bio of psyc disorder exam 2

Psychosis

A mental state in which a person has difficulty distinguishing reality from their own thoughts, beliefs, or perceptions. Common symptoms include delusions, hallucinations, disorganized speech, disorganized behavior, and gross distortions of reality.

Delusions

Fixed beliefs that are not based in reality and are maintained despite evidence to the contrary. Common themes include persecutory, referential, somatic, religious, and grandiose beliefs.

Persecutory Delusions

One of the most common forms and involve believing that others are trying to harm, target, or persecute the person.

Hallucinations

Sensory experiences that occur without an appropriate external stimulus. They may involve hearing, seeing, smelling, tasting, or feeling things that are not actually present.

Auditory hallucinations, such as hearing voices, are the most common in schizophrenia

Perceptual Distortions

changes in how real external stimuli are perceived. For example, hallucinations and familiar things or people may seem changed.

Motor Disturbances

Unusual movement or behavior, such as rigid posture, signs of tension, inappropriate grins or giggles, peculiar repetitive gestures, talking or mumbling to oneself, or glancing around as if hearing voices.

Schizophrenia

A disorder involving psychotic symptoms and disturbances lasting at least six months overall.

Schizophreniform Disorder

Schizophrenia-like symptoms lasting at least one month but less than six months.

Brief Psychotic Disorder

Psychotic symptoms lasting at least one day but less than one month, followed by a return to previous functioning.

Delusional Disorder

Persistent delusions lasting at least one month without meeting the broader criteria for schizophrenia.

Schizoaffective Disorder

Schizophrenia-related symptoms occurring alongside major mood episodes, with at least two weeks of psychosis without a major mood episode.

Substance-induced Psychotic Disorder

Psychotic symptoms caused by a substance or medication.

Psychotic Disorder due to General Medical Condition

Psychotic symptoms directly resulting from a medical condition.

Shared Psychotic Disorder

Delusion that develops in an individual influenced by someone else who has an established delusion.

Paranoid Psychosis

Primarily involves paranoid projection, hostile belligerence, and grandiose expression.

Paranoid Projection

Includes being preoccupied with delusional beliefs, believing people are talking about oneself, believing one is being persecuted or conspired against, or believing people or external forces control one’s actions.

Hostile Belligerence

Involves hostility, suspicion, irritability, resentment, and blaming others.

Grandiose Expression

Involves feelings of superiority, hearing voices that praise, or believing one has unusual powers, is a well-known personality, or has a divine mission.

Disorganized-Excited Psychosis

Involves conceptual disorganization, disorientation, and excitement.

Conceptual Disorganization

Can include giving irrelevant or incoherent answers, drifting from the subject, using neologisms, or repeating words or phrases.

Disorientation

Involve not knowing where one is, the season, the calendar year, or one’s own age.

Excitement

Involve unrestrained feelings, hurried or excessive speech, elevated mood, loud or boisterous speech, overactivity, and restlessness.

Depressive Psychosis

Involves retardation and apathy along with anxious self-punishment and blame.

Retardation and Apathy

Slowed or blocked speech, low or whispered speech, a fixed facial expression, slowed movement, apathy, failure to answer questions, or a poor appearance.

Anxious Self-Punishment and Blame

Blame or condemn themselves, experience anxiety and apprehension, have a depressed mood, express guilt and remorse, experience suicidal thoughts, or feel unworthy or sinful.

Timing of Schizophrenia

Signs of disturbance must last at least six months overall, including at least one month of active-phase symptoms, unless successfully treated sooner.

Symptoms that must be present for at least one month

At least two of the following symptoms must occur, with at least one being delusions, hallucinations, or disorganized speech:

• Delusions

• Hallucinations

• Disorganized speech

• Grossly disorganized or catatonic behavior

• Negative symptoms, such as diminished emotional expression or avolition

Genetic factors of schizophrenia

Having a close biological relative with schizophrenia increases risk, but genetics do not guarantee that someone will develop the disorder.

Environmental factors of schizophrenia

Prenatal complications, early-life adversity, chronic stress, and cannabis use

Positive symptoms

Excess of normal function

Negative symptoms

Reduction in normal function

Cognitive symptoms

Problems involving thought, attention, information processing, and cognitive functioning.

Aggressive/hostile symptoms

Problems involving impulse control and hostility.

Depressive/anxious symptoms

Depressive and anxious symptoms that can occur with schizophrenia.

Alogia

Reduced amount or spontaneity of speech.

Avolition

Reduced motivation and difficulty initiating goal-directed activities.

Associability

Reduced interest in social interactions.

Anhedonia

Reduced ability to experience or anticipate pleasure.

Affective blunting/flattening

Reduced outward emotional expression through facial expressions, voice, or gestures.

Indoleamine

Serotonin (5-HT), derived from the amino acid tryptophan.

Catecholamines

Dopamine, norepinephrine, and epinephrine, derived from the amino acid tyrosine.

Biosynthesis of Catecholamines

1. Tyrosine is converted into L-DOPA by tyrosine hydroxylase (TH)

2. L-DOPA is converted into dopamine by DOPA decarboxylase (DDC/AADC)

3. Dopamine is converted into norepinephrine by dopamine β-hydroxylase (DBH)

4. Norepinephrine is converted into epinephrine by phenylethanolamine N-methyltransferase (PNMT)

Tyrosine hydroxylase (TH)

Converts tyrosine into L-DOPA, rate limiting enzyme in catecholamine synthesis.

DOPA decarboxylase (DDC/AADC)

Converts L-DOPA into dopamine.

Dopamine β-hydroxylase (DBH)

Converts dopamine into norepinephrine.

Phenylethanolamine N-methyltransferase (PNMT)

Converts norepinephrine into epinephrine.

End product inhibition

Occurs when the final product of a biochemical pathway inhibits an earlier enzyme in that pathway. This provides negative feedback and prevents excessive production of the end product.

Monoamine oxidase (MAO)

Intra-cellular - outer membrane of mitochondria. Breaks down monoamines through oxidative deamination.

Helps regulate catecholamine levels and terminate their effects.

Catechol-O-methyltransferase (COMT)

Found in nearly all cells. Inactivates catecholamines by adding a methyl group.

Helps regulate catecholamine levels and terminate their effects.

Isozymes

Different forms of an enzyme that catalyze the same general type of reaction but differ in properties, distribution, or substrate preference.

MAO-A

Preferentially metabolizes serotonin and norepinephrine and also contributes to dopamine breakdown.

MAO-B

Preferentially metabolizes phenylethylamine and contributes to dopamine breakdown.

Function of dopamine

Dopamine contributes to movement, motivation, reward, reinforcement, attention, and aspects of learning.

Which MAO is responsible for dopamine breakdown?

Both MAO-A and MAO-B can metabolize dopamine, with MAO-B often emphasized in dopamine breakdown.

D1-like dopamine receptors

Includes D1 and D5 receptors, which couple Gs/olf proteins and stimulate adenylyl cyclase, increasing cAMP

Generally have excitatory signaling effects

D2-like dopamine receptors

Includes D2, D3, and D4 receptors, which couple to Gi/o proteins and inhibit adenylyl cyclase, decreasing cAMP

Generally have inhibitory signaling effects

Mesolimbic dopamine pathway

Ventral tegmental area (VTA) to limbic regions, including the nucleus accumbens. Involved in reward, motivation, and positive symptoms of schizophrenia.

Mesocortical dopamine pathway

VTA to the prefrontal cortex. Involved in cognition, motivation, and emotional functioning.

Nigrostriatal pathway

Substantia nigra to the striatum. Important for movement and motor control.

Tuberoinfundibular pathway

Hypothalamus to the pituitary region. Dopamine inhibits prolactin release.

Dopamine hypothesis of schizophrenia

Drugs that increase dopamine will produce positive psychotic symptoms, and drugs that decrease dopamine will stop positive symptoms.

Positive symptoms are associated with excessive dopamine signaling in the mesolimbic pathway.

Conventional antipsychotics

Block D2 dopamine receptors. They aim to reduce positive symptoms of schizophrenia, including hallucinations and delusions, by reducing excessive dopamine signaling.

Which pathway is associated with negative symptoms due to a deficiency in dopamine?

The mesocortical pathway is associated with negative symptoms and cognitive difficulties when dopamine signaling is reduced, particularly in the prefrontal cortex.

Neuroleptic-induced deficit syndrome

Negative-symptom-like effects caused or worsened by antipsychotic medication. These may include reduced motivation, reduced emotional expression, decreased spontaneity, and diminished interest or activity.

Extrapyramidal system

Includes neural circuits involved in regulating movement, particularly the basal ganglia and associated pathways.

Hyperactivity of extrapyramidal system

• Chorea: brief, irregular muscle contractions that are not repetitive

• Dyskinesias: impairment of voluntary movement

• Tics: tourette syndrome

Could cause extrapyramidal symptoms (EPS)

Dopamine deficiency of extrapyramidal system

Can cause parkinsonian symptoms, including tremor, rigidity, akinesia, dystonia, and bradykinesia

Tardive dyskinesia

A movement disorder characterized by involuntary, repetitive movements, often involving the face, tongue, jaw, or limbs.

Causes of tardive dyskinesia

It is associated with long-term exposure to dopamine-blocking medications and is linked to changes in dopamine signaling in the nigrostriatal pathway. Caused by chronic treatment with neuroleptics.

Hyperprolactinemia

An abnormally high level of prolactin in the blood. Dopamine normally inhibits prolactin release through the tuberoinfundibular pathway.

Causes of hyperprolactinemia

Blocking D2 receptors can increase prolactin, potentially causing menstrual changes, milk production, sexual dysfunction, and reduced bone density over time.

Dopamine + acetylcholine + muscarinic receptors of extrapyramidal symptoms

Dopamine and acetylcholine interact in the striatum to help regulate movement. Dopamine normally helps balance cholinergic activity. When D2 receptors are blocked, acetylcholine’s influence may become relatively stronger. Blocking muscarinic acetylcholine receptors can restore some of this balance and reduce certain extrapyramidal symptoms.

Glutamate synthesis and removal

Glutamate is synthesized from glutamine by glutaminase in neurons. After release into the synaptic cleft, glutamate binds to its receptors and is removed primarily by excitatory amino acid transporters (EAATs) on neurons and glial cells. In astrocytes, glutamate is converted back into glutamine by glutamine synthetase and returned to neurons for reuse.

NMDA receptor

Ionotropic glutamate receptor that usually requires glutamate binding, a co-agonist binding to the glycine site, and sufficient postsynaptic depolarization to remove the magnesium block. When activated, it allows calcium and sodium to enter the cell and contributes to synaptic plasticity, learning, and memory.

Binding that opens the NMDA receptor

• Glutamate: binds to the glutamate site on the NR2 subunit. This is the main signaling neuron.

• Glycine or D-serine: binds to the co-agonist site on the NR1 subunit. Either can support receptor activation. Glutamate alone isn’t enough, so these act as a required second key. Either one works, so they are interchangeable for opening the channel.

Modulators of NMDA receptor

• Magnesium (Mg²⁺): Blocks the channel pore in a voltage-dependent manner at resting membrane potentials.

• Voltage change: Depolarizes the cell, which repels and removes the magnesium block to allow ion flow.

• Zinc (Zn²⁺): Blocks the NMDA current in a noncompetitive and voltage-independent manner.

• Polyamines: Act as regulatory molecules that can either potentiate or inhibit glutamate-mediated responses.

• Protons (H⁺): Partially inhibit the receptor under normal physiological ambient concentrations.

AMPA receptors

The AMPA receptor is an ionotropic glutamate receptor that mediates much of the brain's fast excitatory synaptic transmission. It is assembled from four subunits, GluA1 through GluA4. Most AMPA receptors primarily allow sodium to enter and potassium to leave. Calcium permeability depends largely on whether the receptor contains edited GluA2 subunits.

Kainate receptors

Ionotropic glutamate receptors that contribute to excitatory neurotransmission. They can mediate postsynaptic excitation and regulate neurotransmitter release at presynaptic terminals.

Metabotropic glutamate receptors (mGluR’s)

G-protein-coupled receptors that regulate neuronal activity through intracellular signaling rather than forming ion channels themselves.

Group I of mGluR’s

mGluR1 and mGluR5. Usually coupled to Gq proteins, activate phospholipase C, and generally increase neuronal excitability

Group II of mGluR’s

mGluR2 and mGluR3. Usually coupled to Gi/o proteins, inhibit adenylyl

cyclase, and often reduce neurotransmitter release

Group III of mGluR’s

mGluR4, mGluR6, mGluR7, and mGluR8. Usually coupled to Gi/o proteins and often reduce neurotransmitter release

Brain morphological abnormalities associated with schizophrenia

• Enlarged lateral ventricles.

• Reduced gray matter volume in some cortical regions.

• Changes in the prefrontal cortex and hippocampus.

• Alterations in neuronal organization and connectivity

Causes of brain abnormalities associated with schizophrenia

Potential explanations include altered neurodevelopment, changes in synaptic connections, reduced neuropil, and possible cellular injury. These findings vary across individuals and are not diagnostic by themselves

Schizophrenia and apoptosis

Schizophrenia is associated with apoptosis (programmed cell death) rather than necrosis. Furthermore, gliosis is generally absent in schizophrenia, which is a key feature distinguishing it from classic progressive neurodegenerative diseases like Alzheimer's or Huntington's disease.

Oxidative stress

Occurs when reactive oxygen species (including superoxide) exceed the body's antioxidant defenses, potentially damaging cells, organs, and tissues

Reactive oxygen species

Reactive oxygen-containing molecules. Superoxide (O₂•⁻) is a ROS and free radical containing an unpaired electron

Superoxide dismutase (SOD)

Converts superoxide into oxygen and hydrogen peroxide

• SOD1: Mainly cytoplasmic, contains copper and zinc

• SOD2: Located in mitochondria, contains manganese

• SOD3: Located extracellularly, contains copper and zinc

Catalase

An antioxidant enzyme that breaks down hydrogen peroxide into water and oxygen, helping protect cells from oxidative damage

Glutamatergic hypofunction

Reduced or impaired glutamate signaling. In schizophrenia, reduced NMDA receptor activity is one proposed mechanism. Impaired glutamatergic signaling in the prefrontal cortex may alter regulation of other brain circuits, including dopamine pathways, and contribute to symptoms

Mitochondrial dysfunction

Occurs when mitochondria do not produce or regulate cellular energy normally. Reduced ATP availability can disrupt ion pumps, membrane potential, and glutamate uptake. These changes may increase neuronal vulnerability to excitotoxicity and oxidative stress. Mitochondrial abnormalities could be caused by oxidative stress.

Ketamine and NMDA receptor

Noncompetitive NMDA receptor antagonist that reduces NMDA receptor activity. At certain doses, it can produce psychosis-like symptoms and cognitive changes in healthy individuals, supporting the idea that reduced NMDA receptor function may contribute to schizophrenia.

NMDA receptor hypothesis and GABAergic dysfunction theory

• The NMDA receptor hypothesis proposes that reduced NMDA receptor activity contributes to schizophrenia.

• One proposed mechanism is that NMDA receptor hypofunction on GABAergic interneurons reduces inhibitory control over excitatory pyramidal neurons.

• This can disrupt cortical signaling and contribute to abnormal glutamate and dopamine activity

Akt and schizophrenia

• An intracellular signaling protein involved in cell survival, growth, and antiapoptotic signaling.

• Some studies have reported altered Akt-related signaling or reduced Akt protein levels in brain regions and cells from people with schizophrenia.

• Reduced glutamatergic signaling may affect pathways involved in cell survival

Brain-derived neurotrophic factor (BDNF)

Supports neuronal survival, growth, and synaptic plasticity. BDNF binds to the TrkB receptor. Reduced BDNF levels have been reported in some brain regions in schizophrenia, and altered glutamate and dopamine signaling may affect BDNF expression.

Serotonin (5-HT) synthesis and removal

Synthesized from tryptophan:

• Tryptophan hydroxylase: Converts tryptophan into 5-hydroxytryptophan (5-HTP)

• Aromatic L-amino acid decarboxylase (AADC): Converts 5-HTP into serotonin

Removed from synaptic cleft primarily by the serotonin transporter (SERT) and is metabolized by MAO-A into products including 5-HIAA

5-HT1 Receptors

Generally inhibit neuronal activity through Gi/o proteins, decreasing adenylyl cyclase activity. The 5-HT1A receptor can act as an autoreceptor that decreases serotonin neuron firing and release.

5-HT2 Receptors

Generally stimulate intracellular signaling through Gq proteins. The 5-HT2A receptor activates phospholipase C and can increase neuronal excitability.

Classic hallucinogens

Produce their effects primarily through 5-HT2A receptor activation. This alters signaling in cortical circuits and can change perception, thought, and sensory processing.

5-HT2A in Parkinson’s disease psychosis

• Parkinson's disease involves degeneration of dopamine-producing neurons, and dopamine replacement treatments can contribute to psychosis in some patients.

• Serotonin signaling, particularly at 5-HT2A receptors, may also contribute to hallucinations and other psychotic symptoms.

• Antipsychotic medications with 5-HT2A antagonism may help reduce psychosis while limiting additional dopamine blockade.