Unit 4 Flashcards
Schizophrenia
Psychopathological disorder characterized by emotional withdraw & flat effect (-), w/ hallucinations & delusions (+)
Schizophrenia symptomology
Flat effect -
Withdraw -
Hallucinations +
Delusions +
Abnormal behavior +
Cognitive impairment +
-Memory, attention, social perception
-Autism relates w/ social cues
Schizophrenia Prevalence
<1% of populations
-60% being M
Onset typically late adolescence /early adulthood
-Large # onset around 40 (usually F, if F, potentially menopause cause)
Schizophrenia & Genetics
Concordance Rates:
-50% MZ
-17% DZ
Genome Wide Asssocation Study (GWAS):
-Genes relating w/ DA (COMT, degrading enzyme), ST, & Glutamate
-Overlaps w/ genes implicated in bipolar & autism spectrum disorder (ASD)
-DISC 1 Gene disruption/disabled
SCZ & Environment
INC rates in urban areas
-INC stress, population, & hazards (lead, ect)
Working class
-Work environment hazards
Migrants
-INC stress, poverty, & nutritional issues
SCZ & Epigenetics
Offspring of older fathers & younger mothers
-Some studies disagree w/ father
-Young mom = INC disposition
-INC ASD risk w/ older mom & dad
Pregnancy difficulties
-Hemorrhaging & T2 diabetes in mom
-Viral infection
*INC viral enzyme in baby brain & CSF (cerebrospinal fluid)
*Jan-Apr baby (cold climates as well)
Low birth weight & small head circumference
Birth difficulties
-lack of O2/emergency C-section
CHICKEN & EGG, WHERE START? CORRELATION!
SCZ Brain structure & function - Ventricles
Enlarged ventricles
-Loss of surrounding neurons
-DISC 1 (wiring & organize neurons) (tested in mice, hard to tell SCZ present)
SCZ Brain structure & function - HPC
Hippocampus
-Small
-DEC glutamatergic neurons
-Abnormal hpc cytoarchitecture
*neurons out of line
MAY explain cognitive deficits, as contributes to behavior, thought, & speech
SCZ brain structure & function - Frontal Cortex & Cortical Tissue
Frontal Cortex
-Overactive
-@ rest during cognitive tasks
-May contribute to - symptoms
*Mood disturbances & social withdraw
Cortical tissue
-Over pruned during adolescence
-Too much lost gray matter from puberty+
SCZ Biochem & treatment
Marijuana use
-Worse symptoms
-MAY trigger onset in genetically predisposed ppl
*COMT
Ppl w/ SCZ have INC endogenous cannabinoids
-Attenuates stress response
THC activates receptors & anandimides
Ppl w/ SCZ have INC CB1 receptors
-Independent of marijuana use
-In CNS
SCZ DA hypothesis
Too much dopamine/DA receptors & synthesis
-May boost response to irrelevant stimuli
-INC cocaine use causes SCZ like symptoms
COMT may cause DA breakdown
-too many receptors
*Causes inability to may attentions (Causing abnormal behavior)
-Changes brain & neuron layout
SCZ DA Hypothesis 2
DA (D2) receptor antagonist revolutionized psychiatry
-Good treating + symptoms
-DA & ST
-Block DA receptor
*Side effects: Tardive dyskinesia (muscle control), pseudo-PD
*DA plays role in muscle movement & control
SCZ Typical VS Atypical antipsychotics
Typical:
Primarily block DA
-No work in 1/4 w/ SCZ
Atypical:
Greater ST receptor block/antagonism
Better treats - symptoms
Produces tardive dyskinesia
INC chance of weight gain
SCZ Glutamate Hypothesis
Glutamate (GLT) is everywhere
-DEC GLT receptors
-DEC glutamate n/t in those w/ SCZ w/ age (IDK???)
-PCP & Ketamine mimic psychotic symptoms
*NMDA receptor agonists
-Glutamate receptor (NMDA) agonist = DANGER!
*Too much = BAD!
Pros & Cons of SCZ Meds
PROS:
No straight jackets & sedatives
Patients involved in activities
Patients can leave hospitals (complicated)
CONS:
Changed roles of psychiatrists (not just prescribing meds)
INC non-compliance outside hospital (no want take meds)
-Leads to homelessness, jail, or prison (New asylums)
*Lack of proper treatment, keeping them jailed
*More likely to try to commit suicide
THERE IS NO MAGIC FIX!
Feeding Behavior
Homeostasis- Internal equilibrium
-We eat because we NEED to!
Regulatory systems (hormones & neurons) defend our set points
-Temp- 98.6F
-Fluid lvls (Vasopressin - BP)
-Body weight & Glucose lvls in blood
*Those on show gained weight after leaving show from not keeping diet
We can make new set points!
Why we eat
Nutrients needed for energy
Satisfaction of eating
-Dorsal striatum (food thought, planning, & eating movement)
-NAc (Nucleus accumbens) & Orbital Frontal Glucoreceptors (OFC)
*Control eating motivation & reward
Complex cultural & psychological
-Overwhelm regulatory systems
-May lead to eating disorders
DIGESTION & PANCREATIC HORMONES
Digestion- fats, proteins, carbs metabolized into usable chemicals in stomach
-ST: Glucose (GLC) stored as glycogen in liver/muscle cells & neurons
*GLC needs maintained at certain lvl
-LT: Excess fat stored in adipose tissue
*Use fat when GLC lvls low
Pancreatic Hormones
GLC regulation (sugar & energy regulation)
1) Insulin moves GLC
-GLC signal pancreas, beta cells release insulin
-Insulin stores GLC in liver & muscle cells as glycogen
-INC ST storage
2) Glucagon: Glycogen to GLC
-Useable for energy
-Still ST
INSULIN & DIABETES
Type 1
-“Childhood”
-Disorder insulin production = No insulin, no GLC storage, RIP (kills) cells & neurons from too much GLC
-Give insulin
INSULIN & DIABETES 2
Type 2
-Adult onset
-Cell receptors don’t recognize insulin/produce energy
-Treat w/ metaphormin, INC receptor sensitivity
-Lifestyle changes needed, obesity risk factor
-Lvls of GLC INC for longer
BIOLOGICAL INITIATION OF FEEDING 1/3
1) Low GLC & fat lvls
Glucoreceptors (in liver) talk w/ feeding initiation center of HPC
-Glucoreceptors → GLC lvls travel vegus nerve, INC feeding
-INC GLC = INC insulin released to store/utilize
BIOLOGICAL INITIATION OF FEEDING 2 & 3 /3
2) Insulin
If low, DEC GLC = INC appetite
Small INC of insulin = DEC appetite
*If too much GLC = hypoglycemia
3) Those w/ T2 diabetes untreated have INC GLC lvls but always hungry from low insulin
BRAIN & HORMONES INTERACT IN FEEDING
Ventromedial Hypothalamus (VMH)- Stops eating
-Lesions here = over eating & obesity (FAT RAT)
-Is our satiety area
Lateral Hypothalamus- Makes hungry
-Lesions here = stop eating & weight loss
When these areas are lesioned, eventually a new set point is made
BRAIN & HORMONES INTERACT IN FEEDING pt 2
Arcuate Nucleus (AN)- Bunch of cell bodies & neurons
-Receive signals about GLC lvls from insulin & other signals
-Fat cell, leptin (hormone), released from adipose tissue
*Generally inhibits feeding hormone
*Those obese have leptin insensitivity, INC feeding
BRAIN & HORMONES INTERACT IN FEEDING pt 3
Gut hormones: ST energy
-Stomach → Ghrelin → hungry
-Intestines → PYY336 → stop eating
*PYY336 low in obese ppl
Neurons in the AN
POMC Neurons- Inhibit appetite / = satiety
NPY- Stimulates appetite / = hunger
-Can inhibit POMC
-Ghrelin activates, causing feeding
B&HIIF pt 4
Insulin & PYY336 inhibit feeding. They dot not activate POMC, they inhibit NPY, DEC appetite
Leptin stimulates POMC while inhibiting NPY, DEC feeding
Feeding is a balance of 2nd order neurons
-Lateral Hypothalamic = Orexigenic = INC appetite
-PVN (Para ventricular nucleus) = anorexigenic = DEC appetite
NST (Nucleus of Solitary Tract) = integrate signal from gut & brain
-Comes in from GI tract
Appetite Modulators
Orexin- Has receptors in hypothalamus
⇅ - STIMULATE feeding in animals
Anandamide- Body’s THC
-CB1 (in brain) & CB2 receptors
Parkinson’s Disease (PD) Def & symptoms
Tremors of hands & face at rest
-Rigid walking
-“mask like” appearance - no face muscle control
-Apraxia - Difficulty engaging in effortful movement
PD Prevelance
1-2% of US ages 65&+
-Rare but not never in Y-A
M x2.5 more than F to get
-Possibly from working in hazardous environments
NEUROBIOLOGY OF PD
Genes
Defect in genes that encode for
-Alpha-synuclein
*Found in synaptic buttons
*Releases n/t (Not enough DP)
-Parkin
*Degrades unneeded proteins
PD NEUROBIOLOGY THEORY
Defects in either gene leading to accumulation of alpha-synuclein
-Forms Lewy bodies, screwing up neurons
*Mitochondria cannot power neuron, killing it
BRAIN AREA COMPROMISED
Midbrain!
Degeneration of DA containing cells in substantia niagra
Dopaminergic neurons project to striatum
-DA to striatum controls voluntary movement
PD TREATMENT
-Agonist at DA receptors (No work well)
-MAOIs (INC DA activity)
-LDOPA
*Precursor for DA
*Can cross BBB (DA cannot)
*Side effects: Tolerance, hallucinations, INC libido
*Only treats symptoms, not cell death
-DBS- Pacemaker stimulates striatum (axon terminal from substantia niagra) to release DA
Exercise and PD
Postmortem examinations reveal DA loss in the substantia nigra pars compacta (SNc), and the consequent loss of DA in the striatum in the brains of PD patients.
-Exercise restores BDNF levels and has has neuroprotective effects against the neurotoxicity induced by 6-OHDA.
-No BDNF = No TH
-TH decrease in both SED group and SED + K252a group
-When K252a added, all groups that received 6-OHDA showed decreases of
TH levels.
-intermittent treadmill exercise employed an increase of BDNF levels
-Treadmill running at 5 days/week during 18 weeks DEC dopaminergic cell loss, INC dopamine and its transporter expression, and consequently improves balance and motor coordination
-The intermittent exercise protocol could be more beneficial than continuous exercise, in addition to being closer to the exercise protocols undertaken in PD patients.
Exercise & PD pt 2
-TH in the CPu, and showed reduced motor symptoms
-treadmill exercise = changes in BDNF lvls = activate TrkB-dependent mechanisms (related to survival of nigrostriatal dopaminergic neurons)
-blockade BDNF–TrkB signaling = worsened neuroprotective effects of exercise after K252a injection
-Physical activity INC serum BDNF, which cross the blood–brain barrier, and may decrease the PD risk
First-rank symptoms of SCZ
Auditory hallucinations
Highly personalized delusions
Changes in affect (emotion)
Supersensitivity Psychosis
Exaggerated “rebound” psychosis when antipsychotic meds are reduced, probably as a consequence of the up-regulation of receptors during drug treatment
Basal Metabolism
Use of energy for
-Heat production
-Maintenance of membrane potentials
-All the other basic life-sustaining functions of the body.
Cephalic Phase of feeding
Triggered by sights, smells, and tastes that we have learned to associate with food
Digestive Phase of feeding
Food entering the digestive tract prompts an additional release of insulin
Absorptive Stage
As digested food is absorbed into the bloodstream, gluco-detectors detect the increase in circulating glucose and signal the pancreas to release still more insulin
Orexigenic Neurons VS Anorexigenic Neurons
Orexigenic neurons promote feeding behavior.
Anorexigenic neurons inhibit feeding behavior.
Cholecystokinin (CCK)
Peptide hormone released by gut after ingestion of food high in protein and/or fat.
