The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Abnormalities in the regulation of vasopressin and corticotropin releasing factor secretion in obsessive-compulsive disorder.

In light of prior data that the central administration of vasopressin in animals is associated with abnormal persistence of behaviors acquired under aversive conditioning, we studied the secretion of arginine vasopressin into the cerebrospinal fluid and plasma in patients with obsessive-compulsive disorder and controls. Patients with obsessive-compulsive disorder had significantly elevated basal levels of arginine vasopressin in the cerebrospinal fluid and significantly increased secretion of arginine vasopressin into the plasma in response to hypertonic saline administration. Moreover, seven of 12 patients with obsessive-compulsive disorder showed a loss of the normal linear relationship between plasma arginine vasopressin level and osmolality. In addition, cerebrospinal fluid corticotropin releasing hormone, which has synergistic effects with arginine vasopressin centrally and at the pituitary gland, was also significantly elevated in patients with obsessive-compulsive disorder compared with controls.

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.

Stress-induced changes in skin barrier function in healthy women.

Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion.

Increased vasopressin and adrenocorticotropin responses to stress in the midluteal phase of the menstrual cycle.

Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely linked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not been clearly described. In nine healthy women, metabolic and hormonal responses to treadmill exercise stress during the early follicular phase of the menstrual cycle, when gonadal steroid levels are low, were compared with responses in the midluteal phase of the cycle, when both progesterone and estrogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject's maximal oxygen consumption during the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopressin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had enhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal steroids during the early follicular phase of the menstrual cycle provide protection from the impact of stress on the HPA axis.

Suppression of hypothalmic-pituitary-adrenal axis responses to stress in lactating women.

In the rat, lactation suppresses a variety of physiological responses to stress. We investigated whether stress-responsive neurohormonal systems are also restrained during breast feeding in humans. We chose treadmill exercise as a stressor because this stimulus produces an exercise intensity-dependent activation of the hypothalamic-pituitary-adrenal axis and the sympathomedullary system that is independent of differences in physical conditioning among subjects. Ten lactating and ten nonlactating women who were between 7 and 18 weeks postpartum performed 20 min of graded treadmill exercise. The final 5 min of exercise was set to elicit 90% of the maximal oxygen uptake of each subject. Plasma ACTH, cortisol, and glucose responses to exercise were significantly attenuated in lactating women (P < 0.001, P < 0.05, and P < 0.001, respectively). Basal norepinephrine levels were also reduced in lactating women (P < 0.05). These results indicate that stress-responsive neurohormonal systems are restrained in lactating women.

Plasma and cerebrospinal fluid measures of arginine vasopressin secretion in patients with bulimia nervosa and in healthy subjects.

Bulimia nervosa is a psychiatric syndrome associated with intense hunger, deficient satiety mechanisms, an obsessional preoccupation with the adverse consequences of eating, ritualistic binge eating, and subsequent purging to forestall the effects of the binge. The morbidity of this illness reflects both the psychological suffering associated with a life organized around pathological eating behaviors, as well as medical complications such as fluid and electrolyte imbalances that occur largely as a result of purging and laxative abuse. We report here a study of the osmoregulation of plasma arginine vasopressin secretion and of vasopressin levels in the cerebrospinal fluid. This study was undertaken because vasopressin not only functions as the antidiuretic hormone, and thus as a principal modulator of fluid and electrolyte balance, but also because, in animals, centrally directed vasopressin delays the extinction of behaviors acquired during aversive conditioning. Thirteen normal-weight female patients with bulimia nervosa were studied after at least 1 month of nutritional stabilization and supervised abstinence from binge eating and purging. Plasma vasopressin, plasma sodium, and subjective thirst were measured serially before and during a 2-h infusion of 3% hypertonic saline (0.1 ml/kg min). In addition, cerebrospinal fluid was obtained by lumbar puncture upon admission and at 1 week before hypertonic saline infusion in 11 of these patients and in an additional 11 female patients who did not participate in the hypertonic infusion study. Fifteen healthy normal weight individuals (4 female, 11 male) served as controls for the hypertonic saline infusion and a separate group of 11 healthy normal weight female controls underwent puncture. Compared to controls, bulimic subjects showed a significant reduction in the plasma vasopressin response to hypertonic saline; in 12/13, plasma vasopressin correlated closely with plasma sodium, whereas in one patient vasopressin fluctuated erratically, with no relation to plasma sodium. Cerebrospinal fluid vasopressin levels were significantly higher in patients, and correlated positively with basal thirst level, which was enhanced in bulimics. Compared to controls, patients showed significant polyuria. We conclude that patients with bulimia nervosa have abnormal levels of vasopressin in their plasma and cerebrospinal fluid during abstinence from binge eating and purging. The disturbance in osmoregulation may aggravate the maintenance of adequate fluid volume in these patients, while the increase in centrally directed vasopressin may have relevance to their obsessional preoccupation with the aversive consequences of eating and weight gain.

