Posted by desolationrower on January 13, 2010, at 11:14:45
Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms.
Pharmacol Ther. 2009 Nov 17. [Epub ahead of print]
Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms.Reynolds GP, Kirk SL.
Department of Psychiatry, Queen's University Belfast, Belfast BT9 7BL.
Obesity and metabolic syndrome, with increased risk of eventual cardiovascular disease and type II diabetes, are significant problems for patients receiving antipsychotic drugs and are likely contribute to their decreased life expectancy. Several drug-related mechanisms may contribute to these problems, including effects both influencing food intake and on glucose and lipid metabolism. The metabolic consequences of different antipsychotic drugs vary substantially; these variations reflect differences in receptor pharmacology and provide clues as to the underlying pharmacological mechanisms. The two drugs with the greatest effects on body weight, olanzapine and clozapine, also have high affinity for the 5-HT2C and histamine H1 receptors, which implicates these receptors in antipsychotic-induced weight gain, while peripheral M3 muscarinic receptor antagonism as well as central 5-HT2C effects may contribute to obesity-independent diabetes. Other receptor mechanisms may have additive or synergistic effects; dopamine D2 receptor antagonism can enhance 5-HT2C-mediated effects on food intake, as well as influencing lipid and glucose metabolism via disinhibition of prolactin secretion. Pharmacogenetic associations of drug-induced weight gain with 5-HT2C receptor and leptin gene polymorphisms, amongst others, have provided further clues. Elevated leptin secretion in the absence of a decrease in food intake indicates drug-induced leptin insensitivity in the hypothalamus. The minimal weight gain seen with ziprasidone and aripiprazole may reflect their having further pharmacological effects that protect against changes in food intake and related metabolic factors. Understanding the pharmacology of metabolic consequences of current antipsychotic drug treatment is clearly key to developing improved pharmacotherapies that avoid these problematic and limiting adverse effects.
Neurobiological Substrates of Dread
Gregory S. Berns,* Jonathan Chappelow, Milos Cekic, Caroline F. Zink, Giuseppe Pagnoni, Megan E. Martin-SkurskiGiven the choice of waiting for an adverse outcome or getting it over with quickly, many people choose the latter. Theoretical models of decision-making have assumed that this occurs because there is a cost to waitingi.e., dread. Using functional magnetic resonance imaging, we measured the neural responses to waiting for a cutaneous electric shock. Some individuals dreaded the outcome so much that, when given a choice, they preferred to receive more voltage rather than wait. Even when no decision was required, these extreme dreaders were distinguishable from those who dreaded mildly by the rate of increase of neural activity in the posterior elements of the cortical pain matrix. This suggests that dread derives, in part, from the attention devoted to the expected physical response and not simply from fear or anxiety. Although these differences were observed during a passive waiting procedure, they correlated with individual behavior in a subsequent choice paradigm, providing evidence for a neurobiological link between the experienced disutility of dread and subsequent decisions about unpleasant outcomes.
Prospection: Experiencing the Future
http://cogs.indiana.edu/spackled/Gilbert-Wilson.pdfFollowing One's Heart: Cardiac Rhythms Gate Central Initiation of Sympathetic Reflexes
Abstract
Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety.
http://www.jneurosci.org/cgi/content/full/29/6/1817Supramaximal training and postexercise parasympathetic reactivation in adolescents.
Buchheit M, Millet GP, Parisy A, Pourchez S, Laursen PB, Ahmaidi S.
Research Laboratory, Physical Activity and Motor Control: Adaptation and Rehabilitation, Faculty of Sport Sciences, University of Picardie Jules Verne, Amiens, France. martin.buchheit@u-picardie.fr
Repeated supramaximal exercise training is an efficient means of improving both aerobic and anaerobic energy system capacities. However, the influence of different levels of supramaximal training on parasympathetic function is unknown. PURPOSE: To compare the effects of repeated-sprint (RS) versus high-intensity intermittent training (HIT) on performance and postexercise parasympathetic reactivation in trained adolescents. METHODS: Fifteen male adolescents (15.6 +/- 0.8 yr) were divided into two groups that performed 9 wk of either RS (repeated all-out 6-s shuttle sprints; 14-20 s of recovery; N = 8) or HIT (15- to 20-s runs at 95% of the speed reached at the end of the 30-15 intermittent fitness test (V(IFT)); 15-20 s of recovery; N = 7). Groups performed intervals twice per week and maintained similar external training programs. Before and after training, performance was assessed by the V(IFT), countermovement jump (CMJ), 10-m sprint time (10 m), mean RS ability time (RSAmean), and heart rate (HRsub) level during a 6-min submaximal (60% V(IFT)) exercise test, where parasympathetic reactivation was assessed during the recovery phase (i.e., HR recovery time constant (HRRtau) and HR variability (HRV)). RESULTS: Parasympathetic function, V(IFT), and RSAmean were improved with HIT but not RS training. In contrast, changes in CMJ and HRsub were similar in both groups. A significant relationship was shown between the decrease in HRRtau and RSAmean (r = 0.62, P < 0.05; N = 15). CONCLUSION: HIT was more effective than RS training at improving postexercise parasympathetic function and physical performance. In addition, HRRtau, which was more sensitive to training than HRV indices, seems to be a useful performance-related measurement.
Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats
Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.
not so helpful to fixing things, but interesting to see where mental health issues originate:
Effects of stress throughout the lifespan on the brain, behaviour and cognitionSonia J. Lupien1, Bruce S. McEwen2, Megan R. Gunnar3 & Christine Heim4 About the authors
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AbstractChronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
http://www.nature.com/nrn/journal/v10/n6/full/nrn2639.html
short version(picture) http://www.nature.com/nrn/journal/v10/n6/images/nrn2639-f2.jpgSuccessful Antidepressant Therapy Restores the Disturbed Interplay Between TNF-α System and HPA Axis
Background
In depressed patients, alterations in the hypothalamo-pituitary-adrenocortical (HPA) system are the most consistent neurobiological finding. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.
MethodsWe examined alterations in plasma levels of tumor necrosis factor-α (TNF-α), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R p75) as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients without inflammation.
ResultsOn admission, TNF-α levels were inversely associated with the ACTH response to the combined dex/CRH test. Changes in TNF-α, sTNF-R p55, and sTNF-R p75 plasma levels from admission to discharge were positively correlated with the dex/CRH test outcome at discharge. Subgroup analysis revealed that this association was restricted to those patients achieving remission. In this subgroup, TNF-α levels at discharge were also positively correlated with dex/CRH test response at discharge.
ConclusionsOur results suggest that elevated HPA axis activity in acute depression suppresses TNF-α system activity, while after remission, when HPA axis activity has normalized, the TNF-α system seems to gain influence on the HPA system.
-d/r
poster:desolationrower
thread:933477
URL: http://www.dr-bob.org/babble/20100113/msgs/933477.html