Fenfluramine and Idiopathic Pain: A Serotonergic Study in Non-Psychiatric Patients with Functional Gastrointestinal Disorder

Background: We investigated prolactin and cortisol response to fenfluramine in non-psychiatric patients with chronic functional gastrointestinal disorder (FGD). Methods: Sixty milligrams fenfluramine was given orally to 55 subjects without any DSM-III axis-1 psychopathology and 29 healthy control subjects matched for sex and age. Serum cortisol and prolactin levels were analysed at base line and after 120, 180, and 240 min. Results: Fenfluramine challenge induced an increase in mean prolactin and cortisol serum values in both patients and controls. Female patients showed lower base-line values of prolactin and higher delta values of cortisol than controls. Male patients and controls showed very uniform values for all variables. Length of illness history influenced delta cortisol values in both sexes. Conclusions: The cortisol and prolactin responses to fenfluramine suggest a psychobiologic gender difference with a possible stress-induced central serotonergic dysfunction in female patients but not in male patients. The close relationship between length of illness and delta cortisol may also suggest an increased state of distress in females with chronic functional gastrointestinal disorder.     

Effect of Fenfluramine Challenge on Cocaine Craving in Addicted Male Users

The authors studied the effects of a challenging dose of the serotonin (5-HT)-releaser/reuptake inhibitor d,l-fenfluramine (FEN) on spontaneous cocaine craving in a group of cocaine-addicted users in order to evaluate the involvement of serotonergic pathways in the modulation of craving for cocaine. Nineteen cocaine-dependent male inpatients received 60 mg of FEN or placebo (double-blind). Data were compared with those obtained in a previous study of another serotonergic probe, the partial postsynaptic agonist meta-chlorophenyl-piperazine (m-CPP). FEN significantly reduced cocaine craving and increased cortisol and prolactin when compared with placebo. When the responses to the two drugs were compared, there were no differences in the cortisol and prolactin rises, but m-CPP was a more potent inhibitor of cocaine craving than FEN. These data suggest that 5-HT releasers/reuptake inhibitors and serotonergic agents with greater postsynaptic activity should be further examined. (Am J Addict 1998; 7:142–155)     

Diffusion tensor measures of the corpus callosum in adolescents with adolescent onset alcohol use disorders

Background: In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent‐onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders‐IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls. Methods: Adolescent subjects (25 males, 7 females) with an AUD (16.9 ± 1.2 years), who were recruited from substance abuse treatment programs and had co‐morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 ± 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan. Results: Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD. Conclusions: Lower MD and higher FA values in the AUD group suggest pre‐morbid vulnerability for accelerated prefrontal and temporo‐parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.     

Alcohol use disorders among emergency department-treated older adolescents: a new brief screen (RUFT-Cut) using the AUDIT, CAGE, CRAFFT, and RAPS-QF

BACKGROUND: Early identification of alcohol use disorders (AUD) among emergency department (ED)-treated patients is important for facilitating intervention and further evaluation outside EDs. A number of brief screening instruments have been developed for identifying patients with AUD, but it is not clear whether they are practical and perform well with older adolescents in an ED setting. This study contrasted four brief screening instruments for detecting DSM-IV-defined AUD and tested a newly developed brief screen for use among ED-treated older adolescents. METHODS: The Alcohol Use Disorders Identification Test (AUDIT), the CAGE, the CRAFFT, and a modified RAPS-QF were given to 93 alcohol-using older adolescents (55% men; aged 18-20 years) in an ED. Receiver operator characteristic analyses were used to evaluate the performance of brief screens against the criterion of a lifetime DSM-IV alcohol abuse or dependence diagnosis. RESULTS: Of existing instruments, the AUDIT had the best overall performance in identifying AUD (sensitivity, 82%; specificity, 78%). A new, shorter screening instrument composed of two AUDIT items, two CRAFFT items, and one CAGE item (RUFT-Cut) performed as well as the AUDIT (sensitivity, 82%; specificity, 78%). CONCLUSIONS: Among existing alcohol screening instruments, the AUDIT performed best for identifying ED-treated older adolescents with alcohol use disorders. The RUFT-Cut is a brief screening instrument for AUD that shows promise for identifying ED-treated older adolescents who are in need of intervention or further evaluation. Future research should focus on use of the RUFT-Cut in other settings with larger, more diverse samples of adolescents.     

Neuroendocrine Evidence for Reduced Serotonergic Neurotransmission During Heavy Drinking

A fenfluramine (60-mg oral dose) challenge test was performed in 19 male heavy drinkers (mean daily consumption 88 g of pure alcohol). Twelve healthy males served as controls. The prolactin and temperature responses to fenfluramine were significantly reduced in the group of heavy drinkers. The results suggest impaired central serotonergic neurotransmission in alcoholism, possibly involving subsensitivity in various serotonin receptor subtypes.     

Alcohol Use Disorder among Adolescents: Impact of Paternal Alcoholism on Drinking Behavior, Drinking Motivation, and Consequences

This study examined the impact of an Alcohol Use Disorder (AUD) in biological fathers on drinking history, context, motivation, and consequences in male and female adolescents dichotomized according to the presence or absence of an AUD. Main effects for paternal history of an AUD were not found on any variable. Significant interactions were observed between father-son diagnostic status with respect to age of first alcohol use ( p < 0.001) and peer relationships ( p < 0.001). No significant interactions were observed between father-daughter diagnostic status. As expected, adolescents with AUD differed from adolescents without AUD on numerous variables pertaining to drinking behavior, history, and consequences. These findings indicate that there is no strong or pervasive effect of paternal AUD on adolescent offspring's AUD characteristics. Key Words: Adolescence, Drug Abuse, Alcoholism, Family History.     

Prefrontal cortex volumes in adolescents with alcohol use disorders: unique gender effects

Background:  Adolescents with alcohol use disorders (AUD) have shown smaller prefrontal cortex (PFC) volumes compared with healthy controls; however, differences may have been due to comorbid disorders. This study examined PFC volumes in male and female adolescents with AUD who did not meet criteria for comorbid mood or attention disorders.
Methods:  Participants were adolescents aged 15 to 17 who met criteria for AUD ( n  = 14), and demographically similar healthy controls ( n  = 17). Exclusions included any history of a psychiatric or neurologic disorder other than AUD or conduct disorder. Magnetic resonance imaging scans occurred after at least 5 days of abstinence from alcohol or drugs. Overall PFC volumes and white matter PFC volumes were compared between groups.
Results:  After controlling for conduct disorder, gender, and intracranial volume, AUD teens demonstrated marginally smaller anterior ventral PFC volumes ( p  = 0.09) than controls, and significant interactions between group and gender were observed ( p  < 0.001 to p  < 0.03). Compared with same-gender controls, females with AUD demonstrated smaller PFC volumes, while males with AUD had larger PFC volumes. The same pattern was observed for PFC white matter volumes.
Conclusions:  Consistent with adult literature, alcohol use during adolescence is associated with prefrontal volume abnormalities, including white matter differences. However, adolescents with AUD demonstrated gender-specific morphometric patterns. Thus, it is possible that gender may moderate the impact of adolescent alcohol use on prefrontal neurodevelopment, and the neurodevelopmental trajectories of heavy drinking boys and girls should be evaluated separately in longitudinal studies.     

Cigarette smoking decreases the prolactin response to serotonergic stimulation in subgroups of alcoholics and controls

BACKGROUND: The prolactin response to serotonergic stimulation has been used as an index of central nervous system serotonin function. We evaluated the prolactin response to d,l-fenfluramine to determine whether subtypes of alcoholics differed in prolactin responsivity compared with nonalcoholics and whether cigarette smoking affected prolactin response. METHODS: One hundred ten healthy, abstinent men across four groups (controls [23% smokers]; alcoholics [72% smokers]; alcoholics with antisocial personality disorder [94% smokers]; nonalcoholic antisocials [88% smokers]) received d,l-fenfluramine (100 mg orally) in a randomized, double-blind, placebo-controlled study. Plasma prolactin levels were obtained at baseline and at half-hour intervals for 5 hr after fenfluramine/placebo administration. Plasma fenfluramine and norfenfluramine levels were obtained hourly. RESULTS: Smokers had a blunted prolactin response to fenfluramine compared with nonsmokers without any alcoholism or antisocial personality effects. Using a cutoff point of delta peak prolactin < 10 ng/ml, more smokers (41/76, 54%) had a dampened response to fenfluramine than did nonsmokers (7/34, 21%) [chi2(1) = 10.6, p < 0.003]. The percentage of low responders was greatest among smokers regardless of whether they were healthy controls, alcoholics, or antisocial. Multiple regression revealed that three variables--(1) number of pack-years of smoking, (2) actual dosage of fenfluramine received, and (3) plasma norfenfluramine level obtained--explained 43% of the variance (R2 = 0.43) in delta prolactin area under the curve. Variables that included alcoholism diagnostic status, antisocial personality diagnostic status, and impulsive aggressive personality, depressive, and suicidal traits failed to explain any additional unique variance. CONCLUSIONS: Cigarette smoking blunted the prolactin response to a pharmacological challenge with d,l-fenfluramine. Pharmacodynamic and pharmacokinetic factors related to smoking both appear to influence fenfluramine-induced prolactin secretion. Phenotypes of alcoholics did not differ in their prolactin response to this serotonergic probe.     