CSF oxytocin and vasopressin levels after recovery from bulimia nervosa and anorexia nervosa, bulimic subtype.

BACKGROUND: When ill, people with eating disorders have disturbances of the neuropeptides vasopressin and oxytocin. METHODS: To avoid the confounding effects of the ill state, we studied women who were recovered (more than 1 year, normal weight, and regular menstrual cycles, no bingeing or purging) from bulimia nervosa (rBN) or binge eating/purging-type anorexia nervosa (rAN-BN), and matched healthy control women. RESULTS: Vasopressin was elevated in rAN-BN and showed a trend towards elevation in rBN. In rBN, elevated cerebrospinal fluid vasopressin may be related to having a lifetime history of major depression. In comparison, cerebrospinal fluid oxytocin was normal in recovered subjects, but elevated levels in some rBN might be related to birth control pill use. CONCLUSIONS: These data confirm and extend the possibility that elevated cerebrospinal fluid vasopressin may be related to the pathophysiology of eating disorders, and/or a lifetime history of major depression.

Cerebrospinal fluid monoamine metabolites in fluoxetine-treated patients with major depression and in healthy volunteers.

Cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were measured in three groups: 46 healthy volunteers; 9 medication-free patients with DSM III-R major depressive disorder, recurrent; and these same 9 patients following at least 4 weeks of fluoxetine treatment at 20 mg/day. CSF monoamine metabolite levels in medication-free patients did not differ from healthy volunteers; however, CSF 5-HIAA and MHPG decreased significantly from 95.9 +/- 24.6 (all values +/- SD) to 64.2 +/- 26.1 pmol/ml and from 46.7 +/- 14.2 to 42.6 +/- 11.6 pmol/ml, respectively, following fluoxetine treatment. Fluoxetine also significantly decreased mean Hamilton Depression Rating Scale scores from 23.2 +/- 6.5 to 17.4 +/- 5.0 and significantly increased the CSF HVA/5-HIAA ratio.

Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable.

In brain, most L-tryptophan is metabolized to indoleamines, whereas in systemic tissues L-tryptophan is catabolized to kynurenine pathway metabolites. Among these latter compounds are: quinolinic acid, an N-methyl-D-aspartate receptor agonist; kynurenic acid, an antagonist of excitatory amino acid receptors that also reduces quinolinic acid-mediated neurotoxicity; and L-kynurenine, a possible convulsant. Because the metabolism of L-tryptophan through the kynurenine pathway is dependent upon adequate nutrition, we sought to determine whether the impaired nutrition characteristic of eating-disordered patients might be associated with specific disturbances in this metabolic pathway. Cerebrospinal fluid levels of L-tryptophan, quinolinic acid, kynurenic acid, L-kynurenine, and 5-hydroxyindoleacetic acid were measured in medication-free female patients meeting DSM-III-R criteria for either anorexia nervosa (n = 10) or normal-weight bulimia nervosa (n = 22), studied at varying stages of nutritional recovery. Eight healthy, normal-weight females served as a comparison group. Cerebrospinal fluid levels of kynurenic acid were significantly reduced in underweight anorectics, compared to normal females, but returned to normal values with restoration of normal body weight. Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa. Furthermore, in the eating-disordered patients, kynurenic acid levels in cerebrospinal fluid correlated positively with percent-of-population average body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Leptin, neuropeptide Y, and peptide YY in long-term recovered eating disorder patients.

BACKGROUND: Disturbances of leptin, neuropeptide Y (NPY), and peptide YY (PYY) have been found in women who are ill with anorexia or bulimia nervosa. It is not certain whether peptide disturbances are cause or consequence of eating disorders. METHODS: Plasma leptin and cerebrospinal fluid leptin, NPY, and PYY concentrations were measured in women who were recovered from anorexia or bulimia nervosa to determine whether alterations persisted after recovery. RESULTS: NPY, PYY, and leptin concentrations were similar across all diagnostic groups. CONCLUSIONS: Alterations in NPY, PYY, and serum leptin concentrations are probably secondary to pathological eating behaviors. Alterations of these peptides are unlikely to be trait-related disturbances that contribute to the etiology of eating disorders.

Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder.

Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive Scale (19 + or - 9 vs. 22 + or - 6). This suggests that these disorders have similar magnitude of impairment from obsessions and compulsions; however, OCD patients endorsed a wide variety of obsessions and compulsions, whereas anorexics tended to endorse symptoms that were related to symmetry and order.

Normal CSF oxytocin and NPY levels in OCD.

