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Biomedical subjects

C S Martin

Publications and source records attributed to C S Martin.

At least 37 records · Page 2Linked to original sources

Toward the DSM-V: the Withdrawal-Gate Model versus the DSM-IV in the diagnosis of alcohol abuse and dependence.

The Diagtnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) classifies as dependent many cases of mild alcohol problems. DSM-IV diagnoses have modest relationships with predictive and some concurrent validators and often improperly sequence the onset of abuse versus dependence, perhaps due to insufficient emphasis on physiological features. Testing reliability, syndrome prevalence, syndrome sequencing, and concurrent and predictive validity, this study contrasted the DSM-IV with the Withdrawal-Gate Model (WGM), in which alcohol withdrawal is necessary and sufficient for the dependence diagnosis. Clinical samples of adults (baseline n = 318) and adolescents (baseline n = 214) meeting abuse or dependence were assessed for DSM-IV alcohol symptoms and external measures of problem severity and reinterviewed at 6 (adults) and 12 months (adults and adolescents). Among DSM-IV dependent cases, the WGM shifted 32% of adults and 80% of adolescents to the abuse category, making both categories more symptomatically severe, but had a negligible effect on the prevalence of total alcohol diagnoses. The WGM was more reliable than the DSM-IV and temporally sequenced abuse before dependence in a greater number of cases. The WGM was superior to the DSM-IV in concurrent and predictive validity on most measures. Future diagnostic systems may be more reliable and valid if they require evidence of withdrawal for substance dependence.

Adolescent↗

Reliability and concurrent validity of DSM-IV subclinical symptom ratings for alcohol use disorders among adolescents.

BACKGROUND: The concurrent validity of subclinical ratings for psychiatric symptoms can help refine symptom definitions and threshold criteria. However, virtually no research has examined subclinical ratings for DSM-IV symptoms in psychiatric diagnostic interviews. This study examined the frequency, reliability, and concurrent validity of subclinical ratings for 11 symptoms of alcohol use disorders among adolescents. METHODS: Subjects were 239 male and 164 female adolescents ages 14 to 18 recruited from treatment and community sources. Symptoms and diagnoses were made with an adapted version of the Structured Clinical Interview for the DSM-IV. RESULTS: Subclinical ratings showed acceptable to high interrater reliability. The proportion of subclinical ratings tended to decrease with increasing levels of alcohol problems. For 10 of the 11 symptoms, subjects with subclinical ratings were distinguished from those with absent and/or those with present ratings. Subjects with subclinical ratings were often distinct from those with present ratings but less often distinct from those with absent ratings. CONCLUSIONS: For most of the DSM-IV alcohol use disorder symptoms, subclinical ratings appear to be reliable and valid and provide information beyond dichotomous symptom classifications for adolescents. Threshold criteria appear to be appropriate in many cases, but boundaries between absent and subclinical ratings are "fuzzy." Practical and research implications are discussed.

Adolescent↗

Risky sexual behaviors among adolescents with alcohol use disorders.

Little is known about risky sexual activity among adolescents with alcohol use disorders. This study of 371 adolescent drinkers found that those with alcohol disorders were more likely than other drinkers to be sexually active, to have greater numbers of partners, and to initiate sexual activity at slightly younger ages. Independent of alcohol group, females were more likely than males to have unprotected sexual encounters.

Adolescent↗

Diagnostic orphans: adolescents with alcohol symptom who do not qualify for DSM-IV abuse or dependence diagnoses.

OBJECTIVE: Little is known about the validity of the DSM-IV criteria for alcohol use disorders when applied to adolescents. This report describes a group of "diagnostic orphans," adolescents with one or two DSM-IV alcohol dependence symptoms who do not meet the DSM-IV criteria for alcohol abuse or alcohol dependence. METHOD: The study included 199 male and 173 female subjects aged 13-19 years. All subjects were regular drinkers, recruited from community sources and alcohol treatment programs. At baseline and at 1-year follow-up, DSM-IV alcohol use disorders were assessed with a version of the Structured Clinical Interview for DSM-III-R, modified for DSM-IV criteria. RESULTS: Diagnostic orphans represented 31% of the drinkers without an alcohol use disorder. The orphans were similar to the alcohol abusers and dissimilar to the other drinkers in alcohol and substance use patterns and in the course of alcohol problems over 1 year. CONCLUSIONS: The results indicate limitations of the DSM-IV criteria for alcohol use disorders when applied to adolescents. Diagnostic orphans should be considered separately from other drinkers in research and treatment efforts.

