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Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 181 records · Page 10Linked to original sources

Prodromes of depression and anxiety. The Stirling County study.

A longitudinal investigation of psychiatric epidemiology in a general population (the Stirling County study) has indicated that the incidence of depression and anxiety disorders is low relative to prevalence, because these disorders have long durations. In an average year approximately nine adults among 1,000 experience a first-ever episode of one of these disorders. Incident cases over the course of a 16-year follow-up were more likely to have had premonitory symptoms than to have been asymptomatic at the beginning of the study. Among the relatively small number of people who exhibited the clearest prodromal manifestations, incidence was 20 per 1,000 annually. It might be possible to intervene before such disorders become fully formed and persistent if the precursors are given attention.

Adult↗

Role of extra-splanchnic organs in the metabolic response to sepsis: effect of insulin.

The effect of sterile inflammation and sepsis on the release of lactate and amino acids by peripheral tissues was investigated in rats by removing the splanchnic organs (liver + small intestines) from the circulation and monitoring changes in blood metabolites over 30 min. Functional hepatectomy was performed in rats 5-7 days following the intraperitoneal introduction of a fecal-agar pellet (sterile vs. Bacteroides fragilis + E. coli). Lactate was significantly (P less than .05) increased in each of the conditions following hepatectomy but was raised to a significantly greater extent in sepsis (P less than .05). A similar response was observed for glutamine while alanine was only significantly (P less than .05) increased in sepsis following hepatectomy. Branched chain amino acids (BCAA) showed differential changes in sepsis compared to control. In control and sterile inflammation, functional hepatectomy was associated with significant decreases (P less than .05) in BCAA. In sepsis, BCAA were not decreased following hepatectomy and were significantly (P less than .05) elevated relative to control or sterile inflammation. Phenylalanine concentrations were not altered in control or sterile inflammation but were significantly elevated in sepsis (P less than .05). Insulin attenuated the accumulation of lactate and amino acids in fed control animals, following functional hepatectomy. However, in septic animals, insulin failed to prevent the rise in plasma lactate following hepatectomy.

Alanine↗

Screening for psychosocial disorders in pediatric practice.

Pediatricians have traditionally placed a high value on screening procedures. Screening tests are a routine part of health maintenance visits and serve the dual function of prevention and early recognition. However, despite the high prevalence of psychiatric disorders, there is no psychosocial screening procedure available. We present the Pediatric Symptom Checklist (PSC), a one-page, 35-item, parent-completed questionnaire that screens school-age children for psychosocial dysfunction. The PSC is administered in the waiting room and can be completed and scored in under five minutes. The PSC is not diagnostic of specific psychiatric disorders but is designed to help the pediatrician select which children may benefit from further clinical evaluation.

Child↗

Effects of Ro 15-4513, fluoxetine and desipramine on the intake of ethanol, water and food by the alcohol-preferring (P) and -nonpreferring (NP) lines of rats.

The effects of the IP administration of RO 15-4513 (1, 2 and 4 mg/kg), fluoxetine (5 and 10 mg/kg) and desipramine (5 and 10 mg/kg) on the intake of 10% ethanol, H2O and food were determined in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats with daily access to fluids being limited to single 2-hour sessions. The imidazobenzodiazepine Ro 15-4513 (a partial inverse benzodiazepine agonist) significantly reduced the intake of 10% ethanol by the P rats to 50-60% of control levels in the first 30 minutes without altering food or H2O intake. The attenuating actions of 2 mg/kg Ro 15-4513 on ethanol intake could be completely blocked by the central benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg). Ro 15-1788, by itself, produced no effects on alcohol and H2O consumption. The 5 mg/kg dose of fluoxetine significantly reduced 10% ethanol intake by the P rats to 20% of control values without altering either H2O or food consumption. The 10 mg/kg dose of fluoxetine further reduced ethanol intake by the P rats, but this dose also reduced daily food intake to approximately 70% of normal. Desipramine at both doses significantly (p less than 0.05) reduced both ethanol and food uptake by the P rats and had a tendency to reduce H2O consumption as well. In general, the three drugs had effects in the NP rats similar to those observed for the P group, although the effects on 10% ethanol intake were difficult to compare because of the low, variable intake of alcohol by the NP group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Effects of acute ethanol administration on monoamine and metabolite content in forebrain regions of ethanol-tolerant and -nontolerant alcohol-preferring (P) rats.

