Life Events and Addiction: a critical review

A number of research studies dealing with the relationship between life events' and the course of the addiction process are reviewed. It is concluded that there are problems involved in drawing unambiguous inferences from these researches. There is an absence of strong theoretical development which makes it difficult to see where the train of research is leading; consequently any association between the main variables can, at present, be viewed as ex post facto support for some version of a life events theory’. In addition, there are methodological problems concerning retrospective recall, the ‘search after meaning’ and the treatment of events as independent separate entities. It is suggested that advances will be made by way of approaches which take into account the dynamic and structural aspects of life courses' and the addiction process, and which pursue a more rigorous line of theoretical development and refinement.     

Estimating drug consumption in opioid users: reliability and validity of a'recent use' episodes method

The efficient and accurate measurement of recent drug use is an essential component of treatment and research among opioid users. Urinalysis results alone will not give sufficient information to either the clinician or researcher, due to limitations in detection and an inability to distinguish extent of use. The present paper describes a ‘recent use episodes method’, adapted from the measurement of alcohol consumption, for obtaining self-reported drug use in eleven different drug categories. Reliability and validity data indicate that the method provides a quick means by which accurate information may be obtained on the overall recent drug use of Opioid users.     

Stress and relapse to drug seeking: studies in laboratory animals shed light on mechanisms and sources of long-term vulnerability

Relapse is a major characteristic of drug addiction disorders and remains the primary problem for treatment. Recently, there has been hope that these disorders may be amenable to pharmacological treatments that have successfully treated other psychopathological disorders. Pharmacological approaches to drug abuse have tended to be guided by the primary drug used by the individual, though substitution has been the guiding principle in some instances, as in the case of methadone maintenance in opioid addiction. Alternatively, blockade or antagonism of the effects of the primary drug being abused has been tried, as in the case of using naltrexone to treat opioid or alcohol addiction. Though reportedly successful in some populations, it is not clear that these approaches effectively control craving for 'highs' or euphoric experiences or a return to drug use as a response to stressful life experiences. Recent experimental studies of the factors that induce craving and relapse to drug use in both humans and laboratory animals, such as drug-related cues, re-exposure to the drug itself, or exposure to stressful events, have shown that the effects of these different events are mediated by dissociable neurochemical circuitry. Another finding that emerges from these studies is that the motivation underlying drug seeking induced by events that precipitate relapse is intensified by the duration and amount of pre-exposure to a drug and the passage of time since withdrawal of the drug. One implication of such findings for the treatment of addiction is that whatever approach is taken, treatment will have to be multifaceted and maintained over an extended period of time after the initial termination of drug use.     

Memory skills elders want to improve

While many research studies have investigated memory training for elders, none have asked which specific memory skills elders would like to improve. This study investigates two related questions. First, which memory skills elders would like to improve? Second, is there a common set of these memory skills? Elders completed a three-part questionnaire. First, it asked for subject demographics. Second, it asked for the first, second, third, and then all other memory skills they would most like to improve. Finally, it asked elders to rate the importance of 10 specific memory skills. The results indicate that elders share a common set of memory skills they wish to improve. They are: (a) people's names, (b) important dates, (c) location of household objects, (d) recent and past events, (e) meetings and appointments, (f) information and facts, (g) general improvement, and (h) medication. One conclusion from these findings is that at least some memory training research should focus on these specific memory skills.     

Validity of self-reported cardiovascular disease events in comparison to medical record adjudication and a statewide hospital morbidity database: the AusDiab study

Epidemiological studies often rely on self-reported cardiovascular disease (CVD) information, but this may be inaccurate. We investigated the accuracy of self-reported CVD (myocardial infarction, stroke, coronary artery bypass surgery and coronary artery angioplasty) during the follow up of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Self-reported CVD events, including the date of the event and hospital admission details, were collected with an interviewer-administered questionnaire. Of the 276 self-reported CVD events, 188 (68.1%) were verified by adjudication of medical records. Furthermore, linkage to the statewide Western Australian Hospital Morbidity Database (WAHMD) showed that CVD events were unlikely to be missed, with only 0.2% of those denying any CVD event being recorded as having had an event on the WAHMD. The adjudication of medical records was as accurate as record linkage to the WAHMD for validation of self-reported CVD, but combining the results from both methods of ascertainment improved CVD event identification.     

