Hypothalamic-pituitary-adrenal System Research Articles

Insulin-like Growth Factor-I (IGF-I) Serum Concentrations in Depressed Patients: Relationship to Saliva Cortisol and Changes during Antidepressant Treatment

The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) system activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA system activity. We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline. Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment. Our findings show IGF-I to be related to HPA system activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA system activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.

P01-270 Plasma cortisol levels and physical aggression in depressed patients

An analysis of the biological mechanisms underlying both aggression and major depression (MD) shows the implication of common features. There is a well known link between MD and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, the HPA axis dysfunction has been identified as a promising predictor of suicidal behaviours in mood disorders.The aim of the study was to examine the relationship between aggressive behaviour and plasma cortisol levels during a Major Depression Episode (MDE).83 patients (M/F = 43/40; mean age 47,70±14,52) with a Mood Disorder during a MDE have been recruited at the Day Clinic of Psychiatry of the Catholic University in Rome.A blood sample for the determination of plasma cortisol levels was collected before antidepressant treatment. Aggression Questionnaire (AQ) was used to evaluate aggression traits such as Verbal Aggression (VA), Physical Aggression (PA), Anger (A), Hostility (H) and total Aggression score (AQtot). No significant correlation between plasma cortisol levels and VA, A, H or AQtot was found. A positive correlation between PA scores and plasma cortisol levels was reported (r = 0.39; p = 0.007).Physical Aggression underline a risk for subsequent inner-directed violence, including suicidal thoughts and behaviours and it is also associated to a serotoninergic system dysfunction. An abnormal interaction between the HPA mechanisms and serotonergic systems has also been suggested in suicidal behaviours.Our results confirm the importance of further research with more sensitive markers to monitor HPA axis activity (e.g. Dexamethasone/CRH test), serotonergic activity and psychopathological features in depressed patients.

An MPC-Based Approach to Robust Control of a Hypothalamic-Pituitary-Adrenal Axis Model

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine control system regulating the stress response of the human body as well as affecting mood and cognition. HPA dysfunction has been associated with a variety of disorders including Fibromyalgia, and chronic fatigue syndrome (CFS). Recently, a lumped parameter model of the HPA axis which includes the effect of pharmacological agents has been proposed. In this work, an analysis of the HPA axis dynamics near rest points is used to develop an approach for robust control of the HPA system.

Impact of Gene-Gender Effects of Adrenergic Polymorphisms on Hypothalamic-Pituitary-Adrenal Axis Activity in Depressed Patients

Objective: There is overwhelming evidence that activation of the hypothalamic-pituitary-adrenal (HPA) system plays a major role in depression and cardiovascular disease in genetically susceptible individuals. We hypothesized that due to the multiple interactions between the sympathetic and the HPA systems via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis activity in major depression. Methods: Using the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test, we investigated the association of α₂-adrenoceptor (ADRA2A –1291C→G) and the β₂-adrenoceptor gene (ADRB2 Arg16Gly) in 189 patients with major depression during the acute state of the disease and after remission. Results: Male ADRA2A –1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). In contrast, female ADRB2 Arg/Arg homozygotes had increased pretreatment ACTH (F = 7.17, d.f. = 2, p = 0.001) and cortisol (F = 8.95, d.f. = 2, p = 0.000) levels. Interestingly, in the respective genotypes, the stress hormones remained elevated in the second DEX/CRH test, despite a reduction in depressive symptoms. Conclusions: This study provides evidence that, depending on gender and polymorphisms, there is continuous HPA axis overdrive in a proportion of patients irrespective of the status of depression. Considering the importance of stress hormones for cardiovascular disorders, our data might suggest that these patients are at high risk of comorbidity between depression and cardiovascular disorders.

