Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism.

Autism spectrum conditions (autism) affect ~1% of the population and are characterized by deficits in social communication. Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings. Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings. A randomized double-blind, placebo-controlled, within-subjects design is used to examine how intranasal administration of 24 IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher. This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli. Eye movements are recorded using eye tracking, providing an objective measurement of looking patterns. The measure is shown to be sensitive to the reduced eye contact commonly reported in autism, with the autism group spending less time looking to the eye region of the face than controls. Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups (transformed mean eye-fixation difference per second=0.082; 95% CI:0.025-0.14, P=0.006). Within the autism group, oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline (Cohen's d=0.86). These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction, providing evidence of a therapeutic effect in a key aspect of social communication.

Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals.

RATIONALE: There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato-thalamo-orbitofrontal circuits, it has been suggested that decision-making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging. METHODS: Decision-making was investigated using the Cambridge Risk Task during H2(15)O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history. RESULTS: During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex. CONCLUSION: Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year.

Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial.

RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. METHODS: Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. RESULTS: There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex.

Diazepam produces disinhibitory cognitive effects in male volunteers.

RATIONALE: Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function. OBJECTIVES: We aimed to determine the impact of diazepam on a variety of executive tasks. METHODS: The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery. RESULTS: Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond. CONCLUSIONS: In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.