Alcohol outcome expectancies and risk for alcohol use problems in women with and without a family history of alcoholism

Studies have shown that alcohol expectancies are positively associated with drinking and alcohol abuse and dependence symptoms among alcohol users. This study looked at the relationship of alcohol expectancies, family history of alcoholism, menstrual cycle and drinking behavior. The present study compared alcohol expectancies using the Alcohol Expectancy Questionnaire (AEQ) in 85 women ranging from 18 to 35 years of age. Forty-one women had a confirmed parental history of alcoholism (family history positive, FHP) and 44 women had no parental history of alcoholism (family history negative, FHN). Participants' mood, alcohol consumption, and daily consequences of alcohol use were prospectively tracked across one menstrual cycle. Alcohol expectancies at screening were significantly greater in FHP women in four of the six AEQ subscales, as well as the composite score. Alcohol expectancies correlated significantly with drinking behavior among FHN women. In FHP women, alcohol expectancies were elevated regardless of their drinking level. Alcohol expectancies decreased among FHP women, but not FHN women, after prospectively tracking their drinking behavior and consequences of drinking. Negative outcomes of drinking were increased among the FHP women who were heavy drinkers. Irrespective of family history status, alcohol use in moderate drinkers increased significantly during menses compared to the follicular and luteal phases of the menstrual cycle. These findings suggest that menstrual cycle may also play a role in alcohol consumption. Thus, the results of the present study indicate that issues related to the level of alcohol consumption, menstrual cycle phase and family history of alcoholism should be considered when addressing alcohol abuse in women.     

Response to alcohol in females with a paternal history of alcoholism

Rationale Several studies have demonstrated that males with a family history of alcoholism (FHP) show less of a response to alcohol (e.g. lower ratings of intoxication) than males without a family history of alcoholism (FHN). The purpose of this pilot study was to determine if FHP females also showed a reduced sensitivity to alcohol compared to FHN females. Objectives To determine if FHP females (n=16) were less sensitive to the subjective effects and performance-impairing effects of alcohol compared to FHN females (n=16). Methods The effects of placebo and alcohol (0.25, 0.50, 0.75 g/kg, based on total body water) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using performance tasks, observer ratings of drug effect and subjective ratings of drug effect. Results There were no differences in breath alcohol levels between FHN and FHP women. FHP women were less impaired by alcohol than FHN women, as shown by DSST scores and observer-ratings. However, FHP women were more impaired on the Digit Recall task after alcohol than FHN women and they tended to have higher ratings of "Good Drug Effect," "Drug Liking" and "Willingness to Take Again." Of note, FHP women reported more dysphoric mood than FHN women in the absence of alcohol administration. Conclusions The results of the present study suggest that FHP women may have a reduced response to alcohol on some measures, but FHP women report greater positive effects on other measures. Overall, the differences between FHP and FHN women are subtle compared to the previous studies demonstrating a reduced response to alcohol in FHP men.     

The effects of smoked cocaine during the follicular and luteal phases of the menstrual cycle in women

RATIONALE: Few studies have systematically determined whether the response to cocaine in human females is related to hormonal fluctuations at different phases of the menstrual cycle. OBJECTIVES: To investigate the responses to repeated doses of smoked cocaine in women during two phases of the menstrual cycle using a within-subject design. METHODS: Eleven non-treatment seeking female cocaine smokers were administered smoked cocaine during the follicular and mid-luteal phases of the menstrual cycle. The order of menstrual cycle phase was counterbalanced across women and the order of cocaine doses was randomized. During each phase, there were four cocaine administration sessions. During each session, participants could smoke up to six doses of cocaine (either 0, 6, 12, or 25 mg cocaine base, depending on the session) at 14-min intervals. RESULTS: The number of cocaine doses administered did not vary between the follicular and luteal phases. After cocaine administration, heart rate and several ratings - such as "good drug effect", "high", "stimulated", and "drug quality ratings" - were increased more during the follicular phase than the luteal phase, although, for some measures, these effects varied based on the cocaine dose. Further, dysphoric mood during the luteal phase was improved after cocaine administration. CONCLUSIONS: These results indicate that the cardiovascular and subjective effects of repeated doses of smoked cocaine are complex and vary as a function of menstrual cycle phase and cocaine dose.     

