The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials.

BACKGROUND: Pregnant smokers are often prescribed counselling as part of multicomponent cessation interventions. However, the isolated effect of counselling in this population remains unclear, and individual randomised controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION CRITERIA: We included RCTs conducted in pregnant women in which the effect of counselling could be isolated and those that reported biochemically validated abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND ANALYSIS: Overall estimates were derived using random effects meta-analysis models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of which examined abstinence at 6 months. The proportion of women that remained abstinent at the end of follow up was modest, ranging from 4 to 24% among those randomised to counselling and from 2 to 21% among control women. The absolute difference in abstinence reached a maximum of only 4%. Summary estimates are inconclusive because of wide confidence intervals, albeit with little evidence to suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08, 95% confidence interval 0.84-1.40). There was no evidence to suggest that efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs examining the isolated effect of smoking cessation counselling in pregnant women are limited but sufficient to rule out large treatment effects. Future RCTs should examine pharmacological therapies in this population.

Single-Cell Analysis of the Periodontal Immune Niche in Type 2 Diabetes.

Periodontitis (PD) is a common source of uncontrolled inflammation in obesity-associated type 2 diabetes (T2D). PD apparently fuels the inflammation of T2D and associates with poor glycemic control and increased T2D morbidity. New therapeutics are critically needed to counter the sources of periodontal infection and inflammation that are accelerated in people with T2D. The precise mechanisms underlying the relationship between PD and T2D remain poorly understood. Every major immune cell subset has been implicated in the unresolved inflammation of PD, regardless of host metabolic health. However, analyses of inflammatory cells in PD with human periodontal tissue have generally focused on mRNA quantification and immunohistochemical analyses, both of which provide limited information on immune cell function. We used a combination of flow cytometry for cell surface markers and enzyme-linked immunospot methods to assess the subset distribution and function of immune cells isolated from gingiva of people who had PD and were systemically healthy, had PD and T2D (PD/T2D), or, for flow cytometry, were systemically and orally healthy. T-cell subsets dominated the cellular immune compartment in gingiva from all groups, and B cells were relatively rare. Although immune cell frequencies were similar among groups, a higher proportion of CD11b+ or CD4+ cells secreted IFNγ/IL-10 or IL-8, respectively, in cells from PD/T2D samples as compared with PD-alone samples. Our data indicate that fundamental differences in gingival immune cell function between PD and T2D-potentiated PD may account for the increased risk and severity of PD in subjects with T2D. Such differences may suggest unexpected therapeutic targets for alleviating periodontal inflammation in people with T2D.

Hair element content in learning disabled children.

Hair samples from 31 learning disabled and 22 normal children were analyzed for content of 14 elements. Significant group differences were determined and a discriminant function was completed which separated the groups with 98 per cent accuracy. Elevated lead and cadmium content in the learning disabled group is viewed as being of particular importance.

Predicting early onset of male antisocial behavior from preschool behavior.

METHODS: Data from a large longitudinal study of boys who were between kindergarten and age 13 years were used to (1) test whether Gray's and Cloninger's personality dimensions measured in kindergarten predicted the early onset of stable, highly delinquent behavior; (2) test whether 1, 2, or 3 dimensions were needed; and (3) test the predictive value of a categorical approach. RESULTS: The impulsivity dimension was the best predictor of the early onset of stable, highly delinquent behavior. Anxiety and reward dependence made significant but weaker contributions. The categorical approach corroborated Cloninger's suggestion that boys who are high in impulsivity, low in anxiety, and low in reward dependence would be more at risk for delinquent involvement. Boys who were high in impulsivity and low in anxiety but high in reward dependence were much less at risk for delinquency. Differences in antisocial behavior among extreme kindergarten personality groups were stable from ages 11 to 13 years. CONCLUSIONS: The behavioral activating system appears to be the major dimension underlying the propensity toward early onset of antisocial behavior, but both the behavioral inhibition system and the need for social rewards play important roles. The behavioral style (personality) that results from the interplay of these systems is clearly in place by the kindergarten year. Preventive efforts should target preschool children with at-risk behavior profiles. However, longitudinal-experimental studies with at least yearly assessments between birth and school-entry age are needed to understand the extent to which the behavioral styles are antecedent to preschool disruptive behavior disorders.

Serotonin and alcohol intake, abuse, and dependence: findings of animal studies.

Despite a relatively large body of literature on the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the functional significance of serotonergic neurotransmission and its relationship to alcohol intake, abuse, and dependence remains to be fully elucidated. In part two of this review, the experimental (animal) data is summarized along two lines: the effects of serotonergic manipulations on the intake of alcohol, and the effects of acute and chronic alcohol intake, as well as the withdrawal of chronic alcohol, on the serotonergic system. It is concluded that serotonin mediates ethanol intake as a part of its larger role in behavior modulation, such that increases in serotonergic functioning decrease ethanol intake, and decreased serotonergic functioning increases ethanol intake. Ethanol produces transient increases in serotonergic functioning that activate the mesolimbic dopaminergic reward system. The results are discussed in light of recent theories describing the regulatory role of serotonin in general behavior.

Serotonin and alcohol intake, abuse, and dependence: clinical evidence.

A large body of literature has emerged concerning the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake and the development of alcoholism. Despite the wealth of information, the functional significance of this neurotransmitter remains to be fully elucidated. This paper, part one of a two-part review, summarizes the available clinical research along two lines: the effects of alcohol on serotonergic functioning and the effects of pharmacological manipulation of serotonergic functioning on alcohol intake in normal (nonalcohol dependent) and alcohol-dependent individuals. It is concluded that considerable evidence exists to support the notion that some alcoholic individuals may have lowered central serotonin neurotransmission.

Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism.

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N = 13) or with no family history of alcoholism (N = 15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N = 1) and comparison subjects with no family history of alcoholism (N = 18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/ no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.

Effects on mood of acute phenylalanine/tyrosine depletion in healthy women.

Catecholamines have been implicated in the etiology and pathophysiology of mood and anxiety disorders. In the present study, we investigated the effects of experimentally reducing catecholamine neurotransmission by means of acute phenylalanine/tyrosine depletion (APTD). Healthy female volunteers ingested: (1) a nutritionally balanced amino acid (AA) mixture (n = 14); (2) a mixture deficient in the serotonin precursor, tryptophan (n = 15); or (3) one deficient in the catecholamine precursors, phenylalanine and tyrosine (n = 12). Mood was measured at three times: at baseline and both immediately before and after an aversive psychological challenge (public speaking and mental arithmetic) conducted 5 hours after AA mixture ingestion. Acute tryptophan depletion (ATD) lowered mood and energy and increased irritability scores. These effects were statistically significant only after the psychological challenge. The effect of APTD on mood was similar to that of ATD. APTD did not attenuate the anxiety caused by the psychological challenge. These findings suggest that, in healthy women, reduced serotonin and/or catecholamine neurotransmission increases vulnerability to lowered mood, especially following exposure to aversive psychological events.

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Alcohol consumption in male social drinkers as a function of situationally induced depressive affect and anxiety.

Forty male subjects were randomly assigned to one of two conditions designed to induce either positive (Incentive Gain Condition) or negative (Incentive Loss Condition) affective states. This procedure was validated by an analysis of pre and post manipulation scores on the Multiple Affect Adjective Check List. Following the incentive manipulation subjects participated in an ad-lib drinking situation (Alcohol Taste Rating Rask) believing that the experiment was concerned with the relationship between intelligence, taste sensitivity and alcohol preferences. Contrary to expectation the analysis revealed that more alcohol was consumed by subjects in the incentive gain condition, this effect being most pronounced in heavy social drinkers in the incentive loss and gain conditions. A second analysis demonstrated that significantly less alcohol was consumed by subjects who, prior to ad lib drinking, evinced greater degrees of depressive affect and anxiety. The discussion focuses on the implications of these findings for tension reduction models of alcoholism.

The effect of dose, novelty, and exploration on amphetamine-produced stereotyped behavior.

Four experiments are presented. The first experiment demonstrated that the incidence of steretyped behavior was a monotonic increasing function of amphetamine dose. Variations in the form of the response to dose are described. The next two studies examined the relationship between environmental novelty and amphetamine-produced stereotypy. This behavior was observed less among subjects placed into novel environments than among subjects placed into familiar environments. The ability of novel stimuli to evoke exploratory responses incompatible with stereotypy was suggested as the basis for this effect. This interpretation was supported in a final experiment, which observed exploratory behavior and general activity, as well as amphetamine-produced stereotypy in subjects exposed to a novel stimulus in an otherwise familiar environment. All four experiments were interpreted as supporting a unified conception of amphetamine-produced and pathological sterotyped behaviors.

The disruption of marijuana intoxication.

Ninety-six males Ss were divided into four drug conditions; coltsfoot, placebo, marijuana low dose, and marijuana high dose. Half of the Ss smoked marijuana while listening to music in a relaxing environment, and half smoked marijuana in the same environment but had two 10-min periods of aversive-noise superimposed over the music. A subjective measure of intoxication demonstrated significant drug and environmental group effects with suppression of self-report of intoxication being especially strong for the marijuana low dose noise group. The usual positive correlation between subjective measures and pulse rate measures of marijuana intoxication was interfered with by the noise effect. Although subjective ratings were suppressed, the noise group demonstrated significantly higher pulse rates than the music group. The results are discussed in terms of the effect of extraneous factors on marijuana intoxication, the significance of dosage in this type of research, and the nature of marijuana intoxication.

Effect of sucrose consumption on alcohol-induced impairment in male social drinkers.

Two studies were conducted to examine the interaction between sucrose and ethanol in normal young fasting adult males. The first experiment employed a 3 (100 g sugar, 35 g sugar, 0 g sugar) x 3 (alcohol, placebo and sober) factorial design, which was carried out double-blind using aspartame to ensure that all the drinks were equally sweet. Subjects were tested for mood, memory, subjective intoxication and psychomotor performance at baseline and at times up to 3.5 h after ingestion of the drinks. An alcohol by sugar interaction was seen at 0.5 after drinking. Sugar attenuated alcohol intoxication at this time without influencing blood alcohol levels. Contrary to previous reports, the combination of alcohol and sugar failed to produce significant hypoglycemia, or any of the adverse behavioral effects associated with hypoglycemia, at later times after drink ingestion. The second experiment involved a simpler design, carried out single-blind in which the subjects receiving no sugar did not get aspartame. This was to rule out the possibility that aspartame was exacerbating alcohol intoxication instead of sugar attenuating it. The second experiment also showed that sugar can attenuate alcohol intoxication in fasting humans without altering blood alcohol levels significantly.

Biochemical aspects of tryptophan depletion in primates.

We studied the degree of plasma tryptophan depletion produced by giving normal human males different amounts of a tryptophan-free (T-) amino acid mixture. From the results of this and other studies we concluded that the maximum degree of tryptophan depletion can be produced by a 31.5 g mixture of seven essential amino acids. Administration of a T- amino acid mixture to vervet monkeys lowered tryptophan and 5-hydroxyindoleacetic acid in the cerebrospinal fluid. Levels of tyrosine and the catecholamine metabolites were unchanged. These data support the idea that the effects of T- mixture on mental function in humans which have been reported previously are due to a decrease in 5-hydroxytryptamine.

A dose-response study of the effects of alcohol on the perceptions of pain and discomfort due to electric shock in men at high familial-genetic risk for alcoholism.

Alcoholics have previously been found to be more sensitive to painful stimulation than controls, and more sensitive to the pain-reducing effects of alcohol. The present study was designed to examine these effects in men at high familial-genetic risk for alcoholism and controls. Subjects were assigned to one of four alcohol doses [0.135 (active placebo), 0.50, 0.75, or 1.00 ml 95% USP alcohol/kg body weight]. Ratings of the amount of discomfort and pain experienced during an aversive shock procedure were taken immediately post-shock, both while subjects were sober and after they had consumed one of the four alcohol doses. High risk men were found to rate the experience of the shock as more uncomfortable and painful overall than the low risk controls. Pharmacologically significant levels of alcohol were found to reduce or eliminate these group differences, suggesting that alcohol has a "normalizing" effect on pain and discomfort perceptions in high risk men. Only the higher doses of alcohol were found significantly to dampen subjects' shock rating scores. High risk males' increased sensitivity to pain and discomfort, combined with the negatively reinforcing effects of reducing these perceptions at moderate to high alcohol doses, may play a role in predisposing high risk males for the development of alcoholism.

Reliability and validity of alcohol-induced heart rate increase as a measure of sensitivity to the stimulant properties of alcohol.

RATIONALE: Alcohol-induced heart rate (HR) stimulation during the rising limb of the blood alcohol curve reliably discriminates between individuals at differential risk for alcoholism, and appears to be a potential psychophysiological index of psychomotor stimulation from alcohol. OBJECTIVES: Three studies are presented which explore the reliability and convergent and discriminant validity of this alcohol response index. METHODS: Young men with and without a multigenerational family history of alcoholism were administered a 1.0 ml/kg dose of 95% USP alcohol. Resting baseline cardiac and subjective measures were assessed before and after alcohol consumption. RESULTS: Study 1 demonstrated that alcohol-induced HR stimulation was significantly and positively related to alcohol-induced changes in mood. Study 2 demonstrated that alcohol-induced HR stimulation was reliable across two alcohol administration sessions (r=0.33-0.66, P<0.01). Study 3 explored the relationship between the proposed index and measures of sensitivity to alcohol previously linked to genetic predisposition to alcoholism. Multiple regression analysis indicated that alcohol-induced HR increase and reduced subjective intoxication (measured using the Subjective High Assessment Scale) were both positively associated with alcohol-induced changes in mood states that have previously been shown to be sensitive to the effects of stimulant drugs and the reinforcing effects of alcohol. CONCLUSIONS: Sensitivity to alcohol-induced heart-rate stimulation during the ascending limb of the blood alcohol curve may be a useful and informative marker for understanding susceptibility to alcoholism.

Tryptophan depletion causes a rapid lowering of mood in normal males.

Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients.

Acute effect of altered tryptophan levels and alcohol on aggression in normal human males.

Normal males received amino acid mixtures designed to raise or lower tryptophan availability, and thus to raise or lower brain serotonin synthesis. They also received alcoholic or non-alcoholic drinks. The subjects were tested in the Taylor Competitive Reaction Time Task in which they competed against a (non-existent) partner in a reaction time task. The magnitude of electric shocks that the subjects were willing to give to their bogus partner was used as a measure of aggression. Lowered tryptophan levels and ingestion of alcohol were associated with increased aggression. Our data support the idea that low serotonin levels may be involved in the etiology of aggression. They suggest that subjects with low brain serotonin levels may be particularly susceptible to alcohol-induced violence.

A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males.

In a previous study we found that a tryptophan-deficient amino acid mixture, designed to lower tissue tryptophan and thus brain 5-hydroxytryptamine (5HT) levels, caused a rapid (5 h) lowering of mood in normal males. Because of the importance of this evidence indicating a direct causal connection between low 5HT and low mood, we have now investigated other possible explanations for the mood lowering effect. Research strongly supports the involvement of environmental setting and cognition in the production and experience of emotions. Therefore we investigated how these factors might influence the mood-lowering effects of tryptophan depletion. In an instructional manipulation subjects were either supplied or not supplied with information designed to account for any possible peripheral sensations that might be related to depressive affect. In an environmental manipulation subjects were exposed either to a supportive and comfortable atmosphere (positive environment), or an unrewarding and unstimulating environment (negative environment). In the control group, which received a balanced amino acid mixture, the positive and negative environments had the expected effects on the scores of the Multiple Affect Adjective Checklist, thus indicating the effectiveness of these procedures. In the tryptophan depletion group neither the instructional nor the environmental manipulation had any influence on the mood lowering effect. It may be that tryptophan depletion lowers mood in normal males because low 5HT influences mood directly rather than via cognitive processes. Our data strongly support the idea that 5HT exerts an effect on mood and that low 5HT may, in some patients, be an important factor contributing to the etiology of clinical depression.

Autonomic hyperreactivity and risk for alcoholism.

1. Studies which illustrate autonomic hyperreactivity in sons of alcoholics are reviewed and discussed. This response is elicited by a wide range of stimuli which vary from the stressful to the incidental. It also occurs independently of coping strategy. This hyperreactivity, which is particularly characteristic of multigenerational sons of alcoholics is significantly dampened by alcohol. This pattern of results supports a negative reinforcement model of alcohol abuse in these individuals.