Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks

Jovanovic, Hristina; Perski, Aleksander; Berglund, Hans; Savić, Ivanka

doi:10.1016/j.neuroimage.2010.12.060

Cited by 123 publications

(101 citation statements)

References 70 publications

(89 reference statements)

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“…In support of this, the G-allele was associated with reduced amygdala activation in normal subjects [156]. Interestingly, in panic disorder and depressed patients the G-allele associated with increased amygdala activation but reduced right prefrontal cortex activation [157,158], suggesting altered fear circuitry [124]. In addition, recent findings have associated the G(-1019) allele with reductions in cognitive functioning in mismatch, attentional and error monitoring paradigms [159 -162].…”

Section: Association Studies Of Htr1a Polymorphisms In Depression-andmentioning

confidence: 77%

“…On the other hand, depression appears to be driven by reduced 5-HT neurotransmission, in part due to an increase in pre-synaptic 5-HT 1A autoreceptors which inhibits the release of 5-HT. As well, depression is associated with reduced levels of 5-HT 1A heteroreceptors, particularly in the hippocampus and prefrontal cortex, that may be induced in part by chronic stress [124]. These results suggest that strategies that target preferentially postsynaptic 5-HT 1A heteroreceptors may have greater effects in anxiety [125], while strategies that both augment 5-HT release and enhance post-synaptic 5-HT 1A signalling would be more effective to treat depression.…”

Section: Implications Of 5-ht 1a Autoreceptor Dysregulation For Mentamentioning

confidence: 80%

“…depression with co-morbid anxiety [150]) or specific endophenotypes (e.g. limbic activation, amygdala volume), appears to provide stronger associations in very small depression cohorts [124,157,173]. However, these studies need independent replication.…”

Section: Association Studies Of Htr1a Polymorphisms In Depression-andmentioning

confidence: 99%

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Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Albert

2012

Phil. Trans. R. Soc. B

118

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The serotonin-1A (5-HT 1A ) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre-and post-synaptic 5-HT 1A receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre-versus post-synaptic 5-HT 1A receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT 1A receptor gene (Htr1a). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT 1A autoreceptor expression in animal models and humans. Its association with altered 5-HT 1A expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene Â environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT 1A heteroreceptors, and rs6295-induced upregulation of 5-HT 1A autoreceptors. Targeted therapeutics to inhibit 5-HT 1A autoreceptor expression and induce 5-HT 1A heteroreceptor expression may ameliorate treatment of anxiety and major depression.

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Section: Association Studies Of Htr1a Polymorphisms In Depression-andmentioning

confidence: 77%

Section: Implications Of 5-ht 1a Autoreceptor Dysregulation For Mentamentioning

confidence: 80%

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Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Albert

2012

Phil. Trans. R. Soc. B

118

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“…Exposure to stressors modulates 5-HT1A levels in a variety of primate and non-primate species (Franklin et al, 2011;Jovanovic et al, 2011;Leventopoulos et al, 2009;Lopez et al, 1998;Spinelli et al, 2010;Wang et al, 2009). Also, in humans, 5-HT1A levels are impacted by a functional C(-1019)G single-nucleotide promoter polymorphism (SNP; rs6295) (Albert, 2012).…”

Section: -Ht1a-mediated Anxiety Phenotypes Are Developmental In Originmentioning

confidence: 99%

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Donaldson

Piel

Santos

et al. 2013

Neuropsychopharmacol

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The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders.

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“…Longterm exposure to stress has also been associated with cognitive impairments measured by neuropsychological testing (8,(32)(33)(34)(35)(36)(37)(38)). Yet it is still unclear whether cognitive failures make one susceptible to stress or if stress causes the cognitive failures.…”

Section: Stress and Cognitionmentioning

confidence: 99%

Changes in self-reported sleep and cognitive failures: a randomized controlled trial of a stress management intervention

Dalgaard¹,

Eskildsen²,

Carstensen³

et al. 2014

Scand J Work Environ Health

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Changes in self-reported sleep and cognitive failures: a randomized controlled trial of a stress management intervention by Dalgaard L, Eskildsen A, Carstensen O, Willert MV, Andersen JH, Glasscock DJ This is the first RCT study of a stress management intervention testing the efficacy of individual cognitive behavior therapy (CBT) in combination with a brief workplace intervention on sleep problems and cognitive failures. Knowledge about these outcomes and their development over time is highly relevant in the treatment of patients on sick leave due to work stress. Objectives This study evaluated the effectiveness of a stress management intervention combining individual cognitive behavioral therapy (CBT) with a brief workplace intervention on self-reported measures of sleep and cognitive functioning among patients on sick leave due to work-related stress complaints. AffiliationMethods Participants were patients referred to the regional Department of Occupational Medicine. Inclusion criteria were (i) sick leave due to work-related stress complaints and (ii) a diagnosis of adjustment disorder/ reactions to stress or mild depression. Participants (N=137) were randomized to either an intervention (N=57) or control (N=80) group. The intervention comprised six sessions with a psychologist and the offer of a small workplace intervention. Questionnaires were answered at baseline and after 4, and 10 months.Results Symptoms were significantly reduced over time in both groups but there was no significant treatment effect on sleep or cognitive outcomes at any time point. From 0-4 months, there was a tendency for larger improvements in the intervention group with regards to sleep and cognitive failures in distraction. Although neither was significant, the results came close to significance depicting a small effect size (Cohen's d) on sleep complaints and distractions (but not memory). ConclusionsThe specific intervention was not superior to the control condition in reducing symptoms of sleep problems and cognitive difficulties at any time point during the 10-month follow-up period. Substantial improvements in symptoms over time were seen in both groups.

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Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks

Cited by 123 publications

References 70 publications

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Changes in self-reported sleep and cognitive failures: a randomized controlled trial of a stress management intervention

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Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks

Cited by 123 publications

References 70 publications

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Changes in self-reported sleep and cognitive failures: a randomized controlled trial of a stress management intervention

Contact Info

Product

Resources

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Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness