[Pharmacotherapy of attention deficit hyperactivity disorder in adults]. / Medikamentöse Therapie der Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung im Erwachsenenalter.

Pharmacotherapy is a central component in the context of an overall therapeutic concept in the treatment of adults with attention deficit hyperactivity disorder (ADHD). In this concept psychosocial interventions with psychoeducation or specific psychotherapy measures also play an important role. In adults three compounds are currently approved for the pharmacological treatment of ADHD in Germany. The long-acting stimulants retarded methylphenidate preparations and lisdexamfetamine can be prescribed. Alternatively, the adrenergic uptake inhibitor atomoxetine can be used. In several meta-analyses good effectiveness and tolerance of these drugs on ADHD psychopathology has been shown. They also improve ADHD-related disorders of emotional regulation capability and disorganization in everyday life. Importantly, an improvement in everyday functionality and quality of life under medication could also be shown in several studies. In this review the evidence for pharmacotherapy of ADHD and its implementation into treatment of adult patients is presented.

[Wender-Reimherr self-report questionnaire on adult ADHD : German version]. / Der Wender-Reimherr-Selbstbeurteilungsfragebogen zur adulten ADHS : Deutsche Version.

BACKGROUND: The Wender-Reimherr adult attention deficit disorder scale (WRAADDS) is an internationally accepted attention-deficit hyperactivity disorder (ADHD) interview with an authorized German translation. The WRAADS not only assesses the symptoms of ADHD but also the severity of the symptoms using the Utah criteria. With the aim of economizing the diagnostic process the original English version of the Wender-Reimherr self-report questionnaire was translated into German (WR-SB) in order to evaluate the test psychometric properties. OBJECTIVES: To explore the psychometric properties of the WR-SB within a classical test theory framework. MATERIAL AND METHODS: The psychometric properties of the WR-SB were determined in a population of 122 adult ADHD patients and 79 healthy controls. RESULTS: For the individual WR-SB subscales the results showed an adequate discriminatory power and a high internal consistency. The correlation between the WRAADS and the WR-SB was significant and the retest reliability was high. CONCLUSION: The WR-SB is a brief, self-report instrument and an economical alternative to assess adult ADHD symptomatology using the Utah criteria. The results of this evaluation study showed the WR-SB to be a valid and reliable measurement for both clinical and research purposes.

[Standardised psychopathological rating scales for the diagnosis of ADHD in adults]. / Standardisierte Skalen zur strukturierten Diagnostik der ADHS im Erwachsenenalter.

Ascertaining the diagnosis of ADHD in adults according to DSM-IV requires determination of the presence of symptoms of inattention, hyperactivity and impulsivity during both childhood and adulthood. Developmental changes of psychopathology, age-related comorbidity and functional and psychosocial problems associated with ADHD have to be taken into account during the diagnostic process. The use of standardised instruments might improve validity and reliability of the diagnosis. These diagnostic tools comprise self and expert ratings as well as observer ratings for the retrospective assessment of childhood and the evaluation of current ADHD symptoms. Here we give an overview of the standardised instruments that are available in German language and present data regarding the validity and reliability of a structured guide for the integrated diagnosis of adult ADHD (IDA) which has been constructed in order to provide a feasible tool for diagnosis of ADHD.

[Age and gender aspects of attention-deficit hyperactivity disorder]. / Alters- und geschlechtsspezifische Besonderheiten der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung.

Attention-deficit hyperactivity disorder (ADHD) is a syndrome with onset in childhood which persists at least partially in about 60% of afflicted individuals. Core symptoms include inattention, hyperactivity, and impulsivity. Additional psychopathology with disorganized behavior and emotional dysregulation is common in adulthood. The vast majority of adults affected also present psychiatric comorbidities. There is severe impairment of everyday life and quality of life. Developmental psychopathologic changes, age-related comorbidity, and functional and psychosocial problems associated with ADHD must be taken into account during the diagnostic process. Regarding clinical subtypes of ADHD according to DSM-IV and particularly gender differences, knowledge about these factors in adults with ADHD is limited.

[Attention deficit hyperactivity disorder in adults. Benchmarking diagnosis using the Wender-Reimherr adult rating scale]. / ADHS-Diagnose bei Erwachsenen. Nach DSM-IV, ICD-10 und den UTAH-Kriterien.

We report on a study comparing different systems for the diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood. Recruited for evaluation were 168 patients referred to our ADHD outpatient unit. We used the Diagnostic and Statistical Manual of Mental Disorders 4th edn. (DSM-IV), International Classification of Diseases 10th edn. (ICD-10), and Utah criteria for diagnostic assessment and the Wender Utah rating scale, ADHD Self Report (ADHD-SR), and Wender Reimherr Adult Attention Deficit Disorder Rating Scale as psychopathological assessment tools. We present basic psychometric data of the Wender-Reimherr Interview (WRI). Internal consistency was determined as 0.82 (alpha). The inter-rater reliability was 1.0 (kappa coefficient) regarding ADHD diagnoses, and the ICC was 0.98 referring to the WRI total scores. The convergent validity with the ADHD-SR was 0.65 (Spearman coefficient). In 126 of 168 patients an ADHD diagnosis was made according to at least one of the three systems. The DSM-IV diagnostic set led to 119 ADHD diagnoses. As compared with the two other systems, this is about the minimum level for an ADHD diagnosis. All of the 87 ADHD diagnoses according to ICD-10 were covered by DSM-IV. The ICD-10 had no independent psychopathological items and therefore offered no additional points for the diagnostic procedure than the DSM-IV. The situation regarding Utah criteria is different. These criteria contain seven psychopathological domains: inattention, hyperactivity, disorganisation, impulsivity, affective lability, overreactivity, and hot temper. They can be assessed by use of the WRI. Ninety-three of 168 patients were diagnosed as having ADHD according to the Utah concept, which is much lower than with the DSM-IV. The particular definition of the disorder by the Utah criteria resulted in seven patients having only a Utah diagnosis but no DSM-IV diagnosis. Thus we are in a position to say that the Utah criteria have a relatively high level for making an ADHD diagnosis but in certain cases move beyond the DSM-IV. Of the patients 56% had ADHD diagnoses according to all three classification instruments. Examining the factor structure of the ADHD psychopathology represented by seven WRI and three ADHD-SR subscales, we found a two-factor solution explaining for 63% of the variance. Factor 1 was designated by impulsivity, affective lability, hyperactivity, and hot temper; factor 2 consisted of inattention, disorganisation, and overreactivity.

Impaired cortical inhibition in adult ADHD patients: a study with transcranial magnetic stimulation.

The aim of this study was to analyze motor inhibition and facilitation of adult ADHD patients using double pulse transcranial magnetic stimulation (TMS). Twenty-six right handed adult ADHD patients according to DSM-IV were investigated and compared to 26 age and sex-matched controls. In the left hemisphere, mean motor inhibition was 0.53 +/- 0.33 (mean +/- SD) in ADHD patients and 0.34 +/- 0.16 (mean +/- SD) in controls (p = 0.012). There were no significant differences in motor excitability concerning facilitation or in the right hemisphere. Decreased motor inhibition correlated with a higher symptom score derived from the Wender Reimherr Interview (WRI) (p = 0.28; p = 0.04) and also with self rated hyperactivity/impulsivity symptoms (p = 0.30; p = 0.03). In conclusion, decreased motor inhibition in adult ADHD corroborate similar findings in children with ADHD (Moll et al., 2000) and reflect disturbed impulsivity and hyperactivity on a neurophysiological level.

[Drug addiction in young prison inmates with and without attention deficit hyperactivity disorder (ADHD)]. / Suchtmittelgebrauch bei jungen erwachsenen Straftätern mit und ohne Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS).

Prospective studies of children with ADHD have shown a high level of substance use disorder comorbidity, particularly when associated with social maladaptation and antisocial behavior. Conversely, studies of drug abusing participants and delinquents revealed a high prevalence of ADHD comorbidity. In this study 129 young male prison inmates were systematically examined for ADHD and substance use disorders. 64,3 % showed harmful alcohol consumption. 67,4 % fulfilled DSM-IV criteria for any drug abuse or dependence. 28,8 % of these participants were diagnosed with ADHD, combined type, other 52,1 % showed ADHD residual type. Opioid dependence was more common in delinquents without ADHD. Addicted delinquents with ADHD showed worse social environment and a higher degree of psychopathology, including externalizing and internalizing behavior, compared to addicted delinquents without ADHD. Neuroticism and conscientiousness ratings of the addicted ADHD group, but not of those without ADHD, differed from non-addicted delinquents. The results underline the need of adequate therapeutic programs for addicted young prison inmates considering ADHD comorbidity, which is associated with additional psychopathology and social problems.

[Awareness of memory deficits in patients with probable Alzheimer's disease]. / Metagedächtnisleistungen bei Alzheimerpatienten.

Thirty-eight patients with Alzheimer's disease were asked to give a qualitative (estimation of memory changes) and quantitative assessment of their own performance on memory tasks and also of their relatives' performance. Qualitative assessment showed to be independent from measured memory-deficits, while the precision of quantitative prediction of performance deteriorated with increased cognitive impairment. Cognitive impairment of the demented patients did not influence the prediction of the performance of their relatives. Both, qualitative and quantitative assessment of memory performance were influenced by premorbid coping-strategies. Patients, who were attributed to use strategies of cognitive avoidance, more often claimed to have no changes in memory function or over-estimated their memory performance. The results of this investigation reveal that methodological issues influence studies on the association of meta-cognitive abilities with the severity of dementia to a great extent. They also suggest that awareness of deficits should be based on a complex, multi-dimensional concept.

[Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist]. / Instrumente zur Diagnostik der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im ErwachsenenalterSelbstbeurteilungsskala (ADHS-SB) und Diagnosecheckliste (ADHS-DC).

We report on the development of a German self-rating behaviour questionnaire (ADHD-SR) and diagnostic checklist (ADHD-DC) for the diagnosis of attention-deficit/hyperactivity disorder in adults according to DSM IV and ICD 10 research criteria. When comparing self-rating with expert rating, we found good concordance measured by intraclass coefficients on the level of single symptoms and syndrome scores. High retest reliability of the ADHD-SR demonstrated the ability to assess time-stable behaviour traits. Evaluation of the psychometric properties revealed good internal consistency and adequate convergent and divergent validity measured by the "big five" derived from the NEO-FFI and the constructs impulsivity, venturesomeness, and empathy of Eysenck's impulsiveness questionnaire. We detected a remarkable correlation with the Wender Utah Rating Scale, which targets the detection of childhood ADHD symptoms. Diagnostic sensitivity for different cutoff points was calculated by ROC analysis at 65--88%. Specificity was 67% to 92%.

[Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder]. / Reliabilität und Validität der Wender-Utah-Rating-Scale-Kurzform. Retrospektive Erfassung von Symptomen aus dem Spektrum der Aufmerksamkeitsdefizit/Hyperaktivitätsstörung.

The diagnosis of adult attention deficit/hyperactivity disorder (ADHD) requires the retrospective assessment of ADHD symptoms in childhood. The Wender Utah Rating Scale (WURS) is helpful in detecting ADHD-associated symptomatology in childhood. A German short version (WURS-k) of this instrument has been made available recently. In the present study, we investigated the validity of the WURS-k. In a population of 63 adult ADHD patients (according to ICD-10 and DSM-IV criteria) and 1,303 male controls, ROC analysis indicated a sensitivity of 85% and specificity of 76% at a cutoff of 30 points. In ADHD patients, seven individual factors explained 70.3% of the variance. The highest diagnostic precision was demonstrated using the WURS-k total score. The seven extracted factors of the WURS-k did not differ in diagnostic value. Significant correlations were found between impulsivity according to Eysenck's Impulsivity Questionnaire (EIQ) and excitability, aggression, emotional lability, and satisfaction on the Freiburg Personality Inventory (FPI-R) in ADHD patients. Concerning a 30-50% persistence of ADHD symptomatology in adults, these correlations underline the diagnostic validity of the WURS-k. The scale manifested excellent internal consistency (alpha=0.91) and a split-half correlation of r(12)=0.85.

