Excretion of paroxetine into breast milk.

BACKGROUND: The study was carried out to quantify the excretion of the selective serotonin reuptake inhibitor paroxetine in breast milk. METHOD: In 6 lactating women, the concentrations of paroxetine in breast milk and serum were studied at the times for assumed minimum (24 hours after dose intake) and maximum (4-7 hours after dose intake) drug levels in milk. Moreover, a seventh subject was studied with frequent and regular sampling throughout a dose interval of 24 hours at 2 different dose levels. RESULTS: The mean milk/serum concentration ratios in the first 6 subjects ranged from 0.39 to 1.11 (overall mean +/- SD = 0.69 +/- 0.29), and the mean estimated dose to the infants ranged from 0.7% to 2.9% (overall mean +/- SD = 1.4% +/- 0.79%) of the weight-adjusted maternal dose. Based on area-under-the-curve data from the seventh subject, the milk/serum concentration ratio was 0.69 at a dose of 20 mg/day and 0.72 at a dose of 40 mg/day; the estimated relative doses to the infant were 1.0% and 2.0%, respectively. The mean increase in milk paroxetine concentrations from assumed minimum to assumed maximum was 61% (range, 4%-172%; p < .01). The mean paroxetine concentration in hindmilk was 78% higher than in foremilk (range, 16%-169%; p < .01), an increase that was parallel to the increase in milk triglyceride levels (r = 0.83, p = .005). No adverse drug reactions or unusual behaviors were reported in the infants. CONCLUSION: The study indicates that the relative dose to a suckling infant for paroxetine is lower than that reported for fluoxetine and citalopram and higher than that reported for sertraline and fluvoxamine.

Pyramidal neuron size in the hippocampus of schizophrenics correlates with total cell count and degree of cell disarray.

Hippocampal pyramidal neuron size was determined in all Cornu Ammonis subregions - CA1-CA4 - in five chronic schizophrenic men and compared with eight controls matched with respect to age and sex. Four out of five probands and the same eight controls had been examined in a previous study showing a significantly lower cell count and disorientation of pyramidal cells in the CA1- CA3 subregions of the schizophrenics. There was also a negative correlation between the total number of cells and the number of disoriented cells. In this study it was shown that the schizophrenic probands also had significantly smaller neurons in all subregions. There was a significant negative correlation between pyramidal neuron size and the number of disarrayed neurons in each subregion, and there was a significant positive correlation between neuron size and the total number of pyramidal cells in CA1 and CA2, but not in CA3 and CA4. The consistency of hippocampal anomalies in these schizophrenics is, thus, demonstrated by the statistical relations between the different parameters examined.

Excretion of citalopram in breast milk.

AIMS: The objective of this study was to measure to secretion of the selective serotonin uptake inhibitor citalopram in breast milk. METHODS: The excretion of citalopram in breast milk was studied at steady-state conditions in two patients with depression and in one healthy volunteer after ingestion of a single dose citalopram. RESULTS: Milk/serum concentration ratios based on single pairs of samples from the two patients ranged from 1.16 to 1.88. Based on milk concentration data from the patients, the absolute dose ingested by a suckling infant would be 4.3-17.6 micrograms kg-1 day-1, and the relative dose 0.7-5.9% of the weight-adjusted maternal dose. Based on area-under-the-time-concentration curves from the healthy volunteer, the milk/serum ratio was 1.00, the absolute dose to the infant during steady-state conditions would be 11.2 micrograms kg-1 day-1 and the relative dose 1.8% of the weight-adjusted maternal dose. CONCLUSION: The study shows that the relative dose to a suckling infant is close to that reported for fluoxetine, and higher than reported for fluvoxamine, paroxetine and sertraline.

Purification and characterisation of isocitrate dehydrogenase and malate dehydrogenase from Mycobacterium tuberculosis and evaluation of their potential as suitable antigens for the serodiagnosis of tuberculosis.

SETTING: Enzymes from Mycobacterium tuberculosis are potent antigens and might thus be of interest in the serodiagnosis of tuberculosis. OBJECTIVE: The purpose of the study was to purify and characterize the two enzymes isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH) from, M. tuberculosis and to evaluate their potential in the serodiagnosis of tuberculosis. DESIGN: The two enzymes were analysed for specificity by electrophoresis and then purified by means of affinity chromatography using reactive dyes and ion exchange chromatography. The two isolated enzyme fractions were analysed by ELISA, using antisera against related organisms. They were then tested as antigens in ELISA together with sera from tuberculous patients and controls. RESULTS: The electrophoretical analyses showed that the two enzymes each differed markedly from the corresponding enzymes of other mycobacteria. The serological analyses, however, could not distinguish between either IDH or MDH from other mycobacteria, but organisms of other genera, such as Nocardia, gave much weaker responses. When IDH and MDH were tested with sera from tuberculous patients and controls the former gave clearly higher optical density values than the latter. CONCLUSION: The enzymes/antigens IDH and MDH may be of value in developing a serological test for tuberculosis. The latter fraction seemed particularly capable of discriminating patients from controls.

Enzymatic and antigenic analyses of strains of Mycobacterium bovis, M. bovis BCG, and M. tuberculosis.

Strains of Mycobacterium bovis, M. bovis BCG, and M. tuberculosis, including a so-called Canetti strain, were analyzed by means of two-dimensional immunoelectrophoresis (2D-IE), 2D-IE combined with enzyme staining, and multilocus enzyme electrophoresis (MEE). The results demonstrated a close antigenic and enzymatic resemblance among all the strains tested, even though the BCG strains could be divided into two groups based on the presence of one precipitinogen. Eight of the precipitinogens were shown to correspond to enzymes in M. bovis BCG and 10 in M. tuberculosis. Thus, catalase, isocitrate dehydrogenase, malate dehydrogenase, peroxidase, and several others were identified. By means of MEE the strains of M. tuberculosis, M. bovis, and M. bovis BCG could be differentiated. The analyses further indicated that the M. tuberculosis strain Canetti was more closely related to M. bovis than to M. tuberculosis.

On perception of complex sound in schizophrenia and mania.

Eleven schizophrenic psychotic and 11 manic psychotic patients have been compared with each other and with a reference group of 34 dentists with respect to their emotional experience of seven complex nonverbal sounds. A rating form was used which measures three factors of emotional perception: tension-relaxation (factor I), gaiety-gloom (factor II), and attraction-repulsion (factor III). Analyses of variance of the factor scores revealed main tendencies between the psychopathological groups in factor I and III, i.e. schizophrenic psychotics rated the sounds generally as more tense and more attractive than manic psychotics. The manic psychotics rated the sounds as generally less tense and very much more attractive than the other groups. In factor II the manic psychotics rated one piece as significantly more gay than the other groups. It is discussed in what ways these differences of complex sound perception may be related to characteristic symptoms of the psychopathological states. No convincing evidence may be drawn from this study supporting the assumption that the two psychopathological groups might differ in a specific way in relation to any elementary structural property of the sounds.

The role of monoamines in suicidal behavior.

Cerebrospinal fluid (CSF), urine, platelet and neuroendocrine challenge tests of monoaminergic function give evidence of monoamines, especially serotonin, playing an important role in suicidal behavior. However, additional clinical, social and biochemical factors are necessary to better define suicide-prone psychiatric patients.

Incidence of cycloid psychosis. A clinical study of first-admission psychotic patients.

The concept of cycloid psychosis has gained increasing acceptance during recent decades. Using the diagnostic criteria of Perris and Brockington, an intelligible delineation of a group of patients has been obtained. Few epidemiological data on cycloid psychosis have been reported so far. The objective of the present study was to describe the one-year incidence of cycloid psychosis in a clinical sample. The diagnostic registers of all patients hospitalized for a functional or an organic psychosis and discharged in the year 1983, in Lund, Sweden were investigated. 514 patients were identified of whom 83 were admitted to hospital for the first time. 29 of these patients had a functional psychosis and were below the age of 50. In this age group 7 cases (4 women, 3 men) fulfilled the diagnostic criteria of cycloid psychosis and thus constituted almost one fourth of all first admissions of functional psychoses that year. The one-year incidence for first admission in cycloid psychosis was 5.0 per 100,000 inhabitants in women and 3.6 per 100,000 inhabitants in men within the age group 15-50 years in the catchment area of 163,175 persons. We conclude that cycloid psychosis constitutes a considerable proportion of functional psychoses in both sexes.

Vascular dementia in the Lundby study. 2. An attempt to identify possible risk factors.

Vascular dementia represents a group of diseases of great medical and social impact. Its etiology is largely unknown but is most likely multifactorial. Factors related to the brain circulation are involved. The aim of the present study was to find out if personality and social background factors might have a clear precipitating or protective value. This study comprises a total population of 2,612 individuals from a geographically delimited area, Lundby, in southern Sweden. In 1957, Hagnell personally examined 99% of the population. A follow-up study of the same individuals, irrespective of domicile, was performed 15 years later. No social background factors proved to be relevant in this study. Personality factors, including psychosomatic reactions, did, however, demonstrate a highly predictive influence on the risk of developing vascular dementia.

HPA-related CSF neuropeptides in suicide attempters.

Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin (AVP), which are regarded as being involved in the HPA-regulation were investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed according to the DSM-III-R, and rated with the MADRS. The neuropeptides were compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF and with post-dexamethasone plasma cortisol. We found strong correlations between CRH and the peptides SOM and beta-END. The latter also correlated positively with SOM. There were no differences between men and women. Patients with major depressive disorders had significantly lower SOM, CRH, and DSIP than other patients. Both SOM and beta-END correlated negatively with post dexamethasone plasma cortisol in all patients. We found no significant relationships between neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had significantly lower CRH than those who had not. No other significant associations between neuropeptides and suicidal subgroups of patients appeared, and there was no indication of specific neuropeptide patterns in patients who later completed suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major depressed patients are findings in line with those by others.

Prediction of suicidal behavior from biologic tests.

Biochemical studies related with suicidal behavior have mainly dealt with monoaminergic and corticosteroidal measures. We used some of these measures in a study of 61 suicide attempters who, except for occasional doses of benzodiazepines, had been medication free for a mean of 16 days. The monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid concentrations below the median of all patients, whereas the concentrations of 3-methoxy-4-hydroxyphenylglycol were mainly above the median. We found no significant differences between violent and nonviolent (N = 43) attempters concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5-hydroxyindoleacetic acid concentrations at or below the median. All completed suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median. Urinary measures and platelet monoamine oxidase activity of completed suicides were in the higher concentration ranges. Patients who repeated suicidal behavior after the index investigation had low 24-hour urinary cortisol levels more often than those who did not repeat. Because our subgroups of patients are small, we cannot draw any firm conclusions about the value of our CSF and urinary biochemical findings predicting suicidal behavior. However, our CSF findings in violent suicide attempters are similar to those observed in other studies.

Vascular dementia in the Lundby study. 1. A prospective, epidemiological study of incidence and risk from 1957 to 1972.

In this study, a total population, the 1957 Lundby cohort, was investigated with regard to the incidence of vascular dementia over a 15-year period, and to provide a succeeding study with basic data concerning the background factors for vascular dementia. The 1957 cohort comprises 2,612 persons who were registered in the geographically delimited Lundby area on July 1, 1957. The lifetime risk of developing vascular dementia was found to be 34.5% in men and 19.4% in women when all degrees of impairment were taken into account, the preponderance for the male sex being very obvious.

Senile dementia of the Alzheimer type in the Lundby Study. II. An attempt to identify possible risk factors.

In recent years research on senile dementia of the Alzheimer type (SDAT) has made progress within the field of pathology and to a certain extent in that of heredity. Within epidemiology, the search for risk factors is intensifying but the findings are still inconclusive. The present study of possible risk factors concentrates on environmental and personality factors. The total population of 2612 persons from a geographically delimited area, Lundby, two neighbouring parishes in southern Sweden, was examined in 1957 by one psychiatrist (Hagnell). A follow-up study of the same population, irrespective of domicile, was performed 15 years later, in 1972. Various precipitating as well as protective personality background factors were found to be significant for the outcome of SDAT, but no environmental factors appeared to be statistically significant in this cohort.

Peripheral serotonergic markers in patients with suicidal behavior.

Peripheral serotonergic parameters were studied in 17 patients with a history of suicidal behavior and in 17 age- and sex-matched healthy controls. Serotonin2 receptor function in platelets, measured as serotonin-induced [32P]phosphatidylinositol 4,5-bisphosphate hydrolysis, was significantly higher in patients than in age- and sex-matched controls. Increased serotonin2 receptor transduction was not correlated to psychiatric diagnosis, drug treatment or a history of violent suicide attempt. Monoamine oxidase activity was lower in platelets from patients with a history of suicidal behavior than in controls. In addition, whole blood serotonin was analyzed but no significant alterations were found in blood from patients.

Senile dementia of the Alzheimer type in the Lundby Study. I. A prospective, epidemiological study of incidence and risk during the 15 years 1957-1972.

In spite of the great impact of senile dementia of the Alzheimer type (SDAT) on society, far too little is known about its epidemiology. In this study of a total, normal population from a geographically delimited area in Sweden, Lundby, 2612 persons were examined in 1957 by one psychiatrist (Hagnell). In 1972 the same population was reexamined irrespective of domicile. The incidence and risk of contracting SDAT during the 15 years were calculated. No cases of SDAT were diagnosed before the age of 60 years. The lifetime risk was for men 25.7% and for women 26.2%. When only the very severely impaired were taken into account, the figures were 14.5% in men and 14.6% in women.

A prospective study of first-incidence depression. The Lundby study, 1957-72.

The present study is based on the so-called 1957 Lundby cohort, a geographically defined normal Swedish population of 2612 individuals who were evaluated for mental disorders in 1957 and 1972. The annual age-standardised first incidence of depression, with or without other psychiatric symptoms, all degrees of impairment included, was found to be 4.3 per 1000 person years in men and 7.6 per 1000 person years in women. Up until 70 years of age, the cumulative probability of suffering a first episode of depression was 27% in men and 45% in women.