Neuroactive steroids in periphery and cerebrospinal fluid

Kancheva, Radmila; Hill, Martin; Novák, Zdeněk; Chrastina, Jan; Kancheva, Lyudmila; Stárka, L.

doi:10.1016/j.neuroscience.2011.05.054

Cited by 77 publications

(60 citation statements)

References 29 publications

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“…Should local CNS production of DHEA still proceed, it would nonetheless be dwarfed by the high net influx of peripheral DHEA into the CNS, the major portion of which is produced in the adrenal cortex (Compagnone and Mellon, 2000; Maninger et al, 2009). Further evidence supporting this model of DHEA synthesis comes from a study of human participants in which serum DHEA levels were shown to correlate with cerebrospinal fluid DHEA levels (Kancheva et al, 2011). DHEA rises steeply during middle childhood and adrenarche (i.e.…”

Section: Methodsmentioning

confidence: 92%

“…6–8 years of age) and remains at high levels throughout adolescence and young adulthood (Campbell, 2011; Remer et al, 2005). Further, the blood-brain barrier is highly permeable to the peripheral levels of DHEA produced by the adrenals (Kancheva et al, 2011; Kancheva et al, 2010). This, coupled with decreased uptake of DHEA into adipose tissue during childhood and adolescence, makes DHEA more available for CNS uptake (Benfield et al, 2008; Campbell, 2011; Dalla Valle et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Nguyen

Lew

et al. 2017

Psychoneuroendocrinology

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Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6–22 years old, mean age: 13.6 +/−3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues.

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Section: Methodsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Nguyen

Lew

et al. 2017

Psychoneuroendocrinology

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“…For example, DHEA can influence neural activity by binding to GABA A receptors (Majewska et al, 1990), whereas cortisol influences neural activity through actions at glucocorticoid and mineralocorticoid receptors (Patel et al, 2008). DHEA is also a neurosteroid present within brain regions supportive of decision-making (Kancheva et al, 2011; Maninger et al, 2009). These different mechanisms of action produce different cognitive effects(e.g., Davis et al, 2008; Shields et al, 2015); for example, DHEA administration reduces risk-taking in decision-making in individuals enrolled in an addiction recovery program (Ohana et al, 2015), whereas cortisol administration increases risk-taking in decision-making in healthy individuals (Putman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA

Shields

Lam

Trainor

et al. 2016

Psychoneuroendocrinology

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Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol.

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“…Furthermore, DHEA levels in the central nervous system are influenced by the peripheral levels of this neurosteroid and of its sulphate ester [35], implying that the increase in plasma DHEA-S we found might represent a real core marker rather than being a mere peripheral trait marker reflecting something that is occurring within the central nervous system of BPD patients. Morning salivary DHEA-S levels were increased in adult BPD women with respect to matched controls, while cortisol was unchanged with a consequent decrease in the CDR [11]; on the other hand, the CDR was found increased in patients with BPD and comorbid major depressive disorder [12], but, again, no previous report of this value in a BPD adolescent population exists.…”

Section: Discussionmentioning

confidence: 99%

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Conti

Nacinovich²,

Bomba³

et al. 2013

Neuropsychobiology

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Background: Borderline personality disorder (BPD) patients display a complex and heterogeneous clinical phenotype that plausibly implies variable underlying pathogenic mechanisms. A dysregulation of peripheral benzodiazepine receptors has previously been shown in BPD peripheral tissues, implying possible alterations of its ligand, the diazepam binding inhibitor (DBI) or of the downstream products of its activation, i.e. neuroactive steroids. Methods: The aim of this work consisted in assessing, by ELISA, fasting plasma levels of DBI and dehydroepiandrosterone sulphate (DHEA-S), including cortisol and the cortisol-to-DHEA-S molar ratio (CDR), in 17 BPD adolescents versus 13 healthy controls, testing the possibility that clinical scales related to depressive or anxious traits (CDI, STAI-Y) or to disease severity (BPDCL) might be associated with a selective dysregulation of these parameters. Results: DBI plasma levels were unchanged, while DHEA-S ones were significantly increased (approx. 70%) and the CDR decreased in BPD patients. No meaningful correlations with clinical variables emerged. Conclusion: Our results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels and that DHEA-S might represent a generalized trait marker for the altered stress response that is associated with this disorder.

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Neuroactive steroids in periphery and cerebrospinal fluid

Cited by 77 publications

References 29 publications

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

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