Exploratory locomotion, a predictor of addiction vulnerability, is oligogenic in rats selected for this phenotype.

Artificially selected model organisms can reveal hidden features of the genetic architecture of the complex disorders that they model. Addictions are disease phenotypes caused by different intermediate phenotypes and pathways and thereby are potentially highly polygenic. High responder (bHR) and low responder (bLR) rat lines have been selectively bred (b) for exploratory locomotion (EL), a behavioral phenotype correlated with novelty-seeking, impulsive response to reward, and vulnerability to addiction, and is inversely correlated with spontaneous anxiety and depression-like behaviors. The rapid response to selection indicates loci of large effect for EL. Using exome sequencing of HR and LR rats, we identified alleles in gene-coding regions that segregate between the two lines. Quantitative trait locus (QTL) analysis in F2 rats derived from a bHR × bLR intercross confirmed that these regions harbored genes affecting EL. The combined effects of the seven genome-wide significant QTLs accounted for approximately one-third of the total variance in EL, and two-thirds of the variance attributable to genetic factors, consistent with an oligogenic architecture of EL estimated both from the phenotypic distribution of F2 animals and rapid response to selection. Genetic association in humans linked APBA2, the ortholog of the gene at the center of the strongest QTL, with substance use disorders and related behavioral phenotypes. Our finding is also convergent with molecular and animal behavioral studies implicating Apba2 in locomotion. These results provide multilevel evidence for genes/loci influencing EL. They shed light on the genetic architecture of oligogenicity in animals artificially selected for a phenotype modeling a more complex disorder in humans.

Firesetting and general criminal recidivism among a consecutive sample of Finnish pretrial male firesetters: A register-based follow-up study.

The rate of criminal reoffending among firesetters varies greatly. Our aim was to investigate firesetting and general criminal recidivism in a consecutive sample of Finnish males who were sent for a forensic psychiatric examination (FPE)1 after committing firesetting offenses. We also wanted to evaluate the relationships between psychopathy and criminal recidivism, and between schizophrenia-spectrum disorders and criminal recidivism. The sample comprised 113 firesetters with a mean age of 32.8 years, and the average follow-up time was 16.9 years. The FPE statements of the firesetters were reviewed and psychiatric diagnoses were collected. The psychopathy assessments were based on the 20-item Hare Psychopathy Checklist-Revised (PCL-R). Information on reoffending was gathered from the Finnish National Police Register. During the follow-up 20 (18%) persons were registered for a new firesetting and 84 (74%) for any new offense. Firesetters with high traits (PCL-R ≥ 25) of psychopathy were more likely than those with low traits (PCL-R < 25) to reoffend with any crime during the follow-up. The risk of general criminal recidivism was lower among firesetters with a schizophrenia-spectrum disorder than among those with non-psychotic disorders. Conclusively, both firesetting and general criminal-recidivism rates were high in this sample of offenders.

Fire-setting performed in adolescence or early adulthood predicts schizophrenia: a register-based follow-up study of pre-trial offenders.

BACKGROUND: Aggressive and disruptive behaviours often precede the onset of serious mental illnesses. Fire-setting is a type of crime that is associated with psychotic disorders. AIM: The aim of this prospective follow-up study was to investigate if fire-setting performed in adolescence or early adulthood was associated with future diagnoses of schizophrenia or schizoaffective disorder. METHODS: The consecutive sample consisted of 111 Finnish 15-25-year old males with fire-setting crimes, decreed to a pre-trial forensic psychiatric examination in 1973-1998, and showing no past nor current psychosis at the time of examination. For each firesetter, four age-, gender-, and place of birth-matched controls were randomly selected from the Central Population Register. The subjects were followed until the death of the individual, until they moved abroad, or until the end of 2012. RESULTS: Fourteen firesetters (12.6%) and five controls (1.1%) were diagnosed with either schizophrenia or schizoaffective disorder later in life, corresponding to a hazard ratio of 12.5. The delay between the fire-setting offense and the future diagnosis was on average nearly 10 years. CONCLUSIONS: Young male offenders undergoing a forensic psychiatric examination because of fire-setting crimes had a significant propensity for schizophrenia and schizoaffective disorder. Accurate assessments should be made both during imprisonment and later in life to detect possible psychotic signs in these individuals.

The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males.

Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and whether the serotonin 2B (5-HT2B) receptor and testosterone have a role in energy metabolism. A cohort of subjects belonging to a founder population that included 98 ASPD males, aged 25-30, was divided into groups based on the presence of a heterozygous 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*; n = 9) or not (n = 89). Serum glucose and insulin levels were measured in a 5 h oral glucose tolerance test (75 g) and indices describing IR, IS, and beta cell activity were calculated. Body mass index (BMI) was also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were measured in cerebrospinal fluid, and testosterone levels from serum. An IR-like state comprising high IR, low IS, and high beta cell activity indices was observed among ASPD subjects without the HTR2B Q20* allele. By contrast, being an ASPD HTR2B Q20* carrier appeared to be preventive of these pathophysiologies. The HTR2B Q20* allele and testosterone predicted lower BMI independently, but an interaction between HTR2B Q20* and testosterone lead to increased insulin sensitivity among HTR2B Q20* carriers with low testosterone levels. The HTR2B Q20* allele also predicted reduced beta cell activity and enhanced glucose metabolism. Reduced 5-HT2B receptor function at low or normal testosterone levels may be protective of obesity. Results were observed among Finnish males having an antisocial personality disorder, which limits the generality.

Hospital-treated suicide attempts among Finnish fire setters: a follow-up study.

BACKGROUND: High rates of attempted and completed suicide have been reported among offenders, but there has been little attention in this respect to fire setters specifically. Aim Our aim was to investigate hospital-treated suicide attempts among male fire setters. METHODS: For each of a consecutive series of 441 pre-trial fire setters, four controls matched for age, gender and place of birth were randomly selected from the Central Population Register. Data on hospitalisation and causes of death over a 39-year period were obtained from the Finnish national registers. RESULTS: The prevalence of suicide attempts was significantly higher among fire setters than among controls. Approximately every fifth fire setter had made at least one suicide attempt which had required hospital treatment. The most common method chosen was intentional self-poisoning or exposure to noxious substances. More than 1 in 10 fire setters with at least one hospitalisation for suicide-related behaviour eventually completed suicide. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: More attention should be paid to detecting and managing suicidal behaviours among fire setters as they are a high-risk group and accurate identification of their needs in this respect may not only be life-saving but also reduce recidivism. Copyright © 2015 John Wiley & Sons, Ltd.

Psychopathic traits among a consecutive sample of Finnish pretrial fire-setting offenders.

BACKGROUND: Psychopathy, a severe disorder of personality, is well represented in the criminal and forensic psychiatric population and is significantly associated with increased risk of violence and crime. Fire-setting is a major source of property damage, injury, and death in many Western countries. The primary aim of this study was to evaluate psychopathic traits in a consecutive sample of Finnish male pretrial fire-setting offenders. Further, we wanted to investigate whether fire-setting recidivists show higher traits of psychopathy than one-time firesetters and whether exclusive firesetters show lower traits of psychopathy than those with criminal versatility. METHODS: The forensic psychiatric examination statements for male firesetters who underwent a pretrial forensic psychiatric evaluation during a 10-year period (1989 -1998) were reviewed. The sample comprised 129 firesetters with normal IQ, 41 of whom were fire-setting recidivists. Fifty men were exclusive firesetters. Assessment of psychopathy-like personality character was performed using the 20-item Hare Psychopathy Checklist-Revised. RESULTS: Two individuals (1.6%, 95% Cl: 0.0-3.7) scored ≥30 points and 19 (14.7%, 95% Cl: 8.6-20.8) ≥ 25 points on the PCL-R. The mean PCL-R total score was 16.1 (SD 6.88), the mean Factor 1 score 5.0 (SD 3.41), and the mean Factor 2 score 9.9 (SD 3.86). No significant differences emerged between the recidivists and the one-time firesetters. The versatile firesetters exhibited significantly higher mean total and factor scores than the exclusive ones. CONCLUSION: Among firesetters, there is a subgroup of persons with significant psychopathic traits, which should be recognized in legal and health care organizations. Although psychopathy was associated with greater criminal versatility, it bore no relationship to fire-setting recidivism.

Basal insulin secretion, PCL-R and recidivism among impulsive violent alcoholic offenders.

Current risk assessment tools have a moderate predicting value for violence. Their power may be enhanced with certain biological indicators, which may serve as predictors of recidivistic violence itself. The aim of our study was to determine the strength of serum insulin levels to predict violence, and compare these results with those from the Revised Psychopathy Checklist (PCL-R). The study population consisted of 105 Finnish alcoholics who were severely violent offenders, recruited from 1991 to 1998. After exclusion, 75 cases were followed until March 2008, or until a new offense was registered. Cox regression analysis was used to evaluate the risk of recidivism. The age and weight adjusted effect of insulin to recidivism risk showed a 7.2% increase for each International Unit (IU), or 19% for the mean difference (2.5IU) between recidivists and non-recidivist, which corresponds to a medium effect size (Cohen׳s d=0.46). Adjusting the insulin model with PCL-R factor 1 enhanced the predictive power slightly. Serum fasting insulin level was equivalent to the PCL-R factor 2 score as a predictor, and better than the total PCL-R score. However, the significance of these results was too low for predicting recidivism in the process of judicial decision-making.

Mortality of firesetters: a follow-up study of Finnish male firesetters who underwent a pretrial forensic examination in 1973-1998.

Little is known about mortality among firesetters. However, they hold many risk factors associated with elevated mortality. This study aimed to investigate mortality rates and patterns in the course of a 39-year follow-up of a consecutive sample (n=441) of pretrial male firesetters evaluated in a forensic psychiatric unit in Finland. For each firesetter, four controls matched for age, sex and place of birth were randomly selected from the Central Population Register. Mortality data was obtained from the Causes of Death statistics. By the end of the follow-up period, 48.0% of the firesetters and 22.0% of the controls had died (OR 2.47, 95% CI 2.00-3.05). Altogether, 24.1% of the firesetters and 17.6% of the control subjects had died of natural causes (OR 1.49, 95% CI 1.16-1.92), whereas 20.9% and 3.8% respectively, died an unnatural death (OR 6.71, 95% CI 4.79-9.40). Alcohol-related deaths were more frequent among firesetters than controls. Our findings confirm that fire-setting behavior is associated with high mortality. More attention must be paid to the treatment of suicidality, psychiatric comorbidities and alcohol use disorders within this group both during and after their sentences.

Decreased GABA(A) benzodiazepine binding site densities in postmortem brains of Cloninger type 1 and 2 alcoholics.

Ethanol modulates the GABA(A) receptor to cause sedative, anxiolytic and hypnotic effects that are qualitatively similar to benzodiazepines and barbiturates. The aim of this study was to explore if GABA(A) receptor density is altered in post-mortem brains of anxiety-prone Cloninger type 1 and socially hostile type 2 alcoholic subtypes when compared to controls. The GABA(A) binding site density was measured by whole-hemisphere autoradiography with tritium labeled flunitrazepam ([(3)H]flunitrazepam) from 17 alcoholic (nine type 1, eight type 2) and 10 non-alcoholic post-mortem brains, using cold flumazepam as a competitive ligand. A total of eight specific brain areas were examined. Alcoholics displayed a significantly (p < 0.001, bootstrap type generalizing estimating equations model) reduced [(3)H]flunitrazepam binding site density when compared to controls. When localized, type 2 alcoholics displayed a significantly (p ≤ 0.05) reduced [(3)H]flunitrazepam binding site density in the internal globus pallidus, the gyrus dentatus and the hippocampus, whereas type 1 alcoholics differed from controls in the internal globus pallidus and the hippocampus. While previous reports have demonstrated significant alterations in dopaminergic and serotonergic receptors between type 1 and type 2 alcoholics among these same subjects, we observed no statistically significant difference in [(3)H]flunitrazepam binding site densities between the Cloninger type 1 and type 2 alcoholics.

Psychopathy, PCL-R, and MAOA genotype as predictors of violent reconvictions.

The Revised Psychopathy Checklist (PCL-R) has shown a moderate association with violence. The efficacy of PCL-R in varying monoamine oxidase A (MAOA) genotypes is, however, unexamined. The aim of this study was to investigate the effect of PCL-R and psychopathy on the risk for violent reconvictions among 167 MAOA genotyped alcoholic offenders. Violent reconvictions and PCL-R scores among violent offenders were assessed after a 7-year non-incarcerated follow-up. Regression analysis was used to evaluate the alcohol exposure and age-adjusted effect of PCL-R score and psychopathy on the risk for reconvictions among differing MAOA genotypes. Results suggest that the PCL-R total score predicts impulsive reconvictions among high-activity MAOA offenders (6.8% risk increase for every one-point increase in PCL-R total score, P = 0.015), but not among low-activity MAOA offenders, whereas antisocial behavior and attitudes predicted reconvictions in both genotypes (17% risk increase among high-activity MAOA offenders and 12.8% increase among low-activity MAOA offenders for every one-point increase in factor 2 score). Both narcissistic self-image with related interpersonal style (factor 1 score) and psychopathy (PCL-R ≥ 30) failed to predict future violence. Results suggest that the efficacy of PCL-R is altered by MAOA genotype, alcohol exposure, and age, which seems important to note when PCL-R is used for risk assessments that will have legal or costly preventive work consequences.

Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations.

BACKGROUND: Ethanol is metabolized by 2 rate-limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses to maximize the chances of capturing functional variation. METHODS: Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case control sample sizes were the following: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72. RESULTS: In all four populations, as well as HapMap populations, 5 haplotype blocks were identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B; (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks and ALDH2 by 1 block. No haplotype or SNP association results were significant after correction for multiple comparisons; however, several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. CONCLUSIONS: The systematic evaluation of alcohol-metabolizing genes in four non-East Asian populations has shown only modest associations with AD, largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin yang haplotypes in several populations warrants further study.

A population-specific HTR2B stop codon predisposes to severe impulsivity.

Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.

MAOA alters the effects of heavy drinking and childhood physical abuse on risk for severe impulsive acts of violence among alcoholic violent offenders.

BACKGROUND: A polymorphism in the promoter region of the monoamine oxidase A gene (MAOA) has been shown to alter the effect of persistent drinking and childhood maltreatment on the risk for violent and antisocial behaviors. These findings indicate that MAOA could contribute to inter-individual differences in stress resiliency. METHODS: Recidivism in severe violent crimes was assessed after 8 years of nonincarcerated follow-up in a male sample of 174 impulsive Finnish alcoholic violent offenders, the majority of whom exhibited antisocial (ASPD) or borderline personality disorder (BPD) or both. We examined whether MAOA genotype alters the effects of heavy drinking and childhood physical abuse (CPA) on the risk for committing impulsive recidivistic violent crimes. RESULTS: Logistic regression analyses showed that both heavy drinking and CPA were significant independent predictors of recidivism in violent behavior (OR 5.2, p = 0.004 and OR 5.3, p = 0.003) among offenders having the high MAOA activity genotype (MAOA-H), but these predictors showed no effect among offenders carrying the low MAOA activity genotype (MAOA-L). CONCLUSION: Carriers of the MAOA-H allele have a high risk to commit severe recidivistic impulsive violent crimes after exposure to heavy drinking and CPA.

Recidivistic offending and mortality in alcoholic violent offenders: a prospective follow-up study.

Predictive data supporting prevention of violent criminality are scarce. We examined risk factors for recidivism and mortality among non-psychotic alcoholic violent offenders, the majority having antisocial or borderline personality disorders, or both, which is a group that commits the majority of violent offences in Finland. Criminal records and mortality data on 242 male alcoholic violent offenders were analysed after a 7- to 15-year follow-up, and compared between themselves and with those of 1210 age-, sex- and municipality-matched controls. Recidivism and mortality rates were high. The risk of recidivistic violence was increased by antisocial or borderline personality disorder, or both, childhood maltreatment, and a combination of these. A combination of borderline personality disorder and childhood maltreatment was particularly noxious, suggesting an additive risk increase for a poor outcome. Accurate diagnosis and careful childhood interview may help to predict recidivism and premature death.

Low non-oxidative glucose metabolism and violent offending: an 8-year prospective follow-up study.

Violent offenders have abnormalities in their glucose metabolism as indicated by decreased glucose uptake in their prefrontal cortex and a low blood glucose nadir in the glucose tolerance test. We tested the hypothesis that low non-oxidative glucose metabolism (NOG) predicts forthcoming violent offending among antisocial males. Glucose metabolism was measured using the insulin clamp method among 49 impulsive, violent, antisocial offenders during a forensic psychiatric examination. Those offenders who committed at least one new violent crime during the 8-year follow-up had a mean NOG of 1.4 standard deviations lower than non-recidivistic offenders. In logistic regression analysis, NOG alone explained 27% of the variation in the recidivistic offending. Low non-oxidative metabolism may be a crucial component in the pathophysiology of habitually violent behavior among subjects with antisocial personality disorder. This might suggest that substances increasing glycogen formation and decreasing the risk of hypoglycemia might be potential treatments for impulsive violent behavior.

HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power--an intermediate phenotype for alcoholism and co-morbid behaviors.

Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD+ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD+ASPD (P=.004). In the Bethesda sample, the same allele predicted lower alpha power (P=7.37e(-5)). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P=.03). One haplotype in the haplotype block at the 3' region of the gene that included rs3782025 was associated with AUD+ASPD in the Finns (P=.02) and with reduced alpha power in the Bethesda population (P=.00009). Another haplotype in this block was associated with alpha power among PI (P=.03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics.

Effects of MAOA-genotype, alcohol consumption, and aging on violent behavior.

BACKGROUND: Environmental factors appear to interact with a functional polymorphism (MAOA-LPR) in the promoter region of the monoamine oxidase A gene (MAOA) in determining some forms of antisocial behavior. However, how MAOA-LPR modulates the effects of other factors such as alcohol consumption related to antisocial behavior is not completely understood. METHODS: This study examines the conjunct effect of MAOA-LPR, alcohol consumption, and aging on the risk for violent behavior. Recidivism in severe impulsive violent behavior was assessed after 7 to 15 years in a sample of 174 Finnish alcoholic offenders, the majority of whom exhibited antisocial or borderline personality disorder or both, and featured impulsive temperament traits. RESULTS: The risk for committing new acts of violence increased by 2.3% for each kilogram of increase in yearly mean alcohol consumption (p = 0.004) and decreased by 7.3% for every year among offenders carrying the high activity MAOA genotype. In contrast, alcohol consumption and aging failed to affect violent behavior in the low activity MAOA genotyped offenders. MAOA-LPR showed no main effect on the risk for recidivistic violence. CONCLUSIONS: Violent offenders carrying the high activity MAOA genotype differ in several ways from carriers with the low activity MAOA risk allele previously associated with antisocial behavior. Finnish high activity MAOA genotyped risk alcoholics exhibiting antisocial behavior, high alcohol consumption, and abnormal alcohol-related impulsive and uncontrolled violence might represent an etiologically distinct alcohol dependence subtype.

Female impulsive aggression: a sleep research perspective.

The rate of violent crimes among girls and women appears to be increasing. One in every five female prisoners has been reported to have antisocial personality disorder. However, it has been quite unclear whether the impulsive, aggressive behaviour among women is affected by the same biological mechanisms as among men. Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Most psychiatric disorders are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep (SWS), the physiologically significant, refreshing part of sleep. Among men with antisocial behaviour with severe aggression, on the contrary, increased SWS has been reported, reflecting either specific brain pathology or a delay in the normal development of human sleep patterns. In our preliminary study among medication-free, detoxified female homicidal offenders with antisocial personality disorder, the same profound abnormality in sleep architecture was found. From the perspective of sleep research, the biological correlates of severe impulsive aggression seem to share similar features in both sexes.

GABRG1 and GABRA2 as independent predictors for alcoholism in two populations.

The chromosome 4 cluster of GABA(A) receptor genes is predominantly expressed in the brain reward circuitry and this chromosomal region has been implicated in linkage scans for alcoholism. Variation in one chromosome 4 gene, GABRA2, has been robustly associated with alcohol use disorders (AUD) although no functional locus has been identified. As HapMap data reveal moderate long-distance linkage disequilibrium across GABRA2 and the adjacent gene, GABRG1, it is possible that the functional locus is in GABRG1. We genotyped 24 SNPs across GABRG1 and GABRA2 in two population isolates: 547 Finnish Caucasian men (266 alcoholics) and 311 community-derived Plains Indian men and women (181 alcoholics). In both the Plains Indians and the Caucasians: (1) the GABRG1 haplotype block(s) did not extend to GABRA2; (2) GABRG1 haplotypes and SNPs were significantly associated with AUD; (3) there was no association between GABRA2 haplotypes and AUD; (4) there were several common (>or=0.05) haplotypes that spanned GABRG1 and GABRA2 (341 kb), three of which were present in both populations: one of these ancestral haplotypes was associated with AUD, the other two were more common in non-alcoholics; this association was determined by GABRG1; (5) in the Finns, three less common (<0.05) extended haplotypes showed an association with AUD that was determined by GABRA2. Our results suggest that there are likely to be independent, complex contributions from both GABRG1 and GABRA2 to alcoholism vulnerability.

Sleep in conduct-disordered adolescents--a polysomnographic and spectral power analysis study.

The aim of the present study was to characterize sleep in conduct-disordered adolescents using polysomnography and spectral power analysis. The two hypotheses were that conduct disorder would be associated with objective sleep problems, and that conduct disorder--as a precursor of adult antisocial personality disorder--would be associated with the same kind of abnormal sleep architecture, with both increased deep sleep and delta power, as previously reported in antisocial personality disorder. The patients consisted of 15 adolescents (age range 13-17 years, mean age 14.7 years) with histories of antisocial behavior so functionally impairing that they were ordered by child welfare to undergo a psychosocial evaluation in a closed social services ward. The healthy age-matched controls comprised 20 volunteers recruited with a newspaper advertisement. Opposite to earlier subjective sleep studies among conduct-disordered children, no significant differences in sleep parameters were observed between the two groups. The adolescents with conduct disorder slept a little bit longer, but the percentage amount of different sleep stages did not differ significantly between the two groups. Relative spectral power of sleep, delta power in particular, was similar in both groups, assessed in total sleep time as well as in first half of it. Different alternative explanations for these findings are discussed.