White matter abnormalities and their impact on attentional performance in adult attention-deficit/hyperactivity disorder.

Inattention is the most important behavioral feature of adult patients with attention-deficit/hyperactivity disorder (ADHD). Neuroimaging studies in ADHD have demonstrated abnormalities primarily in the frontostriatal circuitry and were mostly conducted in children. We investigated white matter (WM) integrity in adult ADHD patients and the correlation of WM microstructure and neuropsychological parameters in 37 (21 men) never-medicated adult ADHD patients and 34 age- and gender-matched healthy controls. All subjects underwent clinical interviews, rating scales, and neuropsychological tests of attentional performance. Diffusion tensor imaging (DTI) was acquired, and 12 WM regions-of-interest (ROIs) within the attentional network were chosen. Group differences of mean fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for each ROI, and patients' DTI measures were then correlated with measures of attentional performance. FA values in ADHD patients were significantly reduced in the left inferior longitudinal fasciculus (ILF), while MD values were significantly increased in ADHD patients in the frontal portion of the left frontooccipital fasciculus (IFO). In ADHD patients, MD values were negatively correlated with attentional performance in the left ILF. Our findings provide further support for disturbed frontostriatal structural connectivity and also point to an involvement of the left temporal white matter with an impact on attentional performance.

Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder.

Inattention and impulsivity are the most prominent clinical features of attention deficit hyperactivity disorder (ADHD) in adulthood. Structural and functional neuroimaging studies of subjects with ADHD have demonstrated abnormalities in several brain areas, including fronto-striatal and fronto-cerebellar networks. Mostly, these studies were based on volumetric measurements and have been conducted in children. We investigated white matter (WM) integrity and correlation with measures of attention and impulsivity in adult patients with ADHD adopting diffusion tensor imaging (DTI). N = 37 (21 males) never-medicated adult patients with ADHD combined subtype and N = 34 (16 males) healthy controls were investigated. ADHD diagnosis (DSM-IV) was assessed with clinical interviews and rating scales, subjects also underwent a large neuropsychological test battery including tests of attention and impulsivity. DTI was acquired, and group differences of fractional anisotropy (FA) and mean diffusivity (MD) as well as correlation analyses with measures of attentional performance and impulsivity were calculated using voxel-based analyses. In adult patients with ADHD, we found reduced FA as well as higher MD bilaterally in orbitomedial prefrontal WM and in the right anterior cingulate bundle, while elevated FA was present bilaterally in temporal WM structures. Measures of attention were correlated with DTI parameters in the right superior longitudinal fasciculus, whereas measures of impulsivity were correlated with FA in right orbitofrontal fibre tracts. This is the first DTI study demonstrating disturbed structural connectivity of the frontal-striatal circuitry in adult patients with ADHD. Moreover, a direct correlation between WM integrity and measures of attention and impulsivity is shown.

Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD.

Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) have shown abnormalities in several brain areas including the frontostriatal circuitry and were mostly conducted in children and adolescents. We investigated 30 never-medicated adult ADHD patients (16 males) and 30 matched healthy control individuals. Functional magnetic resonance imaging was acquired during a working memory paradigm (n-back). Group activation maps and group differences of activation were calculated using voxel-based analyses. The generic activation pattern was more extended in the control group. In ADHD patients, significantly decreased activation was found in the right inferior parietal cortex. Disturbed parietal brain function may particularly contribute to inattention and working memory impairment in ADHD patients.

Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge.

Previous studies suggested altered sensitivity of the GABA/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and nine healthy male control subjects were studied with fMRI while performing a 2-back working memory task. The fMRI scans were performed 1 h after intravenous administration of saline and again 1 h after 0.03 mg/kg lorazepam I.V. After saline, a task x group interaction effect with higher task activation in alcoholic patients in the left cerebellum and the right prefrontal cortex emerged. Additionally, a differential task x drug x group interaction was identified in the right cerebellum with more pronounced reduction in cognitive activation after lorazepam in the patient group. A significant correlation between lorazepam sensitivity and duration of alcohol dependence was detected. The present findings are in line with previous studies suggesting disrupted prefrontal-cerebellar activation with potential compensatory hyperactivation of the compromised brain networks in alcoholism. Moreover, the results suggest enhanced responsivity to an acute GABAergic challenge in the right cerebellum with disease-related disruption of cerebellar functional integrity.

Tiagabine does not attenuate alcohol-induced activation of the human reward system.

