A 9-Year Prospective Population-Based Study on the Association Between the APOE*E4 Allele and Late-Life Depression in Sweden

Skoog, Ingmar; Wærn, Margda; Duberstein, Paul R.; Blennow, Kaj; Zetterberg, Henrik; Börjesson‐Hanson, Anne; Östling, Svante; Guo, Xinxin; Kern, Jürgen; Gustafson, Deborah; Gudmundsson, Pia; Marlow, Thomas; Kern, Silke

doi:10.1016/j.biopsych.2015.01.006

Cited by 73 publications

(87 citation statements)

References 78 publications

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“…Depression increases the risk of dementia even occurring over a decade before dementia onset, although the effect of earlier life depression is primarily in APOE ε4 carriers (Karlsson, et al 2015). Early work concluded that APOE genotype is not a risk factor for depression (Steffens, et al 2003), but recent longitudinal population-based studies found that the ε4 allele was associated with prospectively identified depressive symptoms (Skoog, et al 2015). Studies in depressed older populations report that ε4 carriers exhibit greater depression severity, poorer cognitive performance, and smaller frontotemporal volumes (Corsentino, et al 2009, Kim, et al 2002, Lavretsky, et al 2003, Niti, et al 2009, Qiu, et al 2009, Rajan, et al 2014, Yuan, et al 2010).…”

Section: Introductionmentioning

confidence: 99%

APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults

Taylor

Boyd

Turner

et al. 2016

Brain Imaging and Behavior

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The APOE ε4 allele is associated with cognitive deficits and brain atrophy in older adults, but studies in younger adults are mixed. We examined APOE genotype effects on cognition and brain structure in younger adults and whether genotype effects differed by age and with presence of depression. 157 adults (32% ε4 carriers, 46% depressed) between 20–50 years of age completed neuropsychological testing, 131 of which also completed 3T cranial MRI. We did not observe a direct effect of APOE genotype on cognitive performance or structural MRI measures. A significant genotype by age interaction was observed for executive function, where age had less of an effect on executive function in ε4 carriers. Similar interactions were observed for the entorhinal cortex, rostral and caudal anterior cingulate cortex and parahippocampal gyrus, where the effect of age on regional volumes was reduced in ε4 carriers. There were no significant interactions between APOE genotype and depression diagnosis. The ε4 allele benefits younger adults by allowing them to maintain executive function performance and volumes of cingulate and temporal cortex regions with aging, at least through age fifty years.

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Section: Introductionmentioning

confidence: 99%

APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults

Taylor

Boyd

Turner

et al. 2016

Brain Imaging and Behavior

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“…Results varied across country; evidence for APOE as the ‘G’ in G×E was found for the U.S. and Sweden, but not the Danish sample. Indeed, APOE associations with average depression symptoms and risk for a diagnosis of depression have been mixed across studies, perhaps due to differential population effects or study designs (Skoog et al 2015). APOE has been associated with depressive symptomatology and depression diagnosis in late adulthood in a prospective study of Swedish individuals even when excluding prevalent or incident dementia cases (Skoog et al.).…”

Section: Discussionmentioning

confidence: 99%

“…The APOE gene, coding for the major cholesterol transporter in the brain, and its ε4 haplotype in particular, has demonstrated associations with cognitive decline, Alzheimer’s disease (AD) and dementia (e.g., Bennet et al 2010; Davies et al 2014; Reynolds et al 2006; Schellenberg and Montine 2012). In addition, APOE has also shown some evidence of associations with, or moderation of, risk factors that are predictive of cognitive decline and dementia, including BMI (e.g., Besser et al 2014; Keller et al 2011) and depression (e.g., Karlsson et al 2015; Skoog et al 2015). …”

Section: Introductionmentioning

confidence: 99%

Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

et al. 2015

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Despite emerging interest in gene–environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a ‘variability gene’ across these measures and whether it partly represents the ‘G’ in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable—with both increasing and decreasing age-cohort trends—for different cognitive measures. Results also suggested that APOE may represent a ‘variability gene’ for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.

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“…(C) Heat map of EEF2, demonstrating increased expression in soluble fraction of synaptoneurosomes with brief mTORC1 inhibition. Data obtained from Niere et al, 2015 and (Aragam et al, 2011; De Vry et al, 2016; Dekker et al, 2012; Dlugos et al, 2009; Fatemi et al, 2001; Galeotti and Ghelardini, 2011; Gatt et al, 2015; Gray et al, 2015; Lee et al, 2010b; Liu et al, 2015; Luo et al, 2010; Ogawa and Kunugi, 2015; Ray et al, 2014; Rietschel et al, 2010; Sakaida et al, 2013; Shyn et al, 2011; Skoog et al, 2015; Stachowicz et al, 2015; Tadic et al, 2007; Unschuld et al, 2009; Wagner et al, 2015; Yoshimasu et al, 2015) for bioinformatics analysis.…”

Section: Figurementioning

confidence: 99%

Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression

et al. 2016

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Healthy neurons have an optimal operating range, coded globally by the frequency of action potentials or locally by calcium. The maintenance of this range is governed by homeostatic plasticity. Here, we discuss how new approaches to treat depression alter synaptic activity. These approaches induce the neuron to recruit homeostatic mechanisms to relieve depression. Homeostasis generally implies that the direction of activity necessary to restore the neuron’s critical operating range is opposite in direction to its current activity pattern. Unconventional antidepressant therapies deep brain stimulation and NMDAR antagonists alter the neuron’s “depressed” state by pushing the neuron’s current activity in the same direction but to the extreme edge. These therapies rally the intrinsic drive of neurons in the opposite direction, thereby allowing the cell to return to baseline activity, form new synapses, and restore proper communication. In this review, we discuss seminal studies on protein synthesis dependent homeostatic plasticity and their contribution to our understanding of molecular mechanisms underlying the effectiveness of NMDAR antagonists as rapid antidepressants. Rapid antidepressant efficacy is likely to require a cascade of mRNA translational regulation. Emerging evidence suggests that changes in synaptic strength or intrinsic excitability converge on the same protein synthesis pathways, relieving depressive symptoms. Thus, we address the question: Are there multiple homeostatic mechanisms that induce the neuron and neuronal circuits to self-correct to regulate mood in vivo? Targeting alternative ways to induce homeostatic protein synthesis may provide, faster, safer, and longer lasting antidepressants.

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A 9-Year Prospective Population-Based Study on the Association Between the APOE*E4 Allele and Late-Life Depression in Sweden

Cited by 73 publications

References 78 publications

APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults

APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults

Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression

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