age and ethno-demographic distribution. Results: Repeated measures ANOVA confirmed effects BD (F-5,F-525 = 3.0, p = 0.010) and AUD (F-5,F-525 = 2.9, p = 0.012), but not TSPO polymorphism (p > 0.05). Interactions were confirmed for TSPO x BD (F-5,F-525 = 3.9, p = 0.002) and for TSPO x AUD (F-5,F-525 = 2.8, p = 0.017). Discussion We identified differences in diurnal cortisol rhythm depending on presence/absence of common TSPO polymorphism in BD volunteers with or without AUD and healthy volunteers. These results have wide ranging implications but further validation is needed prior to optimal clinical translation.

【 授权许可】

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