The contents of dopamine (DA), serotonin (5-HT) and their metabolites in the frontal cortex, anterior striatum, nucleus accumbens and hypothalamus of alcohol-tolerant and -nontolerant rats of the alcohol-preferring P line were determined one hour after the IP administration of 2.5 g ethanol/kg body wt. Compared with saline-injected controls, nontolerant P-rats injected with ethanol had (a) 60% higher levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the frontal cortex; (b) 30-60% higher levels of DOPAC and HVA in the anterior striatum and nucleus accumbens; and (c) 20% higher levels of 5-HIAA in all three forebrain regions. In the tolerant group, the effects of IP ethanol on DOPAC and HVA were markedly attenuated or completely eliminated in these three forebrain regions. However, in the case of 5-HIAA, an attenuated response was observed only in the nucleus accumbens of the tolerant group. The IP administration of ethanol had little effect on the contents of DA or 5-HT in any of these three forebrain regions, with the exception that 5-HT levels were elevated in the anterior striatum of both the tolerant and nontolerant groups. In the hypothalamus, there were no significant differences for the contents of DA, 5-HT or their metabolites between the nontolerant or tolerant P rats after IP ethanol. The data indicate that both acute ethanol administration and chronic alcohol intake by the P line of rats alters certain DA and 5-HT systems that may be involved in the brain reward circuitry and in DA pathways involved in motor functions.

3,4-Dihydroxyphenylacetic Acid↗

Pediatric Symptom Checklist: screening school-age children for psychosocial dysfunction.

The Pediatric Symptom Checklist (PSC) is a 35-item screening questionnaire that is completed by parents and designed to help pediatricians in outpatient practice identify school-age children with difficulties in psychosocial functioning. The current study assessed the validity of the PSC by screening 300 children in two pediatric practices, a middle-class group practice and an urban health maintenance organization. Validity was established by comparing the results of PSC screening of 48 children with in-depth interview assessments and pediatricians' ratings. Results indicate that the PSC has a specificity of 0.68 and a sensitivity of 0.95. The screening process was well accepted by parents and pediatricians. Several children whose pediatricians' ratings had indicated adequate functioning were identified by the PSC as having substantial psychosocial dysfunction and requiring further evaluation.

Child↗

Pharmacology of alcohol preference in rodents.

In alcoholism research, two fundamental and closely related questions are: "Why do people drink?" and "Why do some people drink too much?" Humans voluntarily drink alcoholic beverages or self-administer alcohol, more often than not, in a social setting. Environmental factors and how individuals react to them can, therefore, have powerful influences on drinking behavior. On the other hand, the neuropsychopharmacological actions of ethanol and how different individuals react to them can be important biological determinants. Ethanol's action is biphasic, i.e., it can be reinforcing (rewarding) in the low concentration range, but aversive at high concentrations. Perception by the individual of the reinforcing actions of ethanol might be expected to maintain alcohol-seeking behavior, whereas aversive effects would be expected to extinguish this behavior. Identification of the environmental and biological variables that promote and maintain alcohol-seeking or alcohol self-administration behavior is key to our understanding of the disorder alcoholism itself.

Alcoholism↗

Incidence of depression and anxiety: the Stirling County Study.

