Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder.

Rationale: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function.

Objective: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD.

Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy.

Rationale: The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers.

Objectives: We aimed (1) to replicate oculomotor deficits in a psychometric schizotypy sample and (2) to investigate whether the expected deficits can be remedied by compounds shown to ameliorate impairments in schizophrenia.

A validation of cognitive biomarkers for the early identification of cognitive enhancing agents in schizotypy: a three-center double-blind placebo-controlled study.

A number of compounds aimed at improving cognition in schizophrenia have failed to demonstrate efficacy in Phase 2 clinical trials. Translational studies using biomarkers in surrogate populations, such as schizotypy, could be used to assess the efficacy of novel compounds. In this study, we aimed to validate the sensitivity and inter-site reliability of cognitive biomarkers (working memory (N-back), spatial working memory (SWM) and verbal fluency (VF) tasks) to detect the schizotypy phenotype and its reversal by psychotropic drugs.

Response perseveration in stimulant dependence is associated with striatal dysfunction and can be ameliorated by a D(2/3) receptor agonist.

Background: Compulsivity is a hallmark of drug addiction and in animal models is measured by consecutive incorrect responses to a previously rewarded stimulus during reversal learning. The aim of this study was to measure behavioral and neural markers of compulsivity in stimulant-dependent individuals and to test whether these markers could be modulated by treatment with drugs targeting the dopamine system.

Methods: In a randomized, double-blind, placebo-controlled, crossover design, stimulant-dependent individuals (SDIs; n = 18) and healthy volunteers (n = 18) received single doses of dopamine D(2/3) receptor antagonist (amisulpride, 400 mg) and agonist (pramipexole, 0.

Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.

Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine-serotonin interactions?

We report about a clinical observation in a well-characterized group of patients with obsessive-compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D₂/₃ antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive-compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine-serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction.

Validation of experimental medicine methods in psychiatry: the P1vital approach and experience.

In the pharmaceutical industry deciding whether to progress a compound to the next stage of development or choosing between compounds in a development portfolio is laden with risk. This is particularly true of compounds developed to treat CNS disorders. The use of pre-clinical models in CNS drug development is well established but these models often lack predictive validity and many compounds fail when they reach the target patient group.

Impaired visuospatial associative memory and attention in obsessive compulsive disorder but no evidence for differential dopaminergic modulation.

Rationale: Patients with obsessive compulsive disorder (OCD) demonstrate impaired cognition in some selected domains. Although serotoninergic dysfunction has been implicated in OCD, recent evidence suggests that dopamine may play a role as well.

Objective: The aim of the study was to evaluate learning and working memory in OCD and to determine the effects of dopaminergic manipulations on these capacities.

Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

Context: There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges.

Objective: To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges.

The Irritability Questionnaire: a new scale for the measurement of irritability.

Irritability is an important symptom in patients with neuropsychiatric disorders. It is a major source of distress to patients and their carers and can lead to social and family dysfunction. Despite this, there has been little systematic research on irritability in psychiatry.

Obsessive-compulsive disorder: boundary issues.

The boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity.