Effects of hydrolyzed fish protein and autolyzed yeast as substitutes of fishmeal in the gilthead sea bream (Sparus aurata) diet, on fish intestinal microbiome.

BACKGROUND: This study evaluated the effects of partial substitution of dietary fishmeal (FM) with either fish protein hydrolysate (FPH) or autolysed dried yeast (HiCell®, Biorigin, Brazil) on intestinal microbiota of gilthead sea bream (Sparus aurata). A total number of 720 fish of 122.18 ± 6.22 g were fed for 92 days with three different diets in triplicate (3 tanks/diet). A diet based on FM/vegetable meal was used as control. The other two diets were formulated by replacing FM with 5% of either FPH or HiCell®. To analyze the gut microbiota associated to autochthonous and allochthonous microbial communities, the Illumina MiSeq platform for sequencing of 16S rRNA gene and QIIME pipeline were used. RESULTS: A total number of 102 OTUs (operational taxonomic units) at 97% identity were identified in fish gut samples collected at the end of feeding trial. Fourteen OTUs constituted the core gut microbiota, i.e. those OTUs found in at least nine out of fifteen samples per group and shared regardless of the diet. Eight OTUs were assigned to Firmicutes represented by Lactobacillus, Staphylococcus, and Bacillus genera, and six to Proteobacteria phylum. Dietary dried yeast autolysate modulated the intestinal microbiota by promoting the growth of some beneficial bacteria. At order level, fish fed yeast showed an enrichment in Bacillales and Clostridiales as compared to the control group, whereas fish fed FPH showed a significantly lower amount of bacteria belonging to Alteromonadales and Enterobacteriales than the other two feeding groups. Although we did not observe any effect of 5% FM replacement with alternative nitrogen sources at phylum level, at lower taxonomical levels, the composition of gut microbiota, in terms of relative abundance of specific taxa, was significantly influenced by the dietary treatment. CONCLUSIONS: The metabarcoding analysis revealed a clearly intestinal microbiota modulation in response to dietary autolyzed yeast. The abundance of some beneficial bacteria, i.e. indigestible carbohydrate degrading- and SCFA producing bacteria, was positively affected. Autolysed dried yeast obtained by the fermentation of a strain of Saccharomyces cerevisiae could be a valid alternative protein source to FM as well as a valid functional ingredient for aquafeed production [corrected].

Correction to: Effects of hydrolyzed fish protein and autolyzed yeast as substitutes of fishmeal in the gilthead sea bream (Sparus aurata) diet, on fish intestinal microbiome.

An amendment to this paper has been published and can be accessed via the original article.

Olanzapine-induced weight gain in anorexia nervosa: involvement of leptin and ghrelin secretion?

BACKGROUND: Olanzapine (OLA) administration has been reported to induce weight gain in experimental animals and humans, through not yet fully defined mechanisms of action. Aim of this study was to determine whether in patients with Anorexia Nervosa (AN) OLA induces weight gain through the modulation of the hunger-satiety regulatory peptides leptin and ghrelin. METHODS: Twenty anorexic probands received a 3 months course of cognitive-behavioral psychotherapy and programmed nutritional rehabilitation, combined with OLA PO (2.5 mg for 1 month and 5 mg for 2 months) in ten patients and with placebo PO (PL) in the other 10. Weight, measured as body mass index (BMI), leptin and ghrelin plasma values were monitored before starting the therapy and then monthly for 3 months. Plasma leptin was measured by ELISA, and plasma ghrelin by radioimmunoassay. RESULTS: BMI increased significantly but not differently in both treatment groups. Leptin and ghrelin secretion did not change during the course of the treatments. No correlations were observed between BMI values and leptin and ghrelin levels. CONCLUSIONS: Our data suggest that the weight gain observed in our OLA-treated patients was not linked to drug administration. Moreover, leptin and ghrelin secretions were not responsible for BMI changes.

Central dysregulations in the control of energy homeostasis and endocrine alterations in anorexia and bulimia nervosa.

