Increased α2- and β1-adrenoceptor densities in postmortem brain of subjects with depression: Differential effect of antidepressant treatment

Rivero, Guadalupe; Gabilondo, Ane M.; Garcı́a-Sevilla, Jesús A.; Harpe, R. La; Callado, Luís F.; Meana, J. Javier

doi:10.1016/j.jad.2014.06.016

Cited by 33 publications

(15 citation statements)

References 47 publications

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“…All β _________________________________________ receptor subtypes couple to the stimulatory Gprotein (Gs) therefore activate the cyclic adenosine monophosphate (cAMP) signalling. Regarding the association between upregulation of βARs and depression it may be concluded that some classes of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) may downregulate and desensitize these receptors in brain (22,23).The functional polymorphism, G1165C, causing an amino acid variation Gly389Arg in the βAR gene was recently identified. Several lines of study suggest that C allele of this polymorphism may enhance coupling to the Gs protein and thereafter increase adenylyl cyclase activation (24,25).…”

Section: Introductionmentioning

confidence: 99%

Beta Adrenoceptor Polymorphism and Clinical Response to Sertraline in Major Depressive Patients

et al. 2017

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-Purpose: The adrenoceptor family, as one of the main contributors in regulating the noradrenergic system, has been studied in involvement of depression and its treatment. A functional polymorphism of G1165C on beta adrenoceptor (βAR) enhances post receptor signalling and is assumed to be involved in pharmacotherapy of depression. The aim of the present study was to discern the influence of G1165C polymorphism in the β1AR gene on individual differences in response to sertraline. Methods: One hundred newly diagnosed patients completed 6 weeks of sertraline treatment. Response to treatment was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD). Results: The patients who carried CC genotype responded five times more to sertraline comparing with other variants (P=0.005; OR=5.7; 95%CI=1.4-23.9). Moreover, carriers of C allele responded three times more to sertraline than patients with the G allele (P=0.001; OR= 3.3; 95%CI= 1.72-6.50). Conclusion:In conclusion, our results support the hypothesis that genetic variation of β1AR might influence clinical response to sertraline.

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Section: Introductionmentioning

confidence: 99%

Beta Adrenoceptor Polymorphism and Clinical Response to Sertraline in Major Depressive Patients

et al. 2017

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“…These results suggest a resistance of α 2 -ARs to the downregulatory effect of ADTs, a potentially important consideration in the development of future ADTs. However, as the majority of brain tissue used in this study was collected from patients who committed suicide (48), these results also indicate that it is important to consider the role of α 2 -ARs in patients with MDD with respect to suicidality and treatment response.…”

Section: Resultsmentioning

confidence: 95%

“…Using radioligand saturation binding experiments, α 2 - and β 1 -AR densities were found to be higher in the prefrontal cortex of ADT-free patients with MDD than controls, possibly as a compensation associated with altered NE turnover in MDD. In antidepressant-treated patients, α 2 -AR density remained increased over controls, whereas no difference was observed in β 1 -AR densities (48). These results suggest a resistance of α 2 -ARs to the downregulatory effect of ADTs, a potentially important consideration in the development of future ADTs.…”

Section: Resultsmentioning

confidence: 99%

“…Rivero et al (2014) investigated the density of ARs in MDD (48). Using radioligand saturation binding experiments, α 2 - and β 1 -AR densities were found to be higher in the prefrontal cortex of ADT-free patients with MDD than controls, possibly as a compensation associated with altered NE turnover in MDD.…”

Section: Resultsmentioning

confidence: 99%

“…The higher density of α 2 -ARs in both ADT-free and antidepressant-treated patients with depression compared with matched controls suggests that these receptors are resistant to the observed downregulation of β 1 -ARs by ADTs (48). In a preclinical study in rats, treatment with the SSRI citalopram did not result in any adaptive changes in LC neurons, but did indirectly enhance the inhibitory effect of NE on neurons in the LC (94).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review

et al. 2017

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Norepinephrine (NE) is recognized as having a key role in the pathophysiology of major depressive disorder (MDD) and schizophrenia, although its distinct actions via α-adrenergic receptors (α-ARs) are not well defined. We performed a systematic review examining the roles of NE and α-ARs in MDD and schizophrenia. PubMed and ProQuest database searches were performed to identify English language papers published between 2008 and 2015. In total, 2,427 publications (PubMed, n = 669; ProQuest, n = 1,758) were identified. Duplicates, articles deemed not relevant, case studies, reviews, meta-analyses, preclinical reports, or articles on non-target indications were excluded. To limit the review to the most recent data representative of the literature, the review further focused on publications from 2010 to 2015, which were screened independently by all authors. A total of 16 research reports were identified: six clinical trial reports, six genetic studies, two biomarker studies, and two receptor studies. Overall, the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition, arousal, and valence systems associated with MDD and schizophrenia. Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases. Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases, in particular with relation to specific valence systems. Clinical studies that attempt to define associations between specific receptor binding profiles of psychotropics and particular clinical outcomes are needed.

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Polygenic risk scores for neuropsychiatric, inflammatory, and cardio‐metabolic traits highlight possible genetic overlap with suicide attempt and treatment‐emergent suicidal ideation

Fanelli

Sokolowski

Wasserman

et al. 2022

American J of Med Genetics Pt B

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Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts.Results were then meta-analyzed across samples, including a total of 688 patients with SA (N eff = 2,258) and 214 with TWESI (N eff = 785). Stratified genetic covariance analyses were performed to investigate functionally cross-phenotype PRS associations.After Bonferroni correction, PRS for major depressive disorder (MDD) was associated

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Increased α2- and β1-adrenoceptor densities in postmortem brain of subjects with depression: Differential effect of antidepressant treatment

Cited by 33 publications

References 47 publications

Beta Adrenoceptor Polymorphism and Clinical Response to Sertraline in Major Depressive Patients

Beta Adrenoceptor Polymorphism and Clinical Response to Sertraline in Major Depressive Patients

The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review

Polygenic risk scores for neuropsychiatric, inflammatory, and cardio‐metabolic traits highlight possible genetic overlap with suicide attempt and treatment‐emergent suicidal ideation

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