Johannes Thome

Advanced glycation endproducts in ageing and Alzheimer's disease

Accumulation of advanced glycation endproducts (AGE) in the brain is a feature of ageing and degeneration, especially in Alzheimers disease (AD). Increased AGE levels explain many of the neuropathological and biochemical features of AD such as extensive protein crosslinking (beta-amyloid and MAP-tau), oxidative stress and neuronal cell death. Oxidative stress and AGEs initiate a positive feedback loop, where normal age-related changes develop into a pathophysiological cascade. Combined intervention using antioxidants, metal chelators, anti-inflammatory drugs and AGE-inhibitors may be a promising neuroprotective strategy.

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.

Psychopathological rating scales for diagnostic use in adults with attention-deficit/hyperactivity disorder (ADHD)

The diagnosis of attention-deficit hyperactivity disorder (ADHD) in adults is a complex procedure which should include retrospective assessment of childhood ADHD symptoms either by patient recall or third party information, diagnostic criteria according to DSM-IV, current adult ADHD psychopathology including symptom severity and pervasiveness, functional impairment, quality of life and comorbidity. In order to obtain a systematic database for the diagnosis and evaluation of the course ADHD rating scales can be very useful. This article reviews rating instruments that have found general acceptance.The Wender-Utah Rating Scale (WURS) and the Childhood Symptoms Scale by Barkley and Murphy try to make a retrospective assessment of childhood ADHD symptoms. The Connors Adult ADHD Rating Scales (CAARS), the Current Symptoms Scales by Barkley and Murphy (CSS), the Adult Self Report Scale (ASRS) by Adler et al. and Kessler et al. or the Attention Deficit Hyperactivity Disorder—Self Report Scale (ADHD-SR by Rösler et al.) are self report rating scales focusing mainly on the DSM-IV criteria. The CAARS and the CSS have other report forms too. The Brown ADD Rating Scale (Brown ADD-RS) and the Attention Deficit Hyperactivity Disorder-Other Report Scale (ADHD-OR by Rösler et al.) are instruments for use by clinicians or significant others. Both self rating scales and observer report scales quantify the ADHD symptoms by use of a Likert scale mostly ranging from 0 to 3. This makes the instruments useful to follow the course of the disease quantitatively. Comprehensive diagnostic interviews not only evaluate diagnostic criteria, but also assess different psychopathological syndrome scores, functional disability measures, indices of pervasiveness and information about comorbid disorders. The most comprehensive procedures are the Brown ADD Diagnostic Form and the Adult Interview (AI) by Barkley and Murphy. An instrument of particular interest is the Wender Reimherr Interview (WRI) which follows a diagnostic algorithm different from DSM-IV. The interview contains only items delineated from adult psychopathology and not derived from symptoms originally designed for use in children.Other instruments focus on functional impairment, quality of life, comorbid disorders, gender effects and specific psychopathological models.

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.

Anatomical and functional brain imaging in adult attention-deficit/hyperactivity disorder (ADHD) - A neurological view

In this review, we discuss current structural and functional imaging data on ADHD in a neurological and neuroanatomical framework. At present, the literature on adult ADHD is somewhat sparse, and so results from imaging have to therefore be considered mainly from the childhood or adolescence perspective. Most work has considered the impairment of executive functions (motor execution, inhibition, working memory), and as such a number of attention networks and their anatomical correlates are discussed in this review (e. g. the cerebello-(thalamo-)-striato-cortical network seems to play a pivotal role in ADHD pathology from childhood to adulthood).The core findings in ADHD imaging are alterations in the architecture and function of prefrontal cortex and cerebellum. The dorsal part of anterior cingulated cortex (dACC) is an important region for decision making, and executive control is impaired in adult ADHD. Finally, dysfunction of basal ganglia is a consistent finding in childhood and adulthood ADHD, reflecting dysregulation of fronto-striatal circuitry. The cerebellum, and its role in affect and cognition, is also persistently implicated in the pathology of ADHD.