Pharmacological studies on the serotoninergic and nonserotonin-mediated stimulation of prolactin and corticosterone secretion by fenfluramine. Effects of pretreatment with fluoxetine, indalpine, PCPA, and L-tryptophan

Administration of the serotonin-releasing drug fenfluramine to male rats caused a dose-dependent increase in both plasma prolactin and corticosterone levels. The effect of fenfluramine on prolactin was maximal at 30 min after injection, whereas the effect on plasma corticosterone levels reached a maximum 2 h after injection. In order to determine if the effect of fenfluramine on both hormones was mediated via serotonin release, rats were pretreated with the serotonin uptake inhibitors fluoxetine (10 mg/kg i.p.) or indalpine (10 mg/kg i.p.) 30 min prior to administration of fenfluramine (5 mg/kg i.p.). Both fluoxetine and indalpine inhibited the effect of fenfluramine on plasma prolactin levels, but did not modify the effect of fenfluramine on plasma corticosterone levels. Pretreatment of rats with the serotonin precursor L-tryptophan (100 mg/kg i.p.) potentiated the effect of a submaximal dose of fenfluramine (2 mg/kg i.p.) on plasma prolactin levels, but did not affect the corticosterone response. Depletion of serotonin stores by pretreatment with the serotonin inhibitor p-chlorophenylalanine (300 mg/kg i.p.; 72 h) did not significantly prevent the effect of fenfluramine on either hormone. There was a 34% inhibition of the effect of fenfluramine on plasma prolactin levels, but this effect was not statistically significant. The results of the experiments suggest that the effect of fenfluramine on prolactin secretion is mediated, at least in part, by a serotoninergic mechanism, but the effect on corticosterone secretion is not mediated via serotonin release.     

Delay discounting by adolescents experimenting with cigarette smoking

Aims To evaluate delay discounting and self‐reported impulsive behavior in a sample of adolescents experimenting with cigarette smoking compared with adolescents who had never smoked or were daily smokers. Design A cross‐sectional design was used to compare smoking‐status groups. Setting Columbus, Ohio, a city of approximately 780 000 people. Participants A sample of 141 male and female adolescents with a mean age of 15.37 (standard deviation = 1.09) years. Measurements Primary measures included a computerized assessment of delay discounting, a self‐report assessment of impulsivity [Barratt Impulsiveness Scale—adolescent (BIS‐11‐A)] and verifications of cigarette smoking status (breath carbon monoxide and urinary cotinine level). Findings Smokers discounted more by delay and had higher impulsivity scores than non‐smokers. Experimenters had scores intermediate to those of smokers and non‐smokers on both measures. In some analyses the difference between experimenters and non‐smokers was significant, with experimenters showing greater delay discounting, but in no case did experimenters differ significantly from the smokers. Conclusions Young people who experiment with cigarettes appear to be similar to those who smoke regularly in terms of tendency to discount future gains and report impulsive tendencies, and generally higher in these traits than non‐smokers.     

Item response theory analysis of binge drinking and its relationship to lifetime alcohol use disorder symptom severity in an American Indian community sample

Background: Item response theory (IRT) has been used to examine alcohol use disorder (AUD) symptoms and their psychometric properties but has not been previously applied to AUD symptoms from an American Indian sample. Methods: Lifetime DSM‐IV AUD symptoms and binge drinking (5+ drinks men/4+ drinks women) at ≥1, ≥4, ≥8, and ≥15 days per month during the period of heaviest lifetime drinking criteria were assessed in 530 American Indian participants. Exploratory factor analysis was used to examine the factor structure of the 10 AUD symptoms and each alcohol consumption criterion. Two‐parameter IRT models generated marginal maximum likelihood estimates for discrimination (a) and threshold (b) parameters for 10 DSM‐IV AUD symptoms and each consumption criterion. Differential item functioning (DIF) analysis was used to assess AUD symptom severity in groups defined by gender and age at interview. Results: The AUD symptoms of “Withdrawal” and “Activities Given Up” were the most severe symptoms. “Tolerance” and “Social/Interpersonal Problems” were the least severe. All AUD symptoms fell on the moderate portion of the severity continuum, except “Withdrawal,” which fell at the lower end of the severe portion. The consumption criterion of 5+/4+ (male/female) at ≥8 times per month demarcated the portion of the severity continuum where AUD symptoms began to occur at a probability of 50%. DIF analysis showed significant gender and age at interview differences for “Hazardous Use,”“Tolerance,” and “Activities Given Up,” but not for the other AUD symptoms. Conclusions: In this American Indian community sample, alcohol abuse and dependence did not represent distinct disorders. Only one AUD symptom was found outside the moderate portion of the underlying AUD severity continuum. Drinking 5+/4+ (male/female) drinks at a frequency of ≥8 times per month during the period of heaviest lifetime drinking was found to function well as both a risk and a diagnostic criterion for lifetime DSM‐IV AUD. DSM‐IV AUD symptom criteria, as currently assessed, may be limited in their ability to capture the full range of symptom severity of AUDs, at least in this high‐risk population.     

Prefrontal cortex, thalamus, and cerebellar volumes in adolescents and young adults with adolescent-onset alcohol use disorders and comorbid mental disorders

BACKGROUND: In adults, prefrontal, thalamic, and cerebellar brain injury is associated with excessive ethanol intake. As these brain structures are actively maturing during adolescence, we hypothesized that subjects with adolescent-onset alcohol use disorders, compared with control subjects, would have smaller brain volumes in these areas. Thus, we compared prefrontal-thalamic-cerebellar measures of adolescents and young adults with adolescent-onset alcohol use disorders (AUD, defined as DSM-IV alcohol dependence or abuse) with those of sociodemographically similar control subjects. METHODS: Magnetic resonance imaging was used to measure prefrontal cortex, thalamic, and cerebellar volumes in 14 subjects (eight males, six females) with an AUD (mean age, 17.0+/-2.1 years) and 28 control subjects (16 males, 12 females; 16.9+/-2.3 years). All AUD subjects were recruited from substance abuse treatment programs and had comorbid mental disorders. RESULTS: Subjects with alcohol use disorders had smaller prefrontal cortex and prefrontal cortex white matter volumes compared with control subjects. Right, left, and total thalamic, pons/brainstem, right and left cerebellar hemispheric, total cerebellar, and cerebellar vermis volumes did not differ between groups. There was a significant sex-by-group effect, indicating that males with an adolescent-onset AUD compared with control males had smaller cerebellar volumes, whereas the two female groups did not differ in cerebellar volumes. Prefrontal cortex volume variables significantly correlated with measures of alcohol consumption. CONCLUSIONS: These findings suggest that a smaller prefrontal cortex is associated with early-onset drinking in individuals with comorbid mental disorders. Further studies are warranted to examine if a smaller prefrontal cortex represents a vulnerability to, or a consequence of, early-onset drinking.     

d-Fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen-induced alteration

The prolactin (PRL) response to fenfluramine (FEN), a serotonin (5-HT) releasing agent, is used as an index of 5-HT sensitivity in studying disorders associated with central 5-HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid-cycle and late luteal phase with either d-FEN, a more specific 5-HT agent than the racemic mixture, or placebo. Responses to d-FEN were maximal at mid-cycle, lowest during the early follicular phase, with responses premenstrually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated in parallel with neuroendocrine responses to d-FEN. The possible mechanisms are discussed, including an effect that oestradiol may exert at central serotonin sites.     

