Biological markers for suicidal behavior in alcohol dependence.

Alcohol-dependent populations have a high lifetime suicide rate (between 7 and 15%, relative risk = 7), and alcoholism is one of the two psychiatric disorders most frequently found in suicidal cases (between 15 and 25%). Biological factors that would detect patients at risk could thus be of value. Carbohydrate-deficient transferrin, monoamine oxidase B, soluble interleukin-2 receptor and cholesterol have been proposed as markers of suicidal risk in alcohol-dependent patients, although nonspecific and with low predictive value. On the other hand, there is large and convergent data stressing the importance of serotonin dysregulation as increasing the risk for aggressive behaviour toward the self, although it is not clear whether serotonin is involved through the altered behavior inhibition system, enhancement of anxiety and depression, or association with specific subtypes of alcohol-dependence, such as early-onset type II alcoholism. Considering the complex but significant impact of alcohol on serotonin metabolism and turnover, it is likely that serotonin mediates a large part of the proneness of ethanol to commit impulsive-aggressive behavior.     

Negative reinforcement to alter disruptive behavior of an adolescent in a day treatment setting

This report describes the treatment of disruptive behavior in an adolescent in a day treatment program (by a negative reinforcement procedure). The use of a negative reinforcer was necessitated by the unavailability of effective positive reinforcers.     

Family history and diagnosis of alcohol dependence in cocaine dependence

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.     

Prenatal exposure to alcohol impairs social play behavior in adolescent male mice

Prenatal ethanol exposure affects brain development and causes neural impairment, leading to both cognitive and behavioral consequences in the offspring. Therefore, the aim of this study was to investigate the impact of prenatal exposure to small amounts of alcohol on social play behavior in adolescent male offspring. Swiss mice were prenatally exposed to ethanol by feeding pregnant dams with a liquid diet containing 25% alcohol-derived calories during gestation (alcohol group). They were then compared to both pair-fed dams that received an isocaloric liquid diet containing 0% alcohol-derived calories (pair-fed group) and dams with ad libitum access to a liquid control diet (control group). Additionally, maternal behavior was evaluated in terms of neural activation indexed via c-fos expression in the prefrontal cortex. Although dams exposed to alcohol during pregnancy did not alter their maternal behavior, the offspring presented a decrease in their social play behavior compared with both control and pair-fed offspring. The decrease in social play behavior may be associated with a decrease in number of c-fos-positive cells in the prefrontal cortex. The exposure to small amounts of alcohol during intrauterine development causes both a deficit in social play behavior and a reduction in the neuronal activity seen in the prefrontal cortex.     

Increasing diagnosis of nicotine dependence in adolescent mental health patients

OBJECTIVE: The aim of this study was to investigate the routine recording patterns of patients' smoking by clinical staff of an adolescent mental health service over a 3-year period. METHOD: A systematic examination of the clinical files of all patients who underwent an initial assessment or reassessment at the Youth Specialty Service (Mental Health; YSS) over a 2-month period (1 April-31 May) was carried out in 1996, 1997 and 1998. A range of data were collected including: demographics; diagnoses; amount of total information recorded and history of nicotine dependence. RESULTS: A stable historical record of cigarette smoking in the region of 30-40% across the 3 years sampled was found, but the rate of formal diagnosis of nicotine dependence rose from 3.6% in 1996 to 26.3% in 1998. This rise was in the context of relative stability over this time period of: size of reports and relevant sections (alcohol and drug history, cigarette smoking history); three other key diagnoses, major depression, conduct disorder and alcohol dependence; and demographic data. The rise in rate of diagnosis proceeded specific discussion within the clinical team about nicotine dependence. CONCLUSIONS: Adolescent mental health settings are a key venue to address heavy and potentially chronic cigarette smoking, but nicotine dependence has been traditionally a neglected diagnosis in mental health patients. The rate of diagnosis is likely to rise when specific discussion is undertaken within clinical teams.     

Cerebellar volume in offspring from multiplex alcohol dependence families.

BACKGROUND: Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the cerebellum in regulating cognitive functions is being increasingly recognized along with its well-known influence on motor performance. Additionally, developmental changes in cerebellar volume during adolescence have been reported. METHODS: Magnetic resonance imaging was used to measure the cerebellum in 17 high-risk adolescent and young adult offspring from multiplex alcohol dependence families and 16 control subjects matched for gender, age, and IQ. RESULTS: High-risk (HR) adolescents/young adults showed increased total cerebellum volume and total grey in comparison with control subjects. Age-related decreases in total grey volume were seen with age, a pattern that was not seen in HR offspring. CONCLUSIONS: Offspring from multiplex families for AD manifest genetic susceptibility by having larger cerebellar volume, which seems to be related to lesser grey matter pruning for age. Larger cerebellar volumes in adult obsessive compulsive disorder (OCD) patients have been reported. This suggests a possible similarity in structural underpinnings for alcohol dependence and OCD.     

Response to treatments in youth with disruptive behavior disorders

Objective

Predictors of poor response to treatments in youths with disruptive behavior disorders (DBDs), including conduct disorder (CD) and oppositional defiant disorder (ODD), are under-studied. Multimodal psychosocial interventions are the best option, but a significant portion of patients needs adjunctive pharmacotherapy. The concept of “psychopathy”, and namely, the callous (lack of empathy and guilt) and unemotional (shallow emotions) trait, has been considered a possible specifier indicating a more severe subgroup of patients. We explored whether the callous–unemotional trait (CU) may affect the response to multimodal treatment in referred youths with DBDs.

Method

118 youths (102 males, age range 6–14 years, mean age 11.1 ± 2.5 years) completed a 12-month multimodal intervention, 48 of whom (41%) needed an associated pharmacotherapy. The patients were assessed according to psychopathological profile (Child Behavior Checklist, CBCL), severity and improvement (Clinical Global Impression-Severity and Improvement scores, CGI-S and CGI-I), functional impairment (Children-Global Assessment Scale, C-GAS), and psychopathic dimension (Antisocial Process Screening Device, APSD), including CU dimension.

Results

58 patients (49.2%) were non-responders. They had more frequently a diagnosis of CD than ODD, presented a comorbid mood disorder, higher CBCL scores in rule-breaking behavior, and higher APSD (“psychopathic”) scores. Subjects with higher or lower CU differed only according to the rate of responders (35% vs. 60%, p < .05). The linear blockwise regression indicated that pre-treatment functional impairment (C-GAS) and baseline CU trait were predictors of non-response. The logistic regression indicated that only the value of baseline APSD-CU trait was a predictor of non-response.

Conclusions

A careful assessment of baseline clinical functioning and psychopathological features, namely the psychopathic traits, can identify the most problematic patients, and has specific prognostic and treatment implications.     

Identifying comorbid depression and disruptive behavior disorders: comparison of two approaches used in adolescent studies

Interest in commonly co-occurring depression and disruptive behavior disorders in children has yielded a small body of research that estimates the prevalence of this comorbid condition and compares children with the comorbid condition and children with depression or disruptive behavior disorders alone with respect to antecedents and outcomes. Prior studies have used one of two different approaches to measure comorbid disorders: (1) meeting criteria for two DSM or ICD diagnoses or (2) scoring .5 SD above the mean or higher on two dimensional scales. This study compares two snapshots of comorbidity taken simultaneously in the same sample with each of the measurement approaches. The Developmental Pathways Project administered structured diagnostic interviews as well as dimensional scales to a community-based sample of 521 11-12 year olds to assess depression and disruptive behavior disorders. Clinical caseness indicators of children identified as "comorbid" by each method were examined concurrently and 3-years later. Cross-classification of adolescents via the two approaches revealed low agreement. When other indicators of caseness, including functional impairment, need for services, and clinical elevations on other symptom scales were examined, adolescents identified as comorbid via dimensional scales only were similar to those who were identified as comorbid via DSM-IV diagnostic criteria. Findings suggest that when relying solely on DSM diagnostic criteria for comorbid depression and disruptive behavior disorders, many adolescents with significant impairment will be overlooked. Findings also suggest that lower dimensional scale thresholds can be set when comorbid conditions, rather than single forms of psychopathology, are being identified.     

Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders.

The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article.     

Suicidal behavior among adolescents with conduct disorder--the role of alcohol dependence

Our aim was to investigate the association between alcohol dependence and suicidal behavior among adolescent girls and boys suffering from conduct disorder (CD). The original study sample consisted of 387 adolescents (age 12-17) admitted to psychiatric inpatient care between April 2001 and May 2005. DSM-IV-based psychiatric diagnoses and variables measuring suicidal behavior were obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children--Present and Lifetime (K-SADS-PL). Of the total study population, 59 adolescent girls and 82 boys had CD according to DSM-IV criteria. Of all adolescents with CD, 24 (40.7%) girls and 24 (29.3%) boys were suffering from alcohol dependence. Among girls with CD, alcohol dependence increased the risk for suicide attempts up to 3.8-fold (95% CI 1.1-13.4). Among boys with CD, alcohol dependence increased the risk for life-threatening suicide attempt over nine-fold (95% CI 1.2-80.1). In addition, the risk for self-mutilative behavior was as high as 3.9-fold (95% CI 1.1-13.8) among girls and 5.3-fold (95% CI 1.1-26.5) among boys. The results indicate that, among adolescents suffering from CD, the risk of suicidal behavior is considerably increased by co-morbid alcohol dependence, which should therefore be carefully taken into account in clinical work.     

Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking

CONTEXT: Adaptations in gamma-aminobutyric acid type A (GABA(A))-benzodiazepine receptors contribute to the neurobiology of human alcohol dependence and withdrawal. OBJECTIVE: To study GABA(A)-benzodiazepine receptor adaptations in subjects with alcohol dependence over the first month of sobriety. DESIGN: Inpatients who were not receiving medication, were either smokers or nonsmokers, and had alcohol dependence completed 2 iodine I 123-labeled iomazenil single-photon emission computed tomographic scans: 1 scan at a mean +/- SD of 4.9 +/- 2.5 days of sobriety (n = 23) and 1 scan at a mean +/- SD of 29.8 +/- 7.6 days of sobriety (n = 20). Participants in a matched group of healthy subjects (n = 15) completed 1 single-photon emission computed tomographic scan. PARTICIPANTS: Men with alcohol dependence (n = 27) and a matched healthy comparison group (n = 15). MAIN OUTCOME MEASURES: (123)I-iomazenil single-photon emission computed tomographic images were converted to units of distribution volume (regional activity/free (123)I-iomazenil) and were analyzed using voxel-based statistical parametric mapping and regions of interest analyses. The relationships between (123)I-iomazenil distribution volume, clinical features of alcohol dependence, and smoking status were evaluated. RESULTS: (123)I-iomazenil uptake was elevated in several cortical regions, with a more prominent increase in nonsmokers with alcohol dependence as compared with smokers with alcohol dependence at 1 week of abstinence from alcohol. No significant differences were observed at 4 weeks of abstinence. At 1 week of abstinence, frontal (123)I-iomazenil uptake correlated with the severity of alcohol withdrawal and the number of days since the last alcoholic drink was consumed. No significant associations were observed for smokers with alcohol dependence. CONCLUSIONS: These data demonstrate time-dependent regulation of cortical GABA(A)-benzodiazepine receptors associated with the recovery from alcohol dependence. Higher GABA(A)-benzodiazepine receptor levels during acute withdrawal may reflect a compensation for reduced receptor function, which is thought to contribute to alcohol tolerance and withdrawal. The subsequent decline may reflect "normalization" of GABA(A) receptor function with sobriety. Smoking may attenuate GABA(A) receptor adaptations associated with alcohol dependence and may contribute to the comorbidity between alcoholism and smoking.     

The disruptive behavior disorders in the psychiatric emergency service.

Many children and adolescents presenting to the Psychiatric Emergency Service (PES) are diagnosed with the Disruptive Behavior Disorders (DBD), Conduct Disorder (CD), and Oppositional Defiant Disorder (ODD). Sometimes it may be difficult to reliably diagnose these disorders in the PES setting. Given these limitations, a large database of 6 years of PES visits showed 314 patients with DBD compared with 1625 without DBD. More DBD patient visits required the intervention of police and/or the mobile crisis team. These patients are more likely to have additional diagnoses of depression and attention deficit hyperactivity disorder, be in current treatment, or involved with court or the correctional system. They are less frequently referred by other emergency services such as medical ERs. DBD patients do not require emergency medication or psychiatric hospitalization any more frequently than other youngsters presenting to the PES. In the PES setting there is little differentiation between the CD and the ODD population. A more detailed study of the presenting symptomatology of the DBD vs non-DBD patients revealed that DBD patients showed over twice as many disruptive behavior symptoms. Fights and defiance were present significantly more frequently than in controls, with a trend toward increased frequency of bullying and stealing. The clinical and public mental health implications of these findings are discussed.     

Predicting alcohol dependence from multi-site brain structural measures

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.     

Using self-monitoring with an adolescent with disruptive classroom behavior: preliminary analysis of the role of adult feedback

Current research supports the effectiveness of self-monitoring strategies for addressing academic and behavioral challenges within educational settings. Although variations in procedures exist, frequently implementation of self-monitoring involves some form of adult feedback as a method of establishing accurate self-monitoring. To date, however, researchers have not systematically evaluated whether adult feedback is a necessary component for self-monitoring to be effective. In the current investigation, the influence of adult feedback on the effectiveness of self-monitoring was analyzed. The participant was a 13-year-old student receiving educational services in a special education school at a residential facility for youth with conduct problems. The effectiveness of self-monitoring with and without adult feedback was compared. Results suggest that adult feedback may be an important component for establishing self-monitoring as an effective intervention for behavior problems exhibited in academic settings.     

Teacher ratings of DSM-III-R symptoms for the disruptive behavior disorders.

Ratings were collected on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders. Teacher ratings were obtained for 931 boys in regular classrooms in grades K through 8 from around North America. Means and standard deviations for attention-deficit hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), and conduct disorder (CD) scales are reported by age. Frequencies of DSM-III-R symptoms are reported by age, and suggested diagnostic cutoffs are discussed. A factor analysis revealed three factors: one reflecting ODD and several CD symptoms, one on which ADHD symptoms of inattention loaded, and one comprised of ADHD impulsivity/overactivity symptoms. Conditional probability analyses revealed that several hallmark symptoms of ADHD had very poor predictive power, whereas combinations of symptoms from the two ADHD factors had good predictive power. Combinations of ODD symptoms also had very high predictive power. The limited utility of teacher ratings in assessing symptoms of conduct disorder in this age range is discussed.