Neurobiology: Brain PDF

Neurobiology NERVOUS SYSTEM SUBDIVISIONS THE CENTRAL NERVOUS SYSTEM Consists of the spinal cord and the brain ◦ The spinal cord has two functions ◦ Conduit for incoming sensory data and o...

Neurobiology NERVOUS SYSTEM SUBDIVISIONS THE CENTRAL NERVOUS SYSTEM Consists of the spinal cord and the brain ◦ The spinal cord has two functions ◦ Conduit for incoming sensory data and outgoing movement commands ◦ Provides for spinal re exes, which are simple automatic actions not involving the brain ◦ The brain is the control center for the entire nervous system THE PERIPHERAL NERVOUS SYSTEM Gathers information about the external environment and the body’s internal environment for the brain through sensory neurons Serves as the conduit for the brain’s commands to the rest of the body through motor neurons Consists of two parts: ◦ The soma c (or skeletal) nervous system carries sensory input from receptors to the CNS and relays commands from the CNS to the skeletal muscles to control their movement ◦ The autonomic nervous system regulates our internal environment and consists of two parts ◦ The sympathe c nervous system is in control when we are very aroused and prepares us for defensive action (such as running away or ghting) ti ti fl fi  ◦ The parasympathe c nervous system is in control when the aroused state ends to return our body to its normal resting state TYPES OF NEURONS Interneurons exist only in the central nervous system Sensory neurons carry information to the central nervous system from sensory receptors in the eyes, muscles, and glands Motor neurons carry movement commands from the central nervous system to the rest of the body NEURONS AND GLIAL CELLS Neurons are responsible for information transmission throughout the nervous system Glial cells do not directly transmit information, but instead support neurons in their work by disposing of waste products of neurons, keeping their chemical environment stable, and insulating them THE STRUCTURE OF A NEURON Dendrites are the bers that project out of the cell body, receiving informa on from other neurons The cell body contains the nucleus of the cell and other biological machinery to keep the cell alive The axon transmits messages through the neuron The axon terminals are at the end of the axon and send messages to a di erent neuron PRESYNAPTIC VERSUS POSTSYNAPTIC Presynaptic and postsynaptic are terms used to describe the two parts of a synapse, the site where neurons communicate with each other. The presynaptic part releases neurotransmitters, while the postsynaptic part receives and converts them. ti ti fi ff Synaptic cleft ◦ The small gap between the presynaptic and postsynaptic parts is called the synaptic cleft. PRESYNAPTIC The presynaptic part is located at the end of an axon The presynaptic part releases neurotransmitters in response to electrical impulses The presynaptic part contains synaptic vesicles, which are membrane- bound spheres lled with neurotransmitters POSTSYNAPTIC The postsynaptic part is located on a dendrite or soma The postsynaptic part receives neurotransmitters and converts them into electrical and biochemical changes The postsynaptic part generates current, depolarizes the cell, and changes membrane permeability HOW NEURONS COMMUNICATE Communication within a neuron is electrical Communication between neurons is chemical THE ELECTRICAL IMPULSE Information from the dendrites is either excitatory (telling the neuron to generate an electrical impulse) or inhibitory (telling the neuron not to generate an electrical impulse) ◦ The impulse is an “all or nothing” event, meaning that there either is or is not an electrical impulse ◦ Stimuli of varying intensities are encoded by the quantity of neurons generating impulses and the number of impulses generated each second by the neurons The myelin sheath is an insulating layer of fatty white substance that encases the axon, allowing electrical message to be transmitted faster within the neuron ◦ Damage to the myelin sheath will slow electrical impulses, and can result in diseases like multiple sclerosis COMMUNICATION WITHIN NEURONS Axonal conduction obeys two laws: All or None Law – once triggered, an ac on poten al is transmi ed down to the terminal bu on. Rate Law – The number of ac on poten als produced by a neuron determines how strong ac va on of other neurons will be. CHEMICAL COMMUNICATION BETWEEN NEURONS fi ti ti ti ti tt tt ti ti  Axon terminals contains sacs of neurotransmi ers ◦ These neurotransmitters are naturally occurring chemicals in the nervous system that specialize in transmitting information between neurons Between the axon terminals of one neuron and the dendrites of another neuron is a small space called the synap c gap, across which neurotransmitters are sent, allowing neurons to communicate CHEMICAL EVENTS AT THE SYNAPSE Vesicles are tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release. Exocytosis refers to the excretion of the neurotransmitter from the presynaptic terminal into the synaptic cleft. ◦ Triggered by an action potential arriving from the axon. Transmission across the synaptic cleft by a neurotransmitter takes fewer than 10 microseconds. Most individual neurons release at least two or more di erent kinds of neurotransmitters. A neuron may respond to more types of neurotransmitters than it releases. An ionotropic e ect refers to when a neurotransmitter attaches to receptors and immediately opens ion channels. Ionotropic e ects occur very quickly and are very short lasting. Most of the brain’s excitatory ionotropic synapses use glutamate or acetylcholine as a neurotransmitter. Metabotropic e ects refer to when a neurotransmitter attaches to a receptor and initiates a sequence of metabolic reactions that are slower and longer lasting. Metabotropic events include such behaviors as hunger, fear, thirst, or anger. Metabotropic e ects utilize a number of di erent neurotransmitters and are often called neuromodulators because they do not directly excite or inhibit the postsynaptic cell. Instead, neuromodulators: ◦ increase or decrease the release of other neurotransmitters ◦ alter the response of postsynaptic cells to various inputs. Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake. Reuptake refers to when the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses it. Transporters are special membrane proteins that facilitate reuptake. ff ff ff ff ff ti ff tt  ◦ Example: Serotonin is taken back up into the presynaptic terminal. DRUGS AND THE SYNAPSE The study of the in uence of various kinds of drugs has provided us with knowledge about many aspects of neural communication at the synaptic level. Drugs either facilitate or inhibit activity at the synapse. ◦ Antagonistic drugs block the e ects of neurotransmitters (e.g., novacaine, ca eine). ◦ Agonist drugs mimic or increase the e ects of neurotransmitters (e.g., receptors in the brain respond to heroin, LSD and cocaine) Drugs alter various stages of synaptic processing. Drugs work by doing one or more of the following to neurotransmitters: 1. Increasing the synthesis. 2. Causing vesicles to leak. 3. Increasing release. 4. Decreasing reuptake. 5. Blocking the breakdown into inactive chemical. 6. Directly stimulating or blocking postsynaptic receptors. NEUROTRANSMITTERS BEING A NEUROTRANSMITTER: WHAT DOES IT TAKE? Exists presynaptically Synthesis enzymes exist presynaptically Released in response to action potential Postsynaptic membrane has receptors Application at synapse produces response Blockade of release stops synaptic function THE CLASSICAL NEUROTRANSMITTERS Amines ◦Monoamines ◦catecholamines (dopamine, noradrenaline) ◦indoleamines (serotonin, melatonin) ◦Quaternary amines ◦acetylcholine ◦amino acids (glutamate, GABA) fl ff ff ff  MAJOR NEUROTRANSMITTERS IN THE BODY Neurotransmitter Role in the Body Acetylcholine A neurotransmitter used by the spinal cord neurons to control muscles and by many neurons in the brain to regulate memory. In most instances, acetylcholine is excitatory. Dopamine The neurotransmitter that produces feelings of pleasure when released by the brain reward system. Dopamine has multiple functions depending on where in the brain it acts. It is usually inhibitory. Sex and chocolate cake. GABA The major inhibitory neurotransmitter in the brain. (gamma-aminobutyric acid) Glutamate The most common excitatory neurotransmitter in the brain. Glycine A neurotransmitter used mainly by neurons in the spinal cord. It probably always acts as an inhibitory neurotransmitter. Norepinephrine (Noradrenaline) Norepinephrine acts as a neurotransmitter and a hormone. In the peripheral nervous system, it is part of the flight-or-flight response. In the brain, it acts as a neurotransmitter regulating normal brain processes. Norepinephrine is usually excitatory, but is inhibitory in a few brain areas. Serotonin A neurotransmitter involved in many functions including mood, appetite, and sensory perception. In the spinal cord, serotonin is inhibitory in pain pathways. Small molecule neurotransmitters Postsynaptic Type Neurotransmitter effect Acetylcholine Excitatory Gamma aminobutyric Inhibitory Amino acids acidGABA Glycine Inhibitory Glutamate Excitatory Aspartate Excitatory Biogenic amines Dopamine Inhibitory Noradrenaline Excitatory Serotonin Inhibitory Histamine Excitatory Table 3. Localization of Monoamines in the Brain Neurotransmit Cell Bodies Terminals ter Norepinephrin Locus coeruleus Very widespread: cerebral cortex, thalamus, cerebellum, brainstem e (NE) Lateral tegmental area nuclei, spinal cord Basal forebrain, thalamus, hypothalamus, brainstem, spinal cord Epinephrine Small, discrete nuclei in medulla Thalamus, brainstem, spinal cord (EPI) Dopamine Substantia nigra (pars compacta) Striatum (DA) Ventral tegmental area Limbic forebrain, cerebral cortex Arcuate nucleus Median eminence Serotonin (5- Raphe nuclei (median and dorsal), Very widespread: cerebral cortex, thalamus, cerebellum, brainstem HT) pons, medulla nuclei, spinal cord  DOPAMINE Main DA systems: 1. Nigrostriatal (Movement – damage causes Parkinson’s Disease) ◦ Cell bodies located in substantia nigra ◦ Project to caudate nucleus and putamen 2. Mesolimbic (Reward system) ◦ Cell bodies in ventral tegmental area ◦ Project to nucleus accumbens (prefrontal subcortex), amygdala, and hippocampus 3. Mesocortical (STM(Short Term Memory), planning, strategy preparation) ◦ Cell bodies in ventral tegmental area ◦ Project to prefrontal cortex 4. Tuberoinfundibular ◦ Prolactin (lactation when overstimulated in both men and women) DOPAMINE Low levels are associated with Parkinson’s disease, and excessively high levels are associated with schizophrenia L-Dopa is an agonist that increases production of dopamine Anti-psychotic drugs are antagonists that block the receptor sites for dopamine so that this neurotransmitter cannot send its messages Amphetamine acts as an agonist by stimulating the release of dopamine from axon terminals Cocaine is an agonist that blocks the re-uptake of dopamine KEY NEGATIVE SYMPTOMS IDENTIFIED SOLELY ON OBSERVATION DOPAMINE RECEPTORS Receptors ◦ D1, D5 – Located in brain, smooth muscle – Stimulatory role, role in schizophrenia ◦ D2, D3, D4 – Located in brain, cardiovascular system, presynaptic nerve terminals – Inhibitory role, role in schizophrenia MATCH EACH SYMPTOM TO HYPOTHETICALLY MALFUNCTIONING BRAIN CIRCUITS— SCHIZOPHRENIA NOREPINEPHRINE Sythesized from DA Cell bodies of most NE neurons are located in regions of the pons and medulla and the thalamus NE receptors are excitatory and inhibitory Locus coeruleus in the pons – ac va on leads to increased vigilance Arousal: sexual behaviour and food/Binge Stress hormone that a ects attention pathways and impulsivity Also plays a role in the ght or ight response and has a positive drive on the sympathetic nervous system fi ff ti fl ti  CNS activity predominantly due to action of locus ceruleus, which has projections to the cerebral cortex, limbic system, and spinal cord. Also found in lateral tegmental area, which projects to hypothalamus. Role in depression, and appears tightly linked to levels of serotonin and dopamine. Explains why SNRIs have a positive e ect on depression, along with TCAs that also a ect norepinephrine levels. Dysregulation of norepinephrine in locus ceruleus also tied to panic disorder, anxiety disorder, depression, and REM sleep disturbances Receptors ◦ Alpha 1 – Brain, heart, smooth muscle – Vasoconstriction, smooth muscle control ◦ Alpha2 - Brain, pancreas, smooth muscle - Vasoconstriction, presynaptic e ect in GI (relaxant) ◦ Beta1 - Heart, brain - Heart rate (increase) ◦ Beta2 - Lungs, brain, skeletal muscle - Bronchial relaxation, vasodilatation ◦ Beta3 - Postsynaptic e ector cells - Stimulation of e ector cells AGONISTS AND ANTAGONISTS NE agonists: ◦ Phenylephrine ◦ Clonidine ◦ Desipramine ◦ All involved in increasing vigilance (sometimes used to treat mood disorders, eating disorders) through decreased activity of MAO NE antagonists: ◦ Reserpine ◦ Atenolol ◦ Used to treat hallucinations and delusions and sometimes used to treat mania SEROTONIN SEROTONIN is an inhibitory neurotransmi er – which means that it does not s mulate the brain. Adequate amounts of serotonin are necessary for a stable mood and to balance any excessive excitatory (stimulating) neurotransmitter ring in the brain. Within the brain, serotonin is localized mainly in nerve pathways emerging from the raphe nuclei, a group of nuclei at the centre of the reticular formation in the Midbrain, pons and medulla. These serotonergic pathways spread extensively throughout the brainstem , the cerebral cortex and the spinal cord Low serotonin levels leads to an increased appetite for carbohydrates (starchy foods) and trouble sleeping, which are also associated with depression and other emotional disorders. It has also been tied to migraines, irritable bowel syndrome, and bromyalgia. ff ff tt ff fi ff fi ti ff  Low serotonin levels are also associated with decreased immune system function. In addition to mood control, serotonin has been linked with a wide variety of functions, including the regulation of sleep, pain perception, body temperature, blood pressure and hormonal activity Largest amount of serotonin is found in the intestinal mucosa. Although the CNS contains less than 2% of the total serotonin in the body, serotonin plays a very important role in a range of brain functions. It is synthesized from the amino acid tryptophan. SEROTONERGIC PATHWAYS IN THE BRAIN Midline raphe nuclei to cortical and subcortical areas Plays a role in many behaviors: ◦Regulation of mood ◦Control of eating, sleep, arousal ◦Regulation of pain ◦Sexual Function Involved in higher cognition and emotion Disruption a ects the suprachiasmatic nucleus (circadian rhythm) Predominantly produced in the raphe nuclei, of which the caudal raphe nuclei project to the medulla and spinal cord and play a role in the regulation of pain The rostral raphe nuclei project to the limbic system and cerebral cortex, and serotonin here is colocalized with norepinephrine SEROTONIN RECEPTORS ◦ 5-HT1 - Brain, intestinal nerves - Neuronal inhibition, behavioral e ects, cerebral vasoconstriction ◦ 5-HT2 - Brain, heart, lungs, smooth muscle control, GI system, blood vessels, platelets - Neuronal excitation, vasoconstriction, behavioral e ects, depression, anxiety ◦ 5-HT3 - Limbic system, ANS - Nausea, anxiety ◦ 5-HT4 - CNS, smooth muscle - Neuronal excitation, GI ◦ 5-HT5, 6, 7 – Brain – Depression AGONISTS AND ANTAGONISTS 5-HT agonists: ◦ Fen uramine – stimulates release of 5-HT – used to treat eating disorders and depression ◦ Fluoxetine – inhibits reuptake of 5-HT – used to treat eating disorders and depression 5-HT antagonists: ◦ Reserpine – inhibit storage of 5-HT in synaptic vesicles – used to normalize mood states fl ff ff ff  ACETYLCHOLINE Acetylcholine was the rst neurotransmitter to be discovered. Acetylcholine (ACh) was rst identi ed in 1915 by Henry Hallett Dale for its actions on heart tissue. It was con rmed as a neurotransmitter by Otto Loewi, who initially gave it the name Vagussto because it was released from the vagus nerve. It is responsible for much of the stimulation of muscles, including the muscles of the gastro- intestinal system. It is also found in sensory neurons and in the autonomic nervous system, and has a part in scheduling REM (dream) sleep. Excitatory Distribution throughout brain Acetylcholine is transmitted within cholinergic pathways that are concentrated mainly in speci c regions of the brainstem and are thought to be involved in cognitive functions, especially memory. Severe damage to these pathways is the probable cause of Alzheimer’s disease Three areas of importance: ◦ Dorsolateral pons – involved in REM sleep ◦ Basal forebrain – perceptual learning (memory) ◦ Medial septum – modulation of hippocampus and formation of memories ◦ Vestibular control- scopolamine ◦ Extrapyramidal- Striatum B (Cogentin) CHOLINERGIC PATHWAYS IN THE CNS Nucleus basalis to cortex (A) and interneurons in striatum ( B) ACETYLCHOLINE RECEPTORS ◦M1 - Nerves - CNS excitation, gastric acid secretion ◦M2 - Heart, nerves, smooth muscle - Cardiac inhibition, neural inhibition ◦M3 -Glands, smooth muscle, endothelium - Smooth, muscle contraction, vasodilation ◦M4 – CNS - Not known ◦M5 – CNS - Not known ◦NM - Skeletal muscles neuromuscular junction - Neuromuscular transmission ◦NN - Postganglionic cell body dendrites - Ganglionic transmission AGONISTS AND ANTAGONISTS Drugs that facilitate ACh action (agonists): ◦ Black widow spider venom – results in overactivity of ACh which leads to seizures ◦ Nicotine – in small doses has been found to improve perceptual learning ◦ Muscarine – found in Amanita mushrooms - similar e ects to spider venom ◦ Neostigmine – used to treat low ACh levels in those with myasthenia gravis which results from destruction of ACh receptors on muscles fi ff fi fi fi fi ff ACh antagonists (all cause paralysis) : ◦ Botulinum toxin – prevents release of ACh ◦ Curare – blocks ACh receptors ◦ Atropine – blocks ACh receptors ◦ Hemicholinium – prevents recycling of choline and reduces production of ACh ◦ Some of these are used medically in surgery AMINO ACIDS Some amino acids don’t need to be converted to have an action on synapses 1. Glutamate 2. GABA (γ-amino-butyric acid) 3. Glycine Most synaptic communication is accomplished by amino acids Fast acting over short distances GABA Gamma amino butyric acid(GABA) is the major inhibitory neurotransmi er that is o en referred to as “nature’s VALIUM-like substance”. ◦ When GABA is out of range (high or low excretion values), it is likely that an excitatory neurotransmitter is ring too often in the brain. GABA will be sent out to attempt to balance this stimulating over- ring. ◦ People with too little GABA tend to su er from anxiety disorders, and drugs like Valium work by enhancing the e ects of GABA. ◦ Lots of other drugs in uence GABA receptors, including alcohol and barbiturates. ◦ If GABA is lacking in certain parts of the brain, epilepsy results. GABA is derived from glucose, which is transaminated in the Kreb’s cycle to glutamine and then converted to GABA by the enzyme, glutamic acid decarboxylase. AGONISTS AND ANTAGONISTS GABA agonists (mimic GABA at receptor sites): ◦ Muscimol – used to dilate pupils ◦ Benzodiazepines – used to treat anxiety ◦ Barbiturates – used as an anesthetic and to treat seizures in children under the age of 2 (controversy) ◦ Steroids – particularly those used for anesthesia ◦ Alcohol GABA antagonists (block receptors): fi fl ff fi ff tt ft  ◦ Bicuculline – induces convulsions ◦ Picrotoxin – induces convulsions GABA AND GLUTAMATE Anti-anxiety drugs are agonists for GABA Lack of GABA may contribute to epilepsy, a brain disorder resulting in uncontrolled movement and convulsions GLUTAMATE ▪Glutamate is involved in memory storage and pain perception. ▪Excessive glutamate can lead to neuron death; de cient glutamate has been proposed to explain schizophrenia ▪Main excitatory neurotransmitter of the CNS ▪Found in all CNS structures ▪Involved in almost all brain functions AGONISTS AND ANTAGONISTS Glutamate agonists: ◦ AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) ◦ NMDA (N-methyl-D-aspartate) ◦ Kainate ◦ All stimulate their namesake receptors and increase excitation ◦ Behavioural e ects vary depending on neural integration and the nature of the neurons activated ◦ In high doses, all induce seizures Glutamate antagonists: ◦ PCP ◦ Ecstasy ◦ Can lead to memory loss, inebriation, apathy GLYCINE ▪Inhibitory: Seems to be secreted by neurons in the lower brain stem at the same time as GABA ▪Not sure of di erences from GABA ▪No known agonists Antagonists: ◦ Bacterium that causes tetanus – prevents release of glycine and leads to constant contraction of muscles ◦ Strychnine – causes convulsions and death – not sure what its function is in terms of glycine ff ff fi  The Human Brain THE CEREBRUM The largest division of the brain. It is divided into two hemispheres, each of which is divided into four lobes. Cerebral Cortex - The outermost layer of gray matter making up the super cial aspect of the cerebrum. CEREBRAL FEATURES: Gyri - Elevated ridges "winding" around the brain. Sulci - Small grooves dividing the gyri Central Sulcus - Divides the Frontal Lobe from the Parietal Lobe Fissures - Deep grooves, generally dividing large regions/ lobes of the brain Longitudinal Fissure - Divides the two Cerebral Hemispheres Transverse Fissure - Separates the Cerebrum from the Cerebellum - Sylvian/Lateral Fissure - Divides the Temporal Lobe from the Frontal and Parietal Lobes LOBES OF THE BRAIN (4) Frontal Parietal Occipital Temporal * Note: Occasionally, the Insula is considered the fth lobe. It is located deep to the Temporal Lobe. fi fi  THE FOUR LOBES AND THE SENSORY-MOTOR PROCESSING AREAS LOBES OF THE BRAIN - FRONTAL The Frontal Lobe of the brain is located deep to the Frontal Bone of the skull. It plays an integral role in the following functions/actions: Memory Formation Emotions Decision Making/Reasoning Personality FRONTAL LOBE - CORTICAL REGIONS Primary Motor Cortex (Precentral Gyrus) – Cortical site involved with controlling movements of the body. Broca’s Area – Controls facial neurons, speech, and language comprehension. Located on Left Frontal Lobe. Broca’s Aphasia – Results in the ability to comprehend speech, but the decreased motor ability (or inability) to speak and form words. Orbitofrontal Cortex – Site of Frontal Lobotomies * Desired E ects: - Diminished Rage - Decreased Aggression - Poor Emotional Responses * Possible Side E ects: - Epilepsy - Poor Emotional Responses - Perseveration (Uncontrolled, repetitive actions, gestures, or words) Olfactory Bulb - Cranial Nerve I, Responsible for sensation of Smell ff ff  LOBES OF THE BRAIN - PARIETAL LOBE The Parietal Lobe of the brain is located deep to the Parietal Bone of the skull. It plays a major role in the following functions/actions: Senses and integrates sensation(s) Spatial awareness and perception(Proprioception - Awareness of body/ body parts in space and in relation to each other) PARIETAL LOBE - CORTICAL REGIONS Primary Somatosensory Cortex (Postcentral Gyrus) – Site involved with processing of tactile and proprioceptive information. Somatosensory Association Cortex - Assists with the integration and interpretation of sensations relative to body position and orientation in space. May assist with visuo- motor coordination. Primary Gustatory Cortex – Primary site involved with the interpretation of the sensation of Taste. LOBES OF THE BRAIN – OCCIPITAL LOBE The Occipital Lobe of the Brain is located deep to the Occipital Bone of the Skull. Its primary function is the processing, integration, interpretation, etc. of VISION and visual stimuli. OCCIPITAL LOBE – CORTICAL REGIONS Primary Visual Cortex – This is the primary area of the brain responsible for sight -recognition of size, color, light, motion, dimensions, etc. Visual Association Area – Interprets information acquired through the primary visual cortex. LOBES OF THE BRAIN – TEMPORAL LOBE The Temporal Lobes are located on the sides of the brain, deep to the Temporal Bones of the skull. They play an integral role in the following functions: -Hearing -Organization/Comprehension of language -Information Retrieval (Memory and Memory Formation)-Filing cabinet TEMPORAL LOBE – CORTICAL REGIONS Primary Auditory Cortex – Responsible for hearing Primary Olfactory Cortex – Interprets the sense of smell once it reaches the cortex via the olfactory bulbs. (Not visible on the super cial cortex) Wernicke’s Area – Language comprehension. Located on the Left Temporal Lobe. - Wernicke’s Aphasia – Language comprehension is inhibited. Words and sentences are not clearly understood, and sentence formation may be inhibited or non-sensical. Arcuate Fasciculus - A white matter tract that connects Broca’s Area and Wernicke’s Area through the Temporal, Parietal and Frontal Lobes. Allows for coordinated, comprehensible speech. Damage may result in: - Conduction Aphasia - Where auditory comprehension and speech articulation are preserved, but people nd it di cult to repeat heard speech. LOBES AND STRUCTURES OF THE BRAIN fi ffi fi MOTOR STRIP AND HOMUNCULUS Cultural Psychopharmacology CROSS-CULTURAL PSYCHOPHARMACOLOGY A branch of science seeks to determine whether di erences exist between ethnic groups in their response to psychotropic medications, as well as the reasons for such variations, including genetic, biological, environmental, and psychosocial factors Determines whether di erences exist in the pharmacokinetics and pharmacodynamics among various ethnic groups and ,where present, to determine the reasons for such variation DEFINITION REMEMBER Most drug research studies are completed using white male patients. Most data that we receive related to women, children, and other racial ff ff  groups occurs once a drug comes to market. When reviewing research studies for new medications, make sure to examine the research study groups. FACTORS ETHNICITY & CLOZAPINE African Americans Benign Neutropenia prevents selection for clozapine Low white count may result in discontinuation Asians Often excluded due to selection criteria Lower dose, higher plasma levels (30-50%)- Chinese Lower dose, increased side e ects- Koreans Lower dose - Southeast Asians Higher risk of Agranulocytosis 2.4X Hispanics Argentina and Chile - lower doses Ashkenazi Jews PLANNING ff