The Dimensionality of DSM-IV Alcohol Use Disorders Among Adolescent and Adult Drinkers and Symptom Patterns by Age, Gender, and Race/Ethnicity

Background: There is limited information on the validity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) alcohol use disorders (AUD) symptom criteria among adolescents in the general population. The purpose of this study is to assess the DSM‐IV AUD symptom criteria as reported by adolescent and adult drinkers in a single representative sample of the U.S. population aged 12 years and older. This design avoids potential confounding due to differences in survey methodology when comparing adolescents and adults from different surveys. Methods: A total of 133,231 current drinkers (had at least 1 drink in the past year) aged 12 years and older were drawn from respondents to the 2002 to 2005 National Surveys on Drug Use and Health. DSM‐IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Factor analytic and item response theory models were applied to the 11 AUD symptom criteria to assess the probabilities of symptom item endorsements across different values of the underlying trait. Results: A 1‐factor model provided an adequate and parsimonious interpretation for the 11 AUD criteria for the total sample and for each of the gender–age groups. The MIMIC model exhibited significant indication for item bias among some criteria by gender, age, and race/ethnicity. Symptom criteria for “tolerance,”“time spent,” and “hazardous use” had lower item thresholds (i.e., lower severity) and low item discrimination, and they were well separated from the other symptoms, especially in the 2 younger age groups (12 to 17 and 18 to 25). “Larger amounts,”“cut down,”“withdrawal,” and “legal problems” had higher item thresholds but generally lower item discrimination, and they tend to exhibit greater dispersion at higher AUD severity, particularly in the youngest age group (12 to 17). Conclusions: Findings from the present study do not provide support for the 2 separate DSM‐IV diagnoses of alcohol abuse and dependence among either adolescents or adults. Variations in criteria severity for both abuse and dependence offer support for a dimensional approach to diagnosis which should be considered in the ongoing development of DSM‐V.     

Responses to prolactin secretagogues in oestrogen-treated rats suggest that the defect in prolactin regulation produced by oestrogen is at the level of the pituitary gland

Prolactin responses to pharmacological agents were used to characterize the defect in prolactin regulation which occurs after administration of high doses of oestrogen to rats. Animals with chronically implanted venous cannulae were injected with 2 mg oestradiol benzoate in oil and 2-3 days later prolactin concentrations were measured after injections of saline, thyrotrophin-releasing hormone (TRH), fenfluramine, apomorphine and butaclamol. The responses were compared with those in oil-injected animals. Hyperprolactinaemia in oestrogen-treated animals was unresponsive to apomorphine, but was even more sensitive to dopamine receptor blockade than controls. These results suggest that the lactotrophs in oestrogen-treated animals are already maximally suppressed by endogenous dopamine, though ineffectively. Although there was an increased prolactin response to TRH in oestrogen-treated animals, there was an impaired response to fenfluramine, indicating suppressed serotonergic prolactin-releasing factor mechanisms. Maximal endogenous dopaminergic activity and suppressed prolactin-releasing factor mechanisms are appropriate hypothalamic responses to hyperprolactinaemia. The operation of these responses in the earliest stages of the development of pituitary hyperplasia indicates that oestrogen induces a disturbance of prolactin regulation in the lactotroph, independent of hypothalamic control.     

Alcohol screening in young persons attending a sexually transmitted disease clinic

OBJECTIVE: To compare the ability of 3 brief alcohol screens (Alcohol Use Disorders Identification Test [AUDIT], CRAFFT, and CAGE) to identify adolescents and young adults with a current alcohol use disorder (AUD) and to determine whether there are gender-based or race-based differences in screening performance. DESIGN, PARTICIPANTS, AND SETTING: Cross-sectional study of 358 young persons (55% males; 49% blacks; age range, 15-24 years; mean age, 20.6 years) who were attending an urban clinic for sexually transmitted diseases and reported alcohol use during the past year. MEASUREMENTS: Receiver operating characteristic (ROC) curve analysis was used to determine the ability of the 3 screens to discriminate between participants with and without AUDs detected in the Structured Clinical Interview for DSM-IV (SCID). RESULTS: One third (33%) of participants met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for a current AUD (24% with alcohol abuse and 9% with alcohol dependence). The AUDIT performed best at a cut score of 9 (sensitivity, 0.76; specificity, 0.79), CRAFFT at a cut score of 2 (sensitivity, 0.94; specificity, 0.33), and CAGE at a cut score of 1 (sensitivity, 0.69; specificity, 0.63). The AUDIT had the best overall performance (area under the curve [AUC], 0.84), followed closely by CRAFFT (AUC, 0.79) and then CAGE (AUC, 0.70). Performance of screens did not differ by gender. The AUDIT performed slightly better in whites than blacks, but no race-based differences were observed for the CAGE or CRAFFT. CONCLUSIONS: Clinicians should use the AUDIT or CRAFFT, rather than the CAGE, to screen young persons for AUDs. The AUDIT performs best, but its length may limit its utility in this setting. The CRAFFT is a suitable alternative, with excellent sensitivity and no gender-based or race-based differences.     

