Exposure to bisphenol A and behavior in school-age children.

INTRODUCTION: Bisphenol A (BPA) exposure has been shown to affect human brain neurodevelopment and behavior. OBJECTIVE: We aimed to investigate whether environmental exposure to BPA in children was associated with their childhood behavior. METHODS: Urinary BPA concentrations and behavioral characteristics were assessed in 300 children belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11 years of age. BPA concentrations were quantified in urine using liquid chromatography-tandem mass spectrometry (LC-MS-MS), and child behavior reported by parents using the Child Behavior Checklist (CBCL/6-18) under supervision of a psychologist. The association between BPA concentrations and CBCL standardized scores was analyzed using linear regression models, adjusted for important covariates. RESULTS: Median (P25, P75) BPA concentration was 4.76 (2.77, 9.03)µg/L. Mean (±SD) CBCL externalizing and internalizing scores were 56.35 (±8.06) and 51.36 (±9.22), respectively. In multivariate regression analyses, adjusted for maternal and child characteristics, higher BPA concentrations were associated with worse behavioral scores on all scales. Children with BPA concentrations in the 4th quartile had more somatic complaints (ß=2.35; 95% CI: 0.25, 4.46) and social (ß=1.71; 95% CI: 0.19, 3.22) and thought problems (ß=2.58; 95% CI: 0.66, 4.51) in comparison to those in the 1st quartile. Children with values in the 3rd quartile of BPA concentrations also showed greater social problems (ß=1.94; 95% CI: 0.43, 3.45). CONCLUSIONS: Our results suggest that exposure to BPA in childhood may affect children's behavior. Although further investigations are required, preventive measures should be undertaken to reduce inadvertent exposure to BPA.

The role of ovarian steroid hormones in mood.

Fluctuations in ovarian hormones across the menstrual cycle have long been considered a determinant of mood in women. The majority of studies, however, use menstrual cycle phase as proxy for hormone levels. We measured ovarian hormone levels directly in order to examine the relationship between daily hormone levels and mood in non-help-seeking women. Participants (n=19) provided daily information about their positive and negative moods, and collected their first morning-voided urine for 42days, which was analyzed for estrogen and progesterone metabolites (E1G and PdG). The independent contributions of daily E1G, PdG, stress, physical health, and weekly social support, were calculated for 12 daily mood items, and composite measures of positive and negative mood items, using linear mixed models. E1G or PdG contributed to few mood items: E1G measured 2days prior contributed negatively to the model for Motivation, while E1G measured 3days prior contributed negatively to Getting Along with Others, and E1G measured 4days prior contributed negatively to Anxiety. PdG, measured the same day and 1day prior, contributed positively to the models of Irritability, and PdG measured 5days prior contributed positively to Difficulty Coping. By contrast, the variables stress and physical health contributed significantly to all the mood items, as well as both composite positive and negative mood measures. These findings demonstrate that, compared to stress and physical health, ovarian hormones make only a small contribution to daily mood. Thus, fluctuations in ovarian hormones do not contribute significantly to daily mood in healthy women.

Symptom clusters during the late menopausal transition stage: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aims of this study were to identify groups of women in the late menopausal transition stage who experienced the same cluster of symptoms and to identify indicators that predicted membership in these distinct groups. METHODS: The sample consisted of a subset of Seattle Midlife Women's Health Study participants who were in the late menopausal transition stage and provided self-report data on symptoms experienced between 1990 and 2005. Latent class analysis (LCA) was used to identify groups of women who experienced similar clusters of the following five symptoms: problem concentrating, hot flashes, joint ache, mood changes, and awakening at night. LCA with multivariate logistic regression was used to identify covariates that predicted membership in each group. RESULTS: Four groups of women were identified: (1) low severity for all symptoms except for joint ache, which was moderate (65%); (2) high severity for all symptoms except for hot flashes, which was moderate (13%); (3) high severity for hot flashes, joint ache, and awakening at night (12%); and (4) high severity for problem concentrating and joint ache (10%). A clear delineation between groups based on individual characteristics was not fully elucidated. CONCLUSIONS: This analysis demonstrates that LCA may be useful to identify women who may experience poorer outcomes related to a higher propensity for severe symptoms. Shifting the focus from single symptoms to symptom clusters will aid in the identification of phenotypic profiles, thus facilitating symptom management strategies that can be tailored to meet the needs of individual women.

Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities.

OBJECTIVE: To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. BACKGROUND: Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. METHODS: Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. RESULTS: A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride.

BACKGROUND AND OBJECTIVES: Polyuria, polydipsia, and nephrogenic diabetes insipidus have been associated with use of psychotropic medications, especially lithium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The impact of psychotropic medications on urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion was investigated after overnight fluid deprivation, and over 6 h after 40 microg of desmopressin (dDAVP), in patients on lithium (n = 45), compared with those on alternate psychotropic medications (n = 42). RESULTS: Those not on lithium demonstrated normal urinary concentrating ability (958 +/- 51 mOsm/kg) and increased urinary excretion of AQP2 (98 +/- 21 fmol/micromol creatinine) and cAMP (410 +/- 15 pmol/micromol creatinine). Participants taking lithium were divided into tertiles according to urinary concentrating ability: normal, >750 mOsm/kg; partial nephrogenic diabetes insipidus (NDI), 750 to 300 mOsm/kg; full NDI, <300 mOsm/kg. Urinary AQP2 concentrations were 70.9 +/- 13.6 fmol/micromol creatinine (normal), 76.5 +/- 10.4 fmol/micromol creatinine (partial NDI), and 27.3 fmol/micromol creatinine (full NDI). Impaired urinary concentrating ability and reduced urinary AQP2, cAMP excretion correlated with duration of lithium therapy. Other psychotropic agents did not impair urinary concentrating ability. Eleven patients on lithium were enrolled in a randomized placebo-controlled crossover trial investigating the actions of amiloride (10 mg daily for 6 wk) on dDAVP-stimulated urinary concentrating ability and AQP2 excretion. Amiloride increased maximal urinary osmolality and AQP2 excretion. CONCLUSIONS: By inference, amiloride-induced reduction of lithium uptake in the principal cells of the collecting duct improves responsiveness to AVP-stimulated translocation of AQP2 to the apical membrane of the principal cells.

Melatonin excretion with affect disorders over age 60.

Numerous studies have reported low melatonin secretion in depression, but other studies have suggested no deficit or an increase. Alterations of circadian phase or duration of melatonin secretion have also been described. Since melatonin secretion decreases as we age, it seemed interesting to examine melatonin and depression in an aging sample. Volunteers who complained of mood or sleep problems were recruited for studies in which fractional urine specimens were collected for 24 h, both at home and in the laboratory. The major metabolite, 6-sulfatoxymelatonin (aMT6s), was determined by radioimmunoassay. Of 72 volunteers aged 60-78 years, seven had current major depression and 55% had a lifetime history of an affective disorder. A 55-fold range of home aMT6s excretion rates was observed. A lifetime history of any affective disorder was significantly associated with greater log(10)[mesor] aMT6s excretion in home collections and laboratory collections, but current affective disorders were neither significantly related to melatonin excretion nor to aMT6s acrophase timing, onset, offset or duration. These results are only weakly consistent with a photoperiodic hypothesis of depression.

Depression and endogenous melatonin in postmenopausal women.

BACKGROUND: Previous reports on melatonin secretion in depression are numerous but conflicting. There are very few studies relating the duration of the nocturnal melatonin peak to depression, and the results of those studies have been equivocal. METHODS: We studied mood disorders and urinary melatonin excretion in 382 postmenopausal women. Psychiatric diagnoses and global assessment of functioning (GAF) scores were determined based on a Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Urinary 6-sulfatoxymelatonin (6-SMT) samples were collected for two 24-h periods at home. RESULTS: A positive family history of depression was significantly related to a longer duration of 6-SMT excretion. There were marginally significant associations between current major depression and delayed offset of 6-SMT excretion and between later acrophase and lifetime major depression, even with control for age, ethnicity, season, and several medications. LIMITATIONS: The subjects were studied in their home environments, where light effects were not controlled. Data were restricted to postmenopausal women, including a limited number of subjects with current major depression. CONCLUSIONS: These results suggest that there might be a familial vulnerability in the endogenous melatonin signal in subjects prone to depression, and an abnormality in the duration of the melatonin signal in those with current major depression.

Changes in the regression slope correlating between urinary contents of alpha-1-microglobulin and ulinastatin and its relation to severity in mood disorders.

With mood disorders, clinical portrayals alone do not always reflect the exact state and progress of the disease. The present study attempted to evaluate whether changes in regression slope correlating between urinary contents of alpha-1-microglobulin and ulinastatin provided objective information on the severity of mood disorders, based on our previous findings that the regression slope was more steeply inclined in patients with mood disorders than in age-matched healthy subjects. As a result, a close association between scores of the Hamilton Rating Scale for Depression and the regression slopes was found: the more inclined the slope, the greater the severity of symptoms of depression. These results suggest that changes in the slope of the regression plot correlating between urinary contents of alpha 1 M and UT may afford a useful objective index when monitoring the state of patients with mood disorders.

Correlation between serum and urinary calcium levels and psychopathology in patients with affective disorders. Short communication.

To examine whether serum and urinary calcium levels were related to the psychopathology index (i.e. average score in clinically relevant scales of Minnesota Multiphasic Personality Inventory), 24 women aged 35.6 +/- 2.5 years and 20 men aged 34.3 +/- 2.1 years, suffering from affective disorders, were studied. A non-parametric bivariate correlation analysis revealed a negative correlation between PI and serum calcium (r = -0.256, p < 0.01), while urinary calcium levels correlated positively with PI (r = 0.236, p < 0.02). A positive correlation occurred between serum and urinary calcium (r = 0.968, p < 0.0001). When the data were analyzed by categorical classification of patients with normal or abnormal PI scores, serum calcium levels were smaller, and urinary calcium levels higher, in patients with abnormal PI (p < 0.01). The results support to the concept that alterations of calcium homeostasis occur in psychopathology.

Effect of carbamazepine on mean urinary free cortisol excretion in patients with major affective illness.

Carbamazepine, a tricyclic anticonvulsant effective in the treatment of major affective disorder, has been observed to induce cortisol non-suppression following dexamethasone administration. The mechanism of this effect has not been clearly established. In this study, the authors report carbamazepine-induced elevations of mean urinary free cortisol in patients with affective illness. The theoretical and practical implications of these findings are discussed.

Urinary 3-methoxy-4-hydroxyphenylglycol in affective and schizophrenic patients. Behavior and symptom correlates.

The relations between urinary 3-methoxy-4-hydroxyphenylglycol, (MHPG) excretion, ward behavior in two environments (dayroom and gym), and symptomatology were examined in 58 psychiatric inpatients. In the total patient sample, idiosyncratic behaviors and body activity correlated positively with MHPG levels. Among depressed patients MHPG correlated negatively with eating lunch in the dayroom and positively with self-reported appetite loss, suggesting that appetite disturbance in major depression may be due to high norepinephrine turnover. The results support the utility of naturalistic observation instruments in exploring the relations between psychopathology and biological substrates.

RBC choline and renal disorders during lithium treatment.

The authors measured RBC choline level, plasma choline level, and renal concentrating ability in 26 lithium-treated patients, seven psychiatric control subjects, and seven normal control subjects. An analysis of variance revealed no significant relationship between renal concentrating ability and either RBC choline level or RBC/plasma choline ratio.