Sex, puberty, and the timing of sleep EEG measured adolescent brain maturation

The steep adolescent decline in the slow wave (delta, 1-4 Hz) electroencephalogram (EEG) of nonrapid eye movement (NREM) sleep is a dramatic maturational change in brain electrophysiology thought to be driven by cortical synaptic pruning. A perennial question is whether this change in brain electrophysiology is related to sexual maturation. Applying Gompertz growth models to longitudinal data spanning ages 9-18 y, we found that the timing of the delta decline was significantly (P < 0.0001) linked to timing of pubertal maturation. This timing relation remained significant when sex differences in the timing of the delta decline were statistically controlled. Sex differences and the relation to the timing of puberty jointly explained 67% of the between-subject variance in the timing of the delta decline. These data provide a demonstration of a temporal relation between puberty and an electrophysiological marker of adolescent brain development. They can guide research into whether the neuroendocrine events of puberty are mechanistically linked to cortical maturation or whether, instead, the two maturational processes are parallel but independent programs of human ontogenesis.     

Methodological and statistical considerations in measuring alcohol treatment effects

This article addresses the design and selection of outcome methods for treatment research from a statistical perspective. Two of the major statistical and methodological issues relevant to the selection of dependent variable(s) are statistical power and social utility. Power is the paramount issue in research design. Power can be improved by measures and methods tailored to the predicted effects of treatment. These effects should vary from treatment to treatment, suggesting that no single outcome measure is suitable for all purposes. In estimating power, researchers should also consider the time-varying nature of most types of treatment effects. Given these considerations, timeline procedures have advantages because they allow the derivation of measures linked to specific treatment components. They also permit the study of time-varying effects of variables such as life stress. An analysis on the relationship between drinking and self-reported stress is presented as an illustration of how advanced statistical methods, in conjunction with carefully gathered data, can provide process data on how treatment can affect individual responses to stressors or other events. From a social utility perspective, however, having research focus on narrower and narrower slices of behavior in the search for power raises questions about the value of this research to clients and society. For dealing with this dilemma, it will be necessary to build a series of studies linking improvement in specific aspects of short-term outcome to longer term outcome and ultimately benefit to society.     

Phylogenetic modeling of lateral gene transfer reconstructs the pattern and relative timing of speciations

The timing of the evolution of microbial life has largely remained elusive due to the scarcity of prokaryotic fossil record and the confounding effects of the exchange of genes among possibly distant species. The history of gene transfer events, however, is not a series of individual oddities; it records which lineages were concurrent and thus provides information on the timing of species diversification. Here, we use a probabilistic model of genome evolution that accounts for differences between gene phylogenies and the species tree as series of duplication, transfer, and loss events to reconstruct chronologically ordered species phylogenies. Using simulations we show that we can robustly recover accurate chronologically ordered species phylogenies in the presence of gene tree reconstruction errors and realistic rates of duplication, transfer, and loss. Using genomic data we demonstrate that we can infer rooted species phylogenies using homologous gene families from complete genomes of 10 bacterial and archaeal groups. Focusing on cyanobacteria, distinguished among prokaryotes by a relative abundance of fossils, we infer the maximum likelihood chronologically ordered species phylogeny based on 36 genomes with 8,332 homologous gene families. We find the order of speciation events to be in full agreement with the fossil record and the inferred phylogeny of cyanobacteria to be consistent with the phylogeny recovered from established phylogenomics methods. Our results demonstrate that lateral gene transfers, detected by probabilistic models of genome evolution, can be used as a source of information on the timing of evolution, providing a valuable complement to the limited prokaryotic fossil record.     

