Neuropsychiatry addresses the psychiatric consequences of neurological diseases, the neurological basis of psychiatric illnesses, and neurological symptoms that don't match underlying neuropathology.
Paralytic Dementia and Syphilis
Early 20th century: Paralytic dementia was characterized by delusions, grandiosity, euphoria, poor judgment, and impulsivity.
1911: Hideyo Noguchi discovered that paralytic dementia was caused by brain damage due to syphilis, a sexually transmitted bacterial infection.
Prevalence of Psychiatric Disorders
Psychiatric disorders are mainly diagnosed based on behavioral symptoms.
Over one-third of the U.S. population reports symptoms of a major psychiatric disorder at some point in life.
Depression is more prevalent in females, while drug dependency and alcoholism are more prevalent in males.
Schizophrenia
Major symptoms include auditory hallucinations, personalized delusions, changes in affect, and cognitive impairments.
Positive symptoms: Hallucinations, delusions, and excited motor behavior.
Negative symptoms: Slow and impoverished thought and speech, emotional and social withdrawal.
Genetics: The closer the relationship to someone with schizophrenia, the higher the risk of developing it.
Genetic analyses suggest over 100 genes influence schizophrenia risk.
Lobotomy
Lobotomy is a discredited neurosurgical treatment that involves severing connections in the prefrontal cortex.
Moniz's work was influenced by Fulton and Jacobsen's experiments with chimpanzees. Frontal lobectomies in chimpanzees resulted in reduced "frustrational behaviour" and increased timidity.
Psychopharmacology
Chlorpromazine was initially developed as an anesthetic but found to reduce the positive symptoms of schizophrenia.
It was initially promoted as a "lobotomy in a bottle."
Dopamine Hypothesis of Schizophrenia
Antipsychotic drugs block postsynaptic dopamine receptors, especially D2 receptors.
Dopamine hypothesis: Schizophrenia is caused by an excess of dopamine release or dopamine receptors.
Amphetamine and Schizophrenia
Large doses of amphetamine can induce symptoms of paranoia, delusions, auditory hallucinations, suspiciousness, and bizarre motor behavior, resembling schizophrenia (amphetamine psychosis).
Amphetamine exacerbates schizophrenia symptoms.
Amphetamine promotes dopamine release and prolongs its action by blocking reuptake.
Neurochemistry of Schizophrenia
PCP is an NMDA receptor antagonist; it blocks the NMDA receptor's central calcium channel.
Treating monkeys with PCP induces a schizophrenia-like syndrome.
Ketamine, another NMDA receptor antagonist, has similar effects.
Glutamate hypothesis of schizophrenia.
Ventricular Enlargement
Many people with schizophrenia have enlarged cerebral ventricles, especially the lateral ventricles.
Ventricular enlargement predicts later development of schizophrenia in adolescents.
The extent of enlargement relates to responsiveness to antipsychotic drugs; more-enlarged ventricles lead to poorer response.
Ventricular Enlargement and Genetics
Atrophy in the hippocampus and amygdala could cause ventricular enlargement in schizophrenia.
Hypofrontality Hypothesis
People with schizophrenia show less metabolic activity in the frontal lobes.
The hypofrontality hypothesis suggests that frontal lobe dysfunction results in schizophrenia.
Aberrant Salience Hypothesis of Schizophrenia
Hyperdopaminergic state leads to aberrant assignment of salience to experiences.
Dopamine mediates the conversion of neural representations of stimuli into salient events.
Symptoms arise from the aberrant assignment of salience to external objects and internal representations.
Antipsychotics reduce positive symptoms by attenuating aberrant motivational salience via blockade of dopamine D2 receptors.
Depression Symptoms
Clinically significant depression: Unhappy mood, loss of interests, energy, and appetite; difficulty concentrating; and restless agitation.
Depression can lead to suicide.
Many suicides are impulsive acts or prompted by time-limited crises.
One study found that only 6% of people prevented from jumping off the Golden Gate Bridge later committed suicide.
Epidemiology of Depression
Around 8% of adults in the U.S. suffer from severe unipolar depression annually, and 5% suffer from mild forms.
Around 20% of adults experience severe unipolar depression at some point in their lives.
Prevalence rates are similar in Canada, England, France, and many other countries.
Electroconvulsive Therapy (ECT)
ECT is the intentional induction of a large-scale seizure.
Originally used unsuccessfully for schizophrenia, it was later found to rapidly reverse severe depression.
ECT is now used for treatment-resistant depression.
Monoamine Hypothesis
Monoamine hypothesis was suggested by the first antidepressants, which were inhibitors of monoamine oxidase (MAO).
MAO inactivates norepinephrine, dopamine, and serotonin.
MAO inhibitors raise monoamine levels in synapses, suggesting depressed people lack sufficient stimulation at those synapses.
Reserpine, which reduces norepinephrine and serotonin release, can cause profound depression.
Tricyclics inhibit the reuptake of monoamines, boosting synaptic activity.
SSRIs and Ketamine
Selective serotonin reuptake inhibitors (SSRIs) like Prozac are a major class of modern antidepressants.
SSRIs are more effective than MAO inhibitors and tricyclics with fewer side effects.
Ketamine, a glutamate receptor antagonist, relieves depression almost instantly.
Hallucinogens like psilocybin can rapidly relieve depression.
Mechanism of Action
Neurons reabsorb excess neurotransmitters like norepinephrine or serotonin via a reuptake mechanism.
In depression, this reuptake process is too active.
Antidepressants block the reuptake process, enabling NE or 5HT to remain in the synapse longer.
Cushing’s Syndrome and Depression
High levels of circulating glucocorticoids (e.g., cortisol) can cause depression.
Cushing’s syndrome may result from hormone-secreting tumors or therapeutic treatments with synthetic glucocorticoids.
Depression appears early in over 85% of people with Cushing’s syndrome.
HPA Axis
The hypothalamic-pituitary-adrenal system is involved in depression.
ACTH: adrenocorticotropic hormone
CRH: corticotropin-releasing hormone
Circulating cortisol levels are usually higher in people with depression.
Sleep in Depression
Difficulty falling asleep and inability to maintain sleep are common.
People with major depressive disorders show a reduction in slow-wave sleep (SWS).
They enter REM sleep sooner after sleep onset.
Increased amount of REM sleep occurs during the first half of sleep.
The Depressed Brain
The brain circuit involved in unipolar depression includes structures such as the prefrontal cortex (PFC), hippocampus, amygdala, and subgenual cingulate.