Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males

Background: Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans. Methods: This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli. Results: In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed. Conclusions: These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety

Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder

Background: Computational research had determined that adults with obsessive–compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients’ compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD. Methods: Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects’ actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence–action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication. Results: Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients’ confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem. Conclusions: Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing ‘just-right’ compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research

Innovative solutions to novel drug development in mental health

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders

Neuropsychological profile of young adults with spina bifida with or without hydrocephalus

Objectives: To determine the relative impact of hydrocephalus and spinal dysraphism in young adults on intellectual and cognitive functioning. Sub-groups of patients with congenital hydrocephalus and/or spina bifida were assessed between 1995 and 2003. The entry criteria were that individuals should have (i) intact global function, (ii) average verbal intelligence (or above), and (iii) should not have clinical depression. There were three sub-groups: patients with hydrocephalus and spina bifida, patients with hydrocephalus without spina bifida, and patients with spina bifida without hydrocephalus. Methods: Patients were neuropsychologically assessed as part of their normal clinical assessment during their annual medical review. Each individual completed a screening battery assessing global functioning, verbal intelligence, and mood. In addition they completed additional tests including measures of emotional intelligence, memory, attention, and executive function. Results were analysed to compare the performance of the patient sub-groups and to compare them to a healthy control group. Results: Patients with hydrocephalus (with or without spina bifida) were significantly impaired on the vast majority of all test scores as compared to patients with spina bifida and healthy controls. They were particularly poor on measures assessing executive function. By contrast for patients with spina bifida with no associated hydrocephalus, the significant majority of all test scores fell within the average range or above. Conclusions: The neuropsychological profile of patients with hydrocephalus is one of relative impairment and this is so whether or not spina bifida is present. In spina bifida alone, in the absence of hydrocephalus, cognitive function is relatively spared

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

Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder.

Item does not contain fulltextOBJECTIVE: Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. METHOD: The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). RESULTS: Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. CONCLUSIONS: Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.1 februari 201

The neuropsychology of normal pressure hydrocephalus (NPH)

Normal pressure hydrocephalus (NPH) accounts for one of the few known forms of reversible dementia. Varied aetiology and clinical presentation contribute to difficulties with early or differential diagnoses, and delayed surgical treatment may be less efficacious. Clinical neuropsychology provides a means of determining a cognitive profile for NPH, assisting in differential diagnosis, tracking the disorder's progression and assessing the efficacy of treatment. This article will review possible applications of clinical neuropsychology and propose a clinical assessment protocol for NPH