Circadian aspects of mammalian parturition: a review

The identification of circadian clocks in endocrine tissues has added considerable depth and complexity to our understanding of their physiology. A growing body of research reveals circadian clock gene expression in the uterus of non-pregnant and pregnant rodents. This review will focus on the mammalian uterus and its rhythmicity, particularly as it pertains to the circadian timing of parturition. This key event in the reproductive axis shows dramatic species-specific differences in its circadian phase. It is proposed here that these differences in the phasing of mammalian parturition are likely a function of opposite uterine cell responses to humoral cues. The argument will be made that melatonin fulfills many of the criteria to serve as a circadian signal in the initiation of human parturition, including specific actions on uterine smooth muscle cells that are consistent with a role for this hormone in the circadian timing of parturition.     

Development and Validation of a Risk Scoring Model to Predict Net Adverse Cardiovascular Outcomes after Primary Percutaneous Coronary Intervention in Patients Pretreated with 600 mg Clopidogrel: Rationale and Design of the RISK-PCI Study

Background: No comprehensive primary PCI (pPCI) risk model to predict net adverse cardiovascular events (NACE) has been reported with the use of clopidogrel 600 mg, which is now considered the standard loading dose. The primary hypothesis of the RISK-PCI trial is that an accurate risk prediction may be achieved by using clinical, angiographic, and procedural variables available at the time of intervention.
Methods: The present single-center, longitudinal, cohort study will include 1,750 consecutive patients with ST-elevation myocardial infarction (STEMI), undergoing pPCI after pretreatment with 300 mg aspirin and 600 mg clopidogrel. The primary end-points of the trial (NACE) include major adverse cardiovascular events (MACE) and major bleeding. A logistic regression model will be developed to predict 30-day and 1-year NACE after pPCI. A risk score derived from study set data will be validated using validation set data.
Results: Until June 1, 2008, 1,166 patients have been enrolled. Thirty-day follow-up is available in 1,007 patients.
Conclusions: The RISK-PCI study is designed to develop an accurate risk scoring system, using variables available at the time of intervention, to predict long-term adverse outcomes after pPCI.
Trial Registration: Current Controlled Trials Register—ISRCTN83474650— http://www.controlled-trials.com/ISRCTN83474650) .     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Neuroimaging analyses of human working memory

We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal cortex, and a subvocal rehearsal component, which is implemented by left-hemisphere speech areas, including Broca’s area as well as the premotor and supplementary motor areas. We provide a number of neuroimaging dissociations between the storage and rehearsal areas. A second set of studies focuses on spatial working memory and indicates that it is mediated by a network of predominantly right-hemisphere regions that include areas in posterior parietal, occipital, and frontal cortex. We provide some suggestive evidence that these areas, too, divide into storage and rehearsal regions, with right-hemisphere posterior parietal and premotor regions subserving spatial rehearsal. In a final set of studies, we turn to “executive processes,” metaprocesses that regulate the processing of working-memory contents. We focus on the executive process of inhibition as it is used in verbal working memory. We provide evidence that such inhibition is mediated by the left-hemisphere prefrontal region and that it can be dissociated from verbal storage and rehearsal processes.     

Continuous Glucose Monitoring in Newborn Infants: How Do Errors in Calibration Measurements Affect Detected Hypoglycemia?

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data.     

The art and science of continuous positive airway pressure therapy in obstructive sleep apnea

Despite the high prevalence of obstructive sleep apnea (OSA) syndrome, no ideal therapy has emerged to date. Based on recent randomized trials, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Although CPAP can prevent pharyngeal collapse in virtually all patients who choose to wear it, poor patient adherence with treatment limits its effectiveness. Although convincing data exist that treatment with CPAP can alleviate the neurocognitive sequelae of OSA, data on cardiovascular complications are more limited. Several recent reports support a lowering of nocturnal and daytime blood pressure with CPAP, but data on the prevention of myocardial infarction and cerebrovascular events are currently lacking. Patient adherence with CPAP can be improved with optimization of mask comfort, heated humidification, and intensive support and education. For those who remain poorly compliant, alternative therapies such as autotitrating devices and oral positive airway pressure can be considered. Further research into the basic mechanisms underlying OSA will be required for new therapeutic targets to develop.     

Paranoid ideation among elderly African American persons

PURPOSE: The prevalence and correlates of paranoid ideation were investigated. DESIGN AND METHODS: On the basis of a sample of 998 independently living elderly African American persons in a cross-sectional study, the study used the Brief Symptom Inventory to measure paranoid ideation and 14 independent variables, including demographic characteristics, cognitive deficit, depression, self-reported memory functioning, emotional and instrumental support, stressful life events, limitation of daily activities, self-rated health status, and self-rated hearing and vision. RESULTS AND IMPLICATIONS: Paranoid ideation (symptoms of paranoia) was found in 10% of this sample. A multiple regression analysis of the data revealed that of the 14 independent variables used in this study, 6 (income, instrumental support, hearing, stressful life events, self-reported memory deficit, and depression) showed a significant relationship with paranoid ideation.     

Self-administration of drugs in animals and humans as a model and an investigative tool

AIM: To review briefly the methods, assumptions, models, accomplishments, drawbacks and future directions of research using drug self-administration in animals and humans. BACKGROUND: The use of drug self-administration to study addiction is based on the assumption that drugs reinforce the behavior that results in their delivery. A wide range of drug self-administration techniques have been developed to model specific aspects of addiction. These techniques are highly amenable to being combined with a wide variety of neuroscience techniques. CONCLUSIONS: The identification of drug use as behavior that is reinforced by drugs has contributed greatly to the understanding and treatment of addiction. As part of a program of pre-clinical research that also involves screening with a variety of simpler behavioral techniques, drug self-administration procedures can provide an important last step in testing potential treatments for addiction. There is currently a concerted effort to develop self-administration procedures that model the extreme nature of the behavior engendered by addiction. As advances continue to be made in neuroscience techniques, self-administration should continue to provide a means of applying these techniques within a sophisticated and valid model of human drug addiction.     

The effects of personal relevance of topic and information type on older adults' accurate recall of written medical passages about osteoarthritis

OBJECTIVES. This study investigated the influence of information type (based on whether the text affirmed the reader's veridical beliefs or disconfirmed the reader's erroneous beliefs) and self-reported osteoarthritis status on older adults' accurate recall of written medical passages about osteoarthritis. METHODS. One week after reading the passages, adults aged 65 through 80 without osteoarthritis (n = 46) and with osteoarthritis (n = 31) completed a cued recall task that focused on accurate memory of what the passage said. RESULTS. Disconfirming information was less accurately recalled than affirming information. Whereas self-reported osteoarthritis status was not significantly (p >.05) related to accurate recall of affirming information, it was significantly (p <.05) related to accurate recall of disconfirming information. DISCUSSION. Older adults with osteoarthritis were more likely than older adults without osteoarthritis to misrepresent the content of the passages as supporting their misconceptions.     

The legitimacy of addiction treatment in a world of smart people

AIM: This paper discusses what type of legitimacy underpins addiction treatment in contemporary western societies. METHOD: Broad review of the relevant literature. CONCLUSIONS: The legitimacy of professional interventions and the future of service provision will depend largely on the relationship between the professional and the lay referral system. These in turn are intertwined with macro-societal changes. The basic categories in this relationship are, on one hand, the idea of evidence-based practice (i.e. the notion of using the most accurate scientific support for the choice of treatment interventions), and on the other hand the consumer perspective, which conceptualizes addiction treatment as an interactive process between the treatment provider and the consumer. The acceptance of addiction treatment depends in most cases on the client who chooses from a whole range of informal and formal problem solutions. To an extent, experts are thus controlled by their lay counterparts and need their consent to operate and succeed. This process is complicated by the trend towards evidence-based practice, which demands transparency and rigorous procedures and carries with it the basis for distrust in expert knowledge by displaying openly that every statement of fact is open to revision, and thus, to a certain extent, characterized by uncertainty.     

Activity of human hippocampal and amygdala neurons during retrieval of declarative memories

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory.