Changes of Sleep Architecture, Spectral Composition of Sleep EEG, the Nocturnal Secretion of Cortisol, ACTH, GH, Prolactin, Melatonin, Ghrelin, and Leptin, and the DEX-CRH Test in Depressed Patients during Treatment with Mirtazapine

Max Planck Institute of Psychiatry, Munich, Germany.
Neuropsychopharmacology (Impact Factor: 7.05). 05/2006; 31(4):832-44. DOI: 10.1038/sj.npp.1300923
Source: PubMed


The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.9+/-4.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days -3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day -3. The Hamilton Depression score decreased from 32.1+/-7.3 to 15.5+/-6.7 between days -1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin.

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    • "We rejected participants that contained less than eight trials in each condition (N = 2) to reduce the error of the estimated mean and the differences in the variance across conditions (incorrect–low conf.: 220 ± 70; incorrect–high conf.: 40 ± 30; correct–low conf.: 50 ± 20; correct–high conf.: 130 ± 70). In addition , to avoid possible effects of nonhomogenous variance in the data, we performed a nonparametric test (Friedman test with repeated measures) to analyze the statistical difference between levels for each factor (Laganaro, Morand, & Schnider, 2009; Murray, Camen, Andino, Bovet, & Clarke, 2006; Schmid et al., 2006). This test computes the χ 2 Friedman rank sum value for group differences of one factor after possibly adjusting effects of the other factor. "
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    ABSTRACT: Confidence judgments are often severely distorted: People may feel underconfident when responding correctly or, conversely, overconfident in erred responses. Our aim here was to identify the timing of brain processes that lead to variations in objective performance and subjective judgments of confidence. We capitalized on the Partial Report Paradigm [Sperling, G. The information available in brief visual presentations. Psychological Monographs: General and Applied, 74, 1, 1960], which allowed us to separate experimentally the moment of encoding of information from that of its retrieval [Zylberberg, A., Dehaene, S., Mindlin, G. B., & Sigman, M. Neurophysiological bases of exponential sensory decay and top-down memory retrieval: A model. Frontiers in Computational Neuroscience, 3, 2009]. We observed that the level of subjective confidence is indexed by two very specific evoked potential at latencies of about 400 and 600 msec during the retrieval stage and by a stationary measure of intensity of the alpha band during the encoding period. When factoring out the effect of confidence, objective performance shows a weak effect during the encoding and retrieval periods. These results have relevant implications for theories of decision-making and confidence, suggesting that confidence is not constructed online as evidence is accumulated toward a decision. Instead, confidence attributions are more consistent with a retrospective mechanism that monitors the entire decision process.
    Journal of Cognitive Neuroscience 11/2014; 27(6):1-14. DOI:10.1162/jocn_a_00759 · 4.09 Impact Factor
    • "Clinical studies also showed the effectiveness of mirtazapine for nausea and insomnia as well as depression and anxiety in cancer patients [10] [11]. Furthermore, antidepressant therapy with mirtazapine was shown to be associated with an increase in body weight, body fat mass and leptin level, and a decrease in ghrelin levels [12] [13]. Adipocyte-derived leptin is an anorexigenic hormone that decreases food intake and increases energy expenditure [14]. "
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    ABSTRACT: Objective This study investigated the relationship between weight loss, depression and anxiety, and appetite hormones, leptin and ghrelin levels in patients with head and neck cancer (HNC), and the effect of radiotherapy and antidepressant treatment on weight and these hormones. Methods Forty male patients with HNC and twenty physically and mentally healthy male controls were recruited for the study. Psychiatric status was evaluated with clinical interview and psychometric tests. All patients received radiotherapy and antidepressant treatment with mirtazapine was given to patients with psychiatric disorders. Serum leptin and ghrelin levels were measured pre and post-treatment in the patients and once in the controls. Results There was no significant difference between the serum leptin and ghrelin levels of patients and controls. The leptin levels of the patients were decreased by radiotherapy. Eleven patients were diagnosed with major depressive disorder and adjustment disorder and were classed as depressive patients. Depressive patients were affected more by radiotherapy with respect to weight loss. The basal leptin levels of depressive patients were also lower than non-depressive patients and controls. - It seems that depression aggravated weight loss and in addition, decreased leptin levels in cancer patients. Detection and treatment of psychiatric disorders may improve prognosis by preventing weight loss as well as by providing psychiatric treatment in cancer patients.
    General Hospital Psychiatry 09/2014; 37(1). DOI:10.1016/j.genhosppsych.2014.09.002 · 2.61 Impact Factor
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    • "A single dose of clomipramine increased circulating leptin more in obese than in normal-weight participants (Oppert et al., 1997), which was not associated with a corresponding decrease in cortisol. An increase in circulating levels of leptin associated with a decrease in plasma or salivary cortisol during treatment with the antidepressant mirtazapine (Kraus et al., 2002; Schule et al., 2003; Laakmann et al., 2004; Schmid et al., 2006) supported a role of leptin in reducing the activity of the HPA axis. However, cortisol secretion and leptin production did not alter significantly in depressed women following an 8-week course of citalopram, despite a considerable improvement in depression scores (Kauffman et al., 2005). "
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    Behavioural Pharmacology 07/2014; 25(5-6). DOI:10.1097/FBP.0000000000000050 · 2.15 Impact Factor
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