RATIONALE: The rewarding effects of ethanol and other drugs of abuse are mediated by activation of the mesolimbic dopamine system. Recent neuroimaging studies in primates and humans suggest that cocaine-induced dopamine stimulation might be diminished by drugs augmenting gamma-aminobutyric acid A (GABA-A) receptor function such as the GABA transaminase inhibitor vigabatrin. OBJECTIVES: The objective of this study was to test the property of the selective GABA transporter 1 (GAT1) inhibitor tiagabine to block ethanol-induced activation of the mesolimbic reward system in an i.v. ethanol challenge. MATERIALS AND METHODS: Twenty nonaddicted healthy volunteers underwent an i.v. ethanol challenge after 1 week of tiagabine (15 mg/day) administration. Neuronal activation was measured using [(18)F]-fluoro-deoxyglucose positron emission tomography (PET). RESULTS: Tiagabine did not prevent ethanol-induced stimulation of the mesolimbic reward system but augmented ethanol-induced hypometabolism within areas of the visual system and the cerebellum. Tiagabine alone also decreased neuronal metabolism within parts of the right temporal cortex that are highly enriched with GABA-ergic neurons. CONCLUSIONS: Our ethanol challenge imaging study does not provide supporting evidence that the GAT1 inhibitor tiagabine diminishes the rewarding effects of ethanol. Further PET imaging studies using established anticraving compounds, such as the mu-opioid receptor antagonist naltrexone and antiepileptic drugs affecting the GABA-ergic system more broadly, will provide additional important insights on the interaction between the GABA-ergic and the brain reward system in vivo and the suitability of GABA-ergic drugs as anticraving compounds.

[Institutionalisation-index--a simple method to estimate direct treatment costs for institutionalised forms of community mental health care]. / Institutionalisierungsindex - eine einfache Methode zur Schätzung von direkten Behandlungskosten in Institutionen der Gemeindepsychiatrie.

AIM: Investigations of treatment costs are of increasing importance in community mental health care. Yet, they are often difficult and expensive to conduct. This study explores whether and, if so, to what extent direct treatment costs as paid by insurance companies and social welfare in the German health care system can be estimated through a simple Institutionalisation-Index. METHOD: Based on the literature and clinical judgment, a simple Institutionalisation-Index was formed reflecting the degree of institutional protection in supported housing, long-term day care, partial hospitalisation and full hospitalisation programmes. As part of a comprehensive evaluation of a model institution for community mental health care in Berlin, actually paid treatment costs and Institutionalisation-Index (II) were identified for 1194 patients over a total period of 23 years and compared with each other. RESULTS: The Pearson correlation coefficient between II and paid costs was 0.97 (p < 0,001). In calculations for subgroups and different periods of time, II and costs were almost identical, too. CONCLUSIONS: The Institutionalisation-Index provides a sufficiently precise estimate of direct costs as paid by insurance companies and social welfare for different forms of care in community based institutions and hospitals. The II can be adjusted to incorporate further forms of community based care. In systems with similar funding arrangements, the simple method to establish a Institutionalisation-Index should facilitate cost analyses in community mental health care.

[Patient characteristics, length of treatment and costs in a model institution of community mental health care]. / Patientenmerkmale, Behandlungsdauer und Kosten in einem gemeindepsychiatrischen Versorgungsmodell - Eine Analyse über 23 Jahre.

AIM: Since the 1970s, a model institution for community mental health care with three partial hospitalisation programmes and various out-patient services was run in the Berlin district Charlottenburg. The study evaluates, to what extent the institution fulfilled its aim to provide long-term care for severely and chronically ill patients at relatively low costs. It also identified predictors of outcome. METHOD: Case register data of 1194 patients who were treated within a period of 23 years were analysed. Patient characteristics, length of care and treatment costs are presented. Costs were calculated on the basis of daily rates as paid to care providers in 1996. Regression analyses were computed for predicting length of care and costs after the first year. RESULTS: On average, length of care was 2.4 years and costs per year were 57 000,- German Marks ( 29 000,-). Patients with shorter and longer duration of care differed in only a few of the recorded sociodemographic and clinical characteristics. Significant predictors for long-term costs were the legal status of being under a care order and costs in the first year. However, only 18 % of the variance of costs after the first year were explained. CONCLUSIONS: The findings suggest that a) community mental health care in the studied form may not reach all patients with severe mental illness, b) in most cases, the notion of a lifelong treatment in such care systems does not reflect reality, c) the paid costs are lower than for long-term in-patient care, but still rather high, and d) the usually recorded patient characteristics are of little value for predicting long-term outcome.