Downregulation of Melanocortin-4 Receptor during Refeeding and its Modulation by Adrenalectomy in Rats

Melanocortin system and corticotropin releasing hormone (CRH) are implicated in the control of feeding behavior. Besides its anorexigenic effect on food intake, CRH is one of the most important regulators of hypothalamic-pituitary-adrenal (HPA) axis activity. Therefore, there could be an interplay between HPA axis activity and melanocortin system. We investigated the expression of melanocortin-4 receptor (MC4-R) mRNA in the hypothalamus of rats after 14 days of food restriction or after a fasting-refeeding regimen, in sham or adrenalectomized rats. Male Wistar rats were subjected to free access to food or food ingestion restricted for 2 h a day (8-10 AM) during 14 d, when plasma corticosterone, ACTH, insulin, leptin concentrations, and MC4-R mRNA expression were determined before and after refeeding. Another set of rats was fasted for 48 h, followed by refeeding during 2 or 4 h on the seventh day after adrenalectomy (ADX) or sham surgery. On the day of the experiment, rats were anesthetized and perfused and the brain processed for MC4-R mRNA by in situ hybridization. Long-term reduction of food intake, either secondary to food restriction or adrenalectomy, reduced body weight gain and also leptin and insulin plasma concentrations. Food ingestion reduced MC4-R expression in the paraventricular nucleus in naive rats subjected to food restriction and also in sham rats fasted for 48 h. However, after ADX, MC4-R expression was not changed by refeeding. In conclusion, the present data indicate that MC4-R expression is downregulated by food ingestion and this response could be modulated by glucocorticoid withdrawal.

Intranasal insulin attenuates the hypothalamic–pituitary–adrenal axis response to psychosocial stress

Previous studies have shown that intranasally administered insulin exerts an inhibitory influence on the basal hypothalamic-pituitary-adrenal (HPA) axis activity. To date, however, it remains unclear as to whether intranasal insulin does furthermore affect HPA axis responsiveness in situations of stress. Here, we tested whether intranasally administered insulin attenuates the HPA axis response to psychosocial stress. Fifty minutes before being exposed to the Trier Social Stress Test (TSST), 26 healthy young male participants received a single intranasal dose of human insulin (40 I.U.) or placebo in a placebo controlled, double-blind between-subject design. Plasma cortisol, saliva cortisol, heart rate, and blood pressure were measured at resting baseline and in response to the TSST. Plasma cortisol (P<.001) and saliva cortisol (P<.001) increased in response to stress, as did heart rate (P<.001) and blood pressure (P<.001). Intranasal insulin did not influence plasma or saliva cortisol, heart rate, blood pressure, blood glucose, and plasma insulin levels at baseline. However, intranasal insulin diminished the saliva cortisol (two-way ANOVA; treatment by time interaction: P=.05) and plasma cortisol (two-way ANOVA; treatment by time interaction: P=.05) response to the TSST without affecting heart rate, and blood pressure stress reactivity. Our data show that a single intranasal insulin administration effectively lowers stress-induced HPA axis responsiveness. Intranasal insulin may offer a therapeutic potential to prevent hyperactivity of the HPA system.

Effect of Tyr‐MIF‐1 peptides on blood ACTH and corticosterone concentration induced by three experimental models of stress

1. Studies, using a wide variety of stressors, have clearly indicated that the pattern of neuroendocrine response is dependent upon the stress stimulus applied. 2. The Tyr-MIF-1 family of peptides (Tyr-MIF-1s) includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1. These neuropeptides, neuromodulators are able to inhibit the expression of some forms of stress-induced analgesia. 3. The aim of this study was to compare changes in ACTH and corticosterone (CORT) concentration after various stressors (immobilization, cold and heat), as well as after injection of investigated Tyr-MIF-1s peptides. 4. According to our results, hypothalamic-pituitary-adrenal (HPA) system was activated by all the stressors applied. Heat and immobilization are stronger stressors, as the exposure of animals to a high ambient temperature and immobilization resulted in the highest rise of plasma ACTH and CORT concentration when compared with cold stress. Moreover, all the investigated peptides from Tyr-MIF-1 family, administered after application of stressors, inhibited the elevations in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) plasma concentrations significantly. 5. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release. We suggest that Tyr-MIF-1 peptides may possess anti-stressor effects, as they inhibited stress-induced rising in two hormones that were investigated.