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

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 Eysenck's 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.

[Overview of standardised diagnostic instruments of dementia]. / Diagnostik der Demenzen: Standardisierte Untersuchungsinstrumente im Uberblick.

The symptoms of dementia refer to a decline in intellectual abilities and to an impairment of general and instrumental activities of daily living (ADL). Beside cognitive decline and loss of ADL's the diagnosis of dementia requires the documentation of changes in social adaptation, psychopathology and behaviour. There are a large number of scales used in the assessment of the various manifestations of the disease. Some scales focus on a particular aspect of the symptomatology, others prefer a comprehensive approach in the detection of dementia symptoms. We present a list of assessment procedures and scales which seem appropriate to detect different aspects of dementia and which are widely accepted in the scientific community. We describe these scales in detail including their methodology and source of informations, psychometric properties regarding validity and reliability as well as time taken to complete the scales. Our synopsis may serve as an orientation mark in the selection of adequate instruments for the assessment of different symptom domains during the process of diagnosis, the observation of the course of dementia and the efficacy of treatment interventions.

[Presentation and stability of cognitive and noncognitive symptom patterns in patients with Alzheimer's disease. Disease course over a two-year period under constant treatment conditions with rivastigmine]. / Ausprägung, Stabilität und Muster kognitiver und nicht kognitiver Symptome bei Patienten mit Alzheimer-Demenz. Verlaufsbeobachtungen über zwei Jahre unter konstanten Behandlungsbedingungen mit Rivastigmin.

The course of behavioural and psychotic features of patients with Alzheimer's disease treated with an inhibitor of the acetylcholinesterase (rivastigmine), and their association to cognitive impairment is presented in the study. Standardized examination of global functional deterioration (GDS), cognitive impairment (MMSE) and behavioural or psychotic symptoms (Behave-AD) were performed over two years. We could analyse the complete data from 44 of initially 91 patients with mild to moderate Alzheimer's disease. The cognitive component (measured by MMSE, ADAS-cog) and the functional assessment (GDS) showed a continuous decline after a one year period of stabilization, in contrast with behavioural and psychotic symptoms, especially delusions, which still improved after treatment of two years. While cognitive items in correlation with functional aspects formed a homogeneous factor over the two-year period, psychotic features displayed more variability over time evaluated by factor analysis. Nevertheless mood and anxiety disorder in combination with aggressive behaviour as well as hallucinations formed an independent factor in the course of Alzheimer's disease. In addition to other studies of the course of Alzheimer's disease we could demonstrate that distinct behavioural and psychotic symptoms may also present as independent factors in Alzheimer patients under constant treatment conditions with an inhibitor of the acetylcholinesterase (rivastigmine).

[Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults]. / Wender Utah Rating Scale (WURS-k) Die deutsche Kurzform zur retrospektiven Erfassung des hyperkinetischen Syndroms bei Erwachsenen.

This 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.

Potential genetic markers of sporadic Alzheimer's dementia.

Polymorphisms within the genes encoding apolipoprotein E (ApoE), apolipoprotein CI (ApoCI), alpha1-antichymotrypsin (ACT), the low-density lipoprotein (LDL) receptor and lipoprotein lipase were investigated in patients suffering from Alzheimer's dementia and non-demented psychiatric patients as control subjects. The ApoE allele 4, well known as a risk factor in Alzheimer's disease, and the ApoCI allele A2, which is closely linked to the ApoE allele 4, were found elevated in the index group. Concerning the polymorphism within exon 8 of the LDL receptor (alanin/threonin), there was also a predominance of the allele carrying threonin in the index group, which barely missed significance. Distribution of the polymorphisms of ACT and lipoprotein lipase were similar in both groups investigated. We conclude that, apart from the ApoE allele 4, other genetically regulated factors like ApoCI and the LDL receptor modulate the individual risk for Alzheimer's disease.

[Symptoms from the spectrum of Attention-Deficit/Hyperactivity Disorder (ADHD) in sexual delinquents]. / Symptome aus dem Spektrum des hyperkinetischen Syndroms bei Sexualdelinquenten.

The implications of ADHD for sexual delinquent behavior were investigated in a sample of 127 male sexual delinquents for whom social, forensic and psychiatric data were collected. For the retrospective evaluation of ADHD-symptoms, we used the Wender Utah Rating Scale (WURS, 61-item version). We also used the Eysenck Impulsiveness Questionnaire for the assessment of impulsivity. The prevalence of ADHD within the group of sexual delinquents was 27.6 % with a persistence rate of 14.2 % at a cut-off point of 90 in the WURS. The prevalence of ADHD within the control group was 7.8 % with a persistence rate of 3.0 %. The prevalence within the group of sexual delinquents dropped to 15.7 % for childhood ADHD-symptoms and 11.0 % for partial ADHD persistence in adulthood using a cut-off score of 100. In the control group the rates were 4.8 % and 2.4 % respectively. Based on ICD-10 criteria, 35.4 % of the sexual delinquents had no psychiatric disorder. We found personality disorders of the antisocial type (22.1 % of the sample) and paraphilias in 25.2 %. Approximately, half of the delinquents with paraphilia met the criteria of pedophilia. We also found schizophrenia, organic psychiatric disorders and mental retardations in less than 5 %. The criminal careers of the sexual delinquent group with a history of childhood ADHD symptoms started 10 years earlier. We also found a significant correlation between previous convictions and the retrospective diagnosis of ADHD symptoms. This was more prominent when a previous sexual offence could be found in their criminal record. These results illustrate the hypothesis, that in addition to paraphilias the presence of ADHD-symptoms might be an important vulnerability factor for sexual delinquency, esp. when there is a persistence into adulthood. This demonstrates the need for an early therapeutical intervention, since 44.1 % of the sample had previously undergone psychiatric treatment.

[Significance of personality markers in Alzheimer dementia]. / Uber die Bedeutung von Persönlichkeitsmerkmalen bei der Alzheimer-Demenz.

Personality traits are of raising importance in the investigation of the causes of Alzheimer's disease. The examination of possible correlations between personality traits and the presence of dementia is complicated by some methodical problems concerning the objective, reliable, and valid assessment especially of premorbid personality style of demented persons. There is some evidence that a higher level of education can not be considered as protective factors but seems to delay the progression and modify the clinical manifestation of the disease. How other premorbid personality traits influence the course of the disease is still unresolved. A trend towards an uniform personality alteration in the course of the disease seems to exist. Especially when selecting non-pharmacological therapeutical or training strategies or even in the interaction with the patients, it seems to be important to take personality change into consideration.

Cerebellar vermis area in schizophrenic patients - a post-mortem study.

Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.

Polymorphisms of the human apolipoprotein E promoter and bleomycin hydrolase gene: risk factors for Alzheimer's dementia?

In addition to the apolipoprotein E (ApoE) tri-allele polymorphism, genetic variants of the apolipoprotein E promoter (-491A/T) and the bleomycin hydrolase (BH-PEN) gene have also been proposed as genetic risk factors for Alzheimer's dementia (AD). Since reports about the relevance of these polymorphisms for the pathogenesis of AD have been contradictory, we performed an association study with some modifications. First, the control group in this study was made up of non-demented psychiatric inpatients, rather than healthy subjects. This procedure allows the specificity of the relationship between a given genotype and AD (as opposed to other psychiatric disorders) to be determined. Second, as an alternative to preexisting relatively time consuming techniques, BH-PEN polymorphism was determined using a simplified method based on PCR genotyping. We found a significant linkage disequilibrium between the -491A/T and ApoE polymorphisms. However, no direct association was observed between the -491A/T or BH-PEN polymorphism and AD.

Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease.

Alzheimer's 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.