BACKGROUND: Attention has recently been focused on central nervous system neuropeptides as potential mediators of the symptom profile of obsessive-compulsive disorder (OCD). Increased CSF levels of the anxiolytic neuropeptide oxytocin have been reported in OCD. CSF levels of NPY, another anxiolytic neuropeptide, have not been studied. METHODS: We measured CSF oxytocin and NPY in 14 OCD patients and 26 healthy normal volunteers. RESULTS: There were no significant differences between the OCD patients and control subjects in CSF oxytocin or NPY levels. In both the OCD and control groups, women had significantly higher CSF oxytocin levels than men. CONCLUSIONS: These results do not support a prior finding of elevated CSF oxytocin in OCD patients and do not provide any evidence for an abnormality of NPY regulation in OCD.

Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin-releasing factor concentrations in adult primates.

BACKGROUND: The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood. METHODS: Cisternal CSF samples were obtained from those unpredictably reared young adult primates who had been previously studied as juveniles and age-matched ad libitum normally reared controls. Samples were assayed for CSF CRF. RESULTS: Concentrations of CSF CRF were significantly elevated in the unpredictably reared sample in comparison to the ad libitum-reared control group. A significant positive correlation was noted between juvenile and young adult CSF CRF values within the unpredictably reared cohort. CONCLUSIONS: Disturbances of maternal-infant attachment processes have an enduring impact on primate CRF function into young adulthood. The CRF elevations following unpredictable maternal foraging conditions appear traitlike in nature.

No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism.

BACKGROUND: The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc). METHODS: Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Alc randomly selected from a Finnish alcoholic population in which an association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. RESULTS: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in 1 OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Alc, or suicidality. CONCLUSION: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated.

Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients.

Levels of CSF fluid interleukin-2, but not interleukin-1 alpha, were found to be higher in 10 neuroleptic-free schizophrenic patients than in 10 healthy subjects matched for sex and age. Because interleukin-2 increases dopaminergic neurotransmission and participates in autoimmunity and cell growth, the authors postulate that elevated levels of central interleukin-2 might contribute to the increased dopaminergic neurotransmission, autoimmune phenomena, and abnormal brain morphology described in some patients with schizophrenia.

Regional cerebral glucose metabolism in bulimia nervosa.

OBJECTIVE: The authors' purpose in this study was to further delineate the character of cerebral metabolism in bulimia nervosa and to determine if functional links could be made between regional cerebral metabolism and the symptoms of depression, obsessive-compulsive disorder, and bulimia nervosa. METHOD: Regional cerebral glucose metabolism was measured by using positron emission tomography in 11 inpatients with bulimia nervosa and 18 normal comparison subjects matched in sex (all were women), age, and educational level. The bulimic patients were also tested for symptoms of major depression and obsessive-compulsive disorder. RESULTS: The patients with bulimia showed a correlation between lower left anterolateral prefrontal regional cerebral glucose metabolism and greater depressive symptoms. However, the orbitofrontal regional cerebral glucose metabolism of patients with bulimia was not greater than that of comparison subjects, nor was higher orbitofrontal metabolism correlated with greater obsessive-compulsive disorder symptoms. CONCLUSIONS: These findings lead to the conclusion that left anterior lateral prefrontal cortex hypometabolism varies with the depressive symptoms observed in bulimia but that temporal lobe hypermetabolism and asymmetries appear to be independent of the mood state.

Regulation of appetite and cholecystokinin secretion in anorexia nervosa.

Six patients with anorexia nervosa, the same patients after weight normalization, and six healthy control subjects had similar fasting and postprandial plasma cholecystokinin concentrations. These data do not support the hypothesis that low levels of hunger and food intake in anorexic patients reflect hypersecretion of this endogenous hormone, which is thought to inhibit hunger, promote satiety, and reduce feeding.

CSF somatostatin in obsessive-compulsive disorder.

OBJECTIVE: Because the central administration of somatostatin to experimental animals produces behaviors with some similarities to the compulsions of patients with obsessive-compulsive disorder and because serotonin reuptake inhibitors have been reported to reduce brain content of somatostatin, the authors examined central somatostatin activity in patients with obsessive-compulsive disorder. METHOD: CSF for measurement of somatostatin was obtained from 15 drug-free outpatients with obsessive-compulsive disorder and 27 normal volunteers. RESULTS: The mean CSF somatostatin level was significantly higher in the patients with obsessive-compulsive disorder than in the normal subjects. CONCLUSIONS: Although the functional significance of this finding is unknown, these data are consistent with a role for somatostatin in the clinical symptomatology of obsessive-compulsive disorder and its response to neuropharmacological agents. The high levels of CSF somatostatin reported here in a patient subgroup whose predominant symptoms consisted of overly focused, perseverative thought processes are in contrast to the consistently low levels of CSF somatostatin seen in patients with a spectrum of disorders characterized by substantial cognitive deficits.

Symptoms of eating disorders in patients with obsessive-compulsive disorder.

OBJECTIVE: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders. METHOD: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory. RESULTS: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects. CONCLUSIONS: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders.