Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation

<p>Abstract</p> <p>Background</p> <p>The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC).</p> <p>Results</p> <p>This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged.</p> <p>Conclusion</p> <p>The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerability to psychosis by (i) producing the hyperactive mode of the PFC with hyperdopaminergic neurotransmission by dysfunctional chandelier cells and (ii) increasing the probability of the transition to the hyperactive mode from the conventional inverted-U mode by dysfunctional GABAergic interneurons.</p

Dihydrotestosterone is elevated following sprint exercise in healthy young men

Dihydrotestosterone (DHT) exerts both functional and signaling effects extending beyond the effects of testosterone in rodent skeletal muscle. As a primer for investigating the role of DHT in human skeletal muscle function, this study aimed to determine whether circulating DHT is acutely elevated in men following a bout of repeat sprint exercise and to establish the importance of training status and sprint performance to this response. Fourteen healthy active young men (V̇O2max 61.0 ± 8.1 ml·kg body mass-1·min-1) performed a bout of repeat sprint cycle exercise at a target workload based on an incremental work-rate maximum (10 × 30 s at 150% Wmax with 90-recovery). Venous blood samples were collected preexercise and 5 and 60 min after exercise. Five minutes after exercise, there were significant elevations in total testosterone (TT; P &lt; 0.001), free testosterone (FT; P &lt; 0.001), and DHT (P = 0.004), which returned to baseline after 1 h. Changes in DHT with exercise (5 min postexercise - preexercise) correlated significantly with changes in TT (r = 0.870; P &lt; 0.001) and FT (r = 0.914; P &lt; 0.001). Sprinting cadence correlated with changes in FT (r = 0.697; P = 0.006), DHT (r = 0.625; P = 0.017), and TT (r = 0.603; P = 0.022), and habitual training volume correlated with the change in TT (r = 0.569, P = 0.034). In conclusion, our data demonstrate that DHT is acutely elevated following sprint cycle exercise and that this response is influenced by cycling cadence. The importance of DHT in the context of exercise training and sports performance remains to be determined. Copyright © 2013 the American Physiological Society

Ankylosing spondylitis and an aortic arch syndrome.

A 63 year old woman with a 16 year history of ankylosing spondylitis and peripheral joint involvement later presented with a large vessel arteritis affecting the branches of the arch of the aorta