Adolescent↗

Diagnosis and assessment of alcohol use disorders among adolescents.

The diagnostic criteria for alcohol use disorders (AUDs) (i.e., alcohol abuse and alcohol dependence) as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were developed largely from research and clinical experience with adults. Little is known about the validity of these criteria when applied to adolescents. Recent epidemiological and clinical studies of AUDs and their symptoms among adolescents have indicated that the DSM-IV criteria have significant limitations when applied to this age group. Diagnostic interviews and screening tools for adolescent AUDs are discussed. Numerous instruments are available that have shown moderate-to-high reliability and validity in assessing AUDs among adolescents.

Adolescent↗

Alterations in hippocampal non-phosphorylated MAP2 protein expression in schizophrenia.

Microtubule-associated proteins (MAPs) are central to the development of normal neuronal cytoarchitecture and have been suggested in previous studies to be altered in schizophrenia. We investigated hippocampal phosphorylated and non-phosphorylated MAP2 expression in schizophrenia in relation to neuronal orientation and interneuronal distance. One paraffin embedded mid-hippocampal block was obtained from each of 8 schizophrenic and 11 control postmortem brains and immunohistochemistry for the phosphorylated and non-phosphorylated forms of MAP2 performed. Within the corona ammonis (CA) subregions and the subiculum, we assessed densitometry readings for non-phosphorylated MAP2-positive neurones (MAP2-NP), and counted the number of neurones immunopositive for phosphorylated MAP2 (MAP2-P). Using image analysis computer software we measured interneuronal distances and neuronal orientation. While there were no overall alterations in densitometric density of MAP2-NP neurones in any hippocampal subregions, we found a left-sided increase in densitometric density of MAP2-NP neurones within the subiculum (F = 8.740, P < 0.021), and the CA1 (F = 7.044, P < 0.033) of schizophrenic subjects which were unrelated to age, postmortem interval or neuroleptic exposure. There was no accompanying alteration of interneuronal distances, neuronal orientation. The findings support previous work demonstrating altered subicular MAP2 expression in schizophrenia and indicate that the finding may be lateralised. However, in contrast to previous investigations, we have demonstrated this alteration in MAP2 expression is due to an increase in the non-phosphorylated form of MAP2, rather than a decrease in total MAP2 expression. These findings suggest that cytoskeletal assembly is abnormal in schizophrenia and generate testable hypotheses regarding the developmental basis of the disorder.

Adult↗

Immediate, quantitative estimation of blood alcohol concentration from saliva.

OBJECTIVE: Reliable, valid, and noninvasive methods to quantitatively estimate blood alcohol concentration (BAC) are important in forensic, work place, medical and research settings. To date, noninvasive methods for quantitatively estimating BAC have primarily used breath testing. This study evaluated a new device for estimating BAC via saliva that is unique in providing on-the-spot, quantitative results in 2 minutes. The Q.E.D-A150 test (STC Technologies, Inc., Bethlehem, Pa.) is based on the enzymatic oxidation of alcohol by alcohol dehydrogenase. Saliva alcohol concentration (SAC) is read directly from the test device. METHOD: In each of three sessions, 24 male and 15 female social drinkers, aged 21-28 years, provided yoked breath and saliva samples prior to, and at five times following, a dose of 1.0 g (men) or 0.9 g (women) alcohol per kg lean body mass. RESULTS: Intertest reliability, determined by two simultaneous saliva samples, was very high for each measurement time (r's = .97 to .99), for each subject (4's = .95 to .99) and across all observations (r = .98). The coefficient of variation was below 5% in 97% of paired observations. The correlation between breath and saliva estimates was .94 across all observations and ranged from .92 to .98 across measurement times. The difference between breath and saliva estimates was significantly larger on the ascending limb than on the descending limb of the blood alcohol curve at comparable BACs. On the average, SAC estimates were 6 mg/dl higher than breath during ascending BACs and 3 mg/dl higher than breath during descending BACs. Individual differences in the ratio of SAC to breath measures of BAC ranged from 0.99 to 1.15 (average = 1.06). Test performance was not affected by gender, drinking pattern or cigarette smoker status. CONCLUSIONS: The Q.E.D.-A150 device had good reliability and validity for the noninvasive, quantitative estimation of BACs.