In the last decades we have come to understand that the hypothalamus is a key region in controlling energy homeostasis. A number of control models have been proposed to explain the regulation of feeding behavior in physiological and pathological conditions, but all those based on imbalances of single factors fail to explain the disrupted regulation of energy supply in eating disorders such as anorexia nervosa and bulimia nervosa, as well as other psychiatric disorders. A growing amount of evidence demonstrates that many signaling molecules originated within the brain or coming from the adipose tissue or the gastro-enteric tract are involved in the highly complex process controlling food intake and energy expenditure. The recent discovery of leptin, ghrelin, and other factors have made it possible to penetrate in the still undefined pathophysiology of eating disorders with the hope of finding effective treatments for such diseases.

Deranged anterior pituitary responsiveness to hypothalamic hormones in depressed patients.

Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders. In ten, TRH, 500 microgram given intravenously, induced a rise in plasma growth hormone (GH) level, while in eight patients it induced a rise in plasma levels of FSH or LH or both. When LH-RH, 150 microgram was administered intravenously to ten patients, it induced a rise in plasma GH level in one patient and increased plasma prolactin level in three patients. Collectively, in only three of 14 patients was conventional AP responsiveness to hypothalamic neurohormones present. These findings demonstrate the existence of a profound derangement of AP responsiveness to hypothalamic neurohormones in depressed patients and suggest that a primary alteration in the physiologic links between the central nervous system and the AP may be at the origin of the neuroendocrine disturbance.

Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states.

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.

Hormonal circadian rhythms in eating disorders.

The circadian rhythm of several plasma hormones (prolactin, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and melatonin) was simultaneously evaluated in 23 women with anorexia nervosa (AN), in 27 obese (OB) women, and in gender and age-matched healthy controls. A trend toward similar alterations of the circadian pattern of the different hormones was observed in the two groups of patients, with the exception of plasma growth hormone (GH), which exhibited nutrition-dependent impairments. The timing of the peaks for each hormonal rhythm revealed the existence of an internal desynchronization in both eating disorders.

Menstrual cycle-related sensitivity to 35% CO2 in panic patients.

In a double blind, random, cross-over design, 10 patients and seven controls inhaled one vital capacity of 35% CO2-65% O2 during their early-follicular and midluteal phases. Anxiety after CO2 intake was significantly stronger in the early-follicular phase than in the midluteal phase for patients. Controls had no anxiety reactions.

Growth hormone response to growth hormone releasing hormone and to clonidine stimulation in peripubertal patients with major depressive disorder.

The responses of growth hormone (GH) to administration of growth hormone-releasing hormone (GHRH-1 micrograms/kg b.w.) and of clonidine (clon-2.5 micrograms/kg b.w.) and basal levels of somatomedin C (SmC) were measured in nine peripubertal patients with Major Depressive Disorder (MDD) and in 9 age- and gender-matched controls. Basal GH and SmC levels, and GH response to GHRH did not differ in patients and controls, whereas responses to clonidine were significantly higher in some and lower in other patients than in controls.

Dopamine function in obsessive-compulsive disorder: growth hormone response to apomorphine stimulation.

Indirect observations suggest that the dopaminergic system may be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The dopaminergic function of 15 patients with OCD and 15 age/sex-matched controls was evaluated by measuring the growth hormone (GH) responses to stimulation with the dopaminergic agonist apomorphine (APO), which increases growth hormone-releasing hormone (GHRH), GH, and somatomedine C (SMD-C) secretions. Therefore, we measured basal plasma GH and SMD-C concentrations and GH responses to GHRH stimulation to exclude that a downstream pathology of the somatotropic axis could obscure the significance of the results of the APO test. The response of prolactin (PRL) to APO inhibition were also measured. Basal plasma levels of GH, SMD-C, and PRL, GH responses to GHRH stimulation, and PRL responses to APO inhibition did not differ in the two groups of subjects. GH responses to APO stimulation were blunted in obsessive-compulsive (OC) patients. The emetic response to the same stimulation was stronger in patients than in controls. These responses suggest that in our OC patients there is a dysregulation of the dopaminergic system, which is possibly expressed in different ways in the various areas of the central nervous system.

Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessive-compulsive disorders.

Plasma interleukin-1 beta (Il-1 beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured twice, at a 48-hour interval, in 27 drug-free obsessive-compulsive patients (12 women and 15 men) and in 27 sex-age-matched healthy controls. Il-1 beta and TNF-alpha concentrations were significantly lower in patients than in controls, whereas there were no differences in either group between men and women, between the samples of the two days, or, in the patients, between those who had and those who had not been previously treated with psychopharmacologic drugs.

Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation.

Growth hormone (GH) response to clonidine and growth hormone-releasing hormone (GHRH) stimulation, together with baseline somatomedin C (SmC) levels, were examined in parallel in a group of 21 patients with anorexia nervosa (AN) and in 10 controls. In addition, the Hamilton Rating Scale for Depression (HRS) was administered to the patients. Clonidine (2.5 micrograms/kg body weight, iv) induced GH elevations that were not significantly different between patients and controls. In contrast, GHRH (1 microgram/kg body weight, iv) produced a significantly higher GH response in anorectics than in controls. The ratio between GH responses (area under the curve, or AUC) to GHRH and to clonidine was significantly higher in patients than in controls. Baseline SmC levels (6 patients) were significantly lower in anorectics than in controls. Minor depressive symptomatology was present in all patients. When viewed in relation to the GH hyperresponsiveness to GHRH, the apparent normality of the response to clonidine in anorectics reflects the existence of an actual alpha 2-adrenoceptor subsensitivity. As clonidine reportedly acts via release of endogenous GHRH, an excessive, rather than a normal, GH response to clonidine was to be anticipated.

Long-lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans.

BACKGROUND: Fifteen (+/-)3,4-Methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse, and 15 control subjects were included in the study. METHODS: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation. RESULTS: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p < .001; p < .005). The responses of PRL to D-fen were unmodified at 12 months after prolonged abstinence and were significantly reduced in comparison with controls (p < .001). In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p < .05). MDMA users' high scores on the Novelty Seeking (NS) scale on the Tridimensional Personality Questionnaire (TPQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Hostility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores decreased significantly after 12 months of abstinence. PRL AUCs at 12 months were inversely correlated with the measures of MDMA exposure (r = -.538). CONCLUSIONS: Our data indicate long-lasting 5-HT system impairment in abstinent MDMA users although the hypothesis of serotonergic changes attributable to a premorbid condition cannot be excluded. CORT restored responses to D-fen at 12 months, and the correlation of neuroendocrine changes with MDMA exposure suggest that the neuroendocrine impairment may be due to a partially reversible neurotoxic action of MDMA on the human brain.

Secretion pattern of endogenous opioids in chronic schizophrenia.

Baseline plasma levels of beta-endorphin, beta-lipotropin, and ACTH were assayed in 37 patients with chronic schizophrenia: 24 men and 13 women, 28 with hebephrenic and nine with paranoid schizophrenia. None of the patients had received any medication for at least 10 days. The mean values of both opioids were significantly higher in the schizophrenic patients than in 21 age- and sex-matched control subjects. Insulin stimulation and dexamethasone suppression tests were given to eight of the patients, and the circadian rhythms of beta-endorphin, beta-lipotropin, ACTH, and cortisol were assayed in the same eight patients. Insulin stimulation, dexamethasone suppression test results, or circadian rhythmicity was impaired in seven of these eight patients.

Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in heroin addicts.

To determine whether the pituitary-gonadal deficiency in heroin addicts is related to heroin's effect on the hypothalamus, the authors administered gonadotropin hormone-releasing hormone (GnRH) to 10 male heroin addicts and 5 controls and measured follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response. Basal FSH and LH levels were significantly lower in addicts; after GnRH stimulation the addicts' FSH and LH values increased but not significantly compared to controls. The difference between the two groups' response was highly significant. The authors suggest that heroin causes an incomplete blocking of gonadotropin secretion at the pituitary level, inducing a hypophyseal-gonadal deficiency and a long-lasting depletion of the endogenous releasing factor, which accounts for the reduced response to GnRH.

Lymphocyte cholecystokinin concentrations in panic disorder.

Since cholecystokinin (CCK) is known to be anxiogenic in experimental animals and to induce panic attacks in humans, lymphocyte CCK-8 concentrations were measured in 15 patients with panic disorder and 15 age- and sex-matched healthy subjects. The patients' levels were measured again after a 30-day course of alprazolam therapy, 1.5 mg/day. The CCK-8 concentrations were significantly lower in the patients than in the control subjects and did not change after alprazolam therapy. There was no correlation between the peptide values and levels of anxiety or frequency and severity of panic attacks.

Psychopathological aspects of neuroendocrine diseases: possible parallels with the psychoendocrine aspects of normal aging.

Psychological impairments can occur during the course of major endocrine diseases. These impairments range from mild affective-cognitive-behavioral disturbances to frank psychoses. The former are rather specific for each hormonal disorder and disappear with the hormonal correction. The latter, instead, seem to be quite nonspecific and include depression, mania, schizophrenia-like and organic brain syndromes which appear at random in each endocrinopathy, not always regressing with hormonal recovery, and apparently correlating more with the severity than with the nosographic classification of the metabolic disturbances. It is suggested that age-related physiological changes of hormonal and psychological patterns mimic those occurring in neuroendocrine diseases and that, possibly, common brain biochemical changes may underlie the two phenomena.

Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation.

Central dopaminergic dysfunction has been suggested to be involved in the pathogenesis of obsessive compulsive disorder (OCD). In 15 patients with OCD and in 15 age-sex matched controls we evaluated the dopamine (DA) function by measuring the cortisol (CORT) responses to stimulation with the DA agonist apomorphine (APO). The CORT response to acute saline administration was also measured, to exclude the existence of a pathology of the circadian secretion of the hormone which could obscure the significance of the CORT response to APO stimulation. Basal levels of CORT were the same in patients and controls, but the values after saline administration were significantly higher in patients than in controls. APO stimulation-induced CORT rises were significantly higher in patients than in controls, but when the data after APO were corrected for those after saline, there were no significant difference between the two groups of subjects. Our data suggest that there are no alterations of the central dopaminergic function connected with the regulation of the hypothalamo-pituitary-adrenal axis in OCD.

Plasma concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in anorexia and bulimia nervosa.

Plasma interleukin-1 beta (Il-1 beta) interleukin-6 (Il-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in 26 women with Anorexia Nervosa (AN), nine of the restricted type (AN-R) and 17 of the binge-eating/purging type (AN-BP), in 24 women with Bulimia Nervosa (BN) and in 26 healthy age- and sex-matched controls. Concentrations of the cytokines were measured at the beginning of the study before starting any treatment and then after 1 and 3 months of combined cognitive-behavioral and pharmacological therapy (fluoxetine for AN-R and AN-BP, amineptine for AN-BP and BN, and fluvoxamine for BN). Basal values of Il-1 beta, Il-6 and TNF-alpha, were the same in patients and controls and did not change during treatments, in spite of the improvement of the mental disorders. This seems to exclude the possibility that alterations of basal plasma cytokine secretion are involved in the etiopathogenesis of AN and BN.

Alpha 2-adrenergic receptor sensitivity in panic disorder: I. GH response to GHRH and clonidine stimulation in panic disorder.

Baseline levels of GH and somatomedin C (SmC) and GH responses to GHRH (1 microgram/kg b.w.) and to clonidine (150 micrograms) were measured in 10 outpatients with panic disorder before and after 30 days of 2-2.5 mg of alprazolam therapy, and in 10 psychophysically healthy controls. Basal levels of GH were normal in the patients and those of SmC significantly elevated, both before and after therapy. Basal GH responses to GHRH stimulation were normal and did not change change after alprazolam treatment. Basal GH responses to clonidine stimulation were blunted in the patients and improved after therapy, in parallel with an amelioration of the psychopathology. Our data suggest that adrenoceptor sensitivity, investigated by the clonidine test, is reduced in panic disorder.