HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition

Keller, Jennifer; Gomez, Rowena; Williams, Gordon H.; Lembke, Anna; Lazzeroni, Laura C.; Murphy, Greer M.; Schatzberg, Alan F.

doi:10.1038/mp.2016.120

Cited by 616 publications

(359 citation statements)

References 60 publications

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“…Cortisol levels were found to be elevated in psychotic depression and correlated negatively with verbal memory and processing speed across all subjects. This finding was recently replicated and extended to implicate genetic variation in psychotic depression as a mechanism for the relationship between cortisol and cognitive performance (Keller et al 2017). …”

Section: Introductionmentioning

confidence: 76%

Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective

Karcher²,

2018

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Individuals with disorders that include psychotic symptoms (i.e. psychotic disorders) experience broad cognitive impairments in the chronic state, indicating a dimension of abnormality associated with the experience of psychosis. These impairments negatively impact functional outcome, contributing to the disabling nature of schizophrenia, bipolar disorder, and psychotic depression. The robust and reliable nature of cognitive deficits has led researchers to explore the timing and profile of impairments, as this may elucidate different neurodevelopmental patterns in individuals who experience psychosis. Here, we review the literature on cognitive deficits across the life span of individuals with psychotic disorder and psychotic-like experiences, highlighting the dimensional nature of both psychosis and cognitive ability. We identify premorbid generalized cognitive impairment in schizophrenia that worsens throughout development, and stabilizes by the first-episode of psychosis, suggesting a neurodevelopmental course. Research in affective psychosis is less clear, with mixed evidence regarding premorbid deficits, but a fairly reliable generalized deficit at first-episode, which appears to worsen into the chronic state. In general, cognitive impairments are most severe in schizophrenia, intermediate in bipolar disorder, and the least severe in psychotic depression. In all groups, cognitive deficits are associated with functional outcome. Finally, while the generalized deficit is the clearest and most reliable signal, data suggests specific deficits in verbal memory across all groups, specific processing speed impairments in schizophrenia and executive functioning impairments in bipolar disorder. Cognitive deficits are a core feature of psychotic disorders that provide a window into understanding developmental course and risk for psychosis.

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Section: Introductionmentioning

confidence: 76%

Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective

Karcher²,

2018

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“…Prior studies have shown that prenatal Dex exposure can result in increased hypothalamic-pituitary-adrenal (HPA) activity (35,36). The data from human and animal studies have shown that higher HPA activity contributes to major depressive disorders (MDD) (37,38). We therefore examined circulating corticosterone level in F1 and F2 offspring.…”

Section: Prenatal Dex Exposure Increases Crhr1 Gene Expression In Hipmentioning

confidence: 99%

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

Sheng

et al. 2018

FASEB j.

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Pregnant women at risk of preterm labor usually receive synthetic glucocorticoids (sGCs) to promote fetal lung development. Emerging evidence indicates that antenatal sGC increases the risk of affective disorders in offspring. Data from animal studies show that such disorders can be transmitted to the second generation. However, the molecular mechanisms underlying the intergenerational effects of prenatal sGC remain largely unknown. Here we show that prenatal dexamethasone (Dex) administration in late pregnancy induced depression-like behavior in first-generation (F1) offspring, which could be transmitted to second-generation (F2) offspring with maternal dependence. Moreover, corticotropin-releasing hormone (CRH) and CRH receptor type 1 (CRHR1) expression in the hippocampus was increased in F1 Dex offspring and F2 offspring from F1 Dex female rats. Administration of a CRHR1 antagonist to newborn F1 Dex offspring alleviated depression-like behavior in these rats at adult. Furthermore, we demonstrated that increased CRHR1 expression in F1 and F2 offspring was associated with hypomethylation of CpG islands in Crhr1 promoter. Our results revealed that prenatal sGC exposure could program Crh and Crhr1 gene expression in hippocampus across 2 generations, thereby leading to depression-like behavior. Our study indicates that prenatal sGC can cause epigenetic instability, which increases the risk of disease development in the offspring's later life.-Xu, Y.-J., Sheng, H., Wu, T.-W., Bao, Q.-Y., Zheng, Y., Zhang, Y.-M., Gong, Y.-X., Lu, J.-Q., You, Z.-D., Xia, Y., Ni, X. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.

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“…Conversely, people with depression and a history of childhood trauma may have blunted cortisol responses to stress, compared to those with depression and no early-life trauma 128. Stress-induced HPA axis alterations appear interrelated with cognitive function,129 as well as depression subtype or variation in HPA-related genes 130. Stress also has short- and long-term impairing effects on neurogenesis131 and other neural mechanisms 132.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for depression: recent insights, current challenges and future prospects

Strawbridge¹,

Young²,

Cleare³

2017

NDT

306

156

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A plethora of research has implicated hundreds of putative biomarkers for depression, but has not yet fully elucidated their roles in depressive illness or established what is abnormal in which patients and how biologic information can be used to enhance diagnosis, treatment and prognosis. This lack of progress is partially due to the nature and heterogeneity of depression, in conjunction with methodological heterogeneity within the research literature and the large array of biomarkers with potential, the expression of which often varies according to many factors. We review the available literature, which indicates that markers involved in inflammatory, neurotrophic and metabolic processes, as well as neurotransmitter and neuroendocrine system components, represent highly promising candidates. These may be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomic and neuroimaging assessments. The use of novel approaches and systematic research programs is now required to determine whether, and which, biomarkers can be used to predict response to treatment, stratify patients to specific treatments and develop targets for new interventions. We conclude that there is much promise for reducing the burden of depression through further developing and expanding these research avenues.

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HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition

Cited by 616 publications

References 60 publications

Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective

Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

Biomarkers for depression: recent insights, current challenges and future prospects

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