Ulrich Schweiger

CEREBROSPINAL FLUID CONCENTRATIONS OF CORTICOTROPIN-RELEASING HORMONE, VASOPRESSIN, AND SOMATOSTATIN IN DEPRESSED PATIENTS AND HEALTHY CONTROLS: RESPONSE TO AMITRIPTYLINE TREATMENT

The effect of amitriptyline upon hypothalamic‐pituitary‐adrenal [HPA]‐system‐regulating neuropeptides (corticotropin‐releasing hormone [CRH], vasopressin, somatostatin) was studied in a group of depressed elderly patients and controls. A first lumbar puncture was performed in 37 depressed in‐patients. This was followed by a 6‐week medication phase with amitriptyline. Upon its completion a second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients. In 25 healthy controls a first lumbar puncture was done; eleven of these individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate in the follow‐up CSF study. Within the group of depressed patients amitriptyline led to a significant decrease of CSF CRH in treatment responders only (F1,16 = 5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease with amitriptyline treatment (t‐test; P < 0.09). No effects of amitriptyline upon vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02) and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF somatostatin. A trend for CSF CRH to increase with aging was found only in controls (r = 0.3; P < 0.09); patients did not show a significant association here. Finally, CSF neuropeptide concentration at baseline did not differ between the group of depressed patients and healthy controls. Our study corroborates the evolving concept that antidepressants effect various components of the HPA system with the net result of a reduction in its activity. In addition, we found CSF CRH and CSF somatostatin concentrations to be better reflections of age than of depression and, finally, that during aging and during depression the HPA system changes in similar directions. Depression and Anxiety 8:71–79, 1998.

With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.

There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.02) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.005) and ACTH (p < 0.006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.01) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.

Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa

Semi-starvation induced hyperactivity (SIH) occurs in rodents upon caloric restriction. We hypothesized that SIH is triggered by the decline in leptin secretion associated with food restriction. To test this hypothesis, rats, which had established a stable level of activity, were treated with leptin or vehicle via implanted minipumps concomitantly to initiation of food restriction for 7 days. In a second experiment treatment was initiated after SIH had already set in. In contrast to the vehicle-treated rats, which increased their baseline activity level by 300%, the development of SIH was suppressed by leptin. Furthermore, leptin was able to stop SIH, after it had set in. These results underscore the assumed major role of leptin in the adaptation to semi-starvation. Because SIH has been viewed as a model for anorexia nervosa, we also assessed subjective ratings of motor restlessness in 30 patients with this eating disorder in the emaciated state associated with hypoleptinemia and after increments in leptin secretion brought upon by therapeutically induced weight gain. Hypoleptinemic patients ranked their motor restlessness higher than upon attainment of their maximal leptin level during inpatient treatment. Thus, hypoleptinemia might also contribute to the hyperactivity frequently associated with anorexia nervosa.

Testosterone, gonadotropin, and cortisol secretion in male patients with major depression.

OBJECTIVE Previous studies of sex hormone concentrations in depression yielded inconsistent results. However, the activation of the hypothalamic-pituitary-adrenal system seen in depression may negatively affect gonadal function at every level of regulation. The objective of this study was to explore whether major depressive episodes are indeed associated with an alteration of gonadal function. METHODS Testosterone, pulsatile LH secretion, FSH, and cortisol were assessed using frequent sampling during a 24-hour period in 15 male inpatients with major depression of moderate to high severity and in 22 healthy comparison subjects (age range 22-85 years). RESULTS An analysis of covariance model showed that after adjustment for age only, daytime testosterone (p < .01), nighttime testosterone (p < .05), and 24-hour mean testosterone secretion (p < .01) were significantly lower in the depressed male inpatients. There was also a trend for a decreased LH pulse frequency in the depressed patients (p < .08). CONCLUSIONS Gonadal function may be disturbed in men with a depressive episode of moderate to high severity.

The third wave of cognitive behavioural therapies: what is new and what is effective?

Purpose of review The purpose of this study was to shortly characterize the evolving psychotherapeutic methods summarized as ‘third wave psychotherapies’ and to review recent research on the therapeutic impact of these methods. Recent findings ‘Third wave psychotherapies’ comprise a heterogeneous group of treatments, including acceptance and commitment treatment, behavioural activation, cognitive behavioural analysis system of psychotherapy, dialectical behavioural therapy, metacognitive therapy, mindfulness-based cognitive therapy and schema therapy. Several randomized controlled trials, longitudinal case series and pilot studies have been performed during the past 3–5 years, showing the efficacy and effectiveness of ‘third wave psychotherapies’. Summary The third wave of behavioural psychotherapies is an important arena of modern psychotherapy. It has added considerably to the spectrum of empirically supported treatments for mental disorders and influenced research on psychotherapy. The presented methods open up treatment possibilities for patient groups such as borderline personality disorder, chronic depression or generalized anxiety disorder that had received only little specific attention in the past. The available evidence now allows considering all third wave treatments as empirically supported.