The identification and management of ADHD offenders within the criminal justice system: a consensus statement from the UK Adult ADHD Network and criminal justice agencies

The UK Adult ADHD Network (UKAAN) was founded by a group of mental health specialists who have experience delivering clinical services for adults with Attention Deficit Hyperactivity Disorder (ADHD) within the National Health Service (NHS). UKAAN aims to support mental health professionals in the development of services for adults with ADHD by the promotion of assessment and treatment protocols. One method of achieving these aims has been to sponsor conferences and workshops on adult ADHD.This consensus statement is the result of a Forensic Meeting held in November 2009, attended by senior representatives of the Department of Health (DoH), Forensic Mental Health, Prison, Probation, Courts and Metropolitan Police services. The objectives of the meeting were to discuss ways of raising awareness about adult ADHD, and its recognition, assessment, treatment and management within these respective services. Whilst the document draws on the UK experience, with some adaptations it can be used as a template for similar local actions in other countries.It was concluded that bringing together experts in adult ADHD and the Criminal Justice System (CJS) will be vital to raising awareness of the needs of ADHD offenders at every stage of the offender pathway. Joint working and commissioning within the CJS is needed to improve awareness and understanding of ADHD offenders to ensure that individuals are directed to appropriate care and rehabilitation. General Practitioners (GPs), whilst ideally placed for early intervention, should not be relied upon to provide this service as vulnerable offenders often have difficulty accessing primary care services. Moreover once this hurdle has been overcome and ADHD in offenders has been identified, a second challenge will be to provide treatment and ensure continuity of care. Future research must focus on proof of principle studies to demonstrate that identification and treatment confers health gain, safeguards individuals rights, improves engagement in offender rehabilitation programmes, reduces institutional behavioural disturbance and, ultimately, leads to crime reduction. In time this will provide better justice for both offenders and society.

Association of attention deficit hyperactivity disorder-related psychopathology and personality traits with the serotonin transporter promoter region polymorphism

The role of the genetic polymorphism within the promoter region of the serotonin transporter (5-HTT) gene is under discussion as a modulator for personality traits and a risk factor for several mental disorders including attention deficit hyperactivity disorder (ADHD). Here we report a significant association of this polymorphism with scores on the Wender Utah Rating Scale, which was used for the assessment of a history of ADHD-associated symptoms, indicating a higher frequency of the long variant allele in individuals with high scores. We found no association between the 5-HTT polymorphism and personality traits according to the Eysenck Impulsivity Questionnaire and the Freiburg Personality Inventory, respectively, except a significant association with social orientation. Thus, our study supports the recently reported finding of an association of the 5-HTT polymorphism with ADHD. However, since a dimensional assessment of ADHD-related symptomatology was used in our study instead of a diagnostic approach, we are now on the way in performing further studies regarding diagnostic discrimination and comorbidity.

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.

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Alzheimers disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

Kinematic analysis of dopaminergic effects on skilled handwriting movements in Parkinson's disease.

Summary.Patients with Parkinson’s disease (PD) exhibit impairments in the execution of highly practiced and skilled motor actions such as handwriting. The analysis of kinematic aspects of handwriting movements has demonstrated that size, speed, acceleration and stroke duration are affected in PD. Although beneficial effects of dopaminergic therapy in regard to execution of movements have been reported, the effects of pharmacological therapy on these measures have not been examined in detail. The present study has compared kinematic aspects of handwriting movements of 27 healthy subjects and 27 patients with PD both on their usual dopaminergic treatment and following withdrawal of dopaminergic medication. Healthy subjects were matched with PD patients according to age, sex, handedness and education level. A digitising tablet was used for the assessment of handwriting movements. Subjects were asked to perform a simple writing task. Movement time, distance, velocity, acceleration and measures of fluency of handwriting movements were measured. Compared with healthy subjects, the kinematics of handwriting movements in PD patients were markedly disturbed following withdrawal of dopaminergic medication. Although dopaminergic treatment in PD patients resulted in marked improvements in the kinematics of handwriting movements, PD patients did not reach an undisturbed level of performance. The results suggest that dopamine medication results in partial restoration of automatic movement execution.