Understanding Panic Disorder: Symptoms, Neurobiology, and Treatment, Study notes of Neurobiology

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Panic disorder (with or without Agarophobia)

 Isolated panic attack very common 27.7 %

 Panic disorder 1-2% of general population

 5-10% of primary care patients

 Onset bimodal 15-25 or 45-

 Female/male ratio 2-3:

Panic Disorder Epidemiology

Agoraphobia with or without Panic Attacks ICD 10

 If patients with Panic Attacks are agoraphobic-

they will be classified under Agoraphobia (with Panic Attacks) in ICD 10

DSM 5

 In DSM 5 Panic Attacks and Agoraphobia are 2 separate diagnosis and both conditions would have to be diagnosed and coded

Panic Disorder

 Panic Disorder with Agoraphobia has a worse prognosis

 Panic attacks without panic disorder is common (22.7%)

 Between 18-45 % of patients with panic attacks also suffer from nocturnal panic attacks

Comorbidity

 Agoraphobia 30-50 %

 Depression: 40 – 80 %

 Substance abuse: 20 – 40 %

 Bipolar Disorder

 Other Anxiety Disorders

 Other physical or neurological disorders

Differential Diagnosis

 Cardiovascular Disease  Angina  CHF  Hypertension  Mitral valve prolapse  Myocardial Infarction  Paradoxical atrial tachycardia  Pulmonary Disease  Asthma  Pulmonary embolism  Drug intoxication or withdrawal

 Neurological Disease  CVA / TIA  Epilepsy  Meniere’s disease  Migraine  Tumor  Endocrine Disease  Carcinoid syndrome  Hyperthyroidism  Perimenopausal  Pheochromocytoma  Other  SLE  Systemic infection  Heavy metal poisoning

Case example Panic Disorder

(Julie)

 Panic attack video (12 min) with exercise (underlying thoughts anxious and resulting behaviours of patient and short formulation)

 https://www.youtube.com/watch?v=Ii2F HbtVJzc

Prognosis of Panic Disorder

 30 – 40 % become symptom free

 50 % with mild symptoms with little impairment of function

 Cognitive and behavioural treatments including graded exposure are highly effective

 10 – 20 % continue with significant impairment

Some interesting facts about Panic Disorder

 Is frequently associated with genomic duplication on Chr. 15

 Significant concordance rate for monozygotic compared to dizygotic twins

 Association with childhood parental death or separation from mother

 Pacemaker

 Excess caffeine

 Sympathomimetic drugs sodium lactate, pentagastrin, carbon dioxide can induce panic

Neurobiology of Panic

Serotonin

 supported by efficacy of SSRIs

 major nuclei:

MRN limbic/ prefrontal cortex structures  Mediates fear/ anticipatory anxiety DRN prefrontal cortex, basal ganglia, thalamus, LC, substantia nigra, periaqueductal grey  Modulates cognitive/ behavioural components

 strong feedback relationship with LC

MRN: medial raphe nucleus DRN: dorsal raphe nucleus

Neurobiology of Panic

 Amygdala key in conditioned fear aquisition/extinction

 LC: NE neurons

 Implicated in animal studies  Strong feedback relationship with raphe nuclei/5HTIncreased adrenergic activity

 Increased post synaptic response to serotonin

 Increased adrenergic activity

 Decreased sensitivity to GABA ( inhibitory)

 Increasing evidence re significance of NMDA receptor in conditioning

Acid - base balance

 Anxious patients produce more lactate on exercise than controls

 IV lactate produces panic  specific for panic  treatment with imipramine blocks effect  arouses PD patients from sleep  Mechanisms  chemoreceptors more sensitive to pH and hypoxia  induced metabolic alkalosis and hyperventilation

Neuroimaging and Panic Disorder

  Temporal lobe MRI vol  greatest with early onset and severity of illness

 High rate of septo-hippocampal abnormalities (correlates with EEG abnormalities

? Hippocampal functional change   PET glucose metabolism   SPECT rCBF