2 Neuroscience2.11 Integrated neurobiology of syndromes and states
2.11.4 Anxiety disorders
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Written by Resident Doctor Committee · Published
Threat circuits
Structure | Role in threat |
|---|---|
Amygdala | Lateral part handles conditioning; central part drives hypothalamus and brainstem |
Bed nucleus of the stria terminalis | Sustained response to uncertain threat |
Hippocampus | Context memory and threat discrimination |
Insula | Awareness of bodily state and interoceptive threat |
Periaqueductal grey | Defensive responses and analgesia |
Ventromedial prefrontal pathways to the amygdala support extinction recall, and the dorsolateral prefrontal cortex supports reappraisal.
Learning and avoidance
Mowrer's two-factor model combines classical fear conditioning with avoidance maintained by negative reinforcement.
Preparedness may explain why phobias cluster on animals, heights and blood.
Overgeneralisation spreads fear to dissimilar cues and widens avoidance.
Extinction builds safety learning without erasing fear, so fear can return with time, a change of context or an aversive event.
Safety behaviours block corrective learning when safety is credited to them.
In generalised anxiety disorder (GAD), intolerance of uncertainty accompanies overestimated danger and discounted reassurance.
Arousal and panic
Sympathetic arousal starts within seconds, while the hypothalamic-pituitary-adrenal cortisol response develops more slowly.
Hyperventilation causes respiratory alkalosis, with dizziness, tingling and derealisation.
Anxiety sensitivity, the fear of these sensations, maintains panic.
Carbon dioxide, lactate, caffeine and yohimbine provoke panic experimentally.
Transmitters
System | Evidence |
|---|---|
GABA (gamma-aminobutyric acid) | Benzodiazepines enhance GABA-A signalling |
Noradrenaline | Yohimbine increases release; beta-blockers reduce peripheral symptoms |
Serotonin | Selective serotonin reuptake inhibitors act late and may first increase anxiety |
Glutamate | D-cycloserine has been studied as an adjunct to exposure |
Vulnerability
Heritability is usually 30 to 50%, with polygenic overlap with depression.
Kagan's behavioural inhibition, early wariness and withdrawal from novelty, predicts later anxiety, especially social anxiety.
Mechanisms across disorders
Disorder | Main mechanism |
|---|---|
Specific phobia | Cue-related fear learning |
Panic disorder | Catastrophic interpretation of bodily sensations |
Social anxiety disorder | Social-evaluative threat and self-focused attention |
GAD | Sustained uncertainty-related threat and worry |
Agoraphobia | Fear that escape is difficult or help unavailable |
Treatment targets are situational and interoceptive exposure, dropping safety behaviours, outward attention and work on worry and uncertainty.
Hypervigilance is sustained scanning for threat, which drains attention and accompanies fatigue and insomnia.
Attentional bias is preferential attention to threat with difficulty disengaging from it.