A framework for psychopathology

1. Symptoms

2. Neural Causes (systems approach)– A. Which neurotransmitters?– B. ‘Where’ in the brain? which methods measure it?– Other causes: Genetic, Social

3. Neural Treatment– A. Pharmacotherapy– B. Brain stimulation, lesion– Other (e.g., Cognitive behavioral therapy)

Psychopathology

Diseases with localized lesion• Fronto-temporal dementia (last class)• Orbitofrontal lesion (e.g, Traumatic brain injury)• Strokes & other lesions

– Lesion of medio-frontal structures: Akinetic mutism– Lesion of amygdala: impaired processing of fear

Diseases defined initially by their symptoms• Depression• Obsessive compulsive disorder• Huntington’s disease• Autism• Schizophrenia• ADHD• Anxiety

Depression: Symptoms Possible substrates

• Cognitive processes – Reduced concentration DLPFC– impaired memory hippocampus

• Emotion/motivation/self Mid frontal, OFC– Lack of energy– Loss of interest– Slowness of movement– Mood: Pessimism (depressive realism)

• Autonomic processes Ventral cingulate– Changes in Apetite insula– Reduced libido hypothalamus– Changes in Sleep pattern: (Shallow, Fragmented, Early REM onset)– Increased cortisol levels

Depression: Neural changes

• Change activity in– ventral frontal, – midfrontal, – dorsolateral prefrontal– amydgala

Depression: Treatment

• Cognitive behavior therapy• Pharmacotherapy

– SSRI, acts upon serotonin system– MAOi, – tricyclic antidepressants

• Electroconvulsive therapy• Repeated Transcranial Magnetic Stimulation• Deep Brain stimulation

• Sleep deprivation – Selective (REM)– Total (not feasible)

Relation between Depression and Stress

• Stress “activates” depression in susceptible individuals

• High levels of circulating cortisol in hospitalized depression cases and suicide victims

Dexamethasone suppresses waking ACTH release when given at night.

Relation between Depression & Sleep

• Complete loss of SWS• Increased REM – decreased latency to 1st REM• Decreasing REM -> improved functioning• MAOi suppress REM

Obsessive-Compulsive Disorder (OCD)

Symptoms• Recurrent behaviors (compulsive) • Recurrent thoughts (obsessive)• People repeat things until they feel that they have

“gotten it right”• Frequently related to cleanliness or territoriality

OCD: Neural changes

Corticostriatal loop:increased activity in limbic cortex and basal ganglia

OCD: Treatment

• Tricyclic antidepressants alleviate symptoms (particularly 5-HT)

• Brain lesion

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Tourette’s syndrome• Dysfunction of cortico-striatal loop • number of D2 receptors in basal ganglia is increased as revelead by PET• tics reduced by D2 antagonists (neuroleptics)

• abnormal cortico-striatal loop may explain aspects of repetitive behavior in OCD, FTD, autism

Huntington’s disease:single dominant gene (50% chance)basal ganglia pathology (caudate nucleus, putamen)mostly GABAergic neuronsstarts at 30- 45 years of agestarts with minor motor problems (twitches, clumsiness)evolves into involuntary jerky movements of eyes, legs also emotional changes (depression, socially inappropriate behavior)emotional changes sometimes precede motor changes