It's a Brain Thing. Sue Gabriel Molly Gabriel

Transcription

1 Tuesday, 10:00 11:30, A3 It's a Brain Thing Sue Gabriel scgabriel2@gmail.com Objectives: Molly Gabriel Notes: 1. Identify effective methods for the practical application of concepts related to improving the delivery of services for persons with developmental disabilities 2. Identify advances in clinical assessment and management of selected healthcare issues related to persons with developmental disabilities 3. Identify and emphasize attitudes that enhance the opportunities for persons with DD to achieve their optimal potential

2 It s a Brain Thing Sue Gabriel, PMHNP-BC Molly Gabriel, M.A. April 23, 2013 Understanding the Cells Which Make Up the Brain The nervous system is composed of two basic types of cells: neurons and glia Glia: helper cells, act as a glue for the neurons, provide supporting functions, waste management Neurons: information processors Neurons consist of three basic parts: cell body, dendrite, & axon 1

3 The brain has both white matter (axons) and grey matter (blood vessels & neuronal bodies) ANATOMY Left Hemisphere (usually dominant) logical portion of brain Right Hemisphere: artistic, emotional, spatial portion of brain Corpus Collosum: Connects Right and Left Hemispheres Cerebral Cortex: Corrugated surface of the 4 lobes of the brain 2

4 Four Lobes Frontal: endpoint for visuomotor and objectrecognition functions begun by the occipital lobe, BEHAVIOR SELECTION, impulse control, executive function, abstract thinking Parietal: somatosensory processing, movement, spatial cognition Temporal: auditory functioning, visual processes, emotion, spatial navigation, spatial and object memory Occipital: vision Hemispheres separated by the longitudinal fissure and connected by the corpus callosum Lateralization of the brain as a trend, not an absolute! Two Hemispheres 3

5 Two Hemispheres Contralateral body control Right: language (Wernicke s and Broca s areas on the right side of 95% of people) Left: emotion, processing/control of sensory/motor movement Factors which affect lateralization: handedness, sex, environment, individual differences Brain Stem Brain Stem Connects spinal cord (ascending & descending) to the brain, most primitive brain functions such as breathing & cardiovascular activity Hindbrain: Cerebellum: coordinating and learning skilled movement Midbrain: Part of auditory/visual pathways, reflexive movement of eyes/head. Contains substantia nigra that manufactures dopamine Pons: reflex center, contains locus cereleus that manufactures norepinephrin 4

6 More Brain Stem Medulla Oblongata: Conscious control of skeletal muscles; balance, coordination & modulation of sound impulses of the middle ear; reflexes such as heart rate, breathing, swallowing, vomiting, coughing, sneezing Reticular Formation: Core of Brain Stem Reticular activating system (RAS)=sleep/wake cycle; arousing/maintaining consciousness, alertness & attention Diencephalon Diencephalon Majority of connections for sensory, motor and limbic pathways go thru here Thalamus: All sensory pathways go through, relay sensory to the cortex, influence pre-frontal cortex- affect & foresight Epithalamus: Poorly understood but contains the pineal gland: which produces melatonoin Hypothalamus: Four F s: Feeding, Fighting, Fleeing, and Sexual Reproduction. Takes part in nearly ALL motivated behavior. Control center for pituitary gland, stress response center, sleep-wake, cardiac function 5

7 Basal Ganglia Basal Ganglia Collection of nuclei which includes the putamen, globus pallidus, caudate nucleus. Receives projections from all areas of the cortex and send projections through hthe circuit itand dforward dto frontal cortical areas. Functions relate to movement and simple forms of learning (S-R). (Huntington s chorea, Parkinson s disease, Tourette s syndrome) Limbic System 6

8 Limbic System Forms the border (limbus) of the temporal lobes and connects to many other brain structures Subjective emotional experiences, and physical changes associated with emotional states, esp. aggression, submission, sexual behavior, pleasure, memory & learning Also associated with other moods, motivation Limbic System Hippocampus: Consolidates new information about facts and events into long-term memories. Spatial navigation. VULNERABLE TO STRESS (PTSD, childhood abuse) Amygdala: Generates emotions from perceptions and thoughts (with interactions of hypothalamus & prefrontal cortex) Contains many opiate receptors Still More Ventricles: Cavities of space within the brain. Enlargement of ventricles associated with brain damage. Filled with Cerebral Spinal Fluid 7

9 For More Fun NEUROCHEMISTRY! LOTS OF TERMS NEUROTRANSMITTER: CHEMICAL THAT SENDS A SIGNAL FROM ONE BRAIN CELL (NEURON) TO ANOTHER PRESYNAPTIC PORTION OF CELL IS ACTUALLY THE END OF THE CELL POSTSYNAPTIC PORTION IS THE BEGINNING OF THE NEXT CELL 8

10 NEUROTRANSMISSION TRANSMISSION OCCURS WHEN A SIGNAL VIA CHEMICALS IS SENT FROM ONE CELL INTO THE SYNAPSE AND CONNECTS WITH THE NEXT CELL AGONIST NOT AGONY AN AGONIST IS A SUBSTANCE THAT BINDS WITH A RECEPTOR TO CAUSE A CHEMICAL/PHARMACOLOGICAL EFFECT (STUFF HAPPENS) AUTORECEPTORS ARE LOCATED ON THE CELL THAT IS RELEASING THE NT. IT TELLS THE SENDING CELL TO START/STOP FLOW OF TRANSMITTER MORE TERMS EFFICACY: MAGNITUDE OF THE RESPONSE THAT RESULT FROM THE DRUG AND RECEPTOR COMBINATION POTENCY: AFFINITY OF THE DRUG FOR THE RECEPTOR RELATIVE POTENCY: POTENCY OF A DRUG COMPARED TO A SIMILAR DRUG I.E. HALDOL IS MORE POTENT THAN MELLARIL. (BUT CAN BE EQUALLY EFFECTIVE) 9

11 EVEN MORE TERMS UPREGULATION: POSTSYNAPTIC RECPTORS INCREASE IN NUMBER WHEN THE NT IS DECREASED-- NEUROPLASTICITY DOWN- REGULATION: RECEPTORS DECREASE IN NUMBER WHEN THERE IS TOO MUCH NT ANTAGONISTS ANTAGONISTS STOP THE ACTIVATION OF A RECEPTOR BY THE NEUROTRANSMITTER AND THUS CELL ACTION IN THE NEXT CELL (STUFF DOESN T HAPPEN) TYPES OF ANTAGONISTS COMPETITIVE REVERSIBLE ANTAGONISM: AGONIST AND ANTAGONIST COMPETE FOR SAME BINDING SITE, i.e., HALDOL D2 BLOCKER IRREVERSIBLE ANTAGONIST: ANTAGONIST DOES NOT LEAVE RECEPTOR SITE, SO IT CAN NEVER AGAIN BIND WITH AN AGONIST, i.e., RESERPINE. 10

12 REMEMBER AN AGONIST STARTS A CHEMICAL REACTION AN ANTAGONIST STOPS A CHEMICAL REACTION LESS NT= POST SYNAPTIC RECEPTERS INCREASE OR UPREGULATE MORE NT, LESS RECEPTORS = DOWN REGULATION JUST FYI GABA CALMS THINGS DOWN (DECREASE CELL EXCITABILITY) AED S/ ANTI-ANXIETY Rx OFTEN ARE GABANERGIC GLUTAMATE EXCITES CELLS, TOO MUCH EXCITEMENT CAN CAUSE DEATH OF THE CELL (NAMENDA IS SAID TO HELP WITH THIS) RECEPTOR THEORY OF DEPRESSION UP REGULATED RECEPTORS (IN THE PRESENCE OF LESS NT) CORRELATES WITH SX OF DEPRESSION AND IS LINKED TO CAUSE OF DEPRESSION WHEN RX GIVEN, NT REPLENISHES FAIRLY QUICKLY, CLINICAL IMPROVEMENT NOT SEEN UNTIL RECEPTORS DOWN REGULATE 11

13 STRESS THEORY OVERACTIVITY (STRESS) OF THE HPA AXIS RESULT IN CHANGES OF 5HT RECEPTORS: INCREASED 5HT2A (BAD GUY) IN CORTICAL (THINKING) AREA AND DECRESED (GOOD GUY) 5HT1A IN HIPPOCAMPAL (EMOTIONS/MEMORY) AREAS. AGAIN, ANTIDEPRESSANTS REVERSE THESE TRENDS. NE AND 5HT NOREPINEPHRINE AND SEROTONIN ARE BOTH IMPLICATED IN DEPRESSION AND ANXIETY DISORDERS. BOTH CONTAIN SPECIFIC PATHWAYS AUTORECEPTORS (THERMOSTATS), AND RECPTORS. MAY WORK SYNERGISTICALLY. SEROTONIN PRODUCED FROM TRYPTOPHAN CONVERTED INTO 5- HYDROXYTRYPTAMINE (5HT) AND STORED DESTROYED BY MAO INSIDE THE CELL 12

14 SO MANY? 90% OF 5HT IS FOUND IN SPECIALIZED CELLS IN THE GI TRACT THE REST IS FOUND IN PLATELETS AND THE CNS AT LEAST 14 TYPES OF RECEPTOR SUBTYPES CLONED WE DON T KNOW WHAT ALL OT THEM DO, YET! 5HT# 5HT6 & 5HR7 FOUND IN LIMBIC (HPA) SYSTEM, 6 RECEPTORS HAVE A HIGH AFFINITY FOR ANTIDEPRRESSANT DRUGS 5HT3 RECEPTORS ARE IN THE GUT AND RELATED TO VOMITING 5HT2 5HT2A ANTAGONISTS IMPORTANT IN TREATING NEGATIVE SYMPTOMS OF SCHIZOPHRENIA INCREASED 5HT2A RECEPTORS (UPREGULATED DUE TO DECREASED 5HT) IN THE CORTICAL AREAS ASSOCIATED WITH DECREASED 5HT1A AND SUICIDAL BEHAVIORS 13

15 5HT1A THE GOOD GUY 5HT1A: PRESYNAPTIC AUTORECEPTOR ACTS BY DETECTING WHEN 5HT IS PRESENT, CAUSING A SHUT DOWN OF 5HT FLOW. IF BLOCKED OR DOWNREGULATED, IT INCREASES 5HT FLOW, AND THIS IMPROVES DEPRESSION, OCD, ANXIETY, AND BULEMIA SYMPTOMS 5HT1D IN ANOTHER PORTION OF THE BRAIN, LOCATED ON PRESYNAPTIC AXON TERMINAL, IS ANOTHER AUTORECEPTOR. IF THIS IS STIMULATED, IT BLOCKS RELEASE OF 5HT, IMPORTANT IN MIGRAINE CONTROL SSRI S SSRI S BLOCK REUPTAKE PUMP (REMEMBER, 5HT IS DESTROYED INSIDE THE CELL). INCREASED 5HT PROMOTES DOWN REGULATION OF RECEPTORS AND THUS ANTIDEPRESSANT RESPONSE. 14

16 SSRI SIDE EFFECTS 5HT2A: AGITATION AKATHISIA (DA EFFECT) ANXIETY PANIC ATTACKS INSOMNIA SEXUAL DYSFUNCTION 5HT3; NAUSEA GI UPSET DIARRHEA HEADACHE DOPAMINE (DA) MADE IN DOPAMINERGIC NEURONS FROM TYROSINE, USING 2 OF 3 SAME ENZYMES THAT ALSO MAKE NOREPINEPHRINE (NE). DESTROYED BY MONOAMINE OXIDASE (MAO) INSIDE THE CELL AND CATECHOL-O- METHYL TRANSFERASE (COMT) OUTSIDE CELL DOPAMINE RECEPTORS AT LEAST 5 DIFFERENT FAMILIES OF RECEPTORS D1 RECEPTORS IN PREFRONTAL CORTEX REDUCED IN SCHIZOPHRENIA, ASSOCIATED WITH NEGATIVE SYMPTOMS D2 RECEPTORS MOST STUDIED 15

17 4 DA PATHWAYS NIGROSTRIATAL: FROM SUBSTANTIA NIGRA TO BASAL GANGLIA WITH D1 AND D2 RECEPTORS. WHEN DA RECEPTORS ARE BLOCKED HERE, YOU GET EPS LONG-TERM BLOCKADE CAUSES UPREGULATED RECEPTORS, EXTRA MOVEMENTS AND POSSIBLY TD. Extrapyramidal Side Effects: Clinical Costs Symptoms Parkinsonian syndrome Rigidity Cognitive slowing Apathy Dysphoria yp Akathisia Acute dystonia Clinical consequences Associated with poor adherence Associated with increased risk of tardive dyskinesia HPG axis: impact of dopamine blockade Hypothalmus Dopamine (inhibits) Pituitary prolactin 16

18 DA PATHWAYS CONT. TUBEROINFUNDIBULAR PATHWAY: FROM HYPOTHALAMUS TO ANTERIOR PITUITARY GLAND BLOCKED RECEPTORS HERE CAUSE INCREASED PROLACTIN/HORMONAL IRREGULARITIES. POSITIVE SX PATHWAY MESOLIMBIC PATHWAY: MIDBRAIN TO NUCLEUS ACCUMBENS- PRIMARILY D2. BLOCKADE HERE DECREASES POSITIVE SX OF SCHIZOPHRENIA. ALL TYPICALS AND ATYPICALS WORK HERE. NEGATIVE/COGNITIVE PATHWAY MESOCORTICAL PATHWAY: FROM MIDBRAIN TO THE LIMBIC CORTEX LIKELY D1 AND D2 MEDIATED BLOCKADE OF D2 HERE INCREASES NEGATIVE SX AND PROMOTES COGNITIVE DULLING 17

19 OTHER TRANSMITTER EFFECTS MUSCARINIC EFFECTS = ANTICHOLINERGIC EFFECTS, IE, CONSTIPATION, DROWSINESS, DRY MOUTH DA NORMALLY BLOCKS ACETYLCHOLINE ACTIVITY IN THE NIGROSTRIATAL PATHWAY. IF DA BLOCKED, GET INCREASED ACH AND THUS EPS EVEN MORE HISTAMINE (HA) IS A NEUROTRANSMITTER THAT MAY BE ASSOCIATED WITH WAKEFULNESS. MANY ANTIPSYCHOTICS ALSO BLOCK HA THUS CAUSING DROWSINESS, WEIGHT GAIN, AND DECREASED BLOOD PRESSURE. 5HT2A NOT BINGO ATYPICAL ANTIPSYCHOTICS OFTEN HAVE A DUAL ACTION OF D2 BLOCKADE AND 5HT2A BLOCKADE. 5HT2A OPPOSES THE RELEASE OF DA IN THE NIGROSTRIATAL (MOVEMENT) AND TUBEROINFUNDIBULAR (HORMONE) PATHWAYS. THEREFORE, 5HT2A BLOCKADE CREATES MORE DA IN THESE 2 SYSTEMS, SO LESS PROBLEMS 18

20 5HT CONNECTION ANOTHER LIKELY THEORY IS THE INTERACTION OF EXCESS 5HT2A (BAD SEROTONIN) IN THE MESOCORTICAL SYSTEM PROMOTES EVEN GREATER DA DEFICIENCY IN THIS AREA. BY BLOCKING 5HT2A IN THE M-C TRACK, YOU INCREASE DA AND DECREASE NEGATIVE SYMPTOMS. NOW WHAT? WHILE INFORMATION ON BRAIN CHEMISTRY HAS EXPLODED IN THE LAST 20+ YEARS. WE ARE LITTLE PAST THE PRE- SCHOOL LEVEL OF UNDERSTANDING FURTHER UNDERSTANDING WILL HOPEFULLY ALLOW FOR GREATER DIAGNOSTICS AND MOST IMPORTANTLY: UNDERSTANDING AND/OR TREATMENT. 19