Personalized Treatment of Antisocial Personality Disorder with Inherent Impulsivity and Severe Alcoholism: A Brief Review of Relevant Literature

Antisocial personality disorder (ASPD) is a persistent psychiatric disorder. Behaviors and emotions deviate from the norm. Inherent impulsivity, comorbid alcohol dependence, and violation of laws cause severe challenges at individual and societal levels. Both environment and heritability alter the risk for ASPD. Research shows that specific biologic changes predispose to this disorder. Biological factors may lead to novel possibilities to treat and alleviate symptoms with medications or nutritional means. However, treatment of ASPD meets particular challenges due to the inherent symptoms of the disorder, and firm evidence-based personalized treatments are scant. This chapter describes the disorder and associated adverse outcomes in life such as recurrent violent behavior and increased mortality. Moreover, treatment possibilities are discussed covering risk assessment, medication, psychotherapy, and nutrition

Uusintaväkivallan ja kuolleisuuden riskitekijät

Acts of violence lays a great burden on humankind. The negative effects of violence could be relieved by accurate prediction of violent recidivism. However, prediction of violence has been considered an inexact science hampered by scare knowledge of its causes. The study at hand examines risk factors of violent reconvictions and mortality among 242 Finnish male violent offenders exhibiting severe alcoholism and severe externalizing personality disorders. The violent offenders were recruited during a court-ordered 2-month inpatient mental status examination between 1990—1998. Controls were 1210 individuals matched by sex-, age-, and place of birth. After a 9-year non-incarcerated follow-up criminal register and mortality data were obtained from national registers. Risk analyses were applied to estimate odds and relative risk for recidivism and mortality. Risk variables that were included in the analyses were antisocial personality disorder (ASPD), borderline personality disorder (BPD), a comorbidity of ASPD and BPD, childhood adversities, alcohol consumption, age, and monoamine oxidase A (MAOA) genotype. In addition to risk analyses, temperament dimensions (Tridimensional Personality Questionnaire [TPQ]) were assessed. The prevalence of recidivistic acts of violence (32%) and mortality (16%) was high among the offenders. Severe personality disorders and childhood adversities increased the risk for recidivism and mortality both among offenders (OR 2.0–10.4) and in comparison between offenders and controls (RR 4.3–53.0). Offenders having BPD and a history of childhood maltreatment emerged as a group with a particularly poor prognosis. MAOA altered the effects of alcohol consumption and ageing. Alcohol consumption (+2.3%) and age (–7.3%) showed significant effects on the risk for violent reconvictions among the high activity MAOA (MAOA-H) offenders, but not among the low activity MAOA (MAOA-L) offenders. The offenders featured temperament dimensions of high novelty seeking, high harm avoidance, and low reward dependence matching Cloninger’s definition of explosive personality. The fact that the risk for recidivistic acts of violence and mortality accumulated into clearly defined subgroups supports future efforts to provide for evidence based violence prevention and risk assessments among violent offenders.Väkivalta kuormittaa ihmiskuntaa suuresti. Väkivallan moninaisia kielteisiä vaikutuksia pystyisi lieventämään parantamalla väkivallan ennustetarkkuutta. Epätietoisuus väkivallan perimmäisistä syistä vaikeuttaa väkivallan ennustamista. Tämä tutkimus tarkastelee uusintaväkivallan ja kuolleisuuden riskitekijöitä suomalaisessa mies väkivaltarikollisaineistossa, joka kerättiin vuosina 1990—1998 mielentilatutkimusten yhteydessä. Aineiston 242 henkilöllä oli keskimäärin vaikea alkoholismi ja vakava persoonallisuushäiriö. Verrokkiryhmän muodosti 1210 sukupuoli, ikä- ja syntymäpaikkakunta vakioitua yksilöä. Yhdeksän vuoden seuranta-ajan jälkeen suoritettiin riskianalyysit saatujen rikosrekisteriotteiden (Oikeusrekisterikeskus) ja kuolleisuustietojen (Tilastokeskus) perusteella. Analyyseissä käytettiin riskitekijöinä antisosiaalista persoonallisuushäiriötä (ASPD), epävakaata persoonallisuushäiriötä (BPD), ASPD:n ja BPD:n samanaikaista esiintyvyyttä, lapsuuden kielteisiä olosuhteita, alkoholin kulutusta, ikää ja monoamiinioksidaasi A (MAOA) genotyyppiä. Riskianalyysien lisäksi arvioitiin temperamenttia (Tridimensional Personality Questionnaire [TPQ]). Uusintaväkivallan (32%) ja kuolleisuuden (16%) esiintyvyys oli korkea väkivaltarikollisten parissa. Vaikeat persoonallisuushäiriöt ja lapsuuden kielteiset olosuhteet lisäsivät uusintaväkivallan ja kuolleisuuden riskiä sekä väkivaltarikollisten keskinäisissä vertailuissa (riskikerroin 2.0–10.4) että verratessa väkivaltarikollisia verrokkeihin (riskisuhde 4.3–53.0). Lapsena kaltoinkohdeltujen BPD henkilöiden ennuste oli erityisen huono. MAOA genotyyppi vaikutti alkoholin kulutuksen ja iän ennustekykyyn. Alkoholin kulutus (+2.3%) ja ikä (–7.3%) vaikuttivat uusintaväkivaltariskiin korkean MAOA aktiviteetin (MAOA-H) henkilöissä, mutta ei matalan MAOA aktiviteetin (MAOA-L) henkilöissä. Väkivaltarikollisten temperamentille oli tyypillistä korkea virikehakuisuus/impulsiivisuus/kaoottisuus (novelty seeking), korkea ahdistuneisuus (harm avoidance) ja matala sosiaalistuminen (reward dependence), mikä vastaa Cloningerin määritelmää eksplosiivisesta persoonallisuudesta. Uusintaväkivallan ja kuolleisuuden riskit kasaantuivat selviin väkivaltarikollisten alaryhmiin. Vaikeiden persoonallisuushäiriöiden diagnostisointi, lapsuuden ympäristön arviointi, alkoholikulutuksen kartoitus ja MAOA genotyypin määritys saattavat tulevaisuudessa olla uusintaväkivaltaa ja kuolleisuutta ennaltaehkäiseviä sekä vaarallisuusarvioita tarkentavia keinoja.Våld utgör en stor belastning för mänskligheten. De mångahanda negativa återverkningarna av våldshandlingar kunde lindras genom att förbättra precisionen på förutsägelser om våldshandlingar. Ovisshet om de bakomliggande orsakerna till våld gör det emellertid svårt att förutsäga våldshandlingar. Denna studie granskar riskfaktorer för upprepat våld och dödlighet bland 242 finska våldsbrottslingar, vilka led av svår alkoholism och svåra personlighetsstörningar. Materialet samlades i samband med sinnesundersökningar åren 1990—1998. Kontrollgruppen bestod av 1210 ålders- och födelseortstandardiserade män. Efter en uppföljningstid på 9 år genomfördes riskanalyser på basis av brottsregisterutdrag (Rättsregistercentralen) och dödlighetsuppgifter (Statistikcentralen). I de statistiska analyserna användes antisocial personlighetsstörning (ASPD), borderline personlighetsstörning (BDP), samtidig förekomst av ASPD och BPD, negativa barndomsvillkor, alkoholkonsumtion, ålder och monoaminoxidas A (MAOA) genotyp som riskfaktorer. Förutom riskanalyserna, bedömdes temperaments dimensioner (Tridimensional Personality Questionnaire [TPQ]). Förekomsten av upprepad våldsbrottslighet (32%) och dödlighet (16%) var hög bland våldsbrottslingarna. Svåra personlighetsstörningar och negativa barndomsvillkor ökade risken för upprepat våld och dödlighet både internt bland våldsbrottslingar (OR 2.0–10.4) och vid en jämförelse av våldsbrottslingarna med kontrollgruppen (RR 4.3–53.0). Individer med BDP och vilka blivit illa behandlade som barn framstod som en grupp med en särskilt dålig prognos. MAOA genotypen påverkade alkoholkonsumtionens och ålderns prognosförmåga. Alkoholkonsumtionen (+2.3 %) och åldern (–7.3%) påverkade märkbart risken för upprepade våldshandlingar hos individer med hög MAOA aktivitet (MAOA-H), emedan det inte gjorde det hos individer med låg MAOA aktivitet (MAOA-L). Våldsbrottslingarnas temperament präglades av en hög benägenhet att söka stimulans/impulsivitet/kaotiskhet (novelty seeking), stor ångestfylldhet (harm avoidance) och låg socialisation (reward dependence), vilket motsvarar Cloningers definition av explosiv personlighet. Risken för upprepade våldshandlingar och dödlighet skockade sig i vissa undergrupper av våldsbrottslingar. Diagnostisering av personlighetsstörningar, bedömning av barndomsmiljön, kartläggning av alkoholkonsumtionen och analys av MAOA genotyp kan därför i framtiden förebygga upprepat våld och dödlighet samt öka precisionen av farlighets bedömningar

Nonisothermal nucleation in the gas phase is driven by cool subcritical clusters

Nucleation of clusters from the gas phase is a widely encountered phenomenon, yet rather little is understood about the underlying out-of-equilibrium dynamics of this process. The classical view of nucleation assumes isothermal conditions where the nucleating clusters are in thermal equilibrium with their surroundings. However, in all first-order phase transitions, latent heat is released, potentially heating the clusters and suppressing the nucleation. The question of how the released energy affects cluster temperatures during nucleation as well as the growth rate remains controversial. To investigate the nonisothermal dynamics and energetics of homogeneous nucleation, we have performed molecular dynamics simulations of a supersaturated vapor in the presence of thermalizing carrier gas. The results obtained from these simulations are compared against kinetic modeling of isothermal nucleation and classical nonisothermal theory. For the studied systems, we find that nucleation rates are suppressed by two orders of magnitude at most, despite substantial release of latent heat. Our analyses further reveal that while the temperatures of the entire cluster size populations are elevated, the temperatures of the specific clusters driving the nucleation flux evolve from cold to hot when growing from subcritical to supercritical sizes and resolve the apparent contradictions regarding cluster temperatures. Our findings provide unprecedented insight into realistic nucleation events and allow us to directly assess earlier theoretical considerations of nonisothermal nucleation.Peer reviewe

Beneficial Effects of GLP-1 Agonist in a Male With Compulsive Food-Related Behavior Associated With Autism

Individuals with autism spectrum disorder (ASD) frequently display intensely repetitive, restricted thoughts, and behaviors. These behaviors have similarities to compulsions and/ or obsessions in obsessive compulsive disorder (OCD) and are primarily treated with behaviourally-based interventions and serotonin uptake inhibitors (SSRIs). Due to the lack of treatment responses in many cases, however, new treatments are being sought. Here we report beneficial effects of treatment with liraglutide, a glucagon-like peptide-1 (GLP-1) analog, on severe obsessive food craving, binge eating, weight gain, and behavioral problems in an adolescent male with infantile autism and moderate intellectual impairment. Liraglutide treatment reduced weight and unwanted behavior seemingly by preventing food-related repetitive thoughts and compulsions. Our report provides clinical evidence that GLP-1 signaling pathway may represent a novel target for treating food-related behavioral problems and aggressive behavior in ASD.Peer reviewe

Tridimensional Personality Questionnaire data on alcoholic violent offenders: specific connections to severe impulsive cluster B personality disorders and violent criminality

<p>Abstract</p> <p>Background</p> <p>The validity of traditional categorical personality disorder diagnoses is currently re-evaluated from a continuous perspective, and the evolving DSM-V classification may describe personality disorders dimensionally. The utility of dimensional personality assessment, however, is unclear in violent offenders with severe personality pathology.</p> <p>Methods</p> <p>The temperament structure of 114 alcoholic violent offenders with antisocial personality disorder (ASPD) was compared to 84 offenders without ASPD, and 170 healthy controls. Inclusion occurred during a court-ordered mental examination preceded by homicide, assault, battery, rape or arson. Participants underwent assessment of temperament with the Tridimensional Personality Questionnaire (TPQ) and were diagnosed with DSM-III-R criteria.</p> <p>Results</p> <p>The typical temperament profile in violent offender having ASPD comprised high novelty seeking, high harm avoidance, and low reward dependence. A 21% minority scored low in trait harm avoidance. Results, including the polarized harm avoidance dimension, are in accordance with Cloninger's hypothesis of dimensional description of ASPD. The low harm avoidance offenders committed less impulsive violence than high harm avoidance offenders. High harm avoidance was associated with comorbid antisocial personality disorder and borderline personality disorder.</p> <p>Conclusion</p> <p>Results indicate that the DSM based ASPD diagnosis in alcoholic violent offenders associates with impulsiveness and high novelty seeking but comprises two different types of ASPD associated with distinct second-order traits that possibly explain differences in type of violent criminality. Low harm avoidance offenders have many traits in common with high scorers on the Hare Psychopathy Checklist-Revised (PCL-R). Results link high harm avoidance with broad personality pathology and argue for the usefulness of self-report questionnaires in clinical praxis.</p

Homogeneous nucleation of carbon dioxide in supersonic nozzles II : molecular dynamics simulations and properties of nucleating clusters