Alcohol-induced changes in body sway in women at risk for alcoholism: a pilot study

Family history of alcoholism appears to influence acute alcohol responses in young men. We report pilot data from a study designed to expand these observations by measuring blood alcohol levels (BALs), subjective intoxication effects, body sway and cognitive-motor task performance in women. Six young women with (FHP) and six without (FHN) alcoholic first degree relatives provided informed consent and were given 0.56 g/kg ethanol under double-blind conditions. Groups were matched for age, drinking history and height-weight ratio. Subjects performed tasks in random order at 90, 60 and 30 min before drinking alcohol, and 15, 30, 45, 60, 90, 120, 150 and 180 min after drinking alcohol. BALs peaked at 80 mg/dl 30 to 60 min after drinking alcohol. BALs were comparable and disappearance rates were similar for both groups. BALs and intoxication ratings for both FHP and FHN women had highly significant correlations. Alcohol decreased accuracy on an automated version of the Digit Symbol Substitution Test (DSST) for both groups, but FHN women made significantly more errors 30 min after alcohol. Significantly greater alcohol effects on body sway were apparent in FHN women 15, 30, 60, 90 and 120 min after alcohol. Compared with previous findings for men, both FHP and FHN women reported less intoxication at similar BALs, but body sway in FHN women was more affected by alcohol. Small sample size limits generalization of these findings but suggests that some effects of familial alcoholism in women are similar to those observed in men.     

Premenstrual symptomatology, alcohol consumption, and family history of alcoholism in women with premenstrual syndrome

OBJECTIVE: The purpose of this study was to examine the relationship among family history of alcoholism (FH), premenstrual syndrome (PMS) symptoms, and alcohol consumption in women with a PMS diagnosis. METHOD: Participants (N = 46) were predominantly white (73%) women, of whom 17 (37%) reported multigenerational alcoholism on the paternal side (FH positive [FH+]) using the Family Alcohol and Drug Survey. Subjects recorded alcohol consumption and PMS symptoms using a daily record form for 3 consecutive months. RESULTS: Demographics and alcohol consumption during the follicular phase (FOL) and premenstrual phase (PREM) of the menstrual cycle did not differ by FH; however, change in drinking from FOL to PREM was greater in FH+ (mean change = 2.78 drinks/week) versus FH negative (FH-; mean change = -0.72 drinks/week) women. During PREM, FH- women reported more PMS symptomatology compared with FH+ women, and alcohol consumption during PREM was positively correlated with ratings of bloating, craving for alcohol, craving for food, and low energy in FH- but not FH+ women. CONCLUSIONS: Although FH+ women increased their drinking premenstrually, such use was unrelated to PMS symptom severity.     

Increased sensitivity to alprazolam in females with a paternal history of alcoholism

RATIONALE: Few studies have directly examined the effects of benzodiazepines in individuals with a family history of alcoholism, particularly women, to determine whether they are differentially sensitive to their effects. OBJECTIVES: To determine whether females with a confirmed paternal history of alcoholism (FHP; n=14) were differentially sensitive to the mood and performance effects of alprazolam and buspirone compared with females without a first-degree family history of alcoholism (FHN; n=14). METHODS: The acute effects of placebo, alprazolam (0.25, 0.50, 0.75 mg), and buspirone (5, 10, 15 mg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using performance tasks, observer ratings of drug effect, and subjective ratings of mood, drug strength, and drug liking. RESULTS: Alprazolam impaired performance in a dose-related manner on all performance tasks for both groups of females, whereas buspirone had minimal effects on performance. The highest dose of alprazolam impaired the response to the digit symbol substitution test (DSST), digit recall, and word memory more in FHP females than in FHN females. Further, performance on the DSST and immediate word recall was able to accurately predict family history status. Correspondingly, FHP women reported greater increases in "difficulty concentrating" and "unmotivated" and greater decreases in items such as positive mood following alprazolam than FHN women. In contrast, alprazolam produced similar dose-related increases in subject-rated and observer-rated drug strength ratings in both groups of females. Lastly, there was no evidence of an increase in ratings of drug liking in either group following alprazolam. CONCLUSIONS: In contrast to many previous findings with FHP males, these results suggest that FHP females may be more sensitive to the performance-impairing effects and negative subjective effects of alprazolam.     

Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder.

Alterations in central nervous system response to menstrual cycle-related fluctuations in neuroactive steroids are thought to underlie the emergence of negative affect in the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder (PMDD). Such changes in the neuroendocrine milieu may lead to heightened arousal and response to stress in women with PMDD. Using the acoustic startle paradigm, we sought to determine whether women with PMDD have an accentuated physiologic response to a mildly aversive stimulus during the luteal compared to follicular phase. Further, we also examined the impact of visual affective stimuli on acoustic startle response (ASR) magnitude. During the follicular and luteal phases of the menstrual cycle, acoustic stimuli (103 dB) were delivered to 15 women with PMDD and 14 healthy menstruating women of similar age. After obtaining baseline ASR, the procedure was repeated when subjects viewed pleasant, neutral and unpleasant pictures. There was a significant group by menstrual cycle phase interaction for baseline ASR magnitude, which can be attributed to the heightened startle magnitude in women with PMDD compared to healthy women during the luteal relative to the follicular phase. The direction and degree to which picture viewing modulated the startle magnitude did not vary by group or menstrual cycle phase. These data suggest that menstrual cycle phase has a powerful modulatory effect on physiologic reactivity in women with PMDD but not in healthy women. Physiologic response to affective stimuli appears to be intact in women with PMDD across the menstrual cycle.     

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.     

Gonadal hormones and antihormones, serotonin and mood

Gonadal hormones influence activity of several monoaminergic neurotransmitters, and this might be one of the mechanisms by which these hormones are involved in modulation of behavior. Gonadal hormones' levels and mood fluctuate along the normal menstrual cycle; therefore, this might provide a model for the study of the interaction among hormones, mood, and other biochemical variables. The administration of gonadal hormones' antagonists ("antihormones") and the study of their central nervous system (CNS) and behavioral consequences may further elucidate hormonal-neurotransmitter interaction. We have studied several aspects of the serotonergic system along the menstrual cycle. Results show that imipramine receptor-binding in platelets is decreased in women with premenstrual dysphoric changes in the early luteal phase, 5 to 7 days before development of symptoms and shortly after the substantial periovulatory changes in gonadal hormones. The cortisol and prolactin responses to tryptophan were blunted during the late luteal phase compared with the midfollicular phase, and the cortisol, but not prolactin, responses to the serotonergic agonist 1-(m-chlorophenyl) piperazine, (mCPP) was also blunted during that period. An altered postsynaptic serotonergic responsivity might be suggested in these cases. The role of ovulation and gonadal hormones is further demonstrated by the elimination of dysphoric symptoms by the ovulation suppressant danazol.     

Patients with premenstrual dysphoric disorder have increased startle response across both cycle phases and lower levels of prepulse inhibition during the late luteal phase of the menstrual cycle.

Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (p<0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (p<0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (p<0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.     

Working memory, executive processes and the effects of alcohol on Go/No-Go learning: testing a model of behavioral regulation and impulsivity

Rationale: Impulsivity is associated with increased risk for alcoholism. Alcohol also may increase impulsive behavior, although little is known about the processes underlying this effect. Objectives: This study tested a model proposing that the executive processes of working memory (WM) and conditional associative learning (CAL) modulate behavioral inhibition. Subjects had either a positive (FHP) or a negative (FHN) family history of alcoholism. Hypotheses were that alcohol would increase Go/No-Go impulsive responding but only in subjects with low working memory capacity (low-WM), low-CAL ability, or FHP for alcoholism. The model also predicted that WM and CAL modulate inhibitory responses to contingency reversal on a Go/No-Go task. Methods: A Go/No-Go learning task with a midway contingency reversal was administered to 71 FHP and 78 FHN subjects when sober and after drinking one of two moderate doses of alcohol. WM (digits backward) and CAL (conditional spatial association task) were also assessed when sober. Results: Alcohol resulted in more false alarms but only in low-WM subjects. Both WM and CAL modulated learning to inhibit behavior after contingency reversal, suggesting separate modulation mechanisms for WM and CAL. Subjects with low- capacity WM and subjects with low-capacity CAL ability had more difficulty learning response inhibition after contingency reversal. FHPs and FHNs did not differ in their response to alcohol. Conclusions: The results support our model of the modulatory role of WM and CAL in the ongoing regulation of behavioral inhibitory systems. The results also suggest that individuals with low capacity WM are more susceptible to alcohol’s effect of increasing impulsive behavior, suggesting that alcohol reduces the capacity of working memory to modulate response inhibition. Received: 3 March 1999 / Final version: 28 May 1999     

Endogenous opioid activity is associated with obsessive-compulsive symptomology in individuals with a family history of alcoholism.

