Effects of 35% carbon dioxide (CO 2 ) inhalation in patients with post-traumatic stress disorder (PTSD): A double-blind, randomized, placebo-controlled, cross-over trial

Kellner, Michael; Muhtz, Christoph; Nowack, Sven; Wiedemann, Klaus; Yassouridis, Alexander

doi:10.1016/j.jpsychires.2017.10.019

Cited by 19 publications

(17 citation statements)

References 41 publications

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“…Another more recent study in rats showed that early-life maternal separation (a model of childhood separation anxiety) decreases the thresholds of panic-like behaviors elicited in response to electrical stimulation of the dPAG when tested in adulthood some months later 41 . This finding is particularly interestingly when viewed in the context of the recent report showing increased sensitivity to panicogenic challenge in patients with PTSD 42 , which is consistent with development of long-lasting trauma-induced changes in the excitability of the panic circuitry within the dPAG.…”

Section: Involvement Of the Pag In The Pathophysiology Of Ptsd: Long-supporting

confidence: 81%

“…The main type of PTSD is recognized to be associated with hyperarousal and hyperactivation of the amygdala, whereas the dissociative subtype of PTSD (PTSD+DS) is associated with lower amygdala activation, emotional detachment, and hypoarousal. A recent clinical study employed dynamic causal modeling and found that PTSD was characterized by a pattern of predominant bottom-up connectivity from the PAG to the amygdala and PFC, whereas PTSD+DS patients exhibited predominant top-down connectivity from the PFC to the amygdala and PAG 42 . Thus, “bottom-up” connections from the dPAG to the amygdala and ventromedial PFC predominate in individuals with PTSD compared with normal controls 43 .…”

Section: Involvement Of the Pag In The Pathophysiology Of Ptsd: Long-mentioning

confidence: 99%

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Role of the dorsal periaqueductal gray in posttraumatic stress disorder: mediation by dopamine and neurokinin

Brandão

Lovick

2019

Transl Psychiatry

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In susceptible individuals, exposure to intensely traumatic life events can lead to the development of posttraumatic stress disorder (PTSD), including long-term dysregulation of the contextual processing of aversive stimuli, the overgeneralization of learned fear, and impairments in the ability to learn or respond to safety signals. The neuropathophysiological changes that underlie PTSD remain incompletely understood. Attention has focused on forebrain structures associated with fear processing. Here we consider evidence from human and animal studies that long-lasting changes in functional connectivity between the midbrain periaqueductal gray (dPAG) and amygdala may be one of the precipitating events that contribute to PTSD. Long-lasting neuroplastic changes in the dPAG can persist after a single aversive stimulation and are pharmacologically labile. The early stage (at least up to 24 h poststimulation) involves neurokinin-1 receptor-mediated events in the PAG and amygdala and is also regulated by dopamine, both of which are mainly involved in transferring ascending aversive information from the dPAG to higher brain structures, mainly the amygdala. Changes in the functional connectivity within the dPAG-amygdala circuit have been reported in PTSD patients. We suggest that further investigations of plasticity and pharmacology of the PAGamygdala network provide a promising target for understanding pathophysiological circuitry that underlies PTSD in humans and that dopaminergic and neurokininergic drugs may have a potential for the treatment of psychiatric disorders that are associated with a dysfunctional dPAG.

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Section: Involvement Of the Pag In The Pathophysiology Of Ptsd: Long-supporting

confidence: 81%

Section: Involvement Of the Pag In The Pathophysiology Of Ptsd: Long-mentioning

confidence: 99%

Role of the dorsal periaqueductal gray in posttraumatic stress disorder: mediation by dopamine and neurokinin

Brandão

Lovick

2019

Transl Psychiatry

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“…Telch et al [51] provided evidence for this by exposing college students with self-reported high and low levels of anxiety sensitivity to CO 2 -35% and showed that individuals high in anxiety sensitivity were more likely to exhibit panic attacks than their low-anxiety sensitivity peers. Coupled with our findings, a logical next step for researchers would be to conduct step 2a studies comparing panic-like reactions following sodium lactate or CO 2 -35% in individuals with PD, as well as other disorders where elevated anxiety sensitivity is common, such as PTSD, obsessive compulsive disorder, and generalized anxiety disorder [49, 50, 52], respectively.…”

