Anxiety Disorders: Panic Disorder

• Anxiety disorders, trauma- and stressor-related disorders, and obsessive-compulsive and related disorders can be compared by their pathophysiology and clinical manifestations.

Panic Disorder (PD)

• Pathophysiology includes a dysregulated Autonomic Nervous System (ANS) that leads to a hypersensitive fight-or-flight response.
• Decreased Benzodiazepine Receptors cause reduced function of GABA-A receptors, which would normally inhibit overactive responses thus heightening anxiety.
• 20% increased risk among first-degree relatives suggests a genetic contribution.
• Clinical manifestations manifest as sudden, intense episodes of fear or discomfort, or panic attacks.
• Physical symptoms include palpitations, sweating, trembling, chest pain, shortness of breath, dizziness, and nausea.
• Psychological symptoms like fear of dying or losing control are also clinical manifestations.
• Avoidance behavior often develops due to fear of future attacks.

Generalized Anxiety Disorder (GAD)

• Pathophysiology includes decreased serotonin activity because altered serotonin signaling, or increased reuptake, contributes to persistent worry.
• Changes in the norepinephrine system like altered receptor expression, lead to autonomic overactivity.
• Impaired Benzodiazepine Receptor Function leads to reduced inhibitory signaling via GABA.
• Genetic Factors have concordance rates of approximately 30% in female twins.
• Clinical Manifestations include persistent, excessive worry about daily activities and somatic symptoms such as headaches and gastrointestinal issues.
• Restlessness, irritability, muscle tension, fatigue, and sleep disturbances are clinical manifestations.

Post-Traumatic Stress Disorder (PTSD)

• Pathophysiology presents with a reduced hippocampal volume, where the hippocampus, responsible for distinguishing between safe and dangerous stimuli, is reduced in volume.
• Amygdala overactivity from a hyperactive amygdala causes exaggerated fear response.
• Decreased prefrontal cortex function impairs regulation of emotions and control over fear responses.
• Decreased Benzodiazepine Receptor Distribution contributes to heightened arousal and anxiety.
• A dysregulated HPA Axis has elevated cortisol levels initially, but chronic dysregulation can impair feedback loops.
• Clinical manifestations include intrusive thoughts, nightmares, flashbacks, hypervigilance, irritability, exaggerated startle response, sleep disturbances, mood changes, and social withdrawal.
• Avoidance of trauma reminders is also a clinical manifestation.

Obsessive-Compulsive Disorder (OCD)

• Pathophysiology presents with a dysregulated basal ganglia-prefrontal cortex circuit; abnormal communication between the basal ganglia and orbitofrontal cortex leads to intrusive thoughts and compulsive behaviors.
• Increased prefrontal cortex activity and heightened activity leads to difficulty stopping repetitive thoughts.
• Decreased serotonin synthesis as reduced serotonin contributes to compulsive behaviors.
• A genetic component shows a 10-12% risk among first-degree relatives.
• Clinical Manifestations include obsessions, which are persistent, intrusive thoughts, compulsions like repetitive behaviors aimed at reducing distress, and impairment, which is difficulty carrying out daily activities due to compulsions.
• High levels of anxiety and distress when unable to perform compulsions are clinical manifestations.

Comparison Summary

• Panic disorder pathophysiology includes hyperactive ANS, decreased GABA receptor activity, and genetic predisposition, with key clinical features of sudden, intense panic attacks with physical and cognitive symptoms.
• GAD's pathophysiology presents with decreased serotonin and norepinephrine activity, and impaired GABA signaling, with key clinical features of persistent worry, restlessness, fatigue, and somatic complaints.
• PTSD’s pathophysiology shows hippocampal atrophy, amygdala overactivity, and prefrontal dysfunction, with key clinical features including intrusive memories, hypervigilance, and emotional dysregulation.
• OCD's pathophysiology possesses a dysregulated basal ganglia-prefrontal cortex circuit and decreased serotonin, with key clinical features of intrusive obsessions, compulsive behaviors, and functional impairment.