Neuropathological relationship between major depression and dementia: A hypothetical model and review

Kim, Helena Kyunghee; Nunes, Paula; Oliveira, Kátia C.; Young, L. Trevor; Lafer, Beny

doi:10.1016/j.pnpbp.2016.01.008

Cited by 98 publications

(50 citation statements)

References 112 publications

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“…Finally, our exploratory analysis on serologic parameters related to inflammation and oxidative stress processes (performed only in the Greek subsample) showed some nominal associations with the variants investigated. Taking into account that impairment of these 2 processes has been linked with both LOAD [50, 51] and depression [52, 53], this may point at a partial common genetic background between LOAD and depression [54]. Obviously, further studies are needed to confirm these hypotheses, particularly when considering the exploratory nature of these analyses.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

et al. 2019

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Background: Alzheimer’s disease (AD) is a neurodegenerative disorder accounting for 60–70% of dementia cases. Genetic origin accounts for 49–79% of disease risk. This paper aims to investigate the association of 17 polymorphisms within 7 genes involved in neurotransmission (COMT, HTR2A, PPP3CC, RORA, SIGMAR1, SIRT1, and SORBS3) and AD. Methods: A Greek and an Italian sample were investigated, for a total of 156 AD subjects and 301 healthy controls. Exploratory analyses on psychosis and depression comorbidities were performed, as well as on other available clinical and serological parameters. Results: AD was associated with rs4680 within the COMT gene in the total sample. Trends of association were found in the 2 subsamples. Some nominal associations were found for the depressive phenotype. rs10997871 and rs10997875 within SIRT1 were nominally associated with depression in the total sample and in the Greek subsample. rs174696 within COMT was associated with depression comorbidity in the Italian subsample. Discussion: Our data support the role of COMT, and particularly of rs4680, in the pathogenesis of AD. Furthermore, the SIRT1 gene seems to modulate depressive symptomatology in the AD population.

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Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

et al. 2019

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“…van Mierlo et al (22) demonstrated a complex relationship between depression and brain structure in PD: depression scores negatively correlated with bilateral hippocampus and right amygdala volume and positively with anterior cingulate cortex volume. It has been suggested that depression and neurodegenerative processes may share several pathophysiological features, including decreased production of neurotrophic factors, reduced neurogenesis, abnormal synaptic plasticity, and enhanced neuroinflammation in the hippocampus (58). …”

Section: Discussionmentioning

confidence: 99%

Reduced CA2–CA3 Hippocampal Subfield Volume Is Related to Depression and Normalized by l-DOPA in Newly Diagnosed Parkinson’s Disease

et al. 2017

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Hippocampal dysfunctions may play an important role in the non-motor aspects of Parkinson’s disease (PD), including depressive and cognitive symptoms. Fine structural alterations of the hippocampus and their relationship with symptoms and medication effects are unknown in newly diagnosed PD. We measured the volume of hippocampal subfields in 35 drug-naïve, newly diagnosed PD patients without cognitive impairment and 30 matched healthy control individuals. Assessments were performed when the patients did not receive medications and after a 24-week period of l-DOPA treatment. We obtained a T1-weighted 3D magnetization-prepared rapid acquisition gradient echo image at each assessment. FreeSurfer v6.0 was used for image analysis. Results revealed a selectively decreased CA2–CA3 volume in non-medicated PD patients, which was normalized after the 24-week treatment period. Higher depressive symptoms were associated with smaller CA2–CA3 volumes. These results indicate that the CA2–CA3 subfield is structurally affected in the earliest stage of PD in the absence of cognitive impairment. This structural anomaly, normalized by l-DOPA, is related to depressive non-motor symptoms.

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“…In fact, the largest ever and most recent worldwide meta-analysis of cortical thickness reductions in depressed patients relative to controls reported the largest effect sizes in medial orbitofrontal cortices (55). Cognitive decline in the elderly is frequently accompanied by depressed mood (56, 57), and neurodegeneration appears to play an important role in the pathogenesis of depression associated with cognitive complaints (58). Here, we examined predictors of mood scores and found that the only two variables significantly associated with depressive symptoms were medial orbitofrontal atrophy and cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

Roussotte

Hou

Narr

et al. 2017

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Introduction The C677T functional variant in the methylene-tetrahydrofolate reductase (MTHFR) gene leads to reduced enzymatic activity and elevated blood levels of homocysteine. Hyperhomocysteinemia has been linked with higher rates of cardiovascular diseases, cognitive decline, and late-life depression. Methods and Materials Here, 3D magnetic resonance imaging data was analyzed from 738 individuals (age: 75.5 ± 6.8 years; 438 men/300 women) including 173 Alzheimer's patients, 359 subjects with mild cognitive impairment, and 206 healthy older adults, scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results We found that this variant associates with localized brain atrophy, after controlling for age, sex, and dementia status, in brain regions implicated in both intellectual and emotional functioning, notably the medial orbitofrontal cortices. The medial orbitofrontal cortex is involved in the cognitive modulation of emotional processes, and localized atrophy in this region was previously linked with both cognitive impairment and depressive symptoms. Here, we report that increased plasma homocysteine mediates the association between MTHFR genotype and lower medial orbitofrontal volumes, and that these volumes mediate the association between cognitive decline and depressed mood in this elderly cohort. We additionally show that vitamin B12 deficiency interacts with the C677T variant in the etiology of hyperhomocysteinemia. Conclusion This study sheds light on important relationships between vascular risk factors, age-related cognitive decline, and late-life depression, and represents a significant advance in our understanding of clinically relevant associations relating to MTHFR genotype.

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Neuropathological relationship between major depression and dementia: A hypothetical model and review

Cited by 98 publications

References 112 publications

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Reduced CA2–CA3 Hippocampal Subfield Volume Is Related to Depression and Normalized by l-DOPA in Newly Diagnosed Parkinson’s Disease

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

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