Section: Discussionmentioning

confidence: 90%

“…A recent study further highlights this possibility, as the researchers demonstrated that PTSD individuals were more likely to exhibit panic attacks following CO 2 -35% inhalation compared to a control inhalation condition [49]. This response may be present in individuals with PTSD because of a transdiagnostic characteristic also found in PD.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Sodium Lactate Infusion and CO<sub>2</sub>-35% Inhalation for Panic Disorder

Wiese

Boutros

2019

Neuropsychobiology

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Laboratory measures have played an integral role in diagnosing pathology; however, compared to traditional medicine, psychiatric medicine has lagged behind in using such measures. A growing body of literature has begun to examine the viability and development of different laboratory measures in order to diagnose psychopathologies. The present review examines the current state of development of both sodium lactate infusion and CO₂-35% inhalation as potential ancillary measures to diagnose panic disorder (PD). A previously established 3-step approach to identifying laboratory-based diagnostic tests was applied to available literature assessing the ability of both sodium lactate infusion or CO₂-35% inhalation to induce panic attacks in PD patients, healthy controls, and individuals with other psychiatric conditions. Results suggest that across the literature reviewed, individuals with PD were more likely to exhibit panic attacks following administration of sodium lactate or CO₂-35% compared to control participants. The majority of the studies examined only compared individuals with PD to healthy controls, suggesting that these ancillary measures are underdeveloped. In order to further determine the utility of these ancillary measures, research is needed to determine if panic attacks following administration of these chemical agents are unique to PD, or if individuals with related pathologies also respond, which may be indicative of transdiagnostic characteristics found across disorders.

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“…Particularly 35% CO 2 effectively induces DSM specified symptoms ( Griez, 1984 ) that are in striking resemblance to real-life PA ones ( Griez et al, 1987 ; Schruers et al, 2004 ), indicating that an acute disturbance of the acid-base homeostasis might be the mechanism underlying PAs as we previously proposed ( Esquivel et al, 2009 ). PD patients react significantly stronger to CO 2 than patients of many other disorders ( Verburg et al, 1994 ; Perna et al, 1999 ; Kent et al, 2001 ) with the exception of post-traumatic stress disorder patients who are also reactive to CO 2 ( Muhtz et al, 2011 ; Kellner et al, 2018 ). Additionally, social anxiety disorder patients show an intermediate reactivity between healthy individuals and PD patients ( Schutters et al, 2012 ).…”

Section: Panic Attacks In the Laboratorymentioning

confidence: 94%

Assessing Panic: Bridging the Gap Between Fundamental Mechanisms and Daily Life Experience

Leibold

Schruers

2018

Front. Neurosci.

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Panic disorder (PD) is one of the most common psychiatric disorders. Recurrent, unexpected panic attacks (PAs) are the primary symptom and strongly impact patients’ quality of life. Clinical manifestations are very heterogeneous between patients, emphasizing the need for a dimensional classification integrating various aspects of neurobiological and psychological circuits in line with the Research Domain Criteria (RDoC) proposed by the US National Institute of Mental Health. To go beyond data that can be collected in the daily clinical situation, experimental panic provocation is widely used, which has led to important insights into involved brain regions and systems. Genetic variants can determine the sensitivity to experimental models such as carbon dioxide (CO2) exposure and can increase the risk to develop PD. Recent developments now allow to better assess the dynamic course of PAs outside the laboratory in patients’ natural environment. This can provide novel insights into the underlying mechanisms and the influence of environmental factors that can alter gene regulation by changing DNA methylation. In this mini review, we discuss assessment of PAs in the clinic, in the laboratory using CO2 exposure, genetic associations, and the benefits of real-life assessment and epigenetic research.

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Effects of 35% carbon dioxide (CO 2 ) inhalation in patients with post-traumatic stress disorder (PTSD): A double-blind, randomized, placebo-controlled, cross-over trial

Cited by 19 publications

References 41 publications

Role of the dorsal periaqueductal gray in posttraumatic stress disorder: mediation by dopamine and neurokinin

Role of the dorsal periaqueductal gray in posttraumatic stress disorder: mediation by dopamine and neurokinin

Diagnostic Utility of Sodium Lactate Infusion and CO<sub>2</sub>-35% Inhalation for Panic Disorder

Assessing Panic: Bridging the Gap Between Fundamental Mechanisms and Daily Life Experience

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