Neural Underpinnings of Panic Disorder: A Critical Literature Review

Panic disorder (PD) is a prevalent and potentially disabling anxiety disorder characterized by recurrent unexpected panic attacks, persistent concern about future attacks, and associated behavioral changes that may lead to significant functional impairment. Although extensively studied, no single theoretical model fully accounts for the phenomenology, etiology, and neurobiology of panic disorder. This thesis critically reviews contemporary literature on panic disorder with the aim of evaluating existing conceptual and neurobiological models and contributing to the development of a more integrative neurobiological framework. The thesis examines the historical and diagnostic foundations of panic disorder, with particular attention to current DSM diagnostic criteria and their limitations, including challenges related to categorical classification, symptom thresholds, high comorbidity, and cultural variability. Dimensional approaches, such as the Research Domain Criteria (RDoC) framework, are considered as complementary perspectives that may better capture underlying neurobiological processes. Evidence from genetic, neurochemical, neuroimaging, and psychophysiological research is synthesized, indicating a moderate heritable contribution and a complex, polygenic architecture involving multiple neurotransmitter systems, including serotonergic, GABAergic, and noradrenergic pathways. Neurobiological models emphasizing dysregulation within fear and arousal networks, particularly amygdala-brainstem circuitry and its interaction with prefrontal regulatory regions, are critically evaluated. Overall, the thesis seeks to advance an integrative neurobiological perspective in which cognitive, developmental, and contextual factors are conceptualized as interacting with underlying neural vulnerabilities. This approach aims to provide a more coherent account of panic disorder and to inform future research and clinical practice.

Panic disorder (PD) is a prevalent and potentially disabling anxiety disorder characterized by recurrent unexpected panic attacks, persistent concern about future attacks, and associated behavioral changes that may lead to significant functional impairment. Although extensively studied, no single theoretical model fully accounts for the phenomenology, etiology, and neurobiology of panic disorder. This thesis critically reviews contemporary literature on panic disorder with the aim of evaluating existing conceptual and neurobiological models and contributing to the development of a more integrative neurobiological framework. The thesis examines the historical and diagnostic foundations of panic disorder, with particular attention to the current DSM diagnostic criteria and their limitations, including challenges related to categorical classification, symptom thresholds, high comorbidity, and cultural variability. Dimensional approaches, such as the Research Domain Criteria (RDoC) framework, are considered as complementary perspectives that may better capture underlying neurobiological processes. Evidence from genetic, neurochemical, neuroimaging, and psychophysiological research is synthesized, indicating a moderate heritable contribution and a complex, polygenic architecture involving multiple neurotransmitter systems, including serotonergic, GABAergic, and noradrenergic pathways. Neurobiological models emphasizing dysregulation within fear and arousal networks, particularly amygdala-brainstem circuitry and its interaction with prefrontal regulatory regions, are critically evaluated. Overall, the thesis seeks to advance an integrative neurobiological perspective in which cognitive, developmental, and contextual factors are conceptualized as interacting with underlying neural vulnerabilities. This approach aims to provide a more coherent account of panic disorder and to inform future research and clinical practice.