Glucocorticoid interactions with memory function in schizophrenia

Newcomer, John W.; Craft, Suzanne; Askins, Kelly; Hershey, Tamara; Bardgett, Mark E.; Csernansky, John G.; Gagliardi, Amy E; Vogler, George P.

doi:10.1016/s0306-4530(97)00081-4

Cited by 39 publications

(18 citation statements)

References 19 publications

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“…Our results are consistent with other studies focused on exploring the relationship between cortisol levels and memory functions in animals (Wolf, 2003), healthy individuals (Lee et al, 2007;McAllister-Williams & Rugg, 2002), and schizophrenia patients (Newcomer et al, 1998;Ritsner & Strous, 2010;Walder et al, 2000), but in contradiction with the study aimed at studying relationship between HPA axis activity and cognition in patients with first-episode psychosis (Aas et al, 2011). The authors found in patients (not in a control group) a significant correlation only between cortisol awakening response and a more severe deficit in verbal memory; they found no correlation between daytime cortisol levels and cognitive functioning.…”

Section: Discussionsupporting

confidence: 93%

Cognitive impairment and cortisol levels in first-episode schizophrenia patients

Havelka

Prikrylova-Kucerova

Přikryl

et al. 2016

Stress

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Many modalities of cognition are affected in schizophrenia. The most common findings include dysfunctions of episodic and working memory and of executive functions. Although an inverse correlation between cortisol level and memory function has been proven, few studies have focused on the relationship between cortisol level and cognitive impairment in patients with schizophrenia. In an open, naturalistic, prospective study, consecutively hospitalized males diagnosed with first-episode schizophrenia, hypothalamic-pituitary-adrenal axis activity (afternoon cortisol levels, post-dexamethasone cortisol levels) was evaluated before and at the end of acute treatment. Psychopathology was assessed using the positive and negative syndrome scale (PANSS). Cognitive functions (memory, attention, psychomotor, verbal fluency, and executive functions) were tested after symptom alleviation using a neurocognitive test battery. In the total sample (n = 23), significant decreases in total PANSS score (including all subscales), afternoon cortisol levels, and post-dexamethasone cortisol levels occurred during the course of treatment. It was found that higher afternoon cortisol levels at the beginning of treatment were significantly related to impaired performance in memory functions. Afternoon cortisol levels were not significantly associated with other measured cognitive functions. No correlation was discovered between cognitive functions and post-dexamethasone cortisol levels. The determination of afternoon cortisol levels may serve to detect potential candidates for specific cognitive intervention immediately after the first psychotic breakthrough.

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Section: Discussionsupporting

confidence: 93%

Cognitive impairment and cortisol levels in first-episode schizophrenia patients

Havelka

Prikrylova-Kucerova

Přikryl

et al. 2016

Stress

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“…Furthermore, hippocampal atrophy and severity of cognitive impairment in AD patients are correlated with dysfunctions of the HPA axis (72). Corticosteroids can facilitate neuronal apoptosis in the hip- pocampus as well as memory impairment (73)(74)(75)(76). In this report, we found that RCAN1 transcription is tightly regulated, and the stress hormone dexamethasone can specifically up-regulate RCAN1 gene expression by activating the neuronal tissueenriched isoform 1 promoter of the RCAN1 gene.…”

Section: Discussionmentioning

confidence: 64%

Regulator of Calcineurin 1 (RCAN1) Facilitates Neuronal Apoptosis through Caspase-3 Activation

Sun

Chen

et al. 2011

Journal of Biological Chemistry

102

138

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Individuals with Down syndrome (DS) will inevitably developAlzheimer disease (AD) neuropathology sometime after middle age, which may be attributable to genes triplicated in individuals with DS. The characteristics of AD neuropathology include neuritic plaques, neurofibrillary tangles, and neuronal loss in various brain regions. The mechanism underlying neurodegeneration in AD and DS remains elusive. Regulator of calcineurin 1 (RCAN1) has been implicated in the pathogenesis of DS. Our data show that RCAN1 expression is elevated in the cortex of DS and AD patients. RCAN1 expression can be activated by the stress hormone dexamethasone. A functional glucocorticoid response element was identified in the RCAN1 isoform 1 (RCAN1-1) promoter region, which is able to mediate the upregulation of RCAN1 expression. Here we show that overexpression of RCAN1-1 in primary neurons activates caspase-9 and caspase-3 and subsequently induces neuronal apoptosis. Furthermore, we found that the neurotoxicity of RCAN1-1 is inhibited by knock-out of caspase-3 in caspase-3 ؊/؊ neurons. Our study provides a novel mechanism by which RCAN1 functions as a mediator of stress-and A␤-induced neuronal death, and overexpression of RCAN1 due to an extra copy of the RCAN1 gene on chromosome 21 contributes to AD pathogenesis in DS. Down syndrome (DS)4 is the most common genetic cause of mental retardation, affecting approximately one in 800 -1,000 babies (1). Individuals with DS inevitably develop characteristic Alzheimer disease (AD) neuropathology, which includes neuritic plaques, neurofibrillary tangles, and neuronal cell death following middle age (2-5). DS is a valuable model system for understanding AD pathogenesis. Both DS and AD feature prominent neuronal losses in the hippocampus and cortex, resulting in progressive cognitive deficits in AD patients (5). Apoptosis has been implicated in playing a major role in neuronal cell death in both AD and DS (6 -9). Increased immunoreactivity of activated caspase-3 is observed in neurons of AD and DS (7); however, the underlying mechanism leading to neuronal apoptosis in AD and DS remains elusive.The development of DS is caused by the presence of an extra copy of human chromosome 21 (10, 11). The DSCR1 (Down syndrome critical region 1) gene was identified and located on chromosome 21 (12, 13). Dysregulation of a regulatory circuit involving DSCR1-calcineurin-nuclear factor of activated T cells (NFAT) plays an important role in DS development (14). DSCR1 proteins physically interact with calcineurin subunit A and inhibit calcineurin activity in vitro and in vivo (15-19). DSCR1 was accordingly renamed as RCAN1 (regulator of calcineurin 1) (20). RCAN1 is phosphorylated at Ser 112 by BMK1 (big MAP kinase 1), which is the priming site for the subsequent phosphorylation at Ser 108 by GSK-3 (21-24). The phosphorylation form of RCAN1 can release the inhibition effect on calcineurin. Furthermore, phosphorylated RCAN1 is a substrate for calcineurin (79). RCAN1 FLISPP motif phosphorylation could increase its ab...

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“…There have been many reports about associations between memory performances and plasma glucocorticoid concentrations in Alzheimer's dementia, schizophrenia, and depression (Cohen et al, 1982;Reus, 1984;Hatzinger et al, 1995;Newcomer et al, 1998;Dong et al, 2004). Corticosterone, one of the glucocorticoids, is the most abundantly circulating hormone in the rat (Garcia-Bueno et al, 2007) and is produced by the stress-responsive hypothalamic-pituitary-adrenal axis (Newcomer et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

BT‐11 improves stress‐induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains

Shin

Won²,

Heo

et al. 2008

J of Neuroscience Research

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In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.

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Glucocorticoid interactions with memory function in schizophrenia

Cited by 39 publications

References 19 publications

Cognitive impairment and cortisol levels in first-episode schizophrenia patients

Cognitive impairment and cortisol levels in first-episode schizophrenia patients

Regulator of Calcineurin 1 (RCAN1) Facilitates Neuronal Apoptosis through Caspase-3 Activation

BT‐11 improves stress‐induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains

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