Conditioning

and Transference
Jason Ryan, MD, MPH
Behavioral Therapy
• Seeks to modify unwanted behavior (i.e. anxiety)
• Goal: change patient’s response to environment
• Conditioning and reinforcement → behavior
• Therapy aims to alter conditioning/reinforcements
Conditioning
• Linking of stimulus to response
• Pavlov’s dog
• Stimulus: Ringing of a bell
• Response: Salivation
• Classical
• Operant

Maxxl/Wikipedia
Classical Conditioning
• Unconditioned stimulus and response
• Natural stimulus for a particular response
• Food and salivation
• Conditioned stimulus and response
• Unnatural stimulus for a particular response
• Bell and salivation
• Often response is involuntary
• Salivation
• Fear
Classical Conditioning
• Clinical example: Enuresis alarms
• Treatment for bed wetting (enuresis)
• Water-sensitive pad under child’s sheet
• Alarm awakens child
• Over time, child awakens from sensation to urinate
• Unconditioned stimulus and response
• Alarm → awakening
• Conditioned stimulus and response
• Urinary fullness → awakening
Operant Conditioning
• Behavior from reward or punishment
• Reinforces or decreases voluntary behaviors
• Often deals with voluntary behavior

Curtis Neveu/Wikipedia
Operant Conditioning
• Reinforcement: ↑ frequency of behavior (response)
• Positive reinforcement
• Behavior → reward → ↑ frequency
• Child rewarded for good behavior → ↑ good behavior
Operant Conditioning
• Negative reinforcement
• Behavior → removal of aversive stimulus
• “Negative reinforcer”
• Something you don’t want
• Changes behavior
• Wearing sunscreen to avoid sunburn
• Child cleans room to avoid parent yelling
• Different from punishment
• Behavior increases from stimulus (sunburn, yelling)
• Punishment → less behavior
Operant Conditioning
• Punishment: ↓ frequency of behavior
• Positive punishment
• Behavior → aversive stimulus → ↓ frequency
• Negative punishment
• Behavior → removal of desired stimulus → ↓ frequency
Operant Condition Quadrants
Extinction
• Gradual weakening of conditioned response
• Classical conditioning:
• Conditioned and unconditioned stimuli no longer linked
• Operant conditioning
• Behavior no longer reinforced
• Remove reward/punishment
Other Learning Processes
• Habituation
• Repeated exposure → less response
• Child becomes accustomed to MD visits → less anxiety
• Sensitization
• Repeated exposure → more response
• More MD visits for child → more anxiety
Transference
• Unconscious projection by patient onto others
• Often feelings associated with patient’s past
• Patient responds to clinician as a parent
• Example: Patient angry with therapist behavior
• Patient responds to spouse as a parent
Countertransference
• Clinician projects onto patient
• Clinician treats patient as son/daughter
Ego Defenses
Jason Ryan, MD, MPH
Freudian Psychology
• Id - desire
• Superego – societal rules, morality
• Ego - mediator between id and superego

Wikipedia/Public Domain
Ego Defenses
• Adjustments in reality perception
• Mostly unconscious
• Resolve/manage conflict between id and superego
• Minimize anxiety
• Adaptation to stressful circumstances
Acting Out
• Avoiding emotions by bad behavior
• Attention seeking, socially inappropriate behavior
• Examples:
• Child with sick parents misbehaves at school
• Adolescent engages in promiscuous sex during parents’
divorce
Denial
• Refusing to accept unpleasant reality
• Examples:
• Patient thinks doctor is wrong about diagnosis
• Heavy drinker believes she drinks socially

Peter/Flikr
Displacement
• Directing emotions to another person
• Example: Patient angry at doctor after injury
Dissociation
• Detachment from reality
• Often sudden onset after triggering event (i.e. rape)
• Patient may appear detached with flat affect
• Patient may lose track of time

Pixabay/Public Domain
Repression
• “Motivated forgetting”
• Usually forgetting one particular memory/fact
• Often something that happened long ago
• Example: difficult period of childhood
• First defense mechanism described by Freud
• Thoughts repressed to avoid guilt
Fixation
• Failure to develop beyond a childhood growth stage
• Oral fixation
• Stuck in oral phase
• Thumb sucking, eating, chewing pencils
• Adult lives with mother and depends on her
Idealization
• Emphasizing positive thoughts/memories
• De-emphasizing negative thoughts/memories
• Classically done with childhood events
• “Our family vacations were always amazing!”

Clipart/Public Domain
Identification
• Mimicking behavior of someone else
• Can be positive or negative
• Child behaves like school bully with little sister
• Child behaves like other child in new school
Intellectualization
• Avoiding emotions through reasoning
• Spouse going through divorce cites divorce statistics
to friends to avoid admitting sadness

Clipart/Public Domain
Isolation
• Isolating a distressing memory/event
• Failing to experience emotions of event
• Person describes rape without expressing sadness

Clipart/Public Domain
Passive Aggression
• Conflict with others in non-confrontational manner
• Husband uncooperative with wife because he is mad

Clipart/Public Domain
Projection
• Attributing feelings/emotions to others
• A cheater accuses a classmate of cheating off him
• Man with homosexual impulses accuses another man
of being attracted to him

Clipart/Public Domain
Rationalization
• Distorting events so outcome is positive
• “I’m glad I got fired, I needed a change.”

Clipart/Public Domain
Reaction Formation
• Opposite behavior (reaction) to unwanted feelings
• Man who craves alcohol preaches abstinence
• Woman despises mother, throws birthday party
• Parent despises child shows extreme love/affection

Clipart/Public Domain
Regression
• Reverting to behavior of younger person/child
• Stressed adult watches cartoons from childhood
• Sick adult wants parent to stay in hospital with them

Clipart/Public Domain
Splitting
• Categorizing others at extremes
• “Wonderful” or “horrible” people
• Patient likes her doctor but hates nurse
• Common in borderline personality disorder

Clipart/Public Domain
Sublimation
• Using negative emotions in a positive way
• Anxious person becomes a security guard
• Aggressive person becomes a boxer
Altruism
• Practice of concern for others
• Caring for others to reduce stress/anxiety
• Cancer survivors help others with same disease

Clipart/Public Domain
Suppression
• Conscious defense mechanism
• Done intentionally to relive stress/anxiety
• Ignoring stressful thoughts/feelings to cope
• “I’m not going to think about that now.”
Humor
• Relief of anxiety with jokes/laughter
• Medical student jokes about board studying

Clipart/Public Domain
Mature Defenses
• Sublimation
• Altruism
• Suppression
• Humor
Child Abuse
and Neglect
Jason Ryan, MD, MPH
Infant Deprivation
• Normal development requires human interaction
• Attachment
• Child is repeatedly comforted, cared for
• Caregiver consistently meets child's needs
• Warm, consistent loving attention
Infant Deprivation
• Lack of attachment → adverse effects on child
• Failure to thrive
• Poor development
• Lack of social skills
• Death
RAD
Reactive Attachment Disorder

• DSM-V disorder of attachment

• Some similarities to autism spectrum disorders
• Associated with severe early deprivation
• Detached child
• Unresponsive to comforting
• Inhibited (does not show emotions)
• Withdrawn/avoidant
DSED
Disinhibited social engagement disorder

• DSM-V disorder of attachment

• Associated with severe early deprivation
• Little/no reluctance to interact with adults
• Hugging strangers
• Sitting on lap of stranger
Child Maltreatment
• Child (physical) abuse
• Sexual abuse
• Emotional abuse
• Child neglect
Child Abuse
• Injury to a child by parent or caregiver
• Commonly affects children < 1 year of age
• Perpetrator usually closest family member (mother)
• Often identified by healthcare providers
Child Abuse Injuries
History

• Reported minor trauma → major injury

• Caregiver history changes over time
• Severe injury blamed on siblings/pets
Child Abuse Injuries
Bruising

• Most common abuse injury

• Multiple bruises
• Buttocks, trunk, ear, neck

Thirteen Of Clubs/Flikr
Child Abuse Injuries
Fractures

• Often identified by skeletal survey

• X-rays of all bones
• Multiple fractures in different healing stages
• Rib fractures
• Long bone fractures in baby

Gilo1969/Wikipedia
Child Abuse Injuries
Head Trauma

• “Abusive head trauma”

• “Shaken baby syndrome”
• Retinal hemorrhages
• Subdural hematoma

Public Domain
Child Abuse
Selected Risk Factors

• Parent factors
• Single, young parents
• Lower parental level of education
• Parental substance or alcohol abuse
• Parental psychiatric illness
• Child factors
• Unplanned pregnancy
• Unwanted child
• Learning disabilities, behavioral problems
Child Sexual Abuse
• Most common pre-puberty (9-12 years old)
• Perpetrator usually male known to child
• Trauma to mouth, anus, genitals
• Sexually transmitted infection
Emotional Abuse
Psychological Abuse
• Child feels worthless, unloved
• Verbal abuse
• Criticism
• Intimidation (scaring child)
• Humiliation
• Confinement for prolonged periods as punishment
Child Neglect
• Common form of child maltreatment
• 50% cases reported to child protection services
• Inadequate food, shelter, supervision, affection
• Poor clothing and hygiene
• Underweight or malnourished
• Must be reported to protective services
• All 50 states have laws requiring physician reporting
Vulnerable Child Syndrome
• Problem of parental reactions to child
• Parents believe child highly susceptible to disease
• Child illness may be real or perceived
• Risk factors
• Parents with difficult conception
• Difficult pregnancy or post-natal period
• Parental anxiety/depression
• Multiple visits to providers, emergency room
• Often numerous, minor complaints
Childhood
Disorders
Jason Ryan, MD, MPH
Rett Syndrome
• Neurodevelopmental disorder of females
• Contrast with autism: 4x more common in males
• Initially normal development
• Slow symptom onset 1-2 years of age
• Hallmark: regression of cognitive/motor skills
• Diagnostic criteria for disorder

Pixabay/Public Domain
Rett Syndrome
• Deceleration of head growth
• Loss of motor, intellectual, speech abilities
• Loss of balance (ataxia)
• Repetitive hand movements
• Hand-to-mouth licking
• Grabbing of clothing or hair
• Hand wringing

Pixabay/Public Domain
Rett Syndrome
Genetics

• X-linked disorder
• X-linked dominant: 1 abnormal gene → disease
• 99% cases: sporadic gene mutation
• MECP2 gene mutations (X chromosome)
• Significant expression in brain
Rett Syndrome
Genetics

• Females
• One normal MECP2 gene, one abnormal
• Random X inactivation → some cells with normal gene
• Result: survival with symptoms
• Males
• All abnormal MECP2 genes (one X chromosome)
• Lethal
Conduct Disorder
• Childhood behavioral disorder
• Repeated pattern of violating rights of others
• Aggression to people/animals
• Destruction of property
• Lying or stealing
• Adult version: Antisocial personality disorder
Oppositional Defiant Disorder
• Angry, irritable child
• Argues with authority figures
• Defiant
• Vindictive toward parents/teachers

Gerry Thomasen/Flikr
Oppositional Defiant Disorder
Diagnostic Criteria and Treatment

• Occurs with at least one individual who is not a sibling

• Causes problems at work, school or home
• Not caused by substance use, depression or bipolar
• Lasts at least six months
• Treatment: Cognitive behavioral therapy
• Resolves in most children
DMDD
Disruptive mood dysregulation disorder

• New disorder
• Added to DSM-V in 2013
• Controversial
• Some symptoms (irritability) common
• Similarities to ODD
• Few established treatments
DMDD
Disruptive mood dysregulation disorder

• Childhood mood disorder

• Must occur before age 10
• Excessively irritable or angry behavior
• Frequent temper outbursts
• At least three times per week
• At least two settings (home, school, etc.)
• Behavior out of proportion to situation
DMDD
Disruptive mood dysregulation disorder

• Cognitive behavioral therapy

• Anti-depressants
• Stimulants
• Anti-psychotics
 aaron gilson/Flikr

Bad Behavior

ADHD Conduct Disorder

Poor attention Property destruction
Hyperactivity Aggression to animals

ODD DMDD
Argues Temper tantrums
Defiant
Separation Anxiety Disorder
• Childhood anxiety disorder
• Distress when separating home/parents
• Refusal to leave home
• Refusal to go to school
• Worry about losing major attachment figures
• Persistent reluctance/refusal to go out
Separation Anxiety Disorder
• Nightmares about separation
• Repeated complaints of physical symptoms
• Headaches, upset stomach, nausea
• Occurs with separation or in anticipation
• Treated with therapy
• Goal: teach children coping skills
• Cognitive behavioral therapy
• Parent-child interaction therapy

D Sharon Pruitt/Wikipedia
Tourette Syndrome
• Neurologic disorder
• Occurs in children
• Hallmark: recurrent tics
• Sudden, quick repetitive movements or speech
• Commonly co-occurs with other disorders
• Attention deficit hyperactivity disorder (ADHD) – 60%
• Obsessive-compulsive disorder (OCD) – 30%
Tourette Syndrome
• Motor tics
• Sudden, quick movements
• Eye blink
• Head jerk
• Grimace
• Speech (phonic) tics
• Sudden, quick speech, usually few words
• Coprolalia: obscene language
Tourette Syndrome
Diagnostic Criteria

• Based on clinical criteria

• Tics for at least one year
• Onset before 18 years (DSM-5 criteria)
• Multiple motor tics
• One or more phonic tics
• Tics occur many times a day
• Tics not be explained by another cause
Tourette Syndrome
Treatment

• Behavioral therapy (especially if OCD, ADHD)

• Dopamine blockade (high potency neuroleptics)
• Fluphenazine, Risperidone, Haloperidol, Pimozide
• Block postsynaptic D2 receptors

Dopamine

D2
Tourette Syndrome
Treatment

• Tetrabenazine (“dopamine depletion”)

• Inhibits VMAT-2 (vesicular monamine transporter type 2)
• Blocks uptake of dopamine synaptic vesicles (pre-synapse)
• Less dopamine storage/release

VMAT
D

D
D D
Alpha 2 Agonists
Clonidine, Guanfacine
↑ prefrontal cortex activity
Regulate attention/behavior Neuron
Also used in ADHD

Norepinephrine

α2
Neuron
Learning Disability
• Difficulty acquiring, retrieving, and using information
• Often specific problems with math, reading, writing

Pixabay/Public Domain
ADHD
and Autism
Jason Ryan, MD, MPH
ADHD
Attention deficit hyperactivity disorder

• Exact cause unknown

• Limited attention
• Hyperactivity
• Poor impulse control
• Normal intelligence on testing
• But may have difficulty in school

amenclinicsphotos ac/Flikr
ADHD
Diagnostic Criteria

• Frequent symptoms of hyperactivity/impulsivity

• Present in more than one setting (school/home)
• Persist for at least six months
• Present before age of 12
• Impairs social/school functioning
• Excessive for developmental level of the child
ADHD
Epidemiology

• Four times more common in males

• Most cases among children 6 to 12 years old
• Symptoms persist to adulthood up to 2/3 of cases

marviikad/Flikr
ADHD
Treatment

• Behavioral interventions (rewards, time out)

• Behavioral therapy
• Stimulants
• Atomoxetine
• Alpha-2 agonists

Wikipedia/Public Domain
Stimulants
• Increase CNS dopamine and norepinephrine activity
• Increase CNS levels in synapses
• Improve ADHD symptoms
• ADHD children stimulated by activity
• Drugs relieve need to self-stimulate

Dopamine Norepinephrine
Stimulants
• Methylphenidate (Ritalin)
• Amphetamine (Adderall)
• Dexmethylphenidate (Focalin)
Amphetamine

Methylphenidate Dexamethylphenidate
Stimulants

Norepinephrine
Dopamine

- α2
-
Stimulants NE/Dopa Amphetamine
+

α or β
Receptor
Stimulants
Adverse Effects

• Loss of appetite
• Weight loss
• Insomnia
• Abuse potential

Pixabay/Public Domain
Atomoxetine
• Considered a non-stimulant treatment for ADHD
• May have less insomnia, loss of appetite
• Selective norepinephrine re-uptake inhibitor
• No direct effects on dopamine systems in CNS
• Dopamine effects may cause euphoria (abuse potential)

Norepinephrine Atomoxetine
Alpha-2 Agonists
• Clonidine
• Old, rarely used hypertension drug
• Key side effect: sedation
• Guanfacine
• Major effects: alpha-2A receptors prefrontal cortex
• Increases prefrontal cortical activity
• Regulate attention and behavior
 Alpha 2 Receptors
Hypertension Effects

α2 receptors
Presynaptic receptor
Feedback to nerve when NE released
Activation leads to ↓NE release
Neuron

α2
Norepinephrine
NE

Vascular
Smooth Muscle
Alpha 2 Receptors
ADHD Effects

α2 receptors in CNS
Postsynaptic receptor
Neuron

Norepinephrine

α2
Neuron
Autism Spectrum Disorder
• Neurodevelopmental disorder
• Exact cause unknown
• Abnormal social skills (communication/interaction)
• Repetitive behavior patterns
• Limited interests and activities
• Clinical diagnosis

Hepingting/Flikr
Autism Spectrum Disorder
Diagnostic Criteria

• Deficits in social interaction in multiple settings

• Failure of back-and-forth conversation
• Reduced sharing of interests, emotions
• Abnormal eye contact or body language
• Difficulty making friends
• Lack of interest in peers
Autism Spectrum Disorder
Diagnostic Criteria

• Restricted, repetitive patterns

• Repetitive movements, use of objects
• Insistence on sameness, unwavering adherence to routines
• Preoccupation with certain objects
• Symptoms must impair function
• Symptoms must be present in early development
• Often diagnosed about 2 years of age
• Symptoms sometimes present earlier but unnoticed
Autism Spectrum Disorder
Other Features

• Intellectual impairment
• Variable
• Some skills weak (i.e. verbal communication, reasoning)
• Savants
• Some patients have special skills in one area
• Memory, music, art, math
• Classic example: determining day of week for given date
Autism Spectrum Disorder
Clinical Features

• Often identified by pediatrician

• Issues with behavior, language, socialization
• Failure to reach developmental milestones
• Referral to ASD specialists for diagnosis
Autism Spectrum Disorder
Clinical Features

• More common among males

• Four times > females
• Increased head circumference
• 25% of cases: greater than the 97th percentile

Ephert/Wikipedia
Autism Spectrum Disorder
Associated Disorders

• Fragile X syndrome
• X-linked trinucleotide repeat disorder
• Long face, big ears, large testes
• Double Y males (XYY)
• Tall
• Severe acne
Autism Spectrum Disorder
Treatment

• Early intervention
• Behavioral management
• Occupational therapy (teaching skills for daily activity)
• Speech therapy
• No specific effective medical therapy
• Medications only for symptoms
• Hyperactivity
• Depression
Cognitive
Disorders
Jason Ryan, MD, MPH
Disorientation
• Orientation: knowledge of name, date, and place
• “Patient was alert and oriented times three”
• Lost in many cognitive disorders
• Patient becomes disoriented
• Time lost first
• Person last
• Time → place → person
Loss of Orientation
Causes

• Fever/infection
• Alcohol/drugs
• Hypoglycemia
• Electrolytes
• Cognitive disorders (delirium, dementia)
Amnesia
• Loss of memory
• Often caused by CNS injury
• Retrograde amnesia
• Loss of memories in the past
• Retained ability to make new memories
• Anterograde amnesia
• Inability to make new memories
• Dissociative amnesia
• Response to trauma/stress
• NOT caused by CNS injury
Wernicke-Korsakoff Syndrome
• Wernicke: Acute encephalopathy
• Korsakoff: Permanent neurologic condition
• Usually a consequence of Wernicke
• Both associated with:
• Thiamine (B1) deficiency
• Alcoholism
Wernicke-Korsakoff Syndrome
• Atrophy of mammillary bodies common finding

BruceBlaus/Wikipedia
Korsakoff Syndrome
• Confabulation
• Can’t remember so make things up
• Apathy (lack of interest or concern)
• Personality changes
• Amnesia
• Anterograde > retrograde
Cognition
• Mental process
• Acquiring knowledge and understanding
• Involves thought, experience, senses
Cognitive Disorders
• Inability to acquire knowledge and understand
• Disorganized thinking
• Disorientation
• Delirium
• Dementia
Dementia vs. Delirium
• Dementia
• Chronic, progressive cognitive decline
• Usually irreversible
• Delirium
• Acute
• Waxing/waning
• Usually reversible
Delirium
• Loss of focus/attention
• Disorganized thinking
• Hallucinations (usually visual)
• Sleep-wake disturbance
• Up at night
• Sleeping during day

Hyperdrive/Wikimedia Commons
Delirium
Causes

• Rarely a primary disorder

• Usually secondary to another cause
• Infection
• Alcohol
• Withdrawal
• Dementia patient in unknown setting
• Hospitalized
• Fever, pain
• Causes altered mental status in hospital
EEG
Electroencephalogram

• Records voltage changes in brain

• Different leads
• Frontal, parietal, occipital
• Characteristic patterns
• NORMAL in dementia
• ABNORMAL in delirium

Image courtesy of Der Lange

Delirium Treatment
• Fix underlying cause
• Treat infection, withdrawal, etc.
• Maintain O2 levels
• Treat pain
• Hydrate
• Calm, quiet environment
• Drugs
• Haloperidol (vitamin H)
Dementia
• Gradual decline in cognition
• No change level of consciousness (LOC)
• Usually irreversible (unlike delirium)
• Memory deficits
• Impaired judgment
• Personality changes
Dementia Causes
• Alzheimer’s disease (60% of cases)
• Multi-infarct dementia (stroke) ~20% of cases
• Lewy body dementia
• Rare disorders
• Pick’s disease
• Normal pressure hydrocephalus (NPH)
• Creutzfeldt-Jakob
• HIV
• Vitamin deficiencies
• Wilson’s disease
Dementia
Work-up

• Extensive screening/testing is low-yield

• Certain treatable causes should be excluded
• Depression
• Can present with dementia-like complaints
• Hypothyroidism
• Check TSH
• Other testing if indicated
• Neurosyphilis
• Vitamin deficiency
• HIV
Psychosis
Jason Ryan, MD, MPH
Psychosis
• Loss of perception of reality
• Occurs in medical and psychiatric disorders
• Delirium
• Schizophrenia
• Three main manifestations
• Delusions
• Disorganized thought
• Hallucinations
Delusions
• Strongly held beliefs that conflict with reality
• Expressed in speech by patient
• Persecutory delusions
• Someone is after me!
• Grandiose delusions
• I am a millionaire!
• Erotomaniac delusions
• Brad Pitt is in love with me!
Delusions
• Somatic delusions
• There are worms in my chest!
• Delusions of reference
• The television news caster is talking about me!
• Delusions of control
• My body is controlled by aliens!
• I can change the sun!
Disorganized Thought
• Shown by patterns of speech
• Alogia (speech poverty)
• Thought blocking
• Sudden, abrupt stop while talking
• Loosening of association Nevit Dilmen/Wikipedia

• Ideas discussed that do not follow each other

• Tangentiality
• Diverging from topic under discussion to another
Disorganized Thought
• Clanging
• Using words that rhyme but do not make sense
• “The cow said how he had to bow”
• Word salad: incoherent words that make no sense
• Perseveration: repeating words or ideas persistently

Nevit Dilmen/Wikipedia
Hallucinations
• Sensory perceptions without external stimuli
• Many different sub-types
• Visual
• Seeing things that are not there
• Common in hospitalized patients with delirium
• Auditory
• Hearing voices or sounds
• Classic feature of schizophrenia
Hallucinations
Olfactory

• Smell or odor
• Classic feature of aura in temporal lobe epilepsy

RobinH/Wikipedia
Hallucinations
• Gustatory (taste)
• Tactile (feeling/sensation)
• Insects crawling on skin
• Seen in alcohol withdrawal
• Stimulants: cocaine, amphetamines

Wikipedia/Public Domain
Hallucinations
• Hypnagogic
• Occurs while falling asleep (hypna = sleep)
• Hypnopompic
• Occurs just before waking up
• Both seen in patients with narcolepsy

Evgeny Galkovsky aka ZheGal

Psychotic
Disorders
Jason Ryan, MD, MPH
Schizophrenia
• Chronic psychiatric syndrome
• Recurrent episodes of psychosis
• Cognitive dysfunction
• Negative symptoms
Psychosis
• Loss of perception of reality
• Occurs in medical and psychiatric disorders
• Delirium
• Schizophrenia
• Three main manifestations
• Delusions
• Disorganized thought
• Hallucinations
Schizophrenia
Hallucinations and delusions

• Main manifestation is auditory hallucinations

• Hearing voices
• Strange sounds
• Delusions
• Fixed, false beliefs
• Paranoid (“they are coming after me!”)
• Grandiose (“I am king of the world!”)

Pixabay/Public Domain
Schizophrenia
Disorganized thought

• Most commonly tangential or circumstantial speech

• Tangential speech
• Changes topic frequently
• May not answer question
• Circumstantial speech
• Long, round-about answers to questions
Schizophrenia
Cognitive impairment

• Difficulty processing information

• Poor attention
• Poor learning and memory

Onlineassignmenthelps/Wikipedia
Symptoms
• Positive symptoms
• Abnormal behaviors Pixabay/Public Domain

• Hallucinations, delusions, disorganized thought

• Negative symptoms
• Absence of normal behaviors
• Flat affect
• Poverty of speech (alogia)
• Cannot engage in social interactions (asociality)
• Lack of motivation/cannot complete tasks (avolition)
• Cannot feel pleasure (anhedonia)
• Often persist despite therapy
Schizophrenia
Epidemiology

• Lifetime prevalence about 1% adults globally

• Slight male predominance
• Occurs in adolescence/young adulthood
• Men: 18 to 25
• Women: 25 to 35

Brenkee/pixabay
Schizophrenia
Risk Factors

• Living in urban areas (cities)

• Immigration
• UK study: immigrants ten times more risk

Pixabay/Public Domain
Schizophrenia
Risk Factors

• Obstetric complications
• Hemorrhage
• Preterm labor
• Blood-group mismatch
• Fetal hypoxia
• Maternal infection

Øyvind Holmstad/Wikipedia
Schizophrenia
Risk Factors

• Cannabis use
• Usually in adolescence
• Unclear if cause-effect
• Mild symptoms may lead to cannabis use

Chuck Grimmett/Wikipedia
Schizophrenia
Pathology

• Lateral ventricular enlargement

BruceBlaus/Wikipedia
Schizophrenia
Pathology

• Dendritic spines
• Small protrusions of neuron dendrites
• Receives input from other neurons at a synapse
• Spine loss in many brain regions

Quasar Jarosz/Wikipedia
Schizophrenia
Pathology

• Excess central dopamine activity

• Dopamine antagonists used for therapy
Schizophrenia
Diagnosis

• At least one month of two or more:

• Delusions
• Hallucinations
• Disorganized speech
• Disorganized or catatonic behavior
• Negative symptoms
• Continuous signs for at least six months
Schizophreniform Disorder
• Meets criteria for schizophrenia
• Duration less than six months
Brief Psychotic Disorder
• Psychotic symptoms
• Sudden onset
• Full remission within one month
• More common in women than men
• Commonly follows stressful life events
• Death in family
• Loss of job
Schizoaffective Disorder
• Schizophrenia with mania or depression
• Must have some episodes psychosis alone
• Some psychosis in absence of mania/depression
• DSM-V: Two or more weeks with psychosis alone
• Mania or depression with psychotic features
• All psychotic episodes occur with mania/depression
Schizoaffective Disorder
Possible Course

Psychotic Symptoms
(Hallucinations, Delusions)

Mania/
Depression

1 2 3 4 5 6
Mood Disorder with Psychosis
Possible Course

Mood Mood Mood

Psychosis

1 2 3 4 5 6
Delusional Disorder
• One or more delusions
• Lasts one month or longer
• Otherwise, no abnormal behavior
• Man believes he is being followed for past two months
• Frequently checks for someone behind him
• Cannot be persuaded he is safe
• No hallucinations, disorganized thought, negative symptoms
• Folie a deux (madness of two)
• Close friend shares delusions
Schizophrenia
Complications

• High risk of suicide

• 5% schizophrenics commit suicide
• 10% all suicides occur in schizophrenics
Postpartum Psychosis
• Rare disorder (0.1 to 0.2% of births)
• Usually women with known psychiatric disorder
• Most commonly bipolar disorder
• Also depression with psychosis, schizophrenia, schizoaffective
• Especially if meds stopped during pregnancy
• Occurs within 2 weeks after delivery

Pixabay/Public Domain
Postpartum Psychosis
• Delusions, hallucinations, disorganized thought
• Delusions often involve the baby
• Classically delusions related to patient’s mood
• Depressed: “Somethings wrong with my baby!”

Pexels/Public Domain
Postpartum Psychosis
• Risk factors
• Personal or family history of postpartum psychosis
• Bipolar disorder, schizophrenia, or schizoaffective disorder
• First pregnancy
• Discontinuation of psychiatric medications in pregnancy
• Requires hospitalizion
• High risk of suicide
• Risk of harm to baby
• Mother cannot care for herself or baby
• Treatment: medication and ECT
Dissociative
Disorders
Jason Ryan, MD, MPH
Dissociation
• Detachment from reality
• Contrast with psychosis: loss of reality
Dissociative Disorders
• Feeling “like I was outside my own body”
• Extreme cases: becoming another person
• New name, age, job, etc.
• Often associated with psychological trauma
• May allow victim to cope with trauma
Dissociative Identity Disorder
• Multiple personality disorder
• More common in women
• Associated with childhood trauma/abuse
• Especially sexual abuse, often before age 6
Dissociative Identity Disorder
• Two or more distinct identities
• “Personality states”
• Alterations in behavior, memory, thinking
• Observed by others or reported by patient
• Gaps in memory about events
• Symptoms cause distress or problems in functioning
Dissociative Identity Disorder
Comorbidities

• High rate of occurrence with other disorders

• PTSD: up to 100%
• Depression and substance abuse: up to 96%
• Personality disorders: Avoidant and borderline
Dissociative Identity Disorder
Comorbidities

• Somatoform conditions
• Physical symptoms not explained by medical condition

phee/Pixabay/Public Domain
DDD
Depersonalization/Derealization Disorder

• Depersonalization
• Feeling detached or estranged from one’s self
• “Like in a dream”
• “Like I am watching myself”
• Loss of control over thoughts, actions
• Derealization
• Detachment from surrounding world
• Objects seem unreal, foggy, visually distorted
DDD
Depersonalization/Derealization Disorder

• Often triggered by trauma

• Must cause significant distress/impairment
• Intact reality testing
• Differentiates from psychosis
• Patient aware that sensations are not real
Dissociative Amnesia
• Inability to recall autobiographical memories
• Past events
• Job
• Where they live
• Usually follows major trauma/stress
• Potentially reversible (memories may come back)
• Patient not bothered by lack of memory
• Amnesia not explained by another cause
Dissociative Amnesia
Psychogenic Amneisa

• Different from simple amnesia

• Large groups of memories: name, job, home
• Caused by overwhelming stress
• Different from repression
• Loss of autobiographical information: name, job, home
Dissociative Amnesia
Psychogenic Amneisa

• Example:
• Woman attacked in elevator
• Does not recall her job, where she lives, etc.
• Memories resurface later
Dissociative Fugue
• Subtype of dissociative amnesia
• Fugue = Latin for flight or flee
• Sudden travel/wandering in dissociated state
• Example:
• Manager fired from work goes missing
• Found in another state working under different name
• No recollection of prior job
Somatic and
Factitious Disorders
Jason Ryan, MD, MPH
Somatization
• Physical symptoms not explained by medical disease
• Not consciously created for gain (factitious)
• Risk factors
• Female gender
• Less education
• Minority status
• Low socioeconomic status
Somatization
• Pain symptoms
• Headache, back pain, joint pain
• Gastrointestinal symptoms
• Nausea, abdominal pain, bloating, gas
• Cardiopulmonary symptoms
• Chest pain, dizziness, palpitations
• Neurologic symptoms
• Fainting, muscle weakness, blurred vision
• Dyspareunia, dysmenorrhea
Somatization
• Associated with anxiety and depression
• Management
• Avoid debating if symptoms are psychiatric or medical
• Do not challenge belief that symptoms are medical
• Regular visits with same physician
• Limit tests and referrals
• Reassure patient that serious medical diseases are ruled out
• Set goals of functional improvement
• Psychotherapy
Somatic Symptom Disorder
DSM-V Diagnosis

• Somatic symptoms that cause distress

• Persistent thoughts about seriousness of symptoms
• Anxiety about symptoms
• Excessive time and energy devoted to symptoms
• Persistent (usually more than six months)
Illness Anxiety Disorder
DSM-V Diagnosis

• Preoccupation with having undiagnosed illness

• Mild or no somatic symptoms
• Anxiety about health
• Excessive health-related behaviors
• Repeatedly checking for signs of illness
• Present for at least six months
Conversion Disorder
Functional neurologic symptom disorder

• Sudden onset usually following stressor

• Voluntary motor or sensory neurologic symptoms
• Inability to speak or move
• Blindness
• Seizures
• Neurologic work-up normal
• Positive findings incompatible with disease
• Example: absence plantar flexion but can stand on toes
• La belle indifference
• Patient shows lack of concern (indifference) about symptoms
Factitious Disorder on Self
Munchausen syndrome

• Falsified medical or psychiatric symptoms

• Done consciously out of desire for attention
• Patient may feign illness
• May aggravate genuine illness
• Patient often willing to go for tests/surgeries
Factitious Disorder on Self
Munchausen syndrome

• Done for primary (internal) gain from illness

• Patient feels better in sick role
• Sick role solves internal conflict
• Example: patient is afraid of work or afraid to be alone
• Chronic, persistent
• Risk factors:
• Female gender
• Unmarried
• Prior or current healthcare worker
Factitious Disorder on Another
Munchausen by proxy

• Falsified medical symptoms by caregiver

• Often parent of child or caretaker of elderly
Malingering
• Consciously falsified medical symptoms
• Done for secondary (external) gain
• Allows patient to miss work but get paid
• Obtain workman’s compensation
• Self-limited
• Ends when secondary gain achieved
Personality
Disorders
Jason Ryan, MD, MPH
Personality Trait
• Fixed pattern of behavior
• Way of interacting with environment
• No significant distress or impaired function
• Positive traits: kind, confident
• Negative traits: lazy, rude
• Person often aware of own traits
Personality Disorder
• Fixed pattern of behavior
• Fixed way of interacting with environment
• Cause distress or impaired function
• Person often unaware
• Difficult to treat (“enduring”)
• Often strains doctor-patient relationship
Personality Disorders
• Cluster A (Weird)
• Paranoid, schizoid, schizotypal
• Odd and eccentric behavior
• Cluster B (Wild)
• Antisocial, borderline, histrionic, narcissistic
• Dramatic, erratic behavior
• Cluster C (Wacky)
• Avoidant, Obsessive-compulsive, dependent
• Anxious, fearful behavior
Paranoid
Personality Disorder

• Distrust of others even friends/family

• Guarded
• Suspicious
• Struggles to build close relationships
• Hallmark ego defense: projection
• Attributing unacceptable thoughts to others
• Often accuses others of being suspicious

Aaron Tait/Flikr
Schizoid
Personality Disorder

• Chooses social isolation

• More comfortable alone
• Does not enjoys close relationships
• Little/no interest in sexual experiences
• Few/no pleasure activities (hobbies)
• Lacks close friends
• Detachment
• Flat affect

Public Domain
Schizotypal
Personality Disorder

• Fear of social interactions and few close friends

• Odd beliefs or magical thinking
• Superstitious
• Believes in telepathy, sixth sense
• Ideas of reference
• Believe events and happenings somehow related to them
• Key feature: open to challenges to beliefs
• May reconsider superstitions, etc.
• Contrast with delusions in schizophrenia
• Also no hallucinations, cognitive impairment
Antisocial
Personality Disorder

• More common in men

• Disregard for rights of others
• Often breaks the law Public Domain

• Impulsive and lacks remorse

• Child (<18) version: conduct disorder
• 25% girls and 40% boys with CD → ASPD
• Must be at least age 18 years old
• Must have evidence of conduct disorder before 15
Borderline
Personality Disorder

• More common in women

• Unstable personal relationships
• All people are very good or very bad Ingela Hjulfors Berg/Flikr
• Stormy relationships
• “My boyfriend is the greatest guy in the world!”
• “My boyfriend is the devil!”
• Fear of abandonment
• May accuse others of abandoning them
Borderline
Personality Disorder

• Impulsivity
• Spending sprees, sex with strangers, reckless driving
• Self mutilation
• Cutting, burning
• Suicide gestures or attempts
• Relates to fear of abandonment
• “You don’t care about me so I’ll kill myself”
Splitting
• Major defense mechanism in borderline PD
• Black and white thinking (always-never)
• Cannot hold opposing views
• Patent's physician may be great or terrible
• All people-things-events wonderful or horrible

Pathfinder257/Pixabay
Dialectical Behavior Therapy
• Form of cognitive behavioral treatment
• Designed to treat chronical suicidality
• Gold standard for borderline personality disorder
• Weekly therapy for 1-2 years
• Mindfulness
• Distress tolerance
• Emotion regulation
Histrionic
Personality Disorder

• Wants to be the center of attention

• Talks loudly, tells wild stories, uses hand gestures
• Inappropriate sexually provocative behavior
• Often wears provocative clothing
• Touching others frequently
• Very concerned with physical appearance
• Exotic outfits, shoes, hats
Narcissistic
Personality Disorder

• Inflated sense of self

• Brags, thinks everything they do is great
• Lacks empathy for others
• Other people are competitors
• Wants to hear they are great
• Overreacts to criticism with anger/rage
Avoidant
Personality Disorder

• Avoids social interactions

• “Social inhibition”
• Feels inadequate
• Afraid people won’t like them
• Afraid of embarrassment Public Domain

• Struggles with intimate relationships

• “Maybe he/she doesn’t like me”
• Different from schizoid: wants to socialize but can’t
• Schizoid prefers to be alone (aloof)
Obsessive-Compulsive
Personality Disorder

• Preoccupied with order and control

• Loves “To Do” lists
• Always needs a plan
• Inflexible at work or in relationships
• Behaviors help to achieve goals (contrast with OCD)

Pixabay/Public Domain
Obsessive-Compulsive
Personality Disorder

• Ego
• Mediates id (desire) and super-ego (rules, society)
• Egosyntonic
• Behaviors that achieve goals of the ego
• Obsessions/compulsions used to achieve goals
• Seen in obsessive-compulsive personality disorder
• Egodystonic
• Behaviors that conflict with goals of the ego
• Obsessions/compulsions are barriers to goals
• Seen in obsessive-compulsive disorder
Dependent
Personality Disorder

• Clingy
• Low self-confidence
• Struggle to care for themselves Francisco Carbajal/Flikr

• Depend on others excessively

• Rarely alone, always in a relationship
• Hard to make decisions on their own
• Want someone to tell them what to do
• Difficulty expressing an opinion
• May be involved in abusive relationships
Mood Disorders
Jason Ryan, MD, MPH
Mood Disorders
• Abnormal emotional state
• Sadness (depression)
• Extreme happiness (mania)
Wikipedia/Public Domain

Depression Mania
Major Depressive Disorder
• Depressed mood
• Loss of interest in activities (anhedonia)
• Fatigue/loss of energy
• Feeling worthless or guilty
• Suicidal ideation/attempt
• Inability to concentrate, make decisions
• Appetite changes
• Weight loss/gain
• Sleep disturbances
• Psychomotor agitation/retardation
Major Depressive Disorder
Sleep Disturbances

• Difficulty getting to sleep (initial insomnia)

• Waking in the night (middle insomnia)
• Waking earlier than usual (terminal insomnia)
• Hypersomnia: excessive sleeping
• Altered sleep rhythms
• REM starts quicker after sleep onset (↓ REM latency)
• ↑ total REM sleep
• ↓ slow-wave sleep
• Sleep rhythms normalize on anti-depressant drugs
Major Depressive Disorder
Psychomotor agitation/retardation

• Psychomotor agitation
• Excessive motor activity
• Often repetitious
• Feeling of inner tension
• Fidgeting, pacing
• Psychomotor retardation
• Slowing of movements, thinking, or speech
• Slow to answer questions
• Low voice
• Few words
Major Depressive Disorder
Diagnosis and treatment

• At least 5 symptoms (of 9) for 2 weeks

• Sleep disturbance
• Lack of Interest
•
•
Guilt
Energy loss and fatigue
SIG E CAPS
• Concentration problems
• Appetite/weight changes
• Psychomotor symptoms
• Suicidal ideation
• No evidence of mania
• Treatment: antidepressants
Major Depressive Disorder
Subtypes

• Anxiety
• Atypical
• Catatonic
• Melancholic
• Mixed features
• Peripartum
• Psychotic
• Seasonal
Public Domain
Atypical Depression
• Mood reactivity (core unique feature)
• Able to react to pleasurable stimuli
• Feels better when good things happen
• Eating and sleeping all the time
• Increased appetite or weight gain
• Increased sleep (hypersomnia)
• Heavy or leaden feelings in limbs
• Sensitive to rejection
• History of interpersonal rejection sensitivity
Atypical Depression
• Most common subtype in some studies
• Older studies: increased response MAOi drugs
• SSRIs also effective
• Usually treated with SSRIs (less side effects)

