Substance Substance AbuseAbuse

Definition:Definition:Maladaptive pattern of substance use leading to clinically Maladaptive pattern of substance use leading to clinically significant impairment of distresssignificant impairment of distress

Synapses, Reinforcement, & Drug UseSynapses, Reinforcement, & Drug UseExperiments showed dopamine release in the area of the Experiments showed dopamine release in the area of the nucleus accumbens was reinforcingnucleus accumbens was reinforcing

Most abused drugs & ordinary pleasures lead to increased Most abused drugs & ordinary pleasures lead to increased dopamine activitydopamine activity

Recent research has dopamine & nucleus accumbens Recent research has dopamine & nucleus accumbens playing role in attention-getting or arousal rather than playing role in attention-getting or arousal rather than pleasurepleasure

Common Drugs & Their Common Drugs & Their Synaptic EffectsSynaptic Effects

StimulantsStimulantsProduce excitement, alertness, Produce excitement, alertness, elevated mood, decreased elevated mood, decreased fatigue, & sometimes motor fatigue, & sometimes motor activityactivityHighly addictiveHighly addictive

AmphetaminesAmphetaminesIncreases dopamine release from Increases dopamine release from presynaptic terminals by presynaptic terminals by reversing the direction of reversing the direction of dopamine transferdopamine transfer

CocaineCocaineBlocks the reuptake of catechola-Blocks the reuptake of catechola-mines & serotonin at the synapsemines & serotonin at the synapseBehavioral effects are believed to Behavioral effects are believed to be mediated primarily by be mediated primarily by dopamine & secondarily by dopamine & secondarily by serotoninserotonin

Common Drugs & Their Common Drugs & Their Synaptic EffectsSynaptic Effects

Effects of Effects of Amphetamine & Amphetamine & CocaineCocaineShort-lived because of the depletion of Short-lived because of the depletion of dopamine stores & tolerancedopamine stores & tolerance

MethylphenidateMethylphenidateRitalinRitalin

Prescribed for ADHDPrescribed for ADHD

Works like cocaine by blocking reuptake of Works like cocaine by blocking reuptake of dopamine at presynaptic terminalsdopamine at presynaptic terminals

Repeated use of stimulants can have Repeated use of stimulants can have permanent effects on brain functioningpermanent effects on brain functioning

Common Drugs & Their Common Drugs & Their Synaptic EffectsSynaptic Effects

NicotineNicotineStimulates the nicotinic receptor (a Stimulates the nicotinic receptor (a type of acetylcholine receptor) in the type of acetylcholine receptor) in the CNS & neuromuscular junction of CNS & neuromuscular junction of skeletal musclesskeletal muscles

Also increased dopamine release by Also increased dopamine release by attaching to neurons that release attaching to neurons that release dopamine in the nucleus accumbensdopamine in the nucleus accumbens

The nicotine in tobacco is The nicotine in tobacco is 4 ½ times4 ½ times more addicting than heroinmore addicting than heroin

Common Drugs & Their Common Drugs & Their Synaptic EffectsSynaptic Effects

Opiate DrugsOpiate DrugsMorphine, heroin & methadoneMorphine, heroin & methadone

The net effect is of increasing the The net effect is of increasing the release of dopamine by stimulating release of dopamine by stimulating endorphin receptorsendorphin receptors

They decrease the activity in the locus They decrease the activity in the locus coeruleus resulting in a decreased coeruleus resulting in a decreased response to stress & decreased response to stress & decreased memory storagememory storage

Common Drugs & Their Common Drugs & Their Synaptic EffectsSynaptic Effects

MarijuanaMarijuanaContains Contains 99-THC which works by -THC which works by attaching to canabinoid receptorsattaching to canabinoid receptors

Hallucinogenic Hallucinogenic DrugsDrugsDrugs that distort perceptionDrugs that distort perception

Many hallucinogenic drugs Many hallucinogenic drugs resemble serotonin & bind to resemble serotonin & bind to serotonin type 2A receptorsserotonin type 2A receptors

Alcohol & AlcoholismAlcohol & AlcoholismAlcoholism & Alcoholism & Alcohol Alcohol DependenceDependenceA common type of substance abuse A common type of substance abuse that produces significant harm to the that produces significant harm to the lives of others & the drinkerlives of others & the drinker

Alcohol inhibits the NaAlcohol inhibits the Na++ ion flow across ion flow across the neuron membranethe neuron membrane

It decreases serotonin activity, It decreases serotonin activity, facilitates the transmission of GABAfacilitates the transmission of GABAAA receptor & blocks glutamate receptors receptor & blocks glutamate receptors & increases dopamine activity& increases dopamine activity

Types of Types of AlcoholismAlcoholismType I alcoholism: Type I alcoholism: less dependent on less dependent on genetic factors, develops gradually genetic factors, develops gradually over years, affects men & women over years, affects men & women equally & is less severeequally & is less severe

Type II alcoholism: Type II alcoholism: has a strong has a strong genetic basis, is rapid & has an early genetic basis, is rapid & has an early onset, primarily affects men, is more onset, primarily affects men, is more severe & is associated with criminalitysevere & is associated with criminality

Alcohol & AlcoholismAlcohol & AlcoholismRisk Factors for Risk Factors for Alcohol AbuseAlcohol Abuse1. Less than average intoxication after 1. Less than average intoxication after drinking a small to moderate amount of drinking a small to moderate amount of alcoholalcohol

2. Experiencing more than average 2. Experiencing more than average relief from tension after drinking relief from tension after drinking alcoholalcohol

3. Having a smaller than normal 3. Having a smaller than normal amygdala in the right hemisphereamygdala in the right hemisphere

2. AlcoholHigh

(StimulatingOpioid

Receptors)

4. Motivated toConsume More

Alcohol(Increased craving &

Loss of Control)

1. AlcoholConsumption

3. Alcohol HighDiminishes

(Desire to stimulateThe OpioidReceptors)

Major Major DepressionDepression

CharacteristicsCharacteristics::Feeling sad, helpless, lacking Feeling sad, helpless, lacking energy & pleasure for weeks at energy & pleasure for weeks at a time, feelings of worthlessness, a time, feelings of worthlessness, trouble sleeping, can’t trouble sleeping, can’t concentrate, little pleasure from concentrate, little pleasure from food or sex, contemplating food or sex, contemplating suicide & can’t imagine being suicide & can’t imagine being happyhappy

Major Major DepressionDepression

MoreShortnessOf Breath

IncreasedAnxiety

LessEnergy

Tiredness

MoreShortnessOf Breath

MuscleTension

ShallowBreathing

Anxiety

Deprsssion

Major Major DepressionDepression

Evidence of Genetic or Evidence of Genetic or Other Prior Other Prior PredispositionsPredispositionsIf there were relatives with depression that manifests before the age of 30If there were relatives with depression that manifests before the age of 30

It tends to be episodic & there were incoming feelings of depressionIt tends to be episodic & there were incoming feelings of depression

May have normal feelings for weeks, months or years between episodesMay have normal feelings for weeks, months or years between episodes

It is more common among women than men but equally common among It is more common among women than men but equally common among childrenchildren

Most experiencing depression have decreased activity in the left hemisphere Most experiencing depression have decreased activity in the left hemisphere & increased activity in the right prefrontal cortex& increased activity in the right prefrontal cortex

Major Major DepressionDepression

Borna DiseaseBorna DiseaseA viral infection of the nervous A viral infection of the nervous system leading to periods of system leading to periods of frantic activity alternating with frantic activity alternating with periods of inactivityperiods of inactivity

In 1990 study, 30% of severely In 1990 study, 30% of severely depressed persons tested depressed persons tested positive for the Borna viruspositive for the Borna virus

HypoglycemiaHypoglycemiaCauses: too little food, too Causes: too little food, too much insulin or diabetes or much insulin or diabetes or diabetes medication, or extra diabetes medication, or extra activityactivity

A sudden onset may progress A sudden onset may progress to insulin shockto insulin shock

Treatment for Treatment for DepressionDepression

TricyclicsPrevent the presynaptic neuron from reuptake of catecholimes or serotonin

MOA InhibitorsBlock the enzyme monamine oxydase from metabolizing catecholamines & serotonin into active forms

SSRIsSimilar to tricyclics but are specific to serotonin

Atypical AntidepressantsA miscellaneous group of drugs with antidepressant actions & mild side effects; they inhibit reuptake of dopamine & to some extent norepinephrine

Treatment for Treatment for DepressionDepression

Cognitive TherapyCognitive TherapyProduces effects similar to Produces effects similar to drugs for many depressed drugs for many depressed peoplepeopleRecovered are less likely to Recovered are less likely to relapserelapse

Electroconvulsive Electroconvulsive TherapyTherapyInducing seizures with an Inducing seizures with an electric shock to the headelectric shock to the headApplication: every other day for Application: every other day for about 2 weeksabout 2 weeksAbout ½ will relapse within 6 About ½ will relapse within 6 mos.mos.Most depressed people will Most depressed people will enter REM sleep within 45 enter REM sleep within 45 mins. of going to bedmins. of going to bed

Thoughts

EmotionsBehavior

Bipolar DisorderBipolar DisorderManic-Depressive Manic-Depressive DisorderDisorderAlternates between depression & Alternates between depression & maniamania

2 types of bipolar disorder:2 types of bipolar disorder:

Bipolar I disorder:Bipolar I disorder: Has full- Has full-blown episodes of maniablown episodes of mania

Bipolar II disorder: Bipolar II disorder: His milder His milder phases of mania (hypomania)phases of mania (hypomania)

CharacteristicsCharacteristicsMean onset is in the late 20sMean onset is in the late 20s

Brain activity is higher than Brain activity is higher than normal during mania & lower normal during mania & lower than normal during depressionthan normal during depression

There is a strong hereditary basis There is a strong hereditary basis but there is no specific genebut there is no specific gene

Lithium salts are the most Lithium salts are the most effective therapy but it isn’t effective therapy but it isn’t known how they workknown how they work

Drugs used include valproic acid Drugs used include valproic acid and carbamazepineand carbamazepine

Seasonal Affective DisorderSeasonal Affective DisorderUsually in the Usually in the WinterWinterMost common in regions Most common in regions closest to the poles where closest to the poles where the nights are very long the nights are very long and there’s a very short and there’s a very short summersummer

Treatment is with bright Treatment is with bright lights in either the morning lights in either the morning or evening for about 1 houror evening for about 1 hour

SchizophreniaSchizophreniaCharacteristicsCharacteristicsDeteriorating ability to function in Deteriorating ability to function in everyday life, delusions, hallucinations, everyday life, delusions, hallucinations, movement disorders, thought disorders, movement disorders, thought disorders, & inappropriate emotional expression& inappropriate emotional expression

Behavioral SymptomsBehavioral SymptomsPositive Symptoms:Positive Symptoms: (behaviors that (behaviors that should be absent) delusions, should be absent) delusions, hallucinations, inappropriate emotional hallucinations, inappropriate emotional responding, bizarre behavior, & responding, bizarre behavior, & thought disordersthought disorders

Negative Symptoms:Negative Symptoms: (missing behaviors (missing behaviors that should be there) deficits in social that should be there) deficits in social interaction & emotional expressioninteraction & emotional expression

Can be either acute or chronicCan be either acute or chronic

SchizophreniaSchizophreniaDiagnosingDiagnosingDifficult to diagnoseDifficult to diagnose

Conditions with similar Conditions with similar symptoms:symptoms:

1. mood disorder with 1. mood disorder with psychotic featurespsychotic features

2. substance abuse2. substance abuse

3. brain damage3. brain damage

4. undetected hearing loss4. undetected hearing loss

5. Huntington’s disease5. Huntington’s disease

6. nutritional 6. nutritional abnormalitiesabnormalities

Demographic DataDemographic DataOccurs in all ethnic groups & Occurs in all ethnic groups & is about equal in men & is about equal in men & womenwomen

It tends to develop earlier in It tends to develop earlier in menmen

Expressed emotions: hostile Expressed emotions: hostile expressions by a caretaker expressions by a caretaker can aggravate the conditionscan aggravate the conditions

May be the reason for May be the reason for increased number of cases in increased number of cases in the U.S. & Europe compared the U.S. & Europe compared to 3to 3rdrd world countries world countries

The older the father at the The older the father at the time of birth, the greater the time of birth, the greater the riskrisk

SchizophreniaSchizophreniaGeneticsGenetics

There is a 50% concordance for There is a 50% concordance for schizophrenia for monozygotic twins & schizophrenia for monozygotic twins & a 15% concordance for dizygotic twinsa 15% concordance for dizygotic twins

This does not mean that schizophrenia This does not mean that schizophrenia has a purely genetic causehas a purely genetic cause

There are no reliable markers for There are no reliable markers for schizophreniaschizophrenia

Schizophrenia Schizophrenia HypothesesHypotheses

Neurodevelopmental Neurodevelopmental HypothesisHypothesisCaused in large part by Caused in large part by abnormalities to the nervous abnormalities to the nervous system during the prenatal or system during the prenatal or neonatal periodneonatal periodMany schizophrenics had Many schizophrenics had problems before or shortly problems before or shortly after birth that could have after birth that could have affected brain developmentaffected brain developmentRh incompatibility between Rh incompatibility between mother & offspring is mother & offspring is associated with increased associated with increased probability of schizophreniaprobability of schizophreniaSeason-of-birth effect: Season-of-birth effect: tendency for those born in tendency for those born in winter months to have a winter months to have a slightly greater probability of slightly greater probability of schizophreniaschizophrenia

Mild Brain AbnormalitiesMild Brain AbnormalitiesMany schizophrenics have Many schizophrenics have slightly smaller prefrontal slightly smaller prefrontal cortex, temporal cortex, cortex, temporal cortex, hippocampus & amygdalahippocampus & amygdalaHave smaller than normal cell Have smaller than normal cell bodies & some neurons fail to bodies & some neurons fail to arrange themselves in a neat, arrange themselves in a neat, orderly mannerorderly mannerHave slightly larger right Have slightly larger right hemisphere & lower than hemisphere & lower than normal activity in the left normal activity in the left hemispherehemisphereIt appears late if the damage is It appears late if the damage is done early because the done early because the damage is in areas that mature damage is in areas that mature slowly producing minor slowly producing minor symptoms in childhood, but symptoms in childhood, but impairments increase with impairments increase with maturationmaturation

Schizophrenia Schizophrenia HypothesesHypotheses

Dopamine HypothesisDopamine HypothesisSchizophrenia is the result of excess Schizophrenia is the result of excess activity at certain dopamine synapsesactivity at certain dopamine synapsesEvidence comes from drugs that relieve Evidence comes from drugs that relieve the symptoms work on dopaminethe symptoms work on dopamineChlorpromazine:Chlorpromazine: Thorazine was the 1 Thorazine was the 1stst drug used successfullydrug used successfullyAntipsychotic drugs:Antipsychotic drugs: Block dopamine Block dopamine receptorsreceptorsPhenothaizines:Phenothaizines:neuroleptic drugs neuroleptic drugs including chlorpromazineincluding chlorpromazineButyrophenones: Butyrophenones: neuroleptic drugs neuroleptic drugs including haloperidol (Haldol)including haloperidol (Haldol)

Substance-induced Substance-induced Psychotic DisorderPsychotic DisorderCharacterized by hallucinations & Characterized by hallucinations & delusions caused by drugs such as delusions caused by drugs such as cocaine, amphetamine, MDMA & LSD cocaine, amphetamine, MDMA & LSD that increase the activity of dopamine that increase the activity of dopamine synapsessynapsesStress increased the symptoms & causes Stress increased the symptoms & causes release of dopamine from the prefrontal release of dopamine from the prefrontal cortexcortexExcess dopamine is not the only causeExcess dopamine is not the only causeDrugs that block dopamine do so almost Drugs that block dopamine do so almost immediately but behavioral effects over immediately but behavioral effects over 2 or 3 weeks2 or 3 weeksRecent studies show schizophrenics Recent studies show schizophrenics have2 X as many Dhave2 X as many D22 as normals as normals

Schizophrenia Schizophrenia HypothesesHypotheses

Glutamate Glutamate HypothesisHypothesisSchizophrenia is the result of Schizophrenia is the result of deficient activity at certain deficient activity at certain glutamate synapsesglutamate synapses

The brain releases lower than The brain releases lower than normal amounts of glutamate in normal amounts of glutamate in the prefrontal cortex & the prefrontal cortex & hippocampus & has fewer hippocampus & has fewer glutamate receptorsglutamate receptors

Phencyclidine (PCP):Phencyclidine (PCP): blocks blocks glutamate type NDMA receptors glutamate type NDMA receptors & produces a type of psychosis & produces a type of psychosis similar to schizophreniasimilar to schizophrenia

No drugs that treat No drugs that treat schizophrenia directly stimulate schizophrenia directly stimulate glutamate activityglutamate activity

The Search for Improved DrugsThe Search for Improved Drugs

The The MesolimbocorticMesolimbocortical Systemal SystemA set of neurons that project from the midbrain tegmentum to the limbic system

Believed to be the area where antipsychotic drugs have beneficial effects

Tardive Tardive DyskinesiaDyskinesiaCharacterized by tremors & other involuntary movements

Probably due to denervation sensitivity caused by prolonged blockade of dopamine receptors

Atypical Atypical Antipsychotic Antipsychotic DrugsDrugsNew drugs that alleviate the symptoms of schizophrenia while seldom producing movement problems

They have less effect on D2 & stronger effect on D4 & serotonin 5-HT receptors

Alleviate both positive & negative symptoms of schizophrenia

The side effects include increased risk of diabetes & impairment of the immune system