Prevalence studies in psychiatric epidemiology out-number incidence investigations by a wide margin. This report gives descriptive information about the incidence of depression and anxiety disorders in a general population. Using data gathered in a 16-year follow-up of an adult sample selected as part of the Stirling County Study (Canada), the incidence of these types of disorders was found to be approximately nine cases per 1,000 persons per year. The data suggest that for every man who became ill for the first time with one of these disorders, three women became ill. Incidence tended to be higher among relatively young persons. These incidence rates are consistent with prevalence rates of approximately 10 per cent to 15 per cent for depression and anxiety disorders aggregated together, given an estimated average duration of illness of about 10 years. It is concluded that these incidence rates are fairly realistic in view of evidence that disorders of these types tend to be chronic.

Adult↗

Affective disorders and mortality. A general population study.

A 16-year prospective study of a general population sample indicates that those who had reported a depression and/or anxiety disorder at baseline experienced 1.5 times the number of deaths expected on the basis of rates for a large reference population. As part of the Stirling County Study (Canada), the information was gathered from 1003 adults through structured interviews and was analyzed by means of a diagnostic computer program. The risk for mortality was assessed using external and internal standards, controlling for the effects of age and sex as well as for the presence of self-reported physical disorders at baseline. Increased risk was found to be significantly associated with affective but not physical disorders and with depression but not generalized anxiety. When this evidence about mortality was combined with information about subsequent psychiatric morbidity among survivors, 82% of those who were depressed at baseline had a poor outcome.

Adult↗

Performance of screening and diagnostic tests. Application of receiver operating characteristic analysis.

Evaluation of psychiatric screening and diagnostic tests has benefited from the application of sensitivity, specificity, the kappa-statistic, and predictive values. These measures derive their meaning from a single criterion threshold. Receiver operating characteristic (ROC) analysis extends assessment of test performance by providing information about all possible pairs of achievable sensitivity and specificity values. The ROC analysis offers a comprehensive means for comparing different tests or different scoring procedures for one test. As a demonstration we used the ROC analysis to evaluate three types of scoring rules for one psychiatric test, the Health Opinion Survey. The demonstration indicated that ROC analysis can profitably take a place among the standard methods for test evaluation in psychiatric research. In addition, ROC analysis can assist clinicians in selecting appropriate test procedures for particular patient populations.

Borderline Personality Disorder↗

Persistence of tolerance to a single dose of ethanol in the selectively-bred alcohol-preferring P rat.

The persistence of tolerance to a single dose of ethanol was examined in the selectively-bred alcohol-preferring P line of rats. Tolerance was measured by a test that required trained rats to jump onto a descending platform to avoid footshock. On day 0, each trained rat received a single IP injection of 2.5 g ethanol/kg body weight and was tested every 15 minutes for recovery to a criterion of 75% of pre-alcohol training performance. The second ethanol injection of 2.5 g/kg and testing were carried out seven days later for one group (n = 12), and 14 days later for another group (n = 12). Tolerance was assessed by the differences in time required to recover to criterion performance and blood alcohol concentrations (BACs) at time of recovery on day 0 vs. day 7 and day 14. The mean recovery times and BACs on day 0 were 156 +/- 5 minutes and 222 +/- 6 mg%, respectively. The group injected on day 7 exhibited shorter recovery times of 113 +/- 4 minutes and higher BACs at recovery of 261 +/- 4 mg%, while the group injected on day 14 did not show any significant differences from the values obtained on day 0. In a second experiment, the persistence of tolerance in P rats was compared with that of rats from the alcohol-nonpreferring NP line and of stock Wistar rats (n = 6/group). All rats were trained and tested for recovery to criterion after 2.5 g ethanol/kg on day 0 as described for the first experiment. The rats were then injected with ethanol and tested for tolerance on three subsequent occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats.

