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C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

ABSTRACT: C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ?16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.

SUBMITTER: Ancelin ML

PROVIDER: S-EPMC4312833 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

Ancelin M-L ML Farré A A Carrière I I Ritchie K K Chaudieu I I Ryan J J

Translational psychiatry 20150120

C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression sca ...[more]

PMID: 25603415

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Project description:Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.

Project description:OBJECTIVE: Neurobiological and clinical studies suggest that childhood maltreatment may result in functional and structural nervous system changes that predispose the individual to depression. This vulnerability appears to be modulated by a polymorphism in the serotonin gene-linked promoter region (5-HTTLPR). Little is known, however, about the persistence of this vulnerability across the life span, although clinical studies of adult populations suggest that gene-environment interaction may diminish with aging. METHOD: Depressive symptomatology and adverse and protective childhood events were examined in a population of 942 persons aged 65 years and older, taking into account sociodemographic characteristics and proximal competing causes of depression (widowhood, recent life events, vascular and neurologic disorder, and disability). Subjects were recruited between March 1999 and February 2001 and were diagnosed as depressed if they met 1 of 3 criteria: a diagnosis of major depression on the Mini-International Neuropsychiatric Interview, a score higher than 16 on the Center for Epidemiologic Studies-Depression Scale, or current treatment with an antidepressant. RESULTS: Exposure to traumatic events in childhood doubled the risk of late-life depression and increased the risk of repeated episodes. Not all events were found to be pathogenic; significant risk was associated with excessive sharing of parental problems, poverty or financial difficulties, mental disorder in parents, excessive physical punishment, verbal abuse from parents, humiliation, and mistreatment by an adult outside the family. Interactions were observed between the 5-HTTLPR long (L) allele, poverty, and excessive sharing of parental problems. CONCLUSIONS: Certain types of childhood trauma continue to constitute risk factors for depression in old age, outweighing more proximal causes. Gene environment vulnerability interaction is linked in older age to the L-carrying genotype, modulating the effects of general environmental conditions rather than aggressive acts on the individual, perhaps due to increased cardiac reactivity.

Dataset Information

C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

Publications

C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

Similar Datasets

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