T. L. Smith

Partial sleep deprivation reduces natural killer cell activity in humans.

&NA; Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late‐night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NK cell activity.

Electroencephalographic sleep and natural killer activity in depressed patients and control subjects.

&NA; Insomnia is associated with a reduction of natural killer (NK) activity in depression independent of the severity of other depressive symptoms. This study extends these findings by exploring the relationship between objective electroencephalographic (EEG) assessment of sleep and values of NK activity in depressed patients (n = 23) and in control subjects (n = 17). The sleep EEG parameters total sleep time, sleep efficiency, and duration of nonREM sleep were each positively correlated with NK activity in the depressed patients and in the control subjects, demonstrating similar relationships between the amount of sleep and NK activity in the separate groups. These observations support the hypothesis that sleep measures are associated with NK cytotoxicity, independent of the effects of severity of depressive symptoms or the presence of a mood disorder.

Mood and anxiety symptoms among 140 children from alcoholic and control families

OBJECTIVE Children of alcoholics have been reported to have elevated levels of internalizing symptoms, including anxiety and depression. However, many studies have not adequately controlled for the influence of independent (i.e. not substance-induced) parental mood or anxiety disorders and other factors. The present evaluations assess the relationships of the family histories of alcohol use disorders and independent mood and anxiety disorders to internalizing symptoms in children of alcoholic and nonalcoholic subjects. METHOD A behavioral checklist and a structured interview were administered to the parents of 140 children aged 7-18 years. The fathers of these offspring had been recruited 15 years previously from a university population to participate in a prospective study of 453 men from alcoholic and nonalcoholic families. RESULTS While a higher score for one of four measures of internalizing symptoms in the children was found to relate to a higher density of alcoholic relatives, this pattern was more robust in children of parents with mood or anxiety disorders. In a hierarchical regression, the family history of alcohol use disorders did not add significantly to the prediction of any of the four internalizing scores in the children after considering the impact of a family history of independent mood and anxiety disorders. CONCLUSIONS The results indicate that internalizing symptoms in children of alcoholics were more strongly influenced by a positive family history of mood and anxiety disorders than the family history of alcohol use disorders.

The Self-Rating of the Effects of Alcohol Questionnaire as a Predictor of Alcohol-Related Outcomes in 12-Year-Old Subjects

AIMS A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. To date, only one study has evaluated the predictive validity of a second measure of LR as determined by the Self-Report of the Effects of Alcohol (SRE) Questionnaire. The current analyses evaluate the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom. METHODS The subjects were 156 boys (54.5%) and girls from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. RESULTS The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. CONCLUSION The SRE scores appear to have value in predicting future heavier drinking and alcohol problems in 12-year olds that go beyond the information offered by the earlier drinking pattern alone.

A 5‐Year Prospective Evaluation of DSM‐IV Alcohol Dependence With and Without a Physiological Component

BACKGROUND The DSM-III-R removed tolerance and withdrawal as required elements for a diagnosis of alcohol dependence. Although this practice was continued in DSM-IV, the more recent manual asked clinicians to note whether physiological aspects of withdrawal (tolerance and withdrawal) had ever been experienced. Few studies have determined the prognostic meaning of a history of a physiological component to DSM-IV alcohol dependence. METHODS Face-to-face structured interviews were used to evaluate the course of alcohol, drug, and psychiatric problems during the subsequent 5 years for 1094 alcohol-dependent men and women. These subjects had been classified into subgroups at the time of initial interview regarding evidence of tolerance or withdrawal, and all evaluations were based on DSM-IV criteria. At baseline, the application of DSM-IV diagnostic guidelines resulted in 649 (59.3%) individuals having a history of an alcohol withdrawal syndrome, with or without tolerance (group 1); 391 (35.7%) with histories of tolerance but not withdrawal (group 2); and 54 (4.9%) with no lifetime histories of tolerance or withdrawal (group 3). RESULTS During the 5-year follow-up, both the broad (group 1 plus 2 versus group 3) and narrow (group 1 versus group 2 plus group 3) definitions of physiological dependence were associated with more alcohol and drug problems. However, for most items, this differential primarily reflected differences between groups 1 and 3, with a less impressive effect by group 2. Although no group differences were noted for the rate of independent major depressive episodes, substance-induced depressions did differentiate among groups, a finding also most closely related to the distinction between groups 1 and 3. CONCLUSIONS These data support the prognostic importance of noting the presence of a physiological component in alcohol dependence and indicate the potential relevance of limiting the definition of a physiological component to withdrawal.

Predicting Drinking Onset with Discrete-Time Survival Analysis in Offspring from the San Diego Prospective Study

Previous research has shown that an early onset of drinking is associated with a range of problematic drinking outcomes in adulthood. However, earlier drinking is also linked to additional characteristics that themselves predict alcohol problems including male gender, a family history (FH) of alcoholism, age, race, parental alcoholism, depression symptoms, prior drug use, and conduct problems. This study tested the relationship between the age of first drink (AFD) and a range of risk factors that predict the onset of alcohol use. Participants were offspring from the San Diego Prospective Study (SDPS) who were at least 15 years old at the time of their most recent interview (n=147). Discrete-time survival analysis (DTSA) was used to relate multiple characteristics to the hazard function of alcohol onset across a relevant age range. The results demonstrated the predicted relationships to AFD for conduct problems, male gender, prior marijuana use, and a FH of alcoholism, even when these characteristics were estimated together. Furthermore, an interaction occurred such that offspring with both conduct problems and marijuana use were at substantially higher risk for alcohol use onset during this time period than would be predicted from the effect of these two risk factors alone. However, age at interview, ethnicity, parent education, and depressive symptoms did not predict the pattern of onset of drinking. Implications for future research and prevention efforts are discussed.

Level of response to alcohol within the context of alcohol-related domains: an examination of longitudinal approaches assessing changes over time

BACKGROUND The manner in which a low level of response (LR) to alcohol relates to domains that enhance the risk for heavy drinking has traditionally been studied through cross-sectional models. However, many of the relevant domains, such as the maximum number of drinks consumed in 24 hours (MAXDRINK) and drinking among peers (PEER) typically decrease across adulthood. This study evaluated whether a persons LR to alcohol predicted alcohol-related domains at multiple time-points and examined longitudinal relations among these domains in a sample of probands from the San Diego Prospective Study. METHODS LR to alcohol was assessed in 174 male probands from the San Diego Prospective Study at baseline (T1), and measures of MAXDRINK, PEER, and drinking to cope (COPE) were collected at the 15-year (T15), T20, and T25 follow-ups. RESULTS A low LR to alcohol at T1 predicted higher levels of MAXDRINK and COPE at T15, consistent with prior studies. Using latent growth curve models, higher levels of T15 MAXDRINK predicted less decreases in PEER drinking over time. Additional analyses found a time-specific effect of T20 COPE on T25 MAXDRINK even after accounting for the growth factors of both domains. CONCLUSION These evaluations illustrate that LR prospectively predicted relevant outcomes, and clarify how alcohol-related domains related to each other as the probands progressed through middle adulthood. Treatment implications are discussed and drinking to cope may be an important intervention target for problematic alcohol use.