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Biomedical subjects

D B Clark

Publications and source records attributed to D B Clark.

At least 19 recordsLinked to original sources

Treating the substance-abusing suicidal patient.

Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population. Indeed, suicidality (ideation or behavior) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse. Consequently, to date, little is known about the optimal treatment of this population. The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s. This study involved 12 patients, all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt. The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms (including suicidal ideations) and level of drinking. However, substantial residual depressive symptoms and drinking persisted at the end of the trial. Also, because no placebo control group was utilized, the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect. To date, only one double-blind, placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients. The study involved 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. The results of that double-blind, placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. To date, no other double-blind, placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings. Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients.

Adult↗

Alcohol use disorders and risk factor interactions for adolescent suicidal ideation and attempts.

Four hundred eighty-two adolescents who were diagnosed with at least one mental disorder were studied to determine the predictors of suicidal ideation and suicide attempts. Major depression was predictive of suicidal ideation and suicide attempts for both genders. Chronic stress was found predictive of male suicidal ideation, while low self-esteem and high family dysfunction were found to be predictive of suicidal ideation in females. Statistical trends suggest that females with comorbid alcohol use/conduct disorder were approximately three times more likely to have attempted suicide than those with only one of these conditions. Clinicians working with adolescents should be aware that, while depression remains the number one clinical risk forsuicidal behavior, risk factors for suicidal ideation may be different than those for attempted suicide and may vary by gender.

Adolescent↗

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

BACKGROUND: Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. METHODS: The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. RESULTS: Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. CONCLUSIONS: These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

Adolescent↗

Developmental sources of variation in liability to adolescent substance use disorders.

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use. Continued exacerbation of the three components of dysregulation by drug and non-drug stressors during late adolescence is posited to result in neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals. Implications for etiologic research as well as clinical and preventive interventions are discussed.

Adaptation, Psychological↗

Gender differences and similarities in the personality correlates of adolescent alcohol problems.

The personality traits of behavioral under-control (BU) and negative emotionality (NE) are associated with alcohol problems. The authors examined gender differences in the associations of BU and NE with alcohol problems in 710 adolescents recruited from community and treatment sources. Multiple measures were used to characterize each construct, and the specified 2-factor model provided a reasonably good fit to the data. ANCOVAs were used to examine each construct by gender across four groups: never-regular drinkers, regular drinkers, and those with DSM-IV alcohol abuse and alcohol dependence. Males had significantly higher BU and lower NE than did females. BU and NE both increased with degree of alcohol problems. However, there was not a significant Gender x Alcohol Group interaction for BU or NE. Although there are gender differences in levels of BU and NE, mechanisms of alcohol involvement related to these 2 personality traits may operate similarly in adolescent males and females.

Adolescent↗

Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving.

AIMS: To compare a transdermal nicotine patch designed for 24-hour wear with one designed for 16-hour wear for relief of craving and withdrawal, particularly in the morning hours. DESIGN: Smokers were randomly assigned to use one of two common patch regimens: NicoDerm/NiQuitin (24-hour wear, 21 mg nicotine) or Nicotrol/Nicorette (16-hour wear, 15 mg). In a double-dummy design, participants wore two patches during the day, one active, one placebo and one patch while sleeping. SETTING: A smoking cessation research clinic. PARTICIPANTS: Two hundred and forty-four smokers who suffered morning cravings. INTERVENTION: Two patch formulations approved and marketed for over-the-counter use in the US--NicoDerm CQ (labeled as 21 mg over 24 hours) and Nicotrol (labeled as 15 mg over 16 hours)--were each used according to its instructions. Smokers also received behavioral counseling. MEASUREMENTS: For a week of baseline and 2 weeks after quitting, smokers used palm-top computers to assess craving and withdrawal symptoms several times each day. FINDINGS: The 21 mg/24-hour patch yielded consistently better control of craving, not only during the morning hours, but throughout the day, and over the 2-week period of abstinence. Additionally, the 21 mg/24-hour patch yielded greater reductions in anxiety, irritability and restlessness. Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch. CONCLUSIONS: These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence, when symptoms are at their peak, and when relapse is most likely. They confirm the importance of dosing parameters in nicotine replacement products.

Administration, Cutaneous↗

Hippocampal volume in adolescent-onset alcohol use disorders.

OBJECTIVE: Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects. METHOD: Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness. RESULTS: Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.

Adolescent↗

A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development.

BACKGROUND: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. METHODS: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. RESULTS: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. CONCLUSIONS: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.

Adolescent↗

Etiology of early age onset substance use disorder: a maturational perspective.

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation in somatic and neurological maturation, which, in the context of adverse environments, predisposes to affective and behavioral dysregulation as the cardinal SUD liability-contributing phenotype. Dysregulation progresses via epigenesis from difficult temperament in infancy to conduct problems in childhood to substance use by early adolescence and to severe SUD by young adulthood.

Adolescent↗

Psychopathology and substance-related problems during early adolescence: a survival analysis.

Examined the chronological and statistical relations among onsets of psychopathology, alcohol and cannabis use, and substance-related problem psychopathology, alcohol and cannabis use, and substance-related problems from late childhood through early adolescence in boys of fathers with substance use disorder (SUD; high average risk: n = 177) and without SUD (low average risk: n = 203) using survival analysis. Proportional hazard models indicated that antisocial disorders were predicted by risk group and mediated the observed relation between risk group and substance-related problems. Negative affect disorders were predicted by risk group but did not predict substance involvement in early adolescence. Results support a model in which paternal SUD predisposes to increased antisocial and negative affect disorders in boys, and antisocial disorders lead to substance-related problems in early adolescence.

Adolescent↗

Adolescent versus adult onset and the development of substance use disorders in males.

This study examines the influence of adolescent age of onset on the development of substance use disorders (SUD) by comparing adult males (n = 181) with SUD categorized into adolescent-onset, early-adult onset and late-adult onset groups on patterns of substance use and related disorders, time course of the development of substance dependence and rates of comorbid mental disorders. A sample of male adolescents (n = 81) with SUD was also included as a comparison group. The subjects were recruited from intervention programs in the community and participated in semistructured interviews with diagnoses determined by the best estimate method. Adolescent-onset adults, compared with other adult-onset groups, had higher lifetime rates of cannabis and hallucinogen use disorders, shorter times from first exposure to dependence, shorter times between the development of their first and second dependence diagnoses and higher rates of disruptive behavior disorders and major depression. Adolescents were similar to adolescent-onset adults. While the findings must be interpreted in light of methodological limitations, these results suggest that adolescent-onset SUD is a distinct subtype involving different substances and more rapid development than adult-onset SUD.

Adolescent↗

Systematic assessment of social phobia in clinical practice.

The purpose of this review is to propose a systematic approach to the assessment of social phobia for monitoring treatment outcome in clinical settings. A selection of measures is available, including questionnaires and structured interviews varying in length, complexity, and content. To design an assessment protocol for a particular patient or patient population, the clinician needs to be familiar with the characteristics of these available measures. The measures selected for detailed description and discussion here: (a) are specifically designed to assess social anxiety and social phobia, (b) have been demonstrated to have acceptable psychometric characteristics, and (c) have been utilized in treatment outcome research. Five questionnaire measures will be reviewed: (1) the Social Phobia and Anxiety Inventory (SPAI) (Turner et al., 1989a: Psychol Assessment 1:35-40), (2) the Social Interaction and Anxiety Scale (SIAS) (Mattick and Clarke, 1989 in Heimberg et al., 1992), (3) the Social Phobia Scale (SPS) (Mattick and Clarke, 1989 in Heimberg et al., 1992: Behav Therapy 23:53-73), (4) the Fear of Negative Evaluation Scale (FNES) (Watson and Friend, 1969: J Consult Clin Psychol 33:448-457), and (5) The Social Anxiety and Distress Scale (SADS) (Watson and Friend, 1969: J Consult Clin Psychol 33:448-457). Two interview measures will be reviewed, the Liebowitz Social Anxiety Scale (LSAS) (Liebowitz, 1987: Modern Problems Pharmacopsych 22:141-173) and Brief Social Phobia Scale (BSPS) (Davidson et al., 1991: J Clin Psychiatry 52:48-51). Measures developed for specific subgroups, including patients with speech anxiety and musical performance anxiety, as well as the application of other evaluation methods, such as the Behavioral Assessment Test, will also be discussed. Guidelines for selecting appropriate social phobia measures for varying clinical and research situations will be proposed that take into consideration the strengths and weaknesses of these methods.

Anxiety Disorders↗

Psychopathology in preadolescent sons of fathers with substance use disorders.

OBJECTIVE: While preadolescent children of parents with substance use disorders (SUDs) are known to have more behavior problems, depression, and anxiety than expected, psychiatric disorders in these children and their relationships with parental disorders have not been systematically investigated. This study compares the psychiatric disorders of preadolescent boys of fathers with and without SUDs and examines the relationships between offspring and parental psychopathology. METHOD: Fathers (i.e., probands) of boys 10 through 12 years old were recruited to represent families of boys with paternal SUD (high risk or HR: n = 113) and boys without paternal SUD (low average risk or LAR: n = 170). These boys (i.e., index cases) and their biological parents participated in structured diagnostic interviews, and diagnoses were determined by the best-estimate method. RESULTS: Disruptive behavior disorders and anxiety disorders were more prevalent in HR than in LAR index cases. Logistic regression analyses examining the relationships between parental and index case psychopathology indicated that parental childhood psychiatric disorders were more strongly predictive of index case psychiatric disorders than parental adulthood psychiatric disorders, including SUDs. CONCLUSIONS: Inasmuch as HR boys had increased rates of disruptive behavior disorders and anxiety disorders, these disorders may be important targets for early intervention to prevent the development of SUD, as well as the morbidity associated with these disorders. Prevention efforts and studies of the transmission of liability for psychiatric disorders in children should carefully consider parental childhood characteristics.

Case-Control Studies↗

Gender and comorbid psychopathology in adolescents with alcohol dependence.

OBJECTIVE: Although several mental disorders have been shown to be common in adolescents with substance use disorders, prior studies have not specifically focused on alcohol dependence and have not had sufficient sample sizes to examine gender effects. This study contrasts mental disorder diagnoses and symptoms between a sample of adolescents with alcohol dependence and a community control sample of adolescents and incorporates gender analyses. METHOD: Adolescents (aged 14 years 0 months to 18 years 0 months) with alcohol dependence (females: n = 55; males: n = 78) and community-dwelling control adolescents without substance use disorders (females: n = 44; males: n = 42) were assessed by means of a semistructured interview for DSM-III-R. RESULTS: While cannabis and hallucinogen use disorders were common in the alcohol dependence group, females and males had similar rates. Conduct disorder (CD), oppositional defiant disorder, attention-deficit hyperactivity disorder, major depression (MD), and posttraumatic stress disorder (PTSD) had significantly higher rates in the alcohol dependence than in the community control group. Depression and PTSD symptoms were more strongly associated with alcohol dependence in females than in males. A configural frequency analysis showed that CD and MD tended to occur together in both female and male adolescents with alcohol dependence. CONCLUSIONS: While alcohol-dependent females and males similarly exhibited more comorbid disorders than control adolescents, gender affects the relationship of alcohol dependence to MD and PTSD. Rather than reflecting distinct types, the comorbid disorders of CD and MD jointly characterize many adolescents with alcohol dependence.

Adolescent↗

Traumas and other adverse life events in adolescents with alcohol abuse and dependence.

OBJECTIVE: Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. METHOD: The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. RESULTS: Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. CONCLUSIONS: These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.

Adolescent↗

Alcohol use disorder among adolescents: impact of paternal alcoholism on drinking behavior, drinking motivation, and consequences.

This study examined the impact of an Alcohol Use Disorder (AUD) in biological fathers on drinking history, context, motivation, and consequences in male and female adolescents dichotomized according to the presence or absence of an AUD. Main effects for paternal history of an AUD were not found on any variable. Significant interactions were observed between father-son diagnostic status with respect to age of first alcohol use (p < 0.001) and peer relationships (p < 0.001). No significant interactions were observed between father-daughter diagnostic status. As expected, adolescents with AUD differed from adolescents without AUD on numerous variables pertaining to drinking behavior, history, and consequences. These findings indicate that there is no strong or pervasive effect of paternal AUD on adolescent offspring's AUD characteristics.

Adolescent↗

Timing of paternal substance use disorder cessation and effects on problem behaviors in sons.

The developmental timing of paternal substance use disorder (SUD) offset on internalizing and externalizing problem behaviors was examined in prepubertal sons. Analyses revealed a significant main effect of the developmental timing of SUD offset on both internalizing and externalizing problems. No differences were found between sons of control-subject fathers and SUD+ fathers whose offsets occurred before the son's sixth birthday. However, when paternal SUD extended beyond the boys' sixth year, significant increases in internalizing and externalizing problem behaviors were found. The results suggest the importance of early parental SUD intervention in prevention of the intergenerational transmission of behavioral problems.

Age Factors↗

Posttraumatic stress disorder, depression, alcohol use disorders and quality of life in adolescents.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder among adolescents. While the effects of PTSD on quality of life (QOL) have been systematically studied with adults, research on the consequences of PTSD with adolescents has been limited. Among the other psychiatric disorders often associated with PTSD, major depression and alcohol use disorders are prevalent and have their own substantial morbidities. This study was designed to examine and compare the effects of PTSD, major depression, and alcohol use disorders on quality of life during adolescence. The subjects were 540 adolescents (ages 12-18 years old) recruited from clinical and community sources. Psychiatric disorders characterizing the sample included one or more of the three disorders studied (n = 275), other psychiatric disorders (n = 121), or no psychiatric disorders (n = 144). Analysis of covariance was utilized to determine the individual main effects and relative effects sizes of the three primary disorders on QOL variables. PTSD showed significant adverse effects on psychological, physical, and social functioning. Major depression showed a similar pattern. In contrast, alcohol use disorders primarily affected role functioning. While PTSD, major depression, and alcohol use disorders all adversely influenced adolescent QOL, the patterns of their effects differed. Remedial treatment interventions designed to restore QOL for adolescents with these disorders may need to focus on different areas for adolescents with PTSD or major depression than for adolescents with alcohol use disorders.

Achievement↗