Adult↗

Polydrug use in an inpatient treatment sample of problem drinkers.

Over the past 30 years in the United States, there have been marked secular increases in polydrug use. Alcohol and other substance use disorders are highly comorbid. Yet, little research has characterized patterns of polydrug use in persons with alcohol dependence. In particular, little is known about this population's use of alcohol and other drugs in combination or on the same day, which is termed simultaneous polydrug use (SPU). This research assessed patterns of SPU in 212 problem drinkers who participated in an alcohol treatment outcome study. Subjects were given a Time-Line Follow-Back interview that assessed the use of alcohol and nine other drug classes for each day of the 120 days before treatment entry. A majority of subjects (61%) reported SPU during this assessment interval. Subjects who reported SPU were disproportionately younger, male, and unmarried, compared with those who did not report SPU. The most common alcohol/drug combinations were alcohol with cocaine (60% of subjects who reported SPU), alcohol with marijuana (51% of SPU subjects), and alcohol with sedatives (31% of SPU subjects). The most common three-drug combination was alcohol, cocaine, and marijuana (23% of SPU subjects). Alcohol use and drug use were associated at the event level, significantly more than association predicted by the base rates of the individual behaviors. Time-Line Follow-Back data correlated highly with a questionnaire measure of SPU. Results indicate that polydrug use is an important focus for assessment and intervention in alcohol treatment programs.

Adult↗

Executive cognitive functioning predicts reactive aggression in boys at high risk for substance abuse: a prospective study.

This study assessed the ability of executive cognitive functioning (ECF) to predict reactive aggression in boys at high and low risk for substance abuse using a 2-year prospective design. ECF is defined as the self-regulation of goal-directed behavior. Reactive aggression involves impulsive hostile reactions committed with little forethought. ECF was measured using five neuropsychological tests in 198 10- to 12-year-old boys with (SA+) and without (SA-) a paternal history of substance abuse/dependence. Reactive aggression was measured, 2 years later, using a composite index of items derived from two self-report measures. It was hypothesized that ECF would predict reactive aggression, and that this relation would be stronger for the SA+ compared with the SA- boys. SA+ subjects demonstrated lower ECF scores and higher reactive aggression scores, compared with SA- controls. ECF predicted reactive aggression in the SA+ group (beta = 0.37, p = 0.001), but not in the SA- group (beta = 0.09, p = NS). This suggests that compromised ECF may be a risk factor for reactive aggression in SA+ youth. The hypothesis that the relation between ECF and reactive aggression is a manifestation of a mild dysfunction of the prefrontal cortex is discussed.

Aggression↗

Polydrug use in adolescent drinkers with and without DSM-IV alcohol abuse and dependence.

Alcohol and other substance use disorders are highly comorbid, but little is known about patterns of polydrug use in adolescents with different levels of alcohol involvement. This research examined patterns and correlates of polydrug use in 176 adolescent drinkers with DSM-IV alcohol dependence (n = 61), alcohol abuse (n = 57), and no alcohol diagnosis (n = 58). Alcohol and other Substance Use Disorders were assessed using a modified version of the Structured Clinical Interview for the DSM. Lifetime histories of alcohol use and other drug use were assessed using a structured interview. Subjects also completed a questionnaire measure of the frequency of use of specific alcohol-drug combinations. The total number of illicit drugs ever used was greater in the alcohol dependence (mean = 3.8, SD = 2.1) and abuse groups (mean = 3.0, SD = 2.1), compared with the no-alcohol diagnosis group (mean = 1.9, SD = 1.3). Consistent with previous findings, there was a consistent pattern in the age of onset of psychoactive substance use: alcohol, followed by marijuana, followed by other drugs. The recent use of alcohol and other drugs in combination was reported by a greater percentage of subjects in the alcohol dependence (69%) and abuse groups (72%), compared with drinkers without an alcohol diagnosis (45%). The most common alcohol-drug combination was alcohol with marijuana (58% of the total sample), followed by alcohol-hallucinogens (16%). The frequency and extent of polydrug use was associated with being older and having higher levels of behavioral undercontrol and negative emotionality. Adolescent polydrug use, particularly the use of alcohol and other drugs in combination, is an important area for research, treatment, and prevention.

Adolescent↗

Executive cognitive functioning and aggressive behavior in preadolescent boys at high risk for substance abuse/dependence.

OBJECTIVE: This study had three purposes; (1) to assess the underlying factor structure of a battery of neuropsychological tests putatively measuring executive cognitive functioning (ECF) in a sample of boys at high and low risk for substance abuse/dependence; (2) to assess the relationship between ECF and aggressive behavior; and (3) to determine the interactive effects of ECF and a family history (FH) of substance dependence on aggressive behavior. METHOD: Multiple measures of ECF and aggressive behavior were used to test these relationships in a sample of 291 10-12 year old boys with and without a FH of substance dependence. RESULTS: Analyses indicated that the measures of ECF loaded on one factor. ECF was related to aggressive behavior even when accounting for IQ and SES. The interaction between ECF and a FH of substance dependence was also associated with aggressive behavior. CONCLUSIONS: The central finding of this investigation indicates that ECF and its interaction with a FH of substance dependence are associated with aggressive behavior. These results suggest that violence prevention and treatment efforts in high risk groups should incorporate cognitive habilitation focusing on training in ECFs.

Adolescent↗

Staging in the onset of DSM-IV alcohol symptoms in adolescents: survival/ hazard analyses.

OBJECTIVE: This research examined staging in the time to onset of DSM-IV alcohol symptoms in adolescents. Consistent staging in the onset of symptoms provides important tests of the construct validity of diagnostic systems, and aids the development of early case identification strategies. METHOD: The Structured Clinical Interview for the DSM (SCID), adapted to assess DSM-IV alcohol abuse and dependence symptoms, was used to determine time to symptom onset in 102 male and 97 female adolescent drinkers with and without alcohol use disorders. The sample provided a broad range of drinking practices and alcohol-related problems. Symptom onset patterns were examined using survival-hazard analyses. RESULTS: Survival and hazard data suggested three stages of alcohol problems distinguished by time to onset: heavy and heedless drinking with associated social and role obligation problems, psychological dependence, and withdrawal. This three-stage model fit both the male and female data, and described staging patterns in 70% of the subjects. CONCLUSIONS: The symptom onset model suggested a first stage of adolescent alcohol symptoms characterized by heavy and heedless drinking with associated interpersonal and role obligation problems. The data did not support the construct validity of DSM-IV alcohol abuse when applied to adolescents, and suggested staging among DSM-IV alcohol dependence symptoms. Implications for the diagnosis and early identification of adolescent alcohol problems are discussed.

Adolescent↗

Dual luminescence-based reporter gene assay for luciferase and beta-galactosidase.

A unique combined luminescence assay for firefly (Photinus pyralis) luciferase and beta-galactosidase (beta-gal) reporter gene products is described. Luciferase and beta-gal activities are determined with the same aliquot of cell lysate prepared from cells contransfected with both reporter genes, thereby reducing manual labor and increasing experimental accuracy. With the Dual-Light assay system, luciferase activity is measured first with an enhanced luciferase assay, followed by quantitation of beta-gal with Galacton-Plus chemiluminescent substrate and Sapphire-II enhancer. Highly sensitive detection of luciferase (2 fg) and beta-gal (8 fg) is achieved with a dynamic range over seven orders of magnitude of enzyme concentration. Comparative analysis of both independent and combined (Dual-Light) detection methods for cells contransfected with luciferase and beta-gal reporter genes is also described.

Animals↗

Chemiluminescence: sensitive detection technology for reporter gene assays.

A series of enzyme-activated chemiluminescence-based assays of reporter gene expression, useful in many biomedical applications, has been developed. The chemiluminescence detection systems for beta-galactosidase, beta-glucuronidase (GUS), and secreted placental alkaline phosphatase (SEAP) reporter enzymes are all based on use of 1,2-dioxetane substrates. This detection technology also permits the combined luminescence detection of two different reporter enzymes in the same tube, e.g., a dual assay for beta-galactosidase and luciferase. The sensitivity of these chemiluminescence assays is several orders of magnitude greater than that of conventional colorimetric or fluorometric detection methods; e.g., the detection limit for beta-galactosidase by the chemiluminescence assay is 8 fg and by a fluorometric assay is 2 pg. Furthermore, chemiluminescence enables detection of beta-galactosidase, GUS, and SEAP enzyme concentrations over a dynamic range of more than five to six orders in magnitude. These assays offer highly sensitive, quantitative, rapid, nonisotopic detection of reporter enzymes that are widely used in both mammalian cells and plant cells.