Starvation-induced hyperactivity in the rat: the role of endocrine and neurotransmitter changes.

Semistarved rats develop high running wheel activity. This running activity induces increased norepinephrine, dopamine, and serotonin turnover in the hypothalamus. Corticosterone in plasma becomes increased while luteinizing hormone and testosterone are suppressed. In female rats cyclic gonadal function is suppressed. Running activity in the semistarved rats can be suppressed specifically by serotonin 1-c-agonists and by alpha 2-adrenoceptor agonists. This animal model is helpful in the understanding of the combined effects of starvation and hyperactivity, which are observed in many patients with anorexia nervosa. The observation of the serotonergic system might help to develop a pharmacological treatment of hyperactivity in anorectic patients.

Dieting influences the menstrual cycle: vegetarian versus nonvegetarian diet

Eighteen healthy, normal-weight women aged 19 to 27 years who had regular ovulatory menstrual cycles volunteered for the study. Blood was drawn on Mondays, Wednesdays, and Fridays throughout the control cycle and during a 6-week diet period that began with commencement of a new cycle. Nine women followed a vegetarian diet and nine a nonvegetarian diet. Both groups lost an average of 1 kg body weight/week. Seven of nine women in the vegetarian group became anovulatory. During the vegetarian diet the average luteinizing hormone (LH) values were significantly decreased during the midcycle and the luteal phase. Estradiol (E2) and progesterone (P) values were significantly lower during the luteal phase. In contrast, the nonvegetarian group did not show significant reduction of LH, E2, and P values during any part of the menstrual cycle. Seven of nine women in the nonvegetarian diet group maintained ovulatory cycles with no changes in cycle length or in the length of the follicular phase. In one woman who became anovulatory, E2 values did not increase during the follicular phase.

Mood changes and physical complaints during the normal menstrual cycle in healthy young women.

Significant emotional and physical symptoms have been linked to hormonal changes during the menstrual cycle. A critical evaluation of the available studies questions the commonly held belief in menstrual-cycle-related complaints in the majority of normal women. The present study investigated changes in mood, somatic complaints and vegetative variables during the menstrual cycle in 30 healthy young women. Normal cycle function was evaluated and cycle phases were defined according to endocrine data. For all subjects, blood samples were taken at least three times a week to measure estradiol and progesterone. Daily ratings of psychological variables revealed no significant changes in global mood or depression over the cycle. Somatic complaints such as abdominal pain and breast tenderness were significantly related to the luteal, premenstrual, and menstrual phases. Appetite increased in the periovulatory and premenstrual phases. There was a tendency for sexual interest to be highest in the post-menstrual period. Affect and vegetative variables showed no association with hormone levels but were significantly correlated with subjective stress ratings. We conclude that in most healthy young women, cycle-related hormone fluctuations are not accompanied by marked affective changes. Specific physical complaints, however, do occur, particularly in the luteal, premenstrual, and menstrual phases.

Angiogenic factors in patients with current major depressive disorder comorbid with borderline personality disorder

BACKGROUND Major depression has been associated with endocrine and immune alterations, in particular a dysregulation of the hypothalamus-pituitary-adrenal system with subsequent hypercortisolism and an imbalance of pro- and anti-inflammatory cytokines. Recent studies suggest that vascular endothelial growth factor (VEGF), a cytokine involved in angiogenesis and neurogenesis, may also be dysregulated during stress and depression. These observations prompted us to examine VEGF and other angiogenic factors in patients with major depressive disorder. METHODS Twelve medication-free female patients with a major depressive episode in the context of borderline personality disorder (MDD/BPD) and twelve healthy women were included. Concentrations of VEGF, VEGF receptors 1 and 2, basic fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), angiopoetin-2, interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) were determined from serum profiles. RESULTS Increased concentrations of VEGF and FGF-2 were found in MDD/BPD patients compared to the healthy comparator group. No group differences were found concerning the other angiogenic factors examined. CONCLUSION Depressive episodes in the context of borderline personality disorder may be accompanied by increased serum concentrations of VEGF and FGF-2. Similar findings have been observed in patients with major depression without a borderline personality disorder. A dysregulation of angiogenic factors may be another facet of the endocrine and immunologic disturbances frequently seen in patients with depressive episodes.

Diet-induced menstrual irregularities: effects of age and weight loss

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) levels were followed in 22 healthy, normal-weight women (aged 19 to 30 years) for a control and a diet menstrual cycle. During the diet cycle, they lost weight on a high-carbohydrate, vegetarian, 1000-calorie diet. During the control cycle, luteal phase in 5 subjects failed to meet the criteria: length greater than or equal to 8 days and P maximum greater than or equal to 6 ng/ml; during the diet cycle, the number of subjects who failed to meet these criteria was 14 (chi-square test, P less than 0.02). No evidence of follicular phase disturbance was observed during the diet. Age and weight loss significantly changed parameters of the diet luteal phase: length and area under LH, FSH, E2, and P curves. Generally, hormone plasma concentrations during the luteal phase were lower the younger the age and the greater the weight loss.