The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring

Background: Few population‐based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). Methods: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. Results: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. Conclusions: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.     

EFFECT OF FENFLURAMINE ON PROLACTIN SECRETION IN OBESE PATIENTS: EVIDENCE FOR SEROTONINERGIC REGULATION OF PROLACTIN IN MAN

The present investigation was carried out to study the effect of serotoninergic stimulation on prolactin (PRL) secretion in man. Fenfluramine (60 mg, orally), an anorexiant drug which under acute circumstances stimulates the serotoninergic system, was administered to eight obese patients. Compared with placebo, drug administration increased PRL significantly (P less than 0.05 at 180 and 300 min, P less than 0.01 at 240 min). No significant changes were observed after fenfluramine in blood pressure, plasma aldosterone (PA), plasma cortisol, plasma renin activity, serum electrolytes or growth hormone. Since it has been reported that dopaminergic blockade raises PA concentration, the lack of change in PA in obese patients treated with fenfluramine suggests that the observed increase in PRL induced by fenfluramine is likely to be mediated by serotoninergic stimulation.     

Blunted fenfluramine-evoked prolactin secretion in hypertensive rats

Plasma prolactin (PRL) levels after acute administration of fenfluramine (FEN) have been used as a probe of brain serotonin activity. FEN-evoked increases in PRL levels inversely correlate with arterial blood pressure (ABP) in humans (Muldoon et al. Hypertension. 1998;32:972-975), thereby suggesting that brain serotonin activity may be reduced in hypertension. The present study sought to determine whether the relation between FEN-evoked PRL levels and ABP was present in two rat models of hypertension. Experiments were performed in awake male rats that were instrumented with femoral arterial and venous catheters 2 days before experiments. FEN (3.0 mg/kg IV) significantly increased plasma PRL levels in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY); however, FEN-evoked PRL levels were significantly lower in SHR compared with WKY, though baseline levels were similar between strains. Similar results were obtained in rats with chronic hypertension produced by figure-8 renal wrap plus contralateral nephrectomy. In contrast, the increase in PRL levels evoked by the serotonin receptor agonist m-CPP or the dopamine receptor antagonist eticlopride did not differ between SHR and WKY, indicating that PRL secretion is not generally blunted in chronic hypertensive rats. Furthermore, FEN-evoked PRL levels were not attenuated in rats made acutely hypertensive by an infusion of the alpha-adrenergic agonist phenylephrine. Thus, the present findings are consistent with the human data and suggest that chronic hypertension is associated with a presynaptic alteration in brain serotonin function.     

Is Non‐suicidal Self‐injury Related to Impulsivity in Anorexia Nervosa? Results from Self‐report and Performance‐based Tasks

The present study investigates the association between non‐suicidal self‐injury (NSSI) and impulsivity in anorexia nervosa (AN) patients by means of self‐report and behavioural tasks. In total, 60 female AN patients were included in the study, filled out the Barratt Impulsiveness Scale‐11 (BIS‐11) and performed three performance‐based tasks to assess different facets of impulsivity. Overall, 30% of the AN patients engaged in at least one form of NSSI during their lifetime. AN patients with and without NSSI did not significantly differ on the BIS‐11 impulsiveness scale. On the performance‐based measures, few differences emerged between AN patients with and without NSSI. Patients with NSSI showed more perseverations and perseveration errors (p < .05). The associations between self‐report and performance‐based measures were rather low, except for the association between the BIS‐11 and Wisconsin Card Sorting Task perseveration responses and errors (correlations |r| range between .32 and .42). The implications for theory and treatment of AN patients with and without NSSI will be discussed. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.