Petra Retz-Junginger

Nature and Nurture Predispose to Violent Behavior: Serotonergic Genes and Adverse Childhood Environment

Aggressive behavior is influenced by variation in genes of the serotonergic circuitry and early-life experience alike. The present study aimed at investigating the contribution of polymorphisms shown to moderate transcription of two genes involved in serotonergic neurotransmission (serotonin transporter, 5HTT, and monoamine oxidase A, MAOA) to the development of violence and to test for gene–environment interactions relating to adverse childhood environment. A cohort of 184 adult male volunteers referred for forensic assessment participated in the study. Each individual was assigned to either a violent or a nonviolent group. Logistic regression was performed and the best-fitting model, with a predictive power of 74%, revealed independent effects of adverse childhood environment and MAOA genotype. High environmental adversity during childhood was associated significantly with violent behavior. Forty-five percent of violent, but only 30% of nonviolent individuals carried the low-activity, short MAOA allele. Most interestingly, an interaction effect between childhood environment and 5HTT genotype on violent behavior was found in that high adversity during childhood impacted only the later-life violence if the short promoter alleles were present. These findings indicate complex interactions between genetic variation of the serotonergic circuitry and environmental factors arguing against simplistic, mono-causal explanations of violent behavior.

Wender Utah Rating Scale (WURS-k) Die deutsche Kurzform zur retrospektiven Erfassung des hyperkinetischen Syndroms bei Erwachsenen

ZusammenfassungDie diagnostische Abklärung einer Aufmerksamkeitsdefizit/Hyperaktivitätsstörung beim Erwachsenen macht die retrospektive Erfassung von Krankheitssymptomen, die bereits im Kindesalter bestanden, notwendig. Die Wender Utah Rating Scale (WURS) ist ein hierfür entwickelter Fragebogen. In der vorliegenden Arbeit wurde die deutsche Übersetzung der WURS einer statistischen Analyse unterzogen. Grundlage für diese Analyse bildete die Untersuchung von insgesamt 703 Probanden. Anhand der korrigierten Trennschärfeindizes wurde unter Berücksichtigung der mittleren Antwortausprägung sowie inhaltlicher Aspekte der Items eine Itemselektion durchgeführt. Nach der Itemselektion verblieben 21 Items mit einer korrigierten Trennschärfe ri(t–i) zwischen 0,19 und 0,61 in der Fragebogenendform. Die Retestreliabilität der gekürzten Version betrug r=0,9.SummaryThis work presents a statistical analysis of the German version of the Wender Utah rating scale (WURS) for the retrospective diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703 subjects. Item selection according to item-total correlation scores, frequency, and plausibility led to a short version of the scale that includes 21 items with item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was r=0.9.

A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment.

Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, environmental conditions play an important role in its manifestation during childhood development. Here, we report the results of an investigation on the interaction of adverse childhood environment with a functional polymorphism of the serotonin transporter promoter gene (5-HTTLPR) and its impact on ADHD psychopathology in young adult delinquents. Standardized instruments were used to assess childhood and current ADHD and adverse childhood environment in 184 male delinquents. Each subject was genotyped for 5-HTTLPR long (L) and small (S) alleles. Logistic regression analysis revealed independent effects of high childhood environmental adversity and the 5-HTTLPR LL-genotype on self-reported childhood ADHD and on persistent ADHD. In addition, a significant gene by environment interaction was found, indicating that carriers of at least one 5-HTTLPR short allele are more sensitive to childhood environment adversity than carriers of the LL-genotype. The results support prior findings of association between ADHD and 5-HTTLPR LL-genotype and adverse childhood environment, and they underline the need for further investigation of gene by environment interaction with respect to ADHD.

[Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults].

ZusammenfassungDie diagnostische Abklärung einer Aufmerksamkeitsdefizit/Hyperaktivitätsstörung beim Erwachsenen macht die retrospektive Erfassung von Krankheitssymptomen, die bereits im Kindesalter bestanden, notwendig. Die Wender Utah Rating Scale (WURS) ist ein hierfür entwickelter Fragebogen. In der vorliegenden Arbeit wurde die deutsche Übersetzung der WURS einer statistischen Analyse unterzogen. Grundlage für diese Analyse bildete die Untersuchung von insgesamt 703 Probanden. Anhand der korrigierten Trennschärfeindizes wurde unter Berücksichtigung der mittleren Antwortausprägung sowie inhaltlicher Aspekte der Items eine Itemselektion durchgeführt. Nach der Itemselektion verblieben 21 Items mit einer korrigierten Trennschärfe ri(t–i) zwischen 0,19 und 0,61 in der Fragebogenendform. Die Retestreliabilität der gekürzten Version betrug r=0,9.SummaryThis work presents a statistical analysis of the German version of the Wender Utah rating scale (WURS) for the retrospective diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703 subjects. Item selection according to item-total correlation scores, frequency, and plausibility led to a short version of the scale that includes 21 items with item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was r=0.9.

Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology.

Summary. Several lines of evidence indicate that dopaminergic neurotransmission is involved in the regulation of impulsive aggression and violence and that genetically determined variability in dopaminergic gene expression modifies complex traits including that of impulsivity and aggression. In this study we report an association of the dopamine D3 receptor (DRD3) polymorphism with impulsiveness according to Eysencks EIQ and scores on the German short version of the Wender Utah Rating Scale (WURS-k), which we used for the assessment of a history of ADHD-related symptoms. This association was detected in a group of violent offenders, but not in non-violent individuals. Highest scores of EIQ impulsiveness and of the WURS-k were found in heterozygous violent individuals, while homozygotes showed significant lower rating scores, suggesting an heterosis effect. The results of our study suggest that variations of the DRD3 gene are likely involved in the regulation of impulsivity and some psychopathological aspects of ADHD related to violent behavior.

Effects of Two-Year Treatment with the Cholinesterase Inhibitor Rivastigmine on Behavioural Symptoms in Alzheimer’s Disease

Alzheimers disease (AD) is accompanied by prominent behavioural disturbances. They cause significant distress for both caregivers and patients and can play a major role in the decision to institutionalise AD patients. Recent evidence suggests that cholinergic deficiencies not only contribute to the memory and cognitive abnormalities of AD but are also responsible for some behavioural abnormalities seen over the course of the disease. In this study we assessed the ability of rivastigmine, a pseudo-irreversible cholinesterase inhibitor, to improve behavioural and psychopathologic symptoms in AD. The analysis included 34 patients present in the Germanarm of the international study B303 who received and completed long-term treatment with rivastigmine in the open-label study B305. Assessments of behaviour and psychopathological symptoms were performed using the behavioural component of the Clinicians Interview Based Impression of Change Plus (CIBIC-Plus). Results show that long-term treatment with rivastigmine can slow the progression of behavioural and psychopathological symptoms of AD. Behavioural symptoms showing stabilisation included aggressiveness, activity disturbances, hallucinations and paranoid features. Results also suggest that patients treated earlier with rivastigmine may attain a greater benefit compared with patients whose treatment is delayed 6 months. Further studies examining the effects of rivastigmine on behavioural disturbances in AD are therefore warranted.

Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults — A functional magnetic resonance imaging (fMRI) study

Attention deficit hyperactivity disorder (ADHD) is a common, genetically transmitted common childhood-onset disorder with a high rate of persistence in adulthood. Although many studies have shown anatomical and functional abnormalities in children and adolescents, studies with adult patients are rare. Nineteen adults with ADHD (11 ADHD, combined type; 8 ADHD, partially remitted) and 17 controls were included in this functional magnetic resonance imaging (fMRI) study. Brain activation was investigated with a continuous performance test (CPT). Impaired activation of a fronto-striatal and a parietal attentional network was observed during the NoGo condition in ADHD subjects. Correlations of reduced activity of the caudate nuclei, the anterior cingulate cortex, and parietal cortical structures, as well as increased activity in the insular cortex, with inattention and impulsivity symptom scores were found. The activation patterns were similar to those known from children and adolescents with ADHD. In conclusion we found not only a widespread dysfunction of brain regions that are involved in cognitive processing in adults with ADHD compared with controls, but also correlations between symptom severity and dysfunction of neuronal systems across adult subjects with a history of ADHD in childhood but whose symptoms did (persistent ADHD) and did not (not persistent ADHD) qualify for a full diagnosis of ADHD in adulthood.

Psychometric and psychopathological characterization of young male prison inmates with and without attention deficit/hyperactivity disorder

Abstract.There is considerable evidence that attention deficit/hyperactivity disorder (ADHD) is associated with conduct problems, social maladaptation and delinquent behavior. The “Ottweiler Study” was performed to elaborate the prevalence of ADHD and comorbid disorders in 129 young adult detainees of the juvenile prison of Ottweiler (Germany) according to DSM-IV and ICD-10 criteria. Here we report psychopathological characteristics of 28 inmates, who fulfilled the diagnostic criteria for persisting ADHD, and 37 individuals with neither a history nor current ADHD symptoms. Childhood ADHD symptoms but no current ADHD were present in 64 individuals. The Wender–Reimherr Interview (WRI) based on the Utah criteria for adult ADHD, the NEO–five factor personality inventory (NEO–FFI) and the youth self report/young adult self report (YSR/YASR) according to Achenbach were used for the assessment of psychopathology and the description of behavioral problems. Regarding WRI and YSR/YASR we found a significant increase of emotional and internalizing problems in the ADHD group compared to delinquents without ADHD or ADHD history. ADHD delinquents scored higher on the personality dimension neuroticism, and showed lower scores on the dimensions agreeableness and consciousness. Using discriminant analysis, high scores on the WRI subscales disorganization and attention difficulties and NEO–FFI neuroticism were the best predictors of ADHD diagnosis. The results support prior findings of high ADHD prevalence in prison inmates and suggest that emotional and internalizing abnormalities are prominent problems in this population. Further studies are needed to elucidate the role of ADHD as an independent factor for life–persistent criminality, since specific treatment may help to ameliorate the legal prognosis.

Emotional dysregulation in adult ADHD: what is the empirical evidence?

Attention deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder characterized by symptoms of inattention, hyperactivity and impulsivity. There is an ongoing discussion whether symptoms of emotional dysregulation should be added to the conceptualization of ADHD in order to describe the psychopathology of ADHD more precisely, at least in adult patients. Symptoms of emotional dysregulation are well defined and seem to be distinct factors of the psychopathology of adult ADHD. Assessment of this psychopathological dimension has shown sufficient reliability and validity. Empirical studies have confirmed a high prevalence of this psychopathological feature in adults with ADHD that compares to the frequency of the ADHD core symptoms, inattention, hyperactivity and impulsivity. Evidence is given that emotional dysregulation has an independent effect on social problems associated with ADHD in adult life. Moreover, pharmacological and psychotherapeutic interventions help to ameliorate emotional dysregulation together with symptoms of inattention and hyperactivity/impulsivity. Thus, there is growing evidence that emotional dysregulation might be recognized as a core feature of ADHD.

Effects of Group Psychotherapy, Individual Counseling, Methylphenidate, and Placebo in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD. OBJECTIVE To evaluate the efficacy of cognitive behavioral group psychotherapy (GPT) compared with individual clinical management (CM) and that of methylphenidate hydrochloride compared with placebo. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter, randomized clinical trial of 18- to 58-year-old outpatients with ADHD from 7 German study centers. Patients were recruited between January 2007 and August 2010, treatment was finalized in August 2011, and final follow-up assessments occurred in March 2013. INTERVENTIONS Sessions of GPT and CM were held weekly for the first 12 weeks and monthly thereafter (9 months). Patients received either methylphenidate or placebo for 1 year. MAIN OUTCOMES AND MEASURES The primary outcome was the change in the ADHD Index of the Conners Adult ADHD Rating Scale from baseline to the end of the 3-month intensive treatment (blinded observer ratings). Secondary outcomes included ADHD ratings after 1 year, blinded observer ratings using the Clinical Global Impression Scale, and self-ratings of depression. RESULTS Among 1480 prescreened patients, 518 were assessed for eligibility, 433 were centrally randomized, and 419 were analyzed as randomized. After 3 months, the ADHD Index all-group baseline mean of 20.6 improved to adjusted means of 17.6 for GPT and 16.5 for CM, with no significant difference between groups. Methylphenidate (adjusted mean, 16.2) was superior to placebo (adjusted mean, 17.9) (difference, -1.7; 97.5% CI, -3.0 to -0.4; P = .003). After 1 year, treatment effects remained essentially stable. Descriptive analyses showed that methylphenidate was superior to placebo in patients assigned to GPT (difference, -1.7; 95% CI, -3.2 to -0.1; P = .04) or CM (difference, -1.7; 95% CI, -3.3 to -0.2; P = .03). Regarding depression, no significant differences were found. In contrast, GPT was superior to CM for all visits in the Clinical Global Impression global assessment of effectiveness. CONCLUSION AND RELEVANCE Highly structured group intervention did not outperform individual CM with regard to the primary outcome. Psychological interventions resulted in better outcomes during a 1-year period when combined with methylphenidate as compared with placebo. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54096201.