Switching to the bingeing/purging subtype of anorexia nervosa is frequently associated with suicidal attempts

OBJECTIVE: Anorexia nervosa has the highest suicide mortality ratio of psychiatric disorders, suicide being associated with many factors. We assessed the first lifetime occurrence of these factors taking into account their possible overlap. METHOD: Three hundred and four in- and out-patients with anorexia nervosa (DSM-IV) were systematically recruited in three hospitals of Paris suburbs, between December 1999 and January 2003. Patients were assessed by a face-to-face interview (DIGS). Current eating disorder dimensions were measured, and patients interviewed by a trained clinician to assess minimal BMI and, retrospectively, the age at which anorexia nervosa, major depressive disorder, anxiety disorders and switch to bingeing/purging type occurred for the first time, if applicable. RESULTS: Major depressive disorder (p<0.001) and subtype switch from the restrictive to the bingeing/purging type (p<0.001) were the two factors significantly more frequently occurring before suicidal attempts, and remained involved when a multivariate analysis is performed, whether syndromic or dimensional measures are being used. Taking into account lifetime occurrence with a survival analysis, the switch to bingeing/purging type of anorexia appears as a major predictive factor, with a large increase of the frequency of suicidal attempts (OR=15) when compared to patients with neither major depressive disorder nor bingeing/purging type. CONCLUSIONS: Bingeing/purging type of anorexia nervosa is largely associated with suicidal attempts, and may deserve specific attention. If confirmed on a prospectively designed study, these results would argue for early detection and/or more intensive and specific therapeutic intervention on this aspect of bingeing and purging behaviors.     

Naloxone reverses disinhibitory/aggressive behavior in 5,7-DHT-lesioned rats; involvement of GABA(A) receptor blockade?

Effective medical treatment for impulsive aggression and several impulse control disorders is needed. Disinhibited, impulsive behavior of e.g. murderers, arsonists, suicidal patients, and patients suffering from antisocial personality or substance abuse disorders has been associated with signs of a deficiency in brain serotonin (5-HT) systems. Depletion of brain 5-HT consistently produces disinhibition and aggression also in experimental animals. The present series of experiments using a modified Vogel’s conflict test indicates that the disinhibitory behavior of 5-HT-lesioned rats can be reversed by the commonly used opiate receptor antagonist naloxone at doses (0.1–5.0 mg/kg, s.c.) that do not significantly affect behavior in sham-lesioned controls. Moreover, this effect of naloxone, which resembles that previously observed after administration of negative modulators of γ-aminobutyric acid_A (GABA_A)/benzodiazepine receptor complexes, was reversed by a low inert dose (2.0 mg/kg, i.p.) of amobarbital. Furthermore, both naloxone (5.0 mg/kg, s.c.) and Ro 15-4513 (1.0 mg/kg, p.o.; a partial inverse agonist at benzodiazepine receptors) significantly decreased the number of attacks and the time spent in aggressive acts in 5,7-DHT-lesioned male residents. These results taken together with previous behavioral and neurochemical data suggest that the behavioral effects of naloxone observed here may involve an antagonistic action at brain γ-aminobutyric acid_A (GABA_A)/benzodiazepine receptor complexes. Thus, naloxone, its stable analogue naltrexone or other weak negative modulators of brain GABA_A/benzodiazepine receptor complexes may represent a new pharmacological principle for the treatment of impulse control disorders.     

Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers

Rationale: Impulsivity is implicated in drug dependence. Recent studies show problems with alcohol and opioid dependence are associated with rapid discounting of the value of delayed outcomes. Furthermore, discounting may be particularly steep for the drug of dependence. Objectives: We determined if these findings could be extended to the behavior of cigarette smokers. In particular, we compared the discounting of hypothetical monetary outcomes by current, never, and ex-smokers of cigarettes. We also examined discounting of delayed hypothetical cigarettes by current smokers. Methods: Current cigarette smokers (n=23), never-smokers (n=22) and ex-smokers (n=21) indicated preference for immediate versus delayed money in a titration procedure that determined indifference points at various delays. The titration procedure was repeated with cigarettes for smokers. The degree to which the delayed outcomes were discounted was estimated with two non-linear decay models: an exponential model and a hyperbolic model. Results: Current smokers discounted the value of delayed money more than did the comparison groups. Never- and ex-smokers did not differ in their discounting of money. For current smokers, delayed cigarettes lost subjective value more rapidly than delayed money. The hyperbolic equation provided better fits to the data than did the exponential equation for 74 out of 89 comparisons. Conclusions: Cigarette smoking, like other forms of drug dependence, is characterized by rapid loss of subjective value for delayed outcomes, particularly for the drug of dependence. Never- and ex-smokers could discount similarly because cigarette smoking is associated with a reversible increase in discounting or due to selection bias. Received: 3 March 1999 / Final version: 11 May 1999     

Bidirectional Relations of Impulsive Personality and Alcohol Use Across Three Waves of Data Collection

Objective: To explore the bidirectional relations between alcohol use and three impulsive personality traits, to advance understanding of risk processes. Participants: 525 college students (mean age = 18.95 years) recruited in August 2008 and 2009 and followed up annually for three years. Methods: Personality and past/current substance use were assessed. Results: T2 sensation seeking mediated the predictive relationship between T1 and T3 alcohol use, and T2 alcohol use mediated the predictive relationship between T1 and T3 sensation seeking. In addition, T2 alcohol problems mediated the predictive relationship between T1 alcohol use and T3 negative urgency. Conclusions: Findings support a bidirectional relationship between sensation seeking and alcohol use, and drinking anticipates drinking problems, which predict increases in negative urgency. For some individuals, there appears to be an ongoing process of increased risk in the form of increases in both drinking and high-risk personality traits.     

Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders

The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P < 0.0001) association between low-activity MAOA-uVNTR alleles and violent crime. This association was replicated in the group of Caucasian violent offenders (P < 0.01), but reached only a marginal trend (P = 0.08) in their African American counterparts. While violent crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P < 0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors.     

Working memory as a moderator of impulsivity and alcohol involvement: Testing the cognitive-motivational theory of alcohol use with prospective and working memory updating data

Research consistently shows that individuals high in impulsivity are at increased risk for excessive alcohol use and alcohol-related problems including alcohol use disorders (AUDs). Recent theorizing posits that working memory (WM) ability might moderate this association, but extant studies have suffered from methodological shortcomings, particularly mischaracterizing WM as a single, unitary construct and using only cross-sectional designs. This paper reports two studies that attempted to replicate and extend previous investigations of the relationship between WM, impulsivity, and alcohol involvement using two independent samples. Study 1 used a large (N = 489 at baseline), prospective cohort of college students at high and low risk for AUD to investigate interactions between WM capacity and impulsivity on cross-sectional and prospective alcohol involvement. Study 2 used a large (N = 420), cross-sectional sample of participants in an alcohol challenge study to investigate similar interactions between WM updating and impulsivity on recent alcohol involvement. Whereas Study 1 found that WM capacity moderates the relationship between some measures of impulsivity and alcohol involvement, with effects prospectively predicting alcohol involvement for up to three years, Study 2 did not find similar moderation effects when using measures of WM updating. These findings highlight the multifaceted nature of WM, which is often overlooked in the alcohol and impulsivity literature.     

Composite impulsivity-related domains in college students

Impulsivity is a complex, multidimensional construct with prior theoretically and empirically derived characterizations of impulsivity-related behaviors varying considerably among studies. We assessed college students (N = 440) longitudinally with five impulsivity-related self-reported assessments and two computerized behavioral measures. Using a combination of exploratory and confirmatory factor analysis (CFA), we derived then validated several composite impulsivity-related domains (CIRDs). These factors replicated, in large part, findings from a previous study conducted by our group in an independent sample that used a similar analytical approach. The four CIRDs derived in current study are: ‘Impulsive action’, ‘Approach/Appetite Motivation’, ‘Impulsivity/Compulsivity’ and ‘Experience and thrill seeking/Fearlessness’. Subsequent psychometric analyses found these CIRDs were relatively stable over the two-year period. Moreover, multiple regression analysis found that CIRD profiles associated with clinical and behavioral characteristics including anxiety, depression, attention deficit hyperactivity disorder and substance use symptomology. Overall, our data suggest that empirically-derived CIRDs have potential for organizing previous impulsivity-related constructs into a more naturalistic framework where distinct constructs are often expressed together in the same individuals. This framework might facilitate future research of neuropsychiatric disorder risk and etiology.     

NOS1 and SNAP25 polymorphisms are associated with Attention-Deficit/Hyperactivity Disorder symptoms in adults but not in children

Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopmental genes could explain, at least partly these differences. The aim of the present study was to examine possible associations between polymorphisms in SNAP25, MAP1B and NOS1 genes and ADHD symptoms in Brazilian samples of children/adolescents and adults with ADHD. The youth sample consisted of 301 patients whereas the adult sample comprises 485 individuals with ADHD. Diagnoses of ADHD and comorbidities were based on the Diagnostic and Statistical Manual of Mental Disorders–4th edition criteria. The Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) was applied by psychiatrists blinded to genotype. The total SNAP-IV scores were compared between genotypes. Impulsivity SNAP-IV scores were also compared according to NOS1 genotypes. Adult patients homozygous for the C allele at SNAP25 rs8636 showed significantly higher total SNAP-IV scores (F = 11.215; adjusted P-value = 0.004). Impulsivity SNAP-IV scores were also significantly different according to NOS1 rs478597 polymorphisms in adults with ADHD (F = 6.282; adjusted P-value = 0.026). These associations were not observed in children and adolescents with ADHD. These results suggest that SNAP25 and NOS1 genotypes influence ADHD symptoms only in adults with ADHD. Our study corroborates previous evidences for differences in the genetic contribution to adult ADHD compared with childhood ADHD.