The Gilles de la Tourette syndrome : a psychiatrisch - genetic study

The Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with childhood onset and characterized by motor, vocal, sensory and cognitive tics that may vary from relatively mild to very severe. The tics are often accompanied by echo- and coprophenomena, all in a characteristic waxing and waning course. In clinicial populations obsessivecompulsive symptoms, attention deficit disorder with hyperkinesia, conduct disorder and self-injurious behaviors are frequently observed in GTS patients. The severity of the GTS symptoms differs from person to person and may vary within an individual during his life. The results of treatment, that consists of (supportive) counseling, pharmacotherapy and/ or (behavioral) therapy, are often not satisfactory, especially in the more severe cases. The exact etiology of GTS is unknown. Disturbances of the central dopaminergic, noradrenergic, serotonergic, GABA-ergic and endorphin systems in the brain are suggested to be involved in the pathogenesis of GTS. In view of the unknown etiology of this condition and the unsatisfactory treatment outcome in the majority of cases, the American Tourette Syndrome Association has launched research initiatives into the etiology of the disorder. In this program a number of American and European research groups, including a Dutch group, collaborate in trying to unravel the genetic background of GTS. Systematic family studies are carried out to establish the mode of inheritance and ultimately to map and clone the susceptibility gene(s). The study comprised the following steps: 1. The ascertainment of families of GTS probands and the diagnostic classification of the family members (described in section 2). 2. The statistical analysis of the family data to test the most likely mode of inheritance by segregation analysis and the power for linkage analysis by simulation studies (described in section 3). 3. The analysis of DNA marker data by linkage analysis (described in section 4)

A double blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-level study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of ≤ 18 were selected. After a drug-free and a placebo-washout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of ≤ 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23/46 (50%) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied

Implicit and explicit drug-related cognitions during detoxification treatment are associated with drug relapse: An ecological momentary assessment study

Objective: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with relapse. Method: Participants were 68 heroin-dependent inpatients undergoing clinical detoxification at an addiction treatment center. Participants carried around a personal digital assistant for 1 week. Participants completed up to 4 random assessments (RAs) per day. They also completed an assessment when they experienced a temptation to use drugs (TA). At each assessment, participants reported their craving and attitudes to drugs. Implicit cognitions were assessed with a drug Stroop task (attentional bias) and an Implicit Association Test (implicit attitudes). Results: Individuals who relapsed during the study week exhibited a larger attentional bias and more positive implicit attitudes to drugs than did nonrelapsers at TAs (but not RAs). In addition, compared to nonrelapsers, relapsers reported higher levels of craving and more positive explicit attitudes to drugs at TAs than at RAs. Additional within-subject analyses revealed that attentional bias for drugs at TAs increased before relapse. Conclusions: Drug-related cognitive processes assessed with ecological momentary assessments were associated with relapse during drug detoxification. Real-time assessment of craving and cognitions may help to identify which individuals are at risk of relapse and when they are at risk of relapse

Cognitive inflexibility in gamblers is primarily present in reward-related decision making

One hallmark of gambling disorder (GD) is the observation that gamblers have problems stopping their gambling behavior once it is initiated. On a neuropsychological level, it has been hypothesized that this is the result of a cognitive inflexibility.The present study investigated cognitive inflexibility in patients with GD using a task involving cognitive inflexibility with a reward element (i.e., reversal learning) and a task measuring general cognitive inflexibility without such a component (i.e., response perseveration). For this purpose, scores of a reward-based reversal learning task (probabilistic reversal learning task) and the Wisconsin card sorting task were compared between a group of treatment seeking patients with GD and a gender and age matched control group. The results show that pathological gamblers have impaired performance on the neurocognitive task measuring reward-based cognitive inflexibility. However, no difference between the groups is observed regarding non-reward-based cognitive inflexibility. This suggests that cognitive inflexibility in GD is the result of an aberrant reward-based learning, and not based on a more general problem with cognitive flexibility. The pattern of observed problems is suggestive of a dysfunction of the orbitofrontal cortex, the ventrolateral prefrontal cortex, and the ventral regions of the striatum in gamblers. Relevance for the neurocognition of problematic gambling is discussed