What are the biologic causes of panic disorder?

Updated: Mar 21, 2018
  • Author: Mohammed A Memon, MD; Chief Editor: Randon S Welton, MD  more...
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Answer

The apparent neurochemical dysfunction behind panic disorder may involve autonomic imbalance, decreased gamma-aminobutyric acid (GABA)–ergic tone, [13] allelic polymorphism of the catechol-O-methyltransferase (COMT) gene, increased adenosine receptor function, increased cortisol, [14] diminished benzodiazepine receptor function, and disturbances in serotonin, [15] serotonin transporter (5-HTTLPR) [16] and promoter (SLC6A4) genes, [17] norepinephrine, dopamine, cholecystokinin, and interleukin 1–beta. [18]

Some authors theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity. [8] Some epileptic patients have panic as a manifestation of their seizures.

The serotonergic model suggests an exaggerated or inefficient postsynaptic receptor response to synaptic serotonin, potentially in the signal transduction cascade. Some studies report subsensitivity of serotonin 1A (5HT1A) receptors. The 5HT system or one of its subsystems may play a role in the pathophysiology of panic disorder, but further investigation is needed.

The catecholamine model postulates increased sensitivity to or improper processing of adrenergic CNS discharges, with potential hypersensitivity of presynaptic alpha-2 receptors.

Similarly, the locus coeruleus model explains that panic symptoms are due to increased local discharge resulting in adrenergic neuronal stimulation, similar to the more general catecholamine theory. Locus coeruleus activity also affects the hypothalamic-pituitary-adrenal (HPA) axis, which can respond abnormally to clonidine in patients with panic disorder.

The lactate model focuses on symptom production by postulated aberrant metabolic activity induced by lactate. The false suffocation carbon dioxide hypothesis explains panic phenomena by hypersensitive brainstem receptors. The GABA model postulates decreased inhibitory receptor sensitivity, with a resultant excitatory effect.

The neuroanatomic model suggests that panic attacks are mediated by a "fear network" in the brain that involves the amygdala, hypothalamus, and brainstem centers. More generally, the corticostriatal-thalamocortical (CSTC) circuitry is believed to mediate worry, interacting with the more fear-specific circuit in the amygdala. The sensation of fear occurs through reciprocal regulatory activity conceptually initiated in the amygdala and projected to the anterior cingulate cortex and/or orbitofrontal cortex. Projections from the amygdala to the hypothalamus then mediate endocrinologic responses to fear.

The cognitive theory suggests that patients with panic disorder have a heightened sensitivity to internal autonomic cues (e.g., tachycardia).


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