Endogenous opioid activity has been associated with the regulation of mood and inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. We assessed differences in psychological symptomology and naloxone sensitivity in non-alcoholic males and females with a family history of alcoholism (FHP) and without a family history of alcoholism (FHN). This was followed by assessment of the association between naloxone sensitivity and psychological symptomology. Psychological symptomology was measured using the Revised Symptom Checklist (SCL-90-R) during enrollment. Adrenocorticotropin was measured following intravenous administration of naloxone/placebo. FHP males reported more obsessive-compulsive symptomology as well as increased sensitivity to naloxone relative to other groups. A positive association was observed between degree of obsessive-compulsive symptomology and naloxone sensitivity, and the association was strongest among FHP males. These findings suggest that the increased risk of alcoholism in FHP subjects (especially males) may be associated with altered opioid activity, which is expressed through an elevated level of obsessive compulsive symptomology.     

Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism

Individuals family-history positive (FHP) for alcoholism have increased risk for the disorder, which may be mediated by intermediate behavioral traits such as impulsivity. Given the sex differences in the risk for and clinical presentation of addictive disorders, risk for addiction may be differentially mediated by impulsivity within FHP males and females. FHP (N=28) and family-history negative (FHN, N=31) healthy, non-substance-abusing adults completed an fMRI Go/No-Go task and were assessed on impulsivity and alcohol use. Effects of family history and sex were investigated as were associations between neural correlates of impulse control and out-of-scanner measures of impulsivity and alcohol use. FHP individuals showed greater activation in the left anterior insula and inferior frontal gyrus during successful inhibitions, an effect that was driven primarily by FHP males. Higher self-reported impulsivity and behavioral discounting impulsivity, but not alcohol use measures, were associated with greater BOLD signal in the region that differentiated the FHP and FHN groups. Impulsivity factors were associated with alcohol use measures across the FHP and FHN groups. These findings are consistent with increased risk for addiction among FHP individuals being conferred through disrupted function within neural systems important for impulse control.     

Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in experiments involving computer-assisted self-infusion of ethanol (CASE)

Rationale  Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives  To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods  Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results  The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions  This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official view of the National Institute on Alcohol Abuse and Alcoholism or NIH.     

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests

Rationale Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. Objective The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Subjects and methods Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 a.m. Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. Results As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. Conclusion The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.     

Sensitivity to CCK-4 in Women with and without Premenstrual Dysphoric Disorder (PMDD) During Their Follicular and Luteal Phases

The authors determined whether women with premenstrual dysphoric disorder (PMDD) exhibit a heightened sensitivity to the panicogenic effects of CCK-4 administration and whether this enhanced sensitivity to CCK-4 would vary with the phase of the menstrual cycle at the time of CCK-4 injection. Twenty-one normal controls and 18 PMDD women were randomly assigned to receive the first and second CCK-4 injection during the follicular phase and the luteal phase or vice versa. PMDD women showed a greater anxiety and panic response to CCK-4. These preliminary results suggest that the CCK-B system may play a role in the pathophysiology of PMDD.     

Influence of phase-related variability in premenstrual symptomatology, mood, smoking withdrawal, and smoking behavior during ad libitum smoking, on smoking cessation outcome

Emerging evidence suggests that women have a more difficult time quitting smoking than men-possibly due, in part, to sex hormones. The present study characterized mood, premenstrual symptomatology, and smoking withdrawal, as well as smoking behavior, in the follicular and luteal phases during ad libitum smoking in 25 women intending to quit. We also investigated the possible influence of phase-related variability in these measures on likelihood of study adherence and smoking cessation. We found that premenstrual symptomatology, as well as some measures of mood and smoking withdrawal, were significantly higher during the luteal phase than in the follicular phase. Cigarettes/day did not vary by menstrual cycle phase. Phase-related variability in premenstrual symptomatology [F(3, 20)=2.82, p=0.0650)] and urge to smoke [F(2, 21)=4.85, p=0.0186)] were associated with relapse. These data support the inference that sex hormones influence smoking cessation outcome. This knowledge may contribute to the development of more rational and effective smoking cessation interventions for women.     

Differential subjective effects of D-amphetamine by gender,hormone levels and menstrual cycle phase

Estrogen and progesterone interact with monoamines in ways that suggest the potential modulation of responses to psychoactive drugs by endogenous steroids, both between menstrual phases and between the sexes. The present study assessed the subjective and physiological effects of a single dose of D-amphetamine (AMPH; 15 mg oral) in healthy, normally cycling women (n=13), who received amphetamine and placebo (PL) during both the follicular and luteal phases of a single menstrual cycle, and in healthy men (n=7). Females reported greater amphetamine-induced subjective stimulation [Addiction Research Center Inventory (ARCI)-A, ARCI-MBG; Drug Effects Questionnaire (DEQ) Feel Drug, Feel High, Want More] during the follicular phase than the luteal phase. Within the follicular phase, the magnitude of individuals' AMPH-induced stimulation was positively associated with baseline (predrug) salivary estradiol [r=+.55-.78; Profile of Mood States (POMS) Vigor, Positive Mood, Elation], and negatively associated with salivary progesterone [r=-.66-.68; POMS Friendliness; Subjective States Questionnaire (SSQ) Pleasant Sedation]. Sex differences also emerged. Males reported feeling greater AMPH-induced stimulation (ARCI-A, ARCI-MBG; DEQ Feel Drug, Want More) than females in the luteal phase. Thus, higher levels of estrogen and lower levels of progesterone are associated with greater subjective stimulation after AMPH in women, and these hormonal influences contribute to sex differences in amphetamine responding.     

Effects of the menstrual cycle on timing and depth of breathing at rest

Volume and timing components of resting ventilation were measured serially in 40 women aged 18 to 36 yr, during menstrual, follicular and luteal phases of menstrual cycle. Resting minute ventilation (VE) was significantly higher (P < 0.001) in luteal phase than in menstrual and follicular phases; in the two latter phases VE was almost equal. This increment in VE during the luteal phase was due to a significant rise (P < 0.001) in tidal volume (VT). Respiratory frequency (f) was unchanged throughout the cycle. Although there was a mean increases in inspiratory time (T1) during the luteal phase compared to the other two phases, the difference did not reach statistical significance. Duty cycle, T1/Ttot, was also unchanged throughout menstrual cycle. However, mean inspiratory flow, VT/T1, was significantly higher (P < 0.05 and P < 0.01) during luteal phase as compared to that during menstrual or follicular phases respectively. Pulmonary mechanics, as measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid expiratory flow rate (FEF25%, 75%), were within normal limits and remained unaltered during the menstrual cycle. Therefore, in the absence of alteration of pulmonary mechanics, the luteal increase in ventilation and inspiratory flow suggests a possible role for progesterone in stimulating the respiratory drive, either centrally or through the peripheral chemoreceptors or by both.     

The level of response to alcohol in daughters of alcoholics and controls

BACKGROUND: The low level of response (LR) to alcohol is a genetically influenced characteristic related to the development of alcohol use disorders (AUDs). This phenotype is found in men with a family history (FH) of alcoholism, predicts future AUDs, and has heritabilities as high as 60%. However, despite evidence of genetic influences for AUDs in both sexes, the majority of studies evaluating differences in LR across high- and low-risk groups have been conducted on males, and it is unclear how generalizable these results are to women. METHODS: Twenty-five women who are family history positive (FHP) for alcohol dependence were matched with 25 women with no FH of alcoholism (FHN) on factors that may impact LR. Using an alcohol challenge paradigm, data on the reaction to a moderate dose of alcohol were gathered over a period of 3.5 h. Assessments included breath alcohol concentrations (BrACs), the Subjective High Assessment Scale (SHAS), as well as body sway or static ataxia. RESULTS: Family history positives reported lower subjective intoxication than FHNs. In addition, when body sway scores were corrected for skewness, FHPs had significantly lower scores on alcohol-related changes in lateral sway. These differences remained after considering the effects of drinking history and BrAC values. CONCLUSIONS: This study evaluated the LR to alcohol in the largest sample of alcohol challenges in matched FHP and FHN women to date. Overall, the findings are consistent with most data from earlier investigations of smaller sized samples of FHP women. The results suggest that, similar to sons of alcoholics, a low LR to alcohol might also be characteristic of daughters of alcoholics.