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The following is derived from a lecture I gave in April 2004 intended for the teaching of general practitioners. This information is intended for education purposes by health professionals and should not be used as a substitute for any health professionals' individual advice and treatment. Every patient needs to be treated as an individual and individual requirements may differ from general guidelines or principles like those suggested below. Contents
What is high anxiety? What determines the anxiety-performance peak ? What does high anxiety do to the individual? In which disorders does high anxiety occur? Differences between the anxiety disorders Fear circuitry Can trauma alter brain chemistry? Latest neurobiological correlates Can trauma cause structural changes? A neurobiological model of PTSD Management of anxiety disorders
What is high anxiety?
Startle triggers the Fight or Flight Survival Program
… to motivate to action
|
 | Large carnivores |
| Small poisonous animals |
| Heights |
| Strangers |
| Extreme sensory phenomena (dark, bright light, loud noise, rapid movement) |
| Unfamiliar water or land |
| Threat to physical integrity |
| Man made disasters |
| Natural disasters |
| Real or threatened violence |
| Unexpected fright |
| Threat to emotional integrity |
| Loss of family member |
Yerkes-Dodson Curve : anxiety is usually facilitating
Excessive anxiety causes:
| decreased capacity for skilled motor movements |
| decreased complex intellectual tasks |
| decreased perception of new information |
| Panic attacks characterised by:
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| Freely-floating low-grade anxiety | ||||||||||||||||||
| Avoidance behaviour / dissociation |
An individual's genetics interacting with their lifetime experiences
| Massive dose of inherited trait anxiety |
| {Moderate dose of inherited trait anxiety (genetic vulnerability) OR Past environmental triggers sensitising the CNS} |
PLUS
| Current environmental trigger |
| A stable characteristic of biologically-based high emotionality |
| Probably the single most important determinant of symptoms |
| More strongly associated with OCD & GAD, less with PTSD & specific phobia |
| People with high trait anxiety have more life events |
Repeated traumatic stimuli occurring during relevant developmental stages can recalibrate the level of arousal that the individual ends up with, adapting them to their particular environment
| Early life trauma enhances risk of stress related disorders |
| History of child abuse increases risk of panic disorder, social phobia, GAD & PTSD (& MDD & Personality Disorder) |
| Esp. pre-pubertal abuse |
| Loss of parent at early age |
| Lack of perceived parental warmth (neglect/ maternal deprivation) |
(Kendler, Nemeroff & others)
| Anxiety causes distress & suffering |
| Avoidance causes handicap |
| External locus of control |
| Immature defence styles |
| Lack of assertiveness |
| Victim cycle due to learned helplessness |
| Vulnerability to comorbidity |
| Risk of generational transmission |
Anxiety disorders are the tip of the iceberg
| Panic disorder |
| ASD |
| PTSD |
| Other anxiety disorders |
| Social Phobia, Complex PTSD, OCD, GAD |
| Adjustment disorder |
| Depressive disorder |
| Somatoform disorders |
| Sexual disorders |
| Sleep disorders |
| Pain disorders |
| Eating disorders |
| Personality Disorders, D&A, GID, … |
| Panic disorder: | Physical collapse |
| Agoraphobia: | Panic |
| Social phobia: | Negative evaluation & shame |
| Specific phobia: | Improbable harm to self |
| OCD: | Self-caused harm |
| GAD: | Harm to self & loved ones |
| PTSD: | Past personal harm |
| Panic disorder: | Triggers |
| Agoraphobia: | anxiety being in places/situations from which escape difficult or embarrassing leading to avoidance of situations |
| Social phobia: | Social situations |
| Specific phobia: | Object, animal, place |
| OCD: | Obsession triggers Compulsion (to neutralise obsession) |
| GAD: | Everything |
| PTSD: | Symbols or triggers of past event |
| Panic disorder: | Recurrent PAs, ?LOF, ±Ag |
| Social phobia: | Fear of performance or social sitns, PA or anxiety, insight, avoidance, ?LOF, 6 mo(<18yo) |
| Specific phobia: | |
| OCD: | O or C, >1, distress or ?LOF, some insight |
| GAD: | XS anx & worry, can’t divert, somatic Sx, unfocused, distress or ?LOF |
| PTSD: | Traumatic event (threatened integrity, intense response), re-experience event (memories, dreams, flashbacks, hallns), high arousal, avoidance, >1 mo, ?LOF {Chronic >3 mo} {Delayed onset >6 mo} |
| Acute stress disorder: | As above but duration 2d-4w Exclusions: no D&A, GMC |
| Traumatic event
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Re-experience event
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| High arousal | ||||||
| Avoidance / Emotional numbing |
| Accelerated moral development |
| Shake trust in a “just world” & sense of control over own lives |
| >1 mo |
| LOF |
| {Chronic >3 mo} {Delayed onset >6 mo} |
| “Traumatic experiences scar the traumatised individual, weakening their resilience to future stress. |
| Even when individuals seem to have resolved their reaction to trauma, heightened vulnerability that is easily awakened often ensues. |
| Even in combat-related PTSD, it appears that even when PTSD remits, or persists into a more stable form, the afflicted person may become highly sensitised to stress in general. He or she is permanently altered, harbouring the potential for a future response on re-exposure to threatening stimuli. |
| Soloman, |
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 |
| Obsessions | Recurrent thoughts & images |
| Compulsions | Avoidance & dissociation |
| Distress & high arousal | Distress & high arousal |
| Insight | Insight |
In
OCD, genetics appears to play a large part in the development of regional
overactivity in the circuits that evolved to assist people in avoiding contact
with or ingestion of harmful agents
| Knockout HoxB8 (homeobox) gene in mice causes a 5x increase in grooming of self & others, causing bald patches |
| Expressed in caudate & orbitofrontal cortex (OCD circuit) |
(Greer & Capechi, 2003)
| Most people exposed to trauma develop stress symptoms (anxiety) |
| Many who go on to develop PTSD have prior vulnerability (sensitised CNS) |
| Symptoms typically begin within 3 months of traumatic event |
| PTSD is diagnosed when symptoms last more than 1 month |
| <1 mth = Acute Stress Disorder (ASD) |
| Severity & duration vary |
| Some people recover within 6 months, others suffer for decades |
| Spontaneous improvement mostly in the first year |
| Over 40% of untreated patients still have PTSD after 10 years |
| Treatment is associated with shorter duration of PTSD |
| Sleep disturbances |
| Major Depression |
| Panic disorder |
| Irritability or outbursts of anger |
| Substance misuse |
| Alcohol & benzos |
| Exaggeration of personality traits e.g. obsessive compulsive behaviour |
| Impairment in socio-occupational functioning |
| [CRF]CSF overactivity |
| A neuropeptide associated with anxiety & fear & anhedonia |
| Persistently elevated from adverse early life experiences in rodents (separation from mother, erratic food supply) |
| Noradrenergic overactivity |
| An alarm system e.g. activated when cat meets dog |
| Persistent hyperactivity from adverse early life experiences |
| Exaggerated behavioural symptoms, startle & metabolic response when yohimbine given (LC, amygdala) |
Sackeim, 2001
| Cortisol release |
| NA release |
| Other substances released |
| Involved in encoding of traumatic memories, which become indeligible (core of PTSD?) |
| ?Modulated by background CRF & NA levels (e.g. both systems turned on by early adverse life events) |
| Functional interaction b/w CRF & NA -> reverberating stress system |
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Hippocampal shrinkage
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| Changes in other fear circuitry structures
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All
known connections between thalamus and cerebral cortex are reciprocal, two-way
radiations (thalamocortical and corticothalamic), and they contribute
conspicuously to the formation of the internal capsule and corona radiata
Possible sequence of events in PTSD:
| Fear response |
| Causes excessive activation of threat response neural circuitry |
| Inadequate orbital prefrontal feedback |
| Failure to switch off activation of the threat response system |
| Failure of recovery |
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Herbst Mark D, presented at APA 1999 Open label pilot study of mirtazapine in PTSD Connor et al. Int Clin Psychopharmacol, 1999; 14: 29-31 |
| Bahk WM et al. Effects of mirtazapine in patients with post-traumatic stress disorder in Korea: a pilot study. Hum Psychopharmacol 2002; 17: 341-4 |
| Davidson JR et al. Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial. Biol Psychiatry 2003; 53: 188-91 |
| Moon Yong Chung et al. Moon Efficacy and tolerability of mirtazapine and sertraline in elderly Korean veterans with Posttraumatic Stress Disorder: A randomized open label trial (ECNP 2003, submitted) |
