Experimental Human Endotoxemia Enhances Brain Activity During Social Cognition.

Experimental Human Endotoxemia Enhances Brain Activity During Social Cognition.

Soc Cogn Affect Neurosci. 2013 Apr 1;
Kullmann JS, Grigoleit JS, Wolf OT, Engler H, Oberbeck R, Elsenbruch S, Forsting M, Schedlowski M, Gizewski ER

Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind, randomized crossover functional magnetic resonance imaging study, 18 healthy, right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e., Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-?) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness. HubMed – depression

Quantum-chemical approach to determining the high potency of clorgyline as an irreversible acetylenic monoamine oxidase inhibitor.

J Neural Transm. 2013 Apr 2;
Pavlin M, Mavri J, Repi? M, Vianello R

Density functional theory calculations were employed to investigate the nature of chemical bond formation between the flavin co-factor of the enzyme monoamine oxidase (MAO) and its irreversible acetylenic inhibitor clorgyline in its terminally deprotonated anionic form. Since MAOs regulate the level of neurotransmitters in living cells, this reaction is pharmacologically relevant for treating depression and other mood disorders. The results revealed that this pathway is associated with the activation free energy of ?G act (#)  = 17.4 kcal mol(-1), which, together with our previous results, suggests that clorgyline is intrinsically a more effective MAO inhibitor than antiparkinsonian drugs rasagiline and selegiline considering the preferred MAO isoforms in each case, thus displaying a trend in agreement with experimental data. The reaction is facilitated by the pronounced electrophilic character of the flavin moiety, due to its ability to efficiently accommodate excess negative charge from the approaching anionic inhibitor through resonance effect. The investigated mechanism was additionally validated by the inspection of the geometry of the flavin moiety in the formed adduct, which exhibit distortion from planarity consistent with experimental observations. These results offer valuable insight for mechanistic studies on other flavoenzymes and for the design of new antidepressants and antiparkinsonian drugs. HubMed – depression

Sleep and suicide: an analysis of a cohort of 394,000 Taiwanese adults.

Soc Psychiatry Psychiatr Epidemiol. 2013 Apr 2;
Gunnell D, Chang SS, Tsai MK, Tsao CK, Wen CP

BACKGROUND: Sleep problems may lead to, or be symptomatic of, depression and other mental illnesses yet few studies have investigated their association with suicide risk. DESIGN: Prospective cohort study. SETTING: Taiwan. PARTICIPANTS: 393,983 men and women aged 20 or above participating in the MJ health check-up programme. RESULTS: There were 335 suicides over a mean of 7.4 years follow-up. There was a reverse J-shaped association between sleep duration and suicide risk. When compared with those sleeping 6-8 h per night the adjusted hazard ratios (95 % confidence intervals) for suicide associated with 0-4, 4-6 and >8 h sleep were 3.5 (2.0-6.1), 1.5 (1.1-1.9) and 1.5 (1.1-2.0), respectively. People requiring sleeping pills to get to sleep (1.2 % participants) were at over 11-fold increased risk; difficulty falling asleep (11.5 % participants), frequent dreaming (16.7 %) and being easily awoken (30.6 %) were associated with a 2.0-, 1.6- and 1.3-fold increased risk of suicide, respectively. CONCLUSIONS: Less than 6 h sleep duration, sleep disturbances and reported use of sleep medicines are markers of suicide risk. Sleep problems should be assessed when evaluating suicide risk. HubMed – depression

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