P.2.d.009 Cellular and molecular mechanisms underlying increased adult hippocampal neurogenesis induced by agomelatine

Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic–pituitary–adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures.

Hypothalamic–pituitary–adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure

Background Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic–pituitary–adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown. Objective To examine HPA basal levels and stress responsiveness in 3-month olds with prenatal exposure to SSRIs. Methods Salivary cortisol levels in infants of SSRI treated mothers ( n = 31, mean exposure 230.2 ± 72.2 days) were compared with non-SSRI exposed ( n = 45) infants in response to a challenge (infant-controlled habituation task) and under basal conditions in the late afternoon/early evening. Mode of feeding, to account for possible postnatal drug exposure via breast milk, as well as measures of pre and postnatal maternal mood, were included as covariates. Results Lower post-stress cortisol levels were observed in non-SSRI exposed/non-breastfed infants compared with non-SSRI exposed infants who were breastfed at 3 months of age. Stress reactivity patterns among SSRI exposed infants did not differ with mode of feeding. The cortisol reactivity slope (CRS) was significantly lower among non-SSRI exposed non-breastfed infants compared with non-SSRI exposed breastfed infants. Early evening basal cortisol levels were lower in SSRI exposed infants than in non-SSRI exposed infants, controlling for maternal mood and mode of feeding. Postnatal SSRI exposure (infant SSRI drug levels) via breast milk was not associated with stress or basal cortisol levels. Total cortisol, reflected by the AUC measure, did not differ significantly between exposure groups. Conclusions Prenatal SSRI exposure altered HPA stress response patterns and reduced early evening basal cortisol levels. Stress challenge HPA response differences only became apparent when the moderating effect of method of feeding was accounted for. These findings suggest an early “programming” effect of antenatal maternal mood, prenatal SSRI exposure and postnatal maternal care giving on the HPA system.

Pituitary-Adrenal and Sympathetic Nervous System Responses to Stress in Women Remitted From Recurrent Major Depression

To better understand the changes in hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) function after remission of depression. We characterized these systems at baseline and in response to a psychosocial stressor in a cohort of women remitted from recurrent major depression as well as in never-depressed healthy female controls. Baseline HPA function was measured via saliva cortisol sampling at 8 AM and 4 PM over 7 days as well as quantification of urinary overnight cortisol secretion. The HPA system response to a psychosocial stressor was assessed by measuring serum cortisol and adrenocorticotropic hormone (ACTH) levels and SNS reactivity by determining serum epinephrine (E) and norepinephrine (NE) concentrations as well as autonomic nervous system changes by analysis of heart rate variability (HRV). The stressor included a speech task, mental arithmetic, and a cognitive challenge. In all, we studied 22 women remitted from recurrent major depression (age = 51.0 +/- 1.7 years) and 20 healthy controls (age = 54.2 +/- 1.6 years). Morning saliva cortisol concentrations were lower in remitted patients, paralleled by lower serum cortisol concentrations before stress testing. This group also displayed a blunted cortisol and ACTH response to the stressor, as compared with healthy controls. No between-group differences in HRV parameters were observed. In this group of women remitted from recurrent major depressive disorder, we found evidence of HPA system hypoactivity, both in the basal state and in response to a psychosocial stressor.

82. Application of repeated social stress to pregnant gilts during early or late gestation differentially affects HPA axis and immune system activity of the piglets

Early life stress (ELS) affects facial emotion recognition (FER), as well as the underlying brain network. However, there is considerable inter-individual variability in these ELS-caused alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is assumed to mediate neural and behavioural sequelae of ELS, the genetic disposition towards HPA axis reactivity might explain differential vulnerabilities.An additive genetic profile score (GPS) of HPA axis reactivity was built from 6 SNPs in 3 HPA axis-related genes (FKBP5, CRHR1, NR3C1). We studied two independent samples. As a proof of concept, GPS was tested as a predictor of cortisol increase to a psychosocial challenge (MIST) in a healthy community sample of n = 40. For the main study, a sample of n = 170 completed a video-based FER task and retrospectively reported ELS experiences in the Childhood Trauma Questionnaire (CTQ).GPS positively predicted cortisol increase in the stress challenge over and above covariates. CTQ and genetic profile scores interacted to predict facial emotion recognition, such that ELS had a detrimental effect on emotion processing only in individuals with higher GPS. Post-hoc moderation analyses revealed that, while a less stress-responsive genetic profile was protective against ELS effects, individuals carrying a moderate to high GPS were affected by ELS in their ability to infer emotion from facial expressions.These results suggest that a biologically informed genetic profile score can capture the genetic disposition to HPA axis reactivity and moderates the influence of early environmental factors on facial emotion recognition. Further research should investigate the neural mechanisms underlying this moderation. The GPS used here might prove a powerful tool for studying inter-individual differences in vulnerability to early life stress.

Blunted ACTH response to dexamethasone suppression-CRH stimulation in posttraumatic stress disorder

Previous studies have suggested that patients with posttraumatic stress disorder (PTSD) have an enhanced negative feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) system and a blunted ACTH response to corticotropin releasing hormone (CRH). The effects of two dexamethasone dosages (0.75 and 1.5 mg) on the ACTH and cortisol concentrations after CRH stimulation (100 μg) were studied in eight patients with PTSD and matched healthy control subjects. Compared to healthy subjects, patients with PTSD have a blunted ACTH response to CRH. Cortisol concentrations were only significantly influenced by dexamethasone dosage. Our results give further evidence for a central role of the pituitary in reflecting changes of the negative feedback sensitivity of the HPA system in patients with PTSD.

HPA system regulation and adult attachment anxiety: Individual differences in reactive and awakening cortisol

Early life experiences can influence hypothalamus-pituitary-adrenal (HPA) axis regulation in adulthood, in both animals and humans. In humans, they have also been shown to influence adult attachment styles. However, the relationship between adult attachment styles and HPA axis regulation is largely unexplored. The present study investigated the relationship among varying levels of attachment anxiety and avoidance with both the cortisol response to acute stress (CRS) and the cortisol response to awakening (CRA) in 48 adult women. Attachment-unrelated stress was induced by a laboratory stress task. Saliva for free cortisol assessment was sampled before and after the stress task in the laboratory and at home on 2 consecutive days in the morning after awakening. We found that attachment anxiety but not attachment avoidance was associated with cortisol measures. Attachment anxiety was positively correlated with CRS and negatively with CRA. Finally, the two cortisol parameters were negatively associated with one another. The results are discussed with respect to (1) recent findings suggesting that the HPA system and hippocampus are programmed during critical development periods, establishing a certain trajectory of physiological responsiveness throughout life, and (2) a model that links development of the hippocampus with self development.

Antidepressant-Like Effects of Psoralen Isolated from the Seeds of Psoralea corylifolia in the Mouse Forced Swimming Test

The forced swimming test (FST) is suggested to produce abnormalities in the serotonergic and hypothalamic-pituitary-adrenal (HPA) axis systems. Therefore, compounds that attenuate these neurobiological alterations may have potential as antidepressants. The behavioral and biochemical effects of psoralen, a major furocoumarin isolated from Psoralea corylifolia, were investigated in the FST model of depression in male mice. Psoralen significantly reduced immobility and increased swimming without altering climbing in the mouse FST. Psoralen remarkably reversed FST-induced alterations in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in frontal cortex and hippocampus in mice. Furthermore, psoralen attenuated FST-induced elevations in serum corticotropin-releasing factor (CRF) and corticosterone concentrations to normalize the HPA axis activity. These results suggested that psoralen possessed potent antidepressant-like properties which were at least in part mediated by improving the abnormalities in the serotonergic and the HPA axis systems.

Stress and Anxiety in Schizophrenia and Depression: Glucocorticoids, Corticotropin-Releasing Hormone and Synapse Regression

Stress during childhood and adolescence has implications for the extent of depression and psychotic disorders in maturity. Stressful events lead to the regression of synapses with the loss of synaptic spines and in some cases whole dendrites of pyramidal neurons in the prefrontal cortex, a process that leads to the malfunctioning of neural networks in the neocortex. Such stress often shows concomitant increases in the activity of the hypothalamic-pituitary-adrenal system, with a consequent elevated release of glucocorticoids such as cortisol as well as of corticotropin-releasing hormone (CRH) from neurons. It is very likely that it is these hormones, acting on neuronal and astrocyte glucocorticoid receptors (GRs) and CRH receptors, respectively, that are responsible for the regression of synapses. The mechanism of such regression involves the loss of synaptic spines, the stability of which is under the direct control of the activity of N-methyl-d-aspartate (NMDA) receptors on the spines. Glutamate activates NMDA receptors, which then, through parallel pathways, control the extent in the spine of the cytoskeletal protein F-actin and so spine stability and growth. Both GR and CRH receptors in the spines can modulate NMDA receptors, reducing their activation by glutamate and hence spine stability. In contrast, glucocorticoids, probably acting on nerve terminal and astrocyte GRs, can release glutamate, so promoting NMDA receptor activation. It is suggested that spine stability is under dual control by glucocorticoids and CRH, released during stress to change the stability of synaptic spines, leading to the malfunctioning of cortical neural networks that are involved in depression and psychoses.

Effect of Single-Dose Sertraline on the Hypothalamus-Pituitary-Adrenal System, Autonomic Nervous System, and Platelet Function

Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) is thought to decrease coronary risk in patients with depressive disorder. Selective serotonin reuptake inhibitor intake may (1) attenuate the hypothalamus-pituitary-adrenal (HPA) system, (2) improve disturbances of the autonomous nervous system, and (3) dampen the aggregability of platelets. There is only limited information about the influence of acute treatment with SSRIs on these systems, which is especially important for the initiation of therapy in high-risk cardiac patients. We compared the reaction of these systems to physical stress with single-dose SSRI treatment (100 mg) with that of placebo treatment. Using a double-blind, crossover, placebo-controlled design, we assessed HPA system activity via serum cortisol and corticotropin as well as sympathetic nervous system by determining serum norepinephrine and epinephrine levels at baseline and as a response to stress. Analysis of heart rate variability (HRV) provided information on sympathetic/parasympathetic balance. Platelet activity was measured via flow-cytometric determination of platelet surface activation markers along with the serotonin (5-HT) uptake of platelets. We studied 12 healthy young men under placebo and verum conditions. We found higher HPA system activity at baseline and after physical activity under sertraline when compared with placebo, no difference in sympathetic nervous system activity after physical exertion and only slightly heightened baseline epinephrine values after sertraline intake. No difference was seen between sertraline and placebo intake regarding platelet activity and 5-HT uptake, HRV, blood pressure, and HR. Initiating sertraline treatment increases HPA system activity and epinephrine concentrations. We found no clinically relevant effect of single-dose sertraline treatment on autonomous nervous function, platelet activity, or platelet 5-HT uptake. These findings may not be extrapolated to patients with affective or cardiac disorders or to other SSRIs.

Relation between mental stress-induced prefrontal cortex activity and skin conditions: A near-infrared spectroscopy study

Although psychological stress affects skin condition, the neurophysiological mechanism involved is unclear. In this study, we evaluated the relationship between skin condition and left/right asymmetry in prefrontal cortex (PFC) activity during mental stress tasks since recent studies have suggested that the right PFC dominates the regulation of the stress response system, including the hypothalamic-pituitary-adrenal (HPA) axis. Using near-infrared spectroscopy, we measured hemoglobin concentration changes in the bilateral PFC during a mental arithmetic task in normal adults and evaluated the laterality scores (i.e., [(right-left)/(right+left)]) of oxyhemoglobin concentration changes. Elicitation of stress was verified by the State-Trait Anxiety Inventory (STAI) and heart rate. The sebum levels and Propionibacterium acnes populations in the facial skin were measured before the task. The task significantly increased the STAI-II scores (p=0.00079) and heart rate (p=0.0000049). The oxyhemoglobin concentration increased in the bilateral PFC during the task, associated with a decrease in deoxyhemoglobin concentration. The laterality scores of oxyhemoglobin concentration changes were positively correlated with sebum levels (r=+0.50, p=0.026) and P. acnes populations (r=+0.49, p=0.029) in the facial skin before the task. There was a significant positive correlation between heart rate changes and the laterality scores of oxyhemoglobin concentration changes (r=+0.54, p=0.015). These results demonstrate that the subjects with higher sebum levels and higher P. acnes populations in the facial skin have a right dominant PFC activity during a mental stress task and suggest that such subjects are sensitive to mental stress associated with hyperactivity of the stress response system, including the HPA axis system.

Endocrine and behavioral effects of neuromedin S

The present experiments focused on the effects of neuromedin S on hypothalamic–pituitary–adrenal (HPA) activation and behavior. The peptide (0.25–1 nmol) was administered intracerebroventricularly to rats, the behavior of which was monitored by means of telemetry, open field observations and an elevated plus-maze (EPM) test. Autonomic functions such as the temperature and the heart rate were recorded by telemetry. The action on the HPA axis was assessed via measurements of the plasma corticosterone and ACTH levels. To reveal the transmission of the endocrine responses, animals were pretreated with corticotrophin releasing hormone receptor (CRHR) antagonists (1 nmol). In the open field test, the animals were pretreated with either a CRHR 1 antagonist (antalarmin) or haloperidol (10 μg/kg), while in the EPM test they were pretreated with antalarmin or diazepam (1 mg/kg). The dopamine release from striatal and amygdala slices after peptide treatment was measured with a superfusion apparatus. Neuromedin S exerted dose-dependent effects on the HPA system, which were inhibited by antalarmin. It also activated grooming and decreased the entries to and time spent in the open arms during the EPM test. The grooming response was abolished by haloperidol and antalarmin pretreatment, while diazepam and antalarmin showed a tendency to attenuate the response evoked in the EPM test. In the superfusion studies, neuromedin S enhanced the dopamine release from the amygdala slices. These results demonstrate that neuromedin S stimulates the HPA axis through the CRHR 1 pathway and evokes stereotyped behavior and anxiety through mesolimbic dopamine and corticotrophin releasing hormone release.

Roles of prefrontal cortex activity in systemic responses to mental stress: A near infrared spectroscopy study

The prefrontal cortex (PFC) plays important roles in stress responses by regulating the hypothalamic–pituitary–adrenal system and the autonomic nervous system. In order to clarify the nature of these relationships and the underlying mechanisms, we systematically investigated the relationships between the PFC activity and systemic stress responses.

Neue Erkenntnisse zur Pathogenese und Pathophysiologie der Depression

There is now considerable neurobiological evidence on the pathogenesis and pathophysiology of depression. Nevertheless the underlying pathophysiology is far from fully elucidated. Norepinephrine and serotonin deficit hypotheses have been known for quite a long time. Other theories also claim a dysfunction of the dopaminergic and GABA-ergic system in depression, an altered expression of neuropeptides (e.g. of substance P), and neuroimmunologic and neuroendocrinologic mechanisms such as an overdrive of the hypothalamic-pituitary adrenal system. The neurotrophin hypothesis suggests that decreased production of neurotrophic factors and impaired neurogenesis are crucial for the pathophysiology of depression. These upcoming pathophysiological concepts have also initiated novel treatment approaches whose clinical utility still has to be demonstrated.