The occurrence of suicide in severe depression related to the months of the year and the days of the week

The purpose of the present study was to investigate the distribution of suicide during the months of the year and the days of the week in severe depression. A total of 1206 in-patients rated at discharge from the Department of Psychiatry, Lund, Sweden, on a multiaxial diagnostic schedule received the diagnosis severe depression/melancholia between 1956 to 1969. When followed up to 1998, a total of 114 depressed patients had taken their own life. Out of these, 98 patients appeared to have a primary depression. The monthly distribution of suicides showed a significant peak in October/November for men (41 % of all male suicides). No correlation with the onset of depression could be detected. Furthermore, there was a preponderance of suicide on Sundays for both sexes (31 % of all suicides). Received: 28 March 2001 / Accepted: 29 November 2001     

Permutation tests for detecting and estimating mixtures in task performance within groups

We propose a two-sample permutation test incorporating mixture models as a general tool for detecting and quantifying effects on task performance. We illustrate the proposed method with examples where the dependent measures under investigation are recorded for normal controls and relatives of patients with schizophrenia on a delayed response, spatial and object working memory task. Our mixture modelling in relatives allows the component distributions to arise from different continuous parametric families. We also investigate the effects of the within-family correlation and the prior distribution of the mixing proportion on the test results. The power of the test depends on sample sizes, the mixing proportion, the difference in component means and the ratio of component variances.     

Estimation of an errors-in-variables regression model when the variances of the measurement errors vary between the observations

It is common in the analysis of aggregate data in epidemiology that the variances of the aggregate observations are available. The analysis of such data leads to a measurement error situation, where the known variances of the measurement errors vary between the observations. Assuming multivariate normal distribution for the 'true' observations and normal distributions for the measurement errors, we derive a simple EM algorithm for obtaining maximum likelihood estimates of the parameters of the multivariate normal distributions. The results also facilitate the estimation of regression parameters between the variables as well as the 'true' values of the observations. The approach is applied to re-estimate recent results of the WHO MONICA Project on cardiovascular disease and its risk factors, where the original estimation of the regression coefficients did not adjust for the regression attenuation caused by the measurement errors.     

Polymer Delivery of Camptothecin against 9L Gliosarcoma: Release,Distribution, and Efficacy

Camptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro; unfortunately, systemic toxicity has limited its in vivo efficacy. This is the first study to investigate the release, biodistribution, and efficacy of camptothecin from a biodegradable polyanhydride polymer. Tritiated camptothecin was incorporated into biodegradable polymers that were implanted intracranially in 16 male Fischer 344 rats and the animals were followed up to 21 days post-implant. A concentration of 11–45g of camptothecin-sodium/mg brain tissue was within a 3mm radius of the polymer disc, with levels of 0.1g at the outermost margin of the rat brain, 7mm from the site of implantation. These tissue concentrations are within the therapeutic ranges for human and rat glioma lines tested against camptothecin-sodium in vitro. The in vivo efficacy of camptothecin-sodium was evaluated with male Fischer 344 rats implanted intracranially with 9L gliosarcoma and compared with the efficacy of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The animals were divided into four groups. Group 1 (control) had a median survival of 17 days. Group 2 (3.8% BCNU polymer) had a median survival of 23 days (P=0.006). Group 3 (20% camptothecin polymer) had a median survival of 25 days (P=0.023). Group 4 (50% camptothecin polymer) had a median survival of 69 days (P<0.001). Drug loadings of 20% and 50% camptothecin released intact camptothecin for up to 1000h in vitro. We conclude that the biodegradable polymer p(CPP:SA) releases camptothecin-sodium, produces tumoricidal tissue levels, results in little or no systemic toxicity, and prolongs survival in a rat glioma model.     

The role of sex hormones on formalin-induced nociceptive responses

Many chronic pain conditions are more frequent in women than in men. This observation suggests that there is a potential role of sex hormones on pain perception. In the present study, we measured nociceptive responses to the formalin test in normal and gonadectomized male and female rats. The nociceptive responses to formalin injection were divided in four phases: acute (phase I), interphase and late phases (phases II and III). Four groups of rats were tested: (a) males (n = 15), (b) females (n = 16), (c) ovariectomized females (OVX) (n = 15) and (d) castrated males (CAST) (n = 15). Females presented significantly more nociceptive responses than males during phase I, interphase and phase II (P < 0.01). They also presented significantly more nociceptive responses than OVX females during the interphase (P < 0.05). CAST males presented significantly more nociceptive responses during the phases I (P < 0.01), II (P < 0.01) and III (P < 0.05) than the male rats. Finally, the responses of CAST males and OVX females were virtually identical, suggesting that the differences recorded between males and females in the formalin test were related to an activational effect of the sex hormones rather than an organizational effect. In conclusion, these results permit the support of the role of sex hormones on the modulation of pain perception. Interestingly, male and female sex hormones seem to act specifically on the different phases of the formalin test, suggesting some specific roles for sex hormones in different pain conditions.     

Urinary free cortisol and childhood trauma in cocaine dependent adults

OBJECTIVE: To examine whether childhood trauma may have a relationship to hypothalamic-pituitary-adrenal (HPA) axis function as an adult. METHODS: Forty-six withdrawn cocaine dependent patients participated in 24-h urine collections for determination of urinary-free cortisol (UFC) and completed the Childhood Trauma Questionnaire (CTQ). RESULTS: Patients with a mean UFC output below the median had significantly higher CTQ scores for childhood sexual abuse than patients with UFC outputs above the median. Multiple regression analysis showed that both childhood emotional neglect and sexual abuse were independently associated with UFC outputs. CONCLUSION: These cross sectional data, in a sample of middle-aged cocaine dependent patients, suggest the possibility that childhood trauma may have an effect on HPA axis function and thus predispose to psychiatric disorders. Further studies are needed in different samples.     

Women and men exhibit different cortical activation patterns during mental rotation tasks

The strongest sex differences on any cognitive task, favoring men, are found for tasks that require the mental rotation of three-dimensional objects. A number of studies have explored functional brain activation during mental rotation tasks, and sex differences have been noted in some. However, in these studies there was a substantial confounding factor because male and female subjects differed in overall performance levels. In contrast, our functional brain activation study examined cortical activation patterns for males and females who did not differ in overall level of performance on three mental rotation tasks. This allowed us to eliminate any confounding influences of overall performance levels. Women exhibited significant bilateral activations in the intraparietal sulcus (IPS) and the superior and inferior parietal lobule, as well as in the inferior temporal gyrus (ITG) and the premotor areas. Men showed significant activation in the right parieto-occitpital sulcus (POS), the left intraparietal sulcus and the left superior parietal lobule (SPL). Both men and women showed activation of the premotor areas but men also showed an additional significant activation of the left motor cortex. No significant activation was found in the inferior temporal gyrus. Our results suggest that there are genuine between-sex differences in cerebral activation patterns during mental rotation activities even when performances are similar. Such differences suggest that the sexes use different strategies in solving mental rotation tasks.     

Replication of a premenstrual decrease in right-ear advantage on language-related dichotic listening tests of cerebral laterality

Five fused dichotic word tasks measured perceptual asymmetry in 30 women at 4 weekly intervals. The five tasks varied according to whether the stimuli presented were word-word pairs or nonsense word-pairs, or whether they consisted of neutral words paired with positive emotion-evoking words (e.g. hug-tug), neutral words paired with negative emotion-evoking words (e.g. till-kill), or neutral words paired with neutral words (e.g. bean-dean). Overall right-ear advantage (REA) decreased in the premenstrual week relative to the postmenstrual week, replicating previous results using identical measures. In addition, REA scores were similar at menstrual, postmenstrual and midcycle weeks. Additional data from 12 men suggests sex differences in task performance were small or non-existent. In both women and men, there were no effects of repeated testing on REA, but emotional proclivity indices, defined as the tendency to recall words of positive or negative affective tone, increased across the four test sessions. As found previously, there was a trend for women to hear fewer positive words during the premenstrual week. These data are consistent with other research suggesting that a progesterone-mediated decrease in functional asymmetry occurs in the luteal phase. Future research manipulating task demands (e.g. memory load) or the affective valence of the stimuli may be useful in understanding the observed changes in hemispheric advantage.     

Functional cerebral asymmetries during the menstrual cycle: a cross-sectional and longitudinal analysis

This study aims at answering two basic questions regarding the mechanisms with which hormones modulate functional cerebral asymmetries. Which steroids or gonadotropins fluctuating during the menstrual cycle affect perceptual asymmetries? Can these effects be demonstrated in a cross-sectional (follicular and midluteal cycle phases analyzed) and a longitudinal design, in which the continuous hormone and asymmetry fluctuations were measured over a time course of 6 weeks? To answer these questions, 12 spontaneously cycling right-handed women participated in an experiment in which their levels of progesterone, estradiol, testosterone, LH, and FSH were assessed every 3 days by blood-sample based radioimmunoassays (RIAs). At the same points in time their asymmetries were analyzed with visual half-field (VHF) techniques using a lexical decision, a figure recognition, and a face discrimination task. Both cross-sectional and longitudinal analyzes showed that an increase of progesterone is related to a reduction in asymmetries in a figure recognition task by increasing the performance of the left-hemisphere which is less specialized for this task. Cross-sectionally, estradiol was shown to have significant relationships to the accuracy and the response speed of both hemispheres. However, since these effects were in the same direction, asymmetry was not affected. This was not the case in the longitudinal design, where estradiol affected the asymmetry in the lexical decision and the figural comparison task. Overall, these data show that hormonal fluctuations within the menstrual cycle have important impacts on functional cerebral asymmetries. The effect of progesterone was highly reliable and could be shown in both analysis schemes. By contrast, estradiol mainly, but not exclusively, affected both hemispheres in the same direction.