The objective of this study was to determine if the selectively bred P line of alcohol-preferring rats would develop behavioral (neuronal) tolerance with free-choice drinking of ethanol. Adult, male P rats were divided into four groups. One group (FCE) received food, water and a 10% (v/v) ethanol solution ad lib, while the control group (C) had only food and water. The other two groups received either a liquid diet containing 5% (v/v) ethanol (LDE) or a control liquid diet (LDC). All groups were kept on their respective feeding regimens for 14 days. The mean (+/- SEM) ethanol intakes for the FCE and LDE groups were 6.8 +/- 0.5 and 9.9 +/- 0.4 g ethanol/kg body wt./day, respectively. A shock-motivated jumping task was used to test for tolerance. Each rat received an IP injection of 2.5 g ethanol/kg and was tested every 15 minutes for recovery to a criterion of 75% of the performance level achieved with training. All rats were tested twice, once on the day before beginning their feeding regimens (day 0) and again 14 days later. Tolerance was assessed from differences in time of recovery to criterion performance and in blood alcohol concentrations (BACs) at recovery on day 0 vs. day 14. The mean recovery times for the C, FCE, LDC, and LDE groups on day 0 were 177 +/- 6, 170 +/- 6, 143 +/- 10 and 153 +/- 13 minutes, respectively, and the BACs were 219 +/- 6, 222 +/- 5, 220 +/- 19 and 214 +/- 6 mg%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Contents of monoamines in forebrain regions of alcohol-preferring (P) and -nonpreferring (NP) lines of rats.

The contents of monoamine neurotransmitters and metabolites were assayed in the frontal cortex, nucleus accumbens and anterior striatum of rats from the selectively bred alcohol-preferring P and nonpreferring NP lines. Lower levels of serotonin (20-30%) in all three brain regions of P as compared with NP rats lends support to the hypothesis that a decreased metabolic activity and/or innervation by serotonin neurons is associated with the abnormally high volitional intake of ethanol. Of additional interest, however, were the approximately 25% lower contents of dopamine and its major metabolites in the nucleus accumbens of the P rats. This observation may indicate that P rats have a specific deficiency in the dopaminergic projections from the ventral tegmental area to the nucleus accumbens and, since the accumbens is an important structure in brain reward circuitry, it might also be an important determinant of the excessive volitional intake of alcohol by P rats.

3,4-Dihydroxyphenylacetic Acid↗

Primary prevention of psychiatric disorders.

After a general discussion of factors involved in primary prevention of mental disorders, a case is described where community intervention aiming at reversing a process of social disintegration seemed to reduce the prevalence of anxiety and depression. Further experience with community development as an activity integrated into the functioning of a mental health centre is described. It was possible to encourage the growth of social networks that in turn led to several sustained organizations for self help and mutual aid. Even if this is promising from a preventive point of view, the effect upon mental health is not known. Repeated epidemiological studies in the area show a very stable prevalence level over time with high degree of chronicity and few new cases. This means that change in prevalence over a limited period of time only to a very small degree can be caused by primary prevention.

Adaptation, Psychological↗

Alcoholism: is it a model for the study of disorders of mood and consummatory behavior?

Depression, eating disorders, and carbohydrate craving are frequently seen in alcoholics or recovering alcoholics. Accordingly, these disorders may share some mediating pathways. It is now well-established that there is a genetic predisposition to alcoholism. Through genetic means, our laboratory has developed an animal model of alcoholism. Free-fed Wistar rats were selectively bred for the traits of alcohol-preference (the P line) and non-preference (the NP line). After more than 20 generations of selection, the lines show a stable difference of more than six-fold in voluntary ethanol consumption. We have now shown that the P line satisfies all the perceived requirements of an animal model of alcoholism. One major discovered difference between the P and the NP line is the lowered content of serotonin in certain brain regions of the P rats. Interestingly, fluoxetine curbs the alcohol-seeking behavior of the P rats; variation in the carbohydrate content of the diet, however, does not modify voluntary ethanol intake. The P rats are similar in body weight to the NP rats, but are more active in a novel environment than the NP rats.

Alcohol Drinking↗