Brain activation in PTSD in response to trauma-related stimuli

Objective: This article reviews the clinical and epidemiological aspects of anxiety disorders in youngsters, as well as current medical and psychological treatment strategies. The role of the neurobiological models possibly involved in the etiology of these disorders is also discussed.Sources of data: MEDLINE search of papers published in English from 1981 to 2003. The following key words were used: anxiety disorders, neurobiology, childhood, adolescence.Summary of the findings: Childhood-onset anxiety disorders are among the most frequent psychiatric conditions in children and adolescents. Epidemiological data estimate a prevalence of 10% in this population. The neurobiological models involved in the etiology of anxiety disorders in youngsters are closely related to neuroimaging studies with individuals presenting these pathologies. The role of the amygdala in the pathophysiology of these disorders is underscored. To be effective, treatment must combine several interventions, such as cognitive-behavioral, family, and, frequently, drug treatments.Conclusions: Early identification and prompt treatment of anxiety disorders may prevent negative consequences, such as school absenteeism and frequent and unnecessary visits to pediatric services due to somatic complaints related to anxiety disorders. Moreover, it is possible that psychiatric problems could be avoided or attenuated in adulthood.J Pediatr (Rio J). 2004;80(2 Suppl):S28-S34: Anxiety disorders, childhood, adolescence, neurobiology, psychopharmacology, cognitive-behavioral therapy.

Functional abnormalities in the dorsal-anterior-cingulate-cortex (dACC) underlie anxiety disorders and specifically post-traumatic stress disorder (PTSD). Promising and common behavioral approaches have limited effectiveness and many subjects exhibit spontaneous recovery of fear, as also evident in animal models following extinction training. Here, we use low-frequency stimulation (LFS), a protocol shown to induce long-term depression, with the aim of affecting synaptic plasticity induced by fear acquisition and extinction. We use aversive conditioning of either tone or visual stimuli paired with an aversive air-puff to the eye in a trace-conditioning paradigm. We find that LFS in the nonhuman primate (Macaca fascicularis) dACC, when combined with extinction training, was successful in preventing spontaneous recovery of the memory 24 -72 h following extinction. We simultaneously record single-units and local-fieldpotentials across the dACC, and show that LFS gradually depressed evoked responses. Moreover, this decrease in neural excitability predicted the successful reduction of overnight spontaneous recovery on a day-by-day basis. Finally, we show that this effect occurs when using either visual or auditory modality as the conditioned stimulus, and that the reduction was specific to the conditioned modality. Our results suggest that the primate dACC is actively involved in maintaining the original aversive memory, and propose that a combination of LFS with behavioral therapy might significantly improve treatment in severe cases.

This study examined localization of positive versus negative motivational functions mediated by GABA circuits within the accumbens shell. Microinjections of a GABA A agonist (0, 25, 75, and 225 ng/0.5 l muscimol) in rostral shell sites elicited appetitive increases in eating behavior. In contrast, microinjections in caudal shell sites elicited defensive burying or pawtreading behavior. Rats whose microinjections landed bilaterally outside of the accumbens shell did not display either behavior. Defensive treading elicited by caudal shell muscimol microinjection appeared to be a negative motivated response to threat (similar in parameters and orientation to normal defensive burying of a threatening electrified shock prod). The nucleus accumbens shell thus appears functionally heterogeneous in coding motivational valence. The demonstration that muscimol elicits positive eating behavior from rostral shell versus negative defensive behavior from caudal shell suggests in particular that GABAergic substrates of positive and negative types of motivated behavior in the nucleus accumbens shell are segregated along a rostrocaudal gradient.Key words: accumbens shell; GABA; food intake; reward; appetite; motivation; glutamate; dopamine; fear; defense; aggression; mesolimbic; microinjection GABAergic medium spiny neurons in the nucleus accumbens shell are implicated in the control of appetitive behavior and reward. Regarding eating behavior specifically, robust increases in food intake by rats are elicited by microinjection in the medial accumbens shell of either GABA A or GABA B receptor agonists (or non-NMDA glutamate antagonists) (Maldonado-Irizarry et al., 1995;Stratford and Kelley, 1997;Basso and Kelley, 1999).Aside from its role in positive appetitive behavior, the accumbens shell has also been implicated in negative motivational states, such as stress, fear, and defensive behavioral responses elicited by noxious or threatening stimuli (Inoue et al