Clinical Neuroscience (class 12)

The Dopamine Hypothesis

Dopamine plays a complex role in schizophrenia, which suggests an imbalance in dopamine activity contributing to the disorder's symptoms. Specifically, high dopamine activity in certain brain regions is linked to positive symptoms like hallucinations and delusions, while reduced dopamine activity, particularly in the prefrontal cortex, may be associated with negative symptoms like cognitive impairment

Schizophrenia

A psychiatric disorder involving a breakdown of the effective integration of emotion, thought, and action. It affects 1% of the population and is a diverse disorder with multiple types

Symptoms of Schizophrenia

Positive Symptoms: The presence of abnormal thoughts, incoherence, hallucinations, and delusions

Negative Symptoms: The absence of normal flat affect, cognitive deficits, and little speech

Disintegration in Schizophrenia

A breakdown or lack of effective integration of thinking, reasoning, emotion, memory, and other cognitive processes, leading to a mismatch between belief systems and attentional systems. It also involves the disintegration of sensory, higher-level, and lower-level systems

Neuropharmacology

The study of drugs that affect the nervous system. Our understanding of schizophrenia has significantly advanced due to the discovery of drugs that can treat it, making neuropharmacology an older field than even brain imaging

Monoamines

A class of neurotransmitters, including dopamine, whose levels in the brain are affected by older antidepressants like tricyclic antidepressants. Reserpine depletes the brain of dopamine and other monoamines

Vesicles

Small sacs within neurons that store neurotransmitters. Reserpine causes these vesicles to become leaky, leading to a depletion of neurotransmitters like dopamine—bigger ones are found in people with schizophrenia

Feedback Loop (and Drug Tolerance)

A biological mechanism by which the body attempts to maintain homeostatic balance. The development of tolerance to drugs is an example, requiring changes or increases in dosage over time

Atypical Neuroleptic

A newer type of antipsychotic medication, such as clozapine, that can be effective in treating schizophrenia but has a different binding profile to neurotransmitter receptors compared to conventional neuroleptics, acting at D1, D4, and serotonin receptors with only some binding to D2 receptors

Neuroleptics

Drugs that are able to treat schizophrenia. Conventional ones (D2 blockers) are mainly effective for positive symptoms but cause parkison’s like tremors since they also target the basal ganglia

Chlorpromazine

An anti-psychotic for schizophrenia antagonizes (reduces the effect of) dopamine activity by binding to and blocking dopamine receptors, specifically, D2 receptors. The first receptor blocker to be identified, and its discovery changed psychopharmacology.

Reserpine

An anti-psychotic for schizophrenia, no longer used, are not effective for 2-3 weeks, and Parkinson-like motor effects are seen. Depletes the brain of dopamine and other monoamines by making vesicles leaky

L-DOPA

A drug that increases dopamine receptor binding (dopamine agonist) and activity in the basal ganglia and removes tremors associated with Parkinson’s, but if not careful, can cause psychotic symptoms.

Tricyclics

Early anti-depressant medication, block the reuptake of serotonin and norepinephrine, leaving serotonin in the synapse for longer. This gives receptors more opportunity to clear out, increasing the likelihood that it will bind again. More side effects than SSRIs

Norepinephrine

A neurotransmitter that enhances alertness, attention, and memory, whose reuptake is blocked by tricyclic antidepressants and SNRIs (selective norepinephrine-reuptake inhibitors), increasing its availability in the synapse

Monoamine Theory of Depression

An early theory suggesting that depression is linked to reduced levels of monoamines, such as serotonin and norepinephrine, in the brain. Many early antidepressants aimed to increase the availability of these neurotransmitters.

Anterior Cingulate Gyrus

A brain region where chronic electrical stimulation has been found to help relieve depression in some treatment-resistant patients

Dopamine

A neurotransmitter that has a role in movement, reward, motivation, and mood and causes an increase in mesolimbic activity, which results in delusions, hallucinations, and other psychotic symptoms and is thought to have overactivity associated with schizophrenia.

D2 Receptor

A specific type of dopamine receptor that many antipsychotic drugs bind to and block. The extent of this binding is strongly related to their potency

Dopamine Agonist

A substance that increases dopamine effects, such as amphetamine and cocaine which can produce psychosis. L-DOPA is another example

Dopamine Antagonist

A substance that reduces the effect of dopamine activity by binding to and blocking dopamine receptors, like chlorpromazine

Grey Matter Loss

Progressive and broad loss of grey matter, including temporal and cortical thinning in motor regions and association cortices, that tends to increase with age in individuals with schizophrenia

Affective Disorders

Disorders related to mood that can be treated with various types of antidepressants

Serotonin

A neurotransmitter that plays a significant role in regulating mood, sleep, appetite, and other functions. It is often referred to as a "feel-good" chemical, whose reuptake is blocked by tricyclic antidepressants and SSRIs, increasing its availability in the synapse

SSRIs (Selective Serotonin Reuptake Inhibitors)

A common type of antidepressant that selectively inhibits the reuptake of serotonin. Examples include Prozac, Paxil, and Zoloft

Emotional Contagion

The tendency to catch and feel emotions that are similar to and influenced by those of others, potentially based on mirror neurons. Neurons (specifically, mirror neurons) have been identified that activate similarly to the performance and observation of various motor patterns.

• Suggest the possibility of shared neural circuitry for performed and observed actions

• May serve as the basis for perspective taking / empathic concern

• May serve as the basis for observational learning

Emotional Contagion Study

Patients in fMRI (measure blood flow to the brain while doing things)

• These patients see pictures – see a person who is getting their thumb poked or a person not getting a needle

• While they are seeing painful pictures, increased blood flow to brain regions insula – close to limbic system that are close to emotional processing and complex emotional processing.

Anterior Cingulate

A brain region involved in error processing. Every time you make a mistake, you have an “error” signal that goes off in your brain in the anterior cingulate, indicating you made a mistake and goes throughout the brain to say “you’re making a mistake.” Happens even before we make the mistake.

Observed Error Study

When participants watched Dr. Shane do the same task and make a mistake, the anterior cingulate response was the same. So, even when someone else makes a mistake, that signal goes off in your brain, and it may be related to social/observational learning.

Testosterone

A steroid hormone that has a correlation with aggressive behavior in nonhuman animals, though the relationship in humans is not as clear and can be confounded by experience and dominance

Serotonin and Aggression

Aggressive behaviour has been associated with several neurotransmitter systems, especially those involving serotonin

• Ex. Mice that lack a subtype of a serotonin receptor (5-HT1 B) show increased aggression

Amygdala

A limbic system structure involved in emotional processing that shows reductions in size and activation in psychopaths

Prefrontal Cortex (PFC)

A brain region that provides inhibitory inputs to the limbic system and shows reduced activity and thickness in psychopaths, potentially contributing to impulsivity and poor decision-making

Psychopathy

A cluster of personality traits including affective features (lack of guilt/remorse), interpersonal features (manipulative), and impulsive/antisocial behaviors, often associated with instrumental aggression and blunted responses to aversive stimuli