Fear and panic in humans with bilateral amygdala damage

Feinstein, Justin S.; Buzza, Colin; Hurlemann, René; Follmer, Robin L.; Dahdaleh, Nader S.; Coryell, William; Welsh, Michael J.; Tranel, Daniel; Wemmie, John A.

doi:10.1038/nn.3323

Cited by 259 publications

(216 citation statements)

References 24 publications

(34 reference statements)

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“…The BLA is one key region particularly associated with anxiety and mood (Feinstein et al, 2013;Valentino et al, 1993). The BLA receives noradrenergic input from the LC (Asan, 1998;Fallon et al, 1978) and sends projections to the CeA, the prefrontal cortex, nucleus accumbens, and BNST, regions linked to mood regulation, and some with very disparate effects (Tye and Deisseroth, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The basolateral nucleus of the amygdala (BLA) is one key region associated with anxiety behavior (Valentino et al, 1993), including humans (Feinstein et al, 2013). We know that, in rodents, βAR antagonists infused into the amygdala block fear memory enhancement following stressful stimuli Mantsch et al, 2010;Quirarte et al, 1998;Schmidt and Weinshenker, 2014;Vranjkovic et al, 2014); is required for fear conditioning behavior (Cahill et al, 1994;Dębiec and Ledoux, 2004;Rogan et al, 1997); and systemic administration of the βAR antagonist propranolol reduces the spontaneous firing rate of neurons within the BLA (Buffalari and Grace, 2007;Ferry et al, 1997;Huang et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

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Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β 2 -adrenergic receptor (Opto-β 2 AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…To further explore this issue, we tested two additional patients (AM and BG), monozygotic twin sisters with focal bilateral amygdala lesions resulting from Urbach-Wiethe disease [...] As with patient SM, both patients also reported experiencing fear during the CO 2 challenge." (Feinstein et al, 2013) These startling observations affirm that the reaction to carbon dioxide must be due to an alternative alarm system, such as has been proposed for possible suffocation. We have suggested that under conditions of threatened asphyxia the activation of the HPA system would produce a counterproductive hyperoxidative state and is therefore inactivated.…”

Section: Panic and Comorbid Conditionsmentioning

confidence: 85%

“…Further damage to the amygdalocentric fear system theory is provided by Feinstein et al (2013) who studied three patients with amygdala damage produced by Urbach-Wiethe syndrome. It is worth extensive citation:…”

Section: Panic and Comorbid Conditionsmentioning

confidence: 99%

Lifelong Opioidergic Vulnerability Through Early Life Separation: A Recent Extension of the False Suffocation Alarm Theory of Panic Disorder

Preter¹

2016

Panic Disorder

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We briefly reference previous material on Klein's suffocation false alarm theory (SFA) of panic disorder (Klein, 1993) and its amplification in 2008 (Preter andKlein, 2008). We then discuss a recent finding showing a fundamental difference in opioidergic reactivity to a naloxone challenge in psychiatrically and medically healthy adults, based on the presence or absence of childhood separation/parental loss.In 1993, Klein published the original SFA theory of panic disorder (Klein, 1993), attempting to integrate the multiplicity of apparently unrelated clinical and laboratory observations. We posited "that a physiologic misinterpretation by a suffocation monitor misfires an evolved suffocation alarm system. This produces sudden respiratory distress followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor. If other indicators of potential suffocation provoke panic, this theoretical extension is supported." In the original paper, we tested "the theory by examining Ondine's curse as the physiologic and pharmacologic converse of panic disorder, splitting panic in terms of symptomatology and challenge studies, reevaluating the role of hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as well as mass hysteria." (Klein, 1993) Original SFA focused on relating the observed lactate and carbon dioxide hypersensitivity in panic disorder to a putative dysfunction in a hypothesized suffocation alarm. At the time, the underlying pathophysiology that might connect the apparent disparate "phenomena of panic during relaxation and sleep, late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease, separation anxiety, and treatment", was unknown.

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“…Els pacients d'una malaltia rara, la síndrome d'Urbach-Wiethe, que causa la calcifi cació de l'amígdala als dos hemisferis cerebrals, han confi rmat aquesta idea. Aquestes persones mostren una absència de respostes de por a tots els estímuls experimentats (Feinstein i altres, 2011) excepte a la inhalació de diòxid de carboni (Feinstein i altres, 2013 en la seua vida. Per tant, les dades sobre el paper de l'amígdala en les memòries emocionals derivades dels experiments amb animals semblen extrapolables als humans.…”

Section: La Base Neural De Les Memòries Emocionalsunclassified

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varios¹

2016

Anuari

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Fear and panic in humans with bilateral amygdala damage

Cited by 259 publications

References 24 publications

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Lifelong Opioidergic Vulnerability Through Early Life Separation: A Recent Extension of the False Suffocation Alarm Theory of Panic Disorder

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