Association of the Serotonin Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Genotype With Depression in Elderly Persons After Hip Fracture

Lenze, Eric J.; Munin, Michael C.; Ferrell, Robert E.; Pollock, Bruce G.; Skidmore, Elizabeth R.; Lotrich, Francis E.; Rogers, Joan C.; Quear, Tanya; Houck, Patricia R.; Reynolds, Charles F.

doi:10.1097/00019442-200505000-00014

Cited by 45 publications

(31 citation statements)

References 18 publications

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“…We have demonstrated an association between the s allele and depression in participants who were chronically stressed because of an ongoing illness. Indeed, several small studies found an association between the s allele and depression in patients with medical illness, i.e., in patients with Parkinson's disease (18,19), stroke (20), hip fracture (21), and coronary disease (22). Taken together, these findings suggest that chronic medical illness may be a type of stress that is more likely to lead to depression in patients with the s allele than in patients homozygous for the long allele.…”

Section: Discussionmentioning

confidence: 95%

“…Thus, in study groups in which all patients are chronically ill, resulting in a considerable amount of stress, one might expect to find a direct effect of 5-HTTLPR on depression. Indeed, in several small studies the s allele of 5-HTTLPR has been associated with depression in patients with Parkinson's disease (18,19), in those with stroke (20), and in elderly patients after hip fracture (21). One Japanese study suggested that the s allele may be associated with depression in patients after acute coronary syndrome (22).…”

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confidence: 99%

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Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

Otte

McCaffery²,

Ali³

et al. 2007

AJP

134

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Objective-The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established.Method-In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease.Results-Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age-and gender-adjusted odds ratio was also 1.6 (95% CI= 1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 μg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0).Conclusions-Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.The serotonin, or 5-HT (5-hydroxytryptamine), system is critically involved in the pathophysiology of mood and anxiety disorders, and drugs that target serotonergic neurotransmission are efficacious for the treatment of these disorders (1). The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission by facilitating reuptake of 5-HT from the synaptic cleft. A repeat of 20-23 base pairs has been observed as a motif within a polymorphic region of the serotonin transporter gene, and it occurs as two prevalent alleles: one consisting of 14 repeats (the short allele variant) and another of 16 repeats (the long allele variant). This functional polymorphism in the 5-regulatory promoter region, termed 5-HTTLPR (5-HTT-gene-linked polymorphic region), alters transcription of the serotonin transporter gene (2). Specifically, the short allele of the 5-HTTLPR polymorphism is thought to reduce transcription efficiency for the gene, resulting in decreased expression of the serotonin transporter and decreased serotonin uptake in lymphoblast cell lines and blood platelets (3,4) and decreased availability of the serotonin transporter in human imaging studies (5). The s allele appears to exert its effect independent of s allele load, i.e., in a dominant manner (6).With remarkable consistency (exceptions are studies by Surtees et al. [7] and Gill...

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

Otte

McCaffery²,

Ali³

et al. 2007

AJP

134

View full text Add to dashboard Cite

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“…67 Gene polymorphisms in serotonin transporter and 5HT-1A receptor, markers of vulnerability to stress, have also been implicated in the development of depression and impaired function after a hip fracture. 72,73 The presence of depressive symptoms prefracture may also be a risk factor for loss of functional status. 74 …”

Section: Depression Antidepressants and Fracturesmentioning

confidence: 99%

The Complex Interplay of Depression and Falls in Older Adults: A Clinical Review

Iaboni

Flint

2013

The American Journal of Geriatric Psychiatry

227

178

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Depression and falls have a significant bidirectional relationship. Excessive fear of falling, which is frequently associated with depression, also increases the risk of falls. Both depression and fear of falling are associated with impairment of gait and balance, an association that is mediated through cognitive, sensory, and motor pathways. The management of depression in fall-prone individuals is challenging, since antidepressant medications can increase the risk of falls, selective serotonin reuptake inhibitors may increase the risk of fragility fractures, and data are lacking about the effect of fall rehabilitation programs on clinically significant depression. Based on the current state of knowledge, exercise (particularly Tai Chi) and cognitive-behavioral therapy should be considered for the first-line treatment of mild depression in older fallers. Antidepressant medications are indicated to treat moderate to severe depression in fall-prone individuals, but with appropriate precautions including low starting dose and slow dose titration, use of psychotropic monotherapy whenever possible, and monitoring for orthostatic hypotension and hyponatremia. To date, there have been no recommendations for osteoporosis monitoring and treatment in individuals prescribed antidepressant medications, beyond the usual clinical guidelines. However, treatment of the older depressed person who is at risk of falls provides the opportunity to inquire about his or her adherence with osteoporosis and fracture-prevention guidelines. KeywordsAntidepressants; depression; falls; fear of falling; fractures One-third of community-dwelling seniors fall each year, with half of these individuals falling more than once. Ten percent of all falls result in a major injury, which can lead to institutionalization and death. 1 Falls often result in a fear of further falls, leading to fearrelated restriction of activities: this activity restriction has been associated with subsequent impairment in balance, mobility, and disability. 2,3 Send correspondence and reprint requests to Alastair

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“…44,45 On the other hand, some 'positive' studies have been published with samples so small that they cannot be considered to test the hypothesis. 46,47 This could suggest a publication bias with smaller negative studies remaining unpublished or could be explained by other systematic differences between negative and positive studies. The replication studies have used varied designs, samples and measures, precluding direct comparison and metaanalysis.…”

Section: Human Studiesmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Association of the Serotonin Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Genotype With Depression in Elderly Persons After Hip Fracture

Cited by 45 publications

References 18 publications

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

The Complex Interplay of Depression and Falls in Older Adults: A Clinical Review

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

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