Boys with Oppositional Defiant Disorder/Conduct Disorder Show Impaired Adaptation During Stress: An Executive Functioning Study.

Evidence for problems in executive functioning (EF) in children with oppositional defiant disorder/conduct disorder (ODD/CD) is mixed and the impact stress may have on EF is understudied. Working memory, sustained attention, inhibition and cognitive flexibility of boys with ODD/CD (n = 65) and non-clinical controls (n = 32) were examined under typical and stressful test conditions. Boys with ODD/CD showed impaired working memory under typical testing conditions, and impairments in working memory and sustained attention under stressful conditions. In contrast to controls, performance on sustained attention, cognitive flexibility and inhibition was less influenced by stress in boys with ODD/CD. These results suggest that boys with ODD/CD show impairments in adaptation to the environment whereas typically developing boys show adaptive changes in EF.Development Psychopathology in context: clinical setting

Requirements for generic anti-epileptic medicines: a regulatory perspective

Contains fulltext : 81660.pdf (publisher's version ) (Closed access

Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype

Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders

The development of spontaneous facial responses to others’ emotions in infancy. An EMG study

Viewing facial expressions often evokes facial responses in the observer. These spontaneous facial reactions (SFRs) are believed to play an important role for social interactions. However, their developmental trajectory and the underlying neurocognitive mechanisms are still little understood. In the current study, 4- and 7-month old infants were presented with facial expressions of happiness, anger, and fear. Electromyography (EMG) was used to measure activation in muscles relevant for forming these expressions: zygomaticus major (smiling), corrugator supercilii (frowning), and frontalis (forehead raising). The results indicated no selective activation of the facial muscles for the expressions in 4-month-old infants. For 7-month-old infants, evidence for selective facial reactions was found especially for happy faces (leading to increased zygomaticus major activation) and fearful faces (leading to increased frontalis activation), while angry faces did not show a clear differential response. This suggests that emotional SFRs may be the result of complex neurocognitive mechanisms which lead to partial mimicry but are also likely to be influenced by evaluative processes. Such mechanisms seem to undergo important developments at least until the second half of the first year of life

Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntington's Disease Transgenic Mice

Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD). However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST) positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5). and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease

Callous-unemotional traits moderate the relation between prenatal testosterone (2D:4D) and externalising behaviours in children

Children who exhibit callous-unemotional (CU) traits are identified as developing particularly severe forms of externalising behaviours (EB). A number of risk factors have been identified in the development of CU traits, including biological, physiological, and genetic factors. However, prenatal testosterone (PT) remains un-investigated, yet could signal fetal programming of a combination of CU/EB. Using the 2D:4D digit ratio, the current study examined whether CU traits moderated the relationship between PT and EB. Hand scans were obtained from 79 children aged between 5 and 6 years old whose parents completed the parent report ICU (Inventory of Callous Unemotional Traits) and SDQ (Strengths and Difficulties Questionnaire). CU traits were found to moderate the relationship between PT and EB so that children who were exposed to increased PT and were higher in CU traits exhibited more EB. Findings emphasize the importance of recognising that vulnerability for EB that is accompanied by callousness may arise before birth