Alkaline Phosphatase↗

Salivary cortisol responses and the risk for substance abuse in prepubertal boys.

Investigations of adults with a psychoactive substance use disorder (PSUD) or antisocial behavior have reported diminished secretion of the adrenal "stress" hormone, cortisol. Consequently, we determined whether prepubertal sons of PSUD fathers, at high risk for later PSUD, differed from controls on salivary cortisol concentrations before, and after, an anticipated stressor. The roles of problematic behavioral disposition and state anxiety in the cortisol responses were also examined. A significant risk-group x time interaction for salivary cortisol concentrations was found, with high-risk boys secreting less salivary cortisol than controls when anticipating the task. High-risk boys also had significantly higher scores for aggressive delinquency and impulsivity that wholly accounted for the risk-group x time effect on salivary cortisol. Thus, cortisol hyporesponsivity was associated with the dysregulated behaviors prevalent among high-risk boys. The results suggest that cortisol hyporesponsivity could be a "marker" for later antisociality and PSUD.

Adult↗

Cpn60 is exclusively localized into mitochondria of rat liver and embryonic Drosophila cells.

Several reports have claimed that the mitochondrial chaperonin cpn60, or a close homolog, is also present in some other subcellular compartments of the eukaryotic cell. Immunoelectron microscopy studies, using a polyclonal serum against cpn60, revealed that the protein is exclusively localized within the mitochondria of rat liver and embryonic Drosophila cells (SL2). Furthermore, no cpn60 immunoreactive material could be found within the nucleus of SL2 cells subjected to a 1 h 37 degrees C heat-shock treatment. In contrast to these findings, immunoelectron microscopy studies, using a cpn60 monoclonal antibody, revealed mitochondrial and extramitochondrial (plasma membrane, nucleus) immunoreactive material in rat liver cells. Surprisingly, the monoclonal antibody also reacted with fixed proteins of the mature red blood cell. The monoclonal antibody, as well as cpn60 polyclonal sera, only recognize mitochondrial cpn60 in Western blots of liver proteins. Furthermore, none of the cpn60 antibodies used in this study recognized blotted proteins from rat red blood cells. Therefore, we suggest that the reported extramitochondrial localization of cpn60 in metazoan cells may be due to cross-reactivity of some of cpn60 antibodies with conformational epitopes also present in distantly related cpn60 protein homologs that are preserved during fixation procedures of the cells.

Amino Acid Sequence↗

Patterns of DSM-IV alcohol abuse and dependence symptoms in adolescent drinkers.

OBJECTIVE: Diagnostic criteria for alcohol use disorders have largely been developed from research and clinical experience with adults. This research was designed to describe patterns of DSM-IV alcohol use disorder symptoms, and other problem domains, in adolescents with alcohol problems. METHOD: A modified version of the Structured Clinical Interview for the DSM (SCID) was used to assess DSM-IV alcohol abuse and alcohol dependence symptoms in 91 male and 90 female adolescent drinkers with various levels of alcohol consumption and alcohol-related problems. The SCID was expanded to assess other alcohol problem domains thought to be relevant for adolescents. RESULTS: DSM-IV dependence symptoms showed moderate to high covariation, supporting the utility of the alcohol dependence construct in adolescence. Compared to previous reports from adult samples, some symptoms were relatively infrequent (e.g., withdrawal, medical problems). Tolerance had low specificity for the diagnosis of alcohol dependence. There was significant heterogeneity in the symptomatology of subjects with DSM-IV alcohol abuse. Although they are not in the DSM-IV criteria, alcohol-related blackouts, craving and risky sexual behavior were common in adolescents with DSM-IV alcohol dependence and abuse diagnoses. CONCLUSIONS: The data generally support the utility of DSM-IV criteria for alcohol dependence among adolescents. However, tolerance, withdrawal and medical problems appear to present differently in adolescents than has been reported in adults. Those with DSM-IV alcohol abuse diagnoses had very heterogeneous patterns of symptomatology, suggesting limitations of the criteria for DSM-IV alcohol abuse in adolescence. Alcohol-related blackouts, craving and risky sexual behavior are common among adolescents with alcohol use disorders and are an important focus for assessment and treatment efforts.

Adolescent↗