Large scale molecular dynamics simulations of the homogeneous nucleation of carbon dioxide in an argon atmosphere were carried out at temperatures between 75 and 105 K. Extensive analyses of the nucleating clusters' structural and energetic properties were performed to quantify these details for the supersonic nozzle experiments described in the first part of this series [Dingilian et al., Phys. Chem. Chem. Phys., 2020, 22, 19282-19298]. We studied ten different combinations of temperature and vapour pressure, leading to nucleation rates of 10(23)-10(25) cm(-3) s(-1). Nucleating clusters possess significant excess energy from monomer capture, and the observed cluster temperatures during nucleation - on both sides of the critical cluster size - are higher than that of the carrier gas. Despite strong undercooling with respect to the triple point, most clusters are clearly liquid-like during the nucleation stage. Only at the lowest simulation temperatures and vapour densities, clusters containing over 100 molecules are able to undergo a second phase transition to a crystalline solid. The formation free energies retrieved from the molecular dynamics simulations were used to improve the classical nucleation theory by introducing a Tolman-like term into the classical liquid-drop model expression for the formation free energy. This simulation-based theory predicts the simulated nucleation rates perfectly, and improves the prediction of the experimental rates compared to self-consistent classical nucleation theory.Peer reviewe

Homogeneous nucleation of carbon dioxide in supersonic nozzles I : experiments and classical theories

We studied the homogeneous nucleation of carbon dioxide in the carrier gas argon for concentrations of CO(2)ranging from 2 to 39 mole percent using three experimental methods. Position-resolved pressure trace measurements (PTM) determined that the onset of nucleation occurred at temperatures between 75 and 92 K with corresponding CO(2)partial pressures of 39 to 793 Pa. Small angle X-ray scattering (SAXS) measurements provided particle size distributions and aerosol number densities. Number densities of approximately 10(12)cm(-3), and characteristic times ranging from 6 to 13 mu s, resulted in measured nucleation rates on the order of 5 x 10(17)cm(-3)s(-1), values that are consistent with other nucleation rate measurements in supersonic nozzles. Finally, we used Fourier transform infrared (FTIR) spectroscopy to identify that the condensed CO(2)particles were crystalline cubic solids with either sharp or rounded corners. Molecular dynamics simulations, however, suggest that CO(2)forms liquid-like critical clusters before transitioning to the solid phase. Furthermore, the critical clusters are not in thermal equilibrium with the carrier gas. Comparisons with nucleation theories were therefore made assuming liquid-like critical clusters and incorporating non-isothermal correction factors.Peer reviewe

Tridimensional Personality Questionnaire data on alcoholic violent offenders: specific connections to severe impulsive cluster B personality disorders and violent criminality-0

<p><b>Copyright information:</b></p><p>Taken from "Tridimensional Personality Questionnaire data on alcoholic violent offenders: specific connections to severe impulsive cluster B personality disorders and violent criminality"</p><p>http://www.biomedcentral.com/1471-244X/7/36</p><p>BMC Psychiatry 2007;7():36-36.</p><p>Published online 30 Jul 2007</p><p>PMCID:PMC1976096.</p><p></p>ent profile of offenders with low trait harm avoidance followed the control profile and deviated substantially (SD 2.29) from the high HA offender mean. The mean profile of the high HA offenders resembled that of the offenders with antisocial personality disorder. A) Displays that (1) low HA offenders showed no difference compared to controls in trait impulsiveness (NS2); p = .85 (absolute mean rank difference = 19.8), whereas high HA offenders scored higher than controls on trait impulsiveness; p = .0004 (52.7), (2) low HA offenders featured more curiosity and excitement (NS1) than high HA offenders; p = .0001 (78.7), and (3) the total novelty seeking score showed no difference between high and low HA groups; p = 1.0 (14.1). B) Displays that low HA offenders' HA mean score was even lower than the mean score of the lower half of controls; 7.7 SD 3.1 vs. 9.2 SD 2.5; p = .002 (23.0). C) Trait HA1 showed the largest absolute score difference between low and high HA offenders (3.4) indicating that low HA offenders were more optimistic and careless than high HA offenders who were prone to anticipatory worry and anxiety. D) Low HA offenders were dependent on environmental reward (RD3) similarly to controls; p = .12 (42.3), whereas high HA offenders featured greater detachment and individualism than controls; p = .0004 (75.8). Kruskal-Wallis test (df = 2) was applied for comparison of means

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. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe