Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls

Schinke, Christian; Hesse, Swen; Rullmann, Michael; Becker, Georg-Alexander; Luthardt, Julia; Zientek, Franziska; Patt, Marianne; Stoppe, Muriel; Schmidt, Elisa; Meyer, Kara; Meyer, Philipp; Orthgieß, Johannes; Blüher, Matthias; Kratzsch, Jürgen; Ding, Yu‐Shin; Bergh, Florian Then; Sabri, Osama

doi:10.1080/10253890.2018.1511698

Cited by 12 publications

(14 citation statements)

References 49 publications

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“…MS is associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis 34,35 , and one important driver of HPA axis activity is noradrenergic stimulation by brainstem afferents, terminating in the hypothalamus. A negative association between hypothalamic NAT availability and HPA axis responsiveness could recently be shown in other entities with pronounced stress axis activity 36 . Although we cannot support this interpretation by functional data from the same cohort, the lower hypothalamic NAT availability may reflect more pronounced NA transporter occupancy by higher synaptic concentrations of NA or lower NA reuptake in this specific target area.…”

Section: Discussionmentioning

confidence: 89%

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

Schmidt

Schinke

Rullmann

et al. 2020

Sci Rep

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The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood, and exerts antiinflammatory and neuroprotective effects. Alterations of monoamine signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. We assessed central noradrenaline transporter (NAT) availability using positron emission tomography (PET) and the NAT selective radiotracer S,S-[ 11 c] O-methylreboxetine in immunotherapy-naïve patients with relapsing-remitting MS (RRMS; n = 11) compared to healthy controls (HC; n = 12), and its association to lesion load, time since manifestation, the expanded disability status scale (EDSS), the fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI). We found NAT availability to be increased in the thalamus, amygdala, putamen and pons/midbrain of MS patients. No relation to clinical or psychometric variables was found. These first data indicate higher NAT availability in subcortical brain regions of immunotherapy-naïve RRMS patients. If these changes of noradrenergic neurotransmission predispose to psychiatric symptoms or associate with disease activity needs to be investigated in longitudinal studies or a larger sample which allows subgroup analyses. Abbreviations [ 11 C]MRB S,S-[ 11 C]O-methylreboxetine BDI Beck depression inventory BMI Body mass index BP ND Binding potential DMT Disease modifying therapy DRKS German clinical trials register DVR Distribution volume ratio EAE Experimental autoimmune encephalitis EDSS Expanded disability status scale FWHM Full-width at half maximum HC Healthy controls

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Section: Discussionmentioning

confidence: 89%

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

Schmidt

Schinke

Rullmann

et al. 2020

Sci Rep

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“…AVP is mainly produced by the hypothalamic paraventricular nucleus and regulated by various neurons from different brain areas [9]. AVP is a sympathetically activated effector, and its neurons can receive excitatory impulses transmitted from noradrenergic neurons in locus coeruleus during stress [20]. Many studies have shown that AVP is paramount in regulating the cardiovascular system, endocrine system, anxiety, depression, other physical diseases, and behavior and memory [21].…”

Section: Discussionmentioning

confidence: 99%

Correlation between Serum Levels of Sympathetic Nerve Activity Markers and Sleep Quality and Cognitive Function in Patients with Chronic Insomnia Disorder

Chen¹,

Hu²,

Song³

et al. 2021

J. Adv. Neurosci. Res.

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Objectives: To explore the changes of the serum levels of copeptin and α-amylase and the correlations with sleep quality and cognition function in the patients with chronic insomnia disorder (CID). Methods: Fifty-seven CID patients and thirty healthy controls were enrolled continuously. Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG) and Pre-Sleep Arousal Scale (PSAS) were used to assess the insomnia severity and cognitive and somatic manifestations of arousal experienced at bedtime. Montreal Cognitive Assessment scale (MoCA) and Nine-Box Maze were used to respectively assess general cognition and memories. The serum levels of copeptin and α-amylase were detected using Enzyme-Linked ImmunoSorbent Assay. Results: Compared to the controls, the CID patients had increased PSQI and PSAS scores (Z=‒7.678 and ‒7.350; Ps<0.001), decreased MoCA score (t=‒4.625, P<0.001), increased numbers of errors in the object working, spatial working and object recognition (Z=‒2.099, ‒3.935 and ‒2.266; Ps<0.05) memories, and elevated serum levels of copeptin and α-amylase (t=5.414 and 5.597, P <0.001). In the CID patients，the level of copeptin positively correlated with PSQI and PSAS scores (r=0.338 and 0.316; Ps<0.05), and PSG sleep latency, wake time and N1% (r=0.324, 0.325 and 0.278, Ps<0.05), and negatively correlated with PSG N 2% (r=‒0.279, Ps<0.05). Alpha-amylase was positively correlated with waking numbers in PSG (r=0.293, P< 0.05). Multiple linear regression analysis showed that copeptin level affected PSQI score and PSG sleep latency (P<0.05). Conclusions: The serum levels of copeptin and α-amylase elevated in the CID patients, and the serum levels of copeptin may be associated with the poor sleep quality, especially in the individuals of initial sleep difficulties.

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“…Given that AVP is not considered a valid biomarker in MDD and psychiatric disorders in general (28), our results offer first evidence that plasma CoP may represent an alternative stable, easily accessible, and clinically applicable peripheral biomarker of antidepressant treatment response in MDD. CoP has been lately put forth as a possible novel stress marker as some studies have reported CoP to subtly mirror the individual stress level in psychological (63)(64)(65) and physical stress paradigms (66), while CoP has shown a positive correlation with other HPA axis hormones (64,(67)(68)(69)(70). In a previous study of our research group (39), we could show that, following an objective, pharmacological panic challenge, plasma CoP not only delicately responded through a sharp increase to panic provocation and positively correlated with simultaneously assessed ACTH and CORT, but also significantly correlated with subjectively reported panic symptoms, which was not the case for ACTH and CORT.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study

et al. 2020

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Background: Major depressive disorder (MDD) constitutes the leading cause of disability worldwide. Although efficacious antidepressant pharmacotherapies exist for MDD, only about 40-60% of the patients respond to initial treatment. However, there is still a lack of robustly established and applicable biomarkers for antidepressant response in everyday clinical practice.Objective: This study targets the assessment of the vasopressin (AVP) surrogate marker Copeptin (CoP), as a potential peripheral hypothalamic-level biomarker of antidepressant treatment response in MDD.Methods: We measured baseline and dynamic levels of plasma CoP along with plasma ACTH and cortisol (CORT) in drug-naive outpatients with MDD before and after overnight manipulation of the hypothalamic-pituitary-adrenal (HPA) axis [i.e., stimulation (metyrapone) and suppression (dexamethasone)] on three consecutive days and their association with treatment response to 4 weeks of escitalopram treatment.Results: Our findings suggest significantly higher baseline and post-metyrapone plasma CoP levels in future non-responders, a statistically significant invert association between baseline CoP levels and probability of treatment response and a potential baseline plasma CoP cut-off level of above 2.9 pmol/L for future non-response screening. Baseline and dynamic plasma ACTH and CORT levels showed no association with treatment response.Conclusions: This pilot study provide first evidence in humans that CoP may represent a novel, clinically easily applicable, endocrine biomarker of antidepressant response, based on a single-measurement, cut-off level. These findings, underline the role of the vasopressinergic system in the pathophysiology of MDD and may represent a

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Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls

Cited by 12 publications

References 49 publications

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

Correlation between Serum Levels of Sympathetic Nerve Activity Markers and Sleep Quality and Cognitive Function in Patients with Chronic Insomnia Disorder

Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study

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