Influence of Serotonin Transporter Promoter Region Polymorphisms on Hippocampal Volumes in Late-Life Depression

Taylor, Warren D.; Steffens, David C.; Payne, Martha E.; MacFall, James R.; Marchuk, Douglas A.; Svenson, Ingrid K.; Krishnan, K. Ranga Rama

doi:10.1001/archpsyc.62.5.537

Cited by 167 publications

(103 citation statements)

References 69 publications

(81 reference statements)

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“…19 Moreover, patients with a late-onset geriatric depression who were homozygous for the L-allele of the 5-HTTLPR had smaller hippocampal volumes than other groups. 30 One possible explanation may be that the higher reuptake of serotonin in subjects homozygous for the L A -allele is an additional factor that aggravates stressinduced neurotoxic effects during depression. In addition to its role as a neurotransmitter, serotonin acts as a trophic factor modulating developmental processes such as neuronal division, differentiation, migration, synaptogenesis 31,32 and adult neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…15 Furthermore, the L-allele of the 5-HTTLPR, which shows increased 5-HTT expression and increased 5-HT-reuptake in vitro and in vivo, [16][17][18] is associated with hippocampal volume reduction in major depression. 19,20 The L-allele of the 5-HTTLPR can be subtyped into La and Lg alleles, the latter of which is thought to be similar to the S-allele in terms of reuptake efficiency perhaps explaining some of these discrepancies. 21 This polymorphism can then be handled as a triallelic polymorphism.…”

Section: Introductionmentioning

confidence: 99%

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Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

et al. 2008

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The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S-or L G -allele have smaller GM volumes than those with the L A -allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the L A -allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

et al. 2008

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“…Several distinctions between these groups have been identified, and subjects with early-onset depression are more likely to have a family history of psychiatric illness (Brodaty et al, 2001), while subjects with late-onset depression have greater subcortical ischemic disease (Krishnan et al, 1988;Salloway et al, 1996;Taylor et al, 2004). In addition, late-onset depression has been associated with more pronounced temporal lobe atrophy (Greenwald et al, 1997;Kumar et al, 1998) and hippocampal volume reductions (Steffens et al, 2000;Hickie et al, 2005), with specific genotypes possibly mediating this effect (Taylor et al, 2005). If these previous investigations are interpreted to be signs of different causes or risk factors for depression based on age at onset, greater splenium thinning in late-than early-onset depression might indeed point to more prominent atrophic or neurodegenerative processes in temporal connections, possibly reflecting higher risk for cognitive impairment and dementia conversion in the future (Geda et al, 2006;Salloway et al, 1996;Schweitzer et al, 2002;van Ojen et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Ballmaier

Kumar

Elderkin‐Thompson

et al. 2007

Neuropsychopharmacol

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There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are regionspecific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age ¼ 68.00, SD75.83), 22 patients with late-onset depression (mean age ¼ 74.50, SD78.09) and 34 elderly control subjects (mean age ¼ 72.38; SD76.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late-vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late-from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late-and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than earlyonset depression, with potentially important implications for research and therapy.

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“…transporter (5-HTTLPR) were shown to influence hippocampal size in individuals with depression 11 and to influence the reactivity of the amygdala of healthy people 32 and those with social phobia 33 toward salient environmental cues. A longitudinal study found that genetic variation of the serotonin transporter was associated with the development of depres sion following stressful life events, suggesting a gene-byenvironment interaction in which the response to environmental insults is moderated by genetic factors.…”

Section: J Psychiatry Neurosci 2010;35(2)mentioning

confidence: 99%

“…Another possibility is that preexisting small hippocampal size increases the risk for developing anxiety or affective disorders. 10,11 However, structural brain imaging studies in social phobia are lacking. Given the fact that patients with traumatic and nontraumatic anxiety disorders share a pattern of medial temporal hyperactivity during functional neuroimaging, 1 investigation into structural aspects of the amygdala and hippocampus in social phobia are warranted.…”

Section: Introductionmentioning

confidence: 99%

Reduced amygdalar and hippocampal size in adults with generalized social phobia

Irle

Ruhleder

Lange

et al. 2010

jpn

121

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Background: Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. Methods: In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. Results: Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. Limitations: Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. Conclusion: We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response. Brief ReportReduced amygdalar and hippocampal size in adults with generalized social phobia IntroductionPresent evidence from functional brain imaging studies suggests that patients with social phobia, posttraumatic stress disorder (PTSD) or specific phobia share a pattern of hyperactivity of the amygdala and surrounding cortices, including the hippocampus, linked to negative emotional responses. 1 The majority of studies including patients with social phobia suggest that these changes may be most pronounced in the generalized subtype of social phobia (GSP). 2-4 A recent study suggests that these changes may resolve after successful psychotherapeutic or psychopharmacologic treatment of social phobia. 5 There is now an extensive body of evidence suggesting that PTSD 6 and major depressive disorder 7,8 are related to abnormal amygdalar and hippocampal size. However, the mechanisms underlying these changes are not well understood. Research in nonhuman primates has suggested that stress and prolonged glucocorticoid exposure may damage the hippocampus, 9 thus raising the possibility that stress may also induce hippocampal degeneration in humans with anxiety or affective disorders. Another possibility is that preexisting small hippocampal size increases the risk for developing anxiety or affective disorders. 10,11 However, structural brain imaging studies in social phobia are lacking. Given the fact that patients with traumatic and nontraumatic anxiety disorders share a pattern of medial temporal hyperactivity during functional neuroimaging, 1 investigation into structural aspects of the amygdala and hippocampus in social phobia are warranted. Furthermore, because the more severe form of social phobia (i.e., GSP) is likely associated with continuous and extreme stress, the possibility of a reduction of the size of the amygdal...

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Influence of Serotonin Transporter Promoter Region Polymorphisms on Hippocampal Volumes in Late-Life Depression

Cited by 167 publications

References 69 publications

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Reduced amygdalar and hippocampal size in adults with generalized social phobia

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