Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD

Butler, Robert W.; Braff, David L.; Rausch, Jeffrey L.; Jenkins, Melissa; Sprock, Joyce; Geyer, Mark A.

doi:10.1176/ajp.147.10.1308

Cited by 220 publications

(44 citation statements)

References 18 publications

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“…The recognition of the importance of these symptoms dates back over 50 years! Classic studies determined that, in schizophrenia, anxiety disorders, including posttraumatic stress disorder (PTSD), and bipolar and unipolar depression, increased vigilance and REM sleep drive (increased REM duration, decreased REM latency, hypervigilance, etc., usually coupled with decreases in slow wave sleep-SWS) are major, incapacitating symptoms (Braff et al 1978; Butler et al 1990; Caldwell and Domino 1967; Coble et al 1976; Feinberg et al 1969; Jus et al 1973; Krupfer 1976; Ross et al 1989; Shalev et al 1992; Zarcone et al 1975). Most patients with schizophrenia, bipolar depression, male obsessivecompulsive disorder, and panic attacks develop the disorder postpubertally (~80% between the ages of 15 and 25, during the normal decrease in REM sleep in humans (Roffwarg et al 1966)), while unipolar depression in adolescents is very high (Garcia-Rill 1997).…”

Section: Three Questionsmentioning

confidence: 99%

Gamma band activity in the RAS-intracellular mechanisms

et al. 2013

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Gamma band activity participates in sensory perception, problem solving, and memory. This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit gamma band activity, and describes the intrinsic membrane properties behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine Subcoeruleus nucleus dorsalis (SubCD) all fire in the gamma band range when maximally activated, but no higher. The mechanisms involve high threshold, voltage-dependent P/Q-type calcium channels or sodium-dependent subthreshold oscillations. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. We address three necessary next steps resulting from these discoveries, an intracellular mechanism responsible for maintaining gamma band activity based on persistent G-protein activation, separate intracellular pathways that differentiate between gamma band activity during waking vs during REM sleep, and an intracellular mechanism responsible for the dysregulation in gamma band activity in schizophrenia. These findings open several promising research avenues that have not been thoroughly explored. What are the effects of sleep or REM sleep deprivation on these RAS mechanisms? Are these mechanisms involved in memory processing during waking and/or during REM sleep? Does gamma band processing differ during waking vs REM sleep after sleep or REM sleep deprivation?

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Section: Three Questionsmentioning

confidence: 99%

Gamma band activity in the RAS-intracellular mechanisms

et al. 2013

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“…A primary symptom of PTSD that is not common in depression is hyperarousal, which can manifest as increased acoustic startle reactivity at baseline (e.g. (Butler et al, 1990) and greater startle responses in aversive contexts, (reviewed in (Grillon and Baas, 2003; Risbrough, 2010). PTSD may also be associated with decreased sensorimotor gating as measured by reduced habituation to repeated stimuli and reduced inhibition of startle as measured by prepulse inhibition (PPI) (reviewed in (Clark et al, 2009)).…”

Section: Introductionmentioning

confidence: 99%

Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1) on startle behavior and sensorimotor gating

Flandreau

Risbrough²,

et al. 2015

Psychoneuroendocrinology

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The corticotropin-releasing factor (CRF) family of peptides and receptors coordinates the mammalian endocrine, autonomic, and behavioral responses to stress. Excessive CRF production has been implicated in the etiology of stress-sensitive psychiatric disorders such as posttraumatic stress disorder (PTSD), which is associated with alterations in startle plasticity. The CRF family of peptides and receptors mediate acute startle response changes during stress, and chronic CRF activation can induce startle abnormalities. To determine what neural circuits modulate startle in response to chronic CRF activation, transgenic mice overexpressing CRF throughout the central nervous system (CNS; CRF-COECNS) or restricted to inhibitory GABAergic neurons (CRF-COEGABA) were compared across multiple domains of startle plasticity. CRF overexpression throughout the CNS increased startle magnitude and reduced ability to inhibit startle (decreased habituation and decreased prepulse inhibition (PPI)), similar to previous reports of exogenous effects of CRF. Conversely, CRF overexpression confined to inhibitory neurons decreased startle magnitude but had no effect on inhibitory measures. Acute CRF receptor 1 (CRF1) antagonist treatment attenuated only the effects on startle induced by CNS-specific CRF overexpression. Specific deletion of CRF1 receptors from forebrain principal neurons failed to alter the effects of exogenous CRF or stress on startle, suggesting that these CRF1 expressing neurons are not required for CRF-induced changes in startle behaviors. These data indicate that the effects of CRF activation on startle behavior utilize an extensive neural circuit that includes both forebrain and non-forebrain regions. Furthermore, these findings suggest that the neural source of increased CRF release determines the startle phenotype elicited. It is conceivable that this may explain why disorders characterized by increased CRF in cerebrospinal fluid (e.g. PTSD and major depressive disorder) have distinct symptom profiles in terms of startle reactivity.

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“…Prior work has also demonstrated an enhanced amygdala response to negative emotional stimuli for patients with anxiety compared to healthy individuals (Shah, et al, 2009). Further, high trait anxiety has been repeatedly linked with an exaggerated peripheral emotional response to aversive stimuli (Butler et al, 1990; Cook et al, 1992; Grillon et al, 1994, 1998, 2002; Knight et al, 2011), as well as increased amygdala reactivity (Brühl et al, 2011; Indovina et al, 2011) in anticipation of aversive events. Therefore, identifying the relationship between trait anxiety and the threat-elicited neurophysiological response may provide a more complete understanding of these emotional processes in general.…”

mentioning

confidence: 99%

The amygdala mediates the emotional modulation of threat-elicited skin conductance response.

Wood

Hoef

Knight

2014

Emotion

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The ability to respond adaptively to threats in a changing environment is an important emotional function. The amygdala is a critical component of the neural circuit that mediates many emotion- related processes, and thus likely plays an important role in modulating the peripheral emotional response to threat. However, prior research has largely focused on the amygdala’s response to stimuli that signal impending threat, giving less attention to the amygdala’s response to the threat itself. From a functional perspective, however, it is the response to the threat itself that is most biologically relevant. Thus, understanding the factors that influence the amygdala’s response to threat is critical for a complete understanding of adaptive emotional processes. Therefore, we used functional magnetic resonance imaging (fMRI) to investigate factors (i.e. valence and arousal of co-occurring visual stimuli) that influence the amygdala’s response to threat (loud white-noise). We also assessed whether changes in amygdala activity varied with the peripheral expression of emotion (indexed via skin conductance response; SCR). The results showed that threat-elicited amygdala activation varied with the arousal, not valence of emotional images. More specifically, threat-elicited amygdala activation was larger to the threat when presented during high arousal (i.e. negative & positive) vs. low arousal (i.e. neutral) images. Further, the threat-elicited amygdala response was positively correlated with threat-elicited SCR. These findings indicate the amygdala’s response to threat is modified by the nature (e.g. arousal) of other stimuli in the environment. In turn, the amygdala appears to mediate important aspects of the peripheral emotional response to threat.

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Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD

Cited by 220 publications

References 18 publications

Gamma band activity in the RAS-intracellular mechanisms

Gamma band activity in the RAS-intracellular mechanisms

Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1) on startle behavior and sensorimotor gating

The amygdala mediates the emotional modulation of threat-elicited skin conductance response.

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