Tom Varco/Wikipedia
Manic Episode
• Abnormally elevated mood and energy level
• Talking fast, pressured speech
• ↓ need for sleep
• But not tired
• Different from insomnia (tired but cannot sleep)
• Psychomotor agitation (pacing, fidgeting)
• Flight of ideas
Manic Episode
• Disinhibition and irresponsibility
• Waste money, wearing no clothes
• Grandiosity
• Increased self-esteem, confidence
• “I can do anything!”
• Typical case:
• Change in mood to elevated state
• Not sleeping
• Altered behavior
• Disruption of social functioning
Manic Episode
Diagnosis

• Symptoms at least one week, most of the day

• Distractibility
• Irresponsibility
•
•
Grandiosity
Flight of ideas
DIG FAST
• Agitation
• Less Sleep
• Talking too much, pressured speech
Hypomanic Episode
• Similar to those of mania but less severe
• Key feature: little/no impairment in functioning
• Inflated self-esteem but no delusions of grandeur
• More organized thought than mania
• More energy but leads to productive activity
• Contrast with mania: unproductive
• Milder risk taking behavior
Hypomanic Episode
• Lasts at least 4 days
• Resolves over weeks
• No psychotic symptoms
• By definition psychotic symptoms = mania
• Typical case:
• Change in mood to elevated state
• Continued social functioning
• Resolves in few weeks
Bipolar Disorder
Manic Depression

• Symptoms of mania and depression

• Can present with mania, hypomania or depression
• Treatment with antidepressants may cause mania
• Bipolar I
• Manic episode +/- depression +/- hypomania
• Manic episodes = bipolar I
• Bipolar II
• Hypomania and depression
• No manic episodes
Bipolar Disorder
Course

• Fluctuation: mania-hypomania-depression
• May have periods of euthymia (normal mood)
Bipolar Disorder
Treatment

• Mood stabilizers
• Most are also anticonvulsants
• Valproic acid
• Carbamazepine
• Lamotrigine
• Lithium
• Antipsychotics
• Antidepressants may cause mania
Psychotic Features
• Often hallucinations or delusions
• Associated with severe forms of mood disorders
• May occur in depression or bipolar disorder
• Always occur together with mood symptoms
• Psychosis without mood symptoms: schizoaffective
Cyclothymic Disorder
• Mild mania symptoms
• Mild depressive symptoms
• Do not meet criteria for hypomania or MDD
• Symptoms come/go over at least two years
• Come/go with ups and downs
• Occur at least half of the time
• Never absent for more than two consecutive months
Persistent Depressive Disorder
Dysthymic Disorder

• Low grade form of depression

• Less severe but more chronic
• Depressed mood most of the time
• Lasts for at least two years
• No symptom free periods lasting >2 months
Suicide
• Seen in depression and bipolar disorder
• 95% successful attempts have psychiatric diagnosis
• Depression, bipolar, substance abuse, schizophrenia
• Women: more attempts, less successful
• Men: fewer attempts, more successful
• Most common method: firearms
• Increased risk with access to guns

Augustas Didžgalvis
Suicide
Risk Factors

• Sad person scale (0-10pts)

•
•
Sex (male)
Age (young adults or elderly)
SAD PRESONS
• Depression
• Prior attempt (higher risk group)
• Ethanol or drugs
• Rational thinking loss (psychosis)
• Sickness (medical illness)
• Organized plan
• No spouse (or lack of social support)
• Stated intent
Acute Grief
• Normal response to loss of loved one
• Five stages (Kübler-Ross model)
• Denial (“He can’t be gone there must be a mistake”)
• Anger (“This is your fault!”)
• Bargaining (“I’ll do anything if she could be alive again”)
• Depression
• Acceptance
• Visions/voices of dead person may occur
• Usually resolves within 6 months
Persistent Grief
• Lasts longer than 6 months
• Interferes with functioning
• May lead to major depressive disorder

Tim Green/Flikr
Postpartum Mood Disorders
• Postpartum blues (up to 85% some studies)
• Depressed mood, insomnia, fatigue, poor concentration
• Mild symptoms that starts 2-3 days after delivery
• Resolves within two weeks
• Treatment: supportive
• Postpartum depression (~15%)
• Symptoms that persist after two weeks
• Treatment: CBT and medications (SSRIs)
• Postpartum psychosis (rare)

Øyvind Holmstad/Wikipedia
Mood Disorders
Treatment

• Cognitive behavioral therapy (CBT)

• Antidepressants
• Mood stabilizers
• Lithium
• Valproic acid
• Electroconvulsive therapy
ECT
Electroconvulsive Therapy

• Performed under general anesthesia

• Electricity administered → seizure
• Used in refractory depression
• May cause amnesia
• Retrograde amnesia (memories before procedure)
• Antegrade amnesia (few weeks after)
• Can be used in pregnancy

Wikipedia/Public Domain
Anxiety
Disorders
Jason Ryan, MD, MPH
Panic Attack
• Sudden onset of intense fear
• Often occur with no trigger
• Sometimes triggered by stressful event
• Brief: lasts for minutes to an hour
Panic Attack
• Physical symptoms caused by panic
• Palpitations, racing heart
• Sweating
• Trembling or shaking
• Chest pain or discomfort
Panic Attack
Diagnosis
• Four or more of the following:
• Palpitations, pounding heart, or accelerated heart rate
• Sweating
• Trembling or shaking
• Sensations of shortness of breath or smothering
• Feelings of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, light-headed, or faint
• Chills or heat sensations
• Paresthesias (numbness or tingling sensations)
• Fear of losing control or "going crazy"
• Fear of dying
• Derealization
• Depersonalization
Panic Attack
Diagnosis

• Derealization
• Items in room look foggy, unreal
• Feel like in a foreign place despite being at home
• Often intensely scary
• Depersonalization
• “Out of body” experience
• Detached, looking at self from above
Panic Disorder
Diagnosis

• Recurrent unexpected panic attacks

• Not post-traumatic
• Not in response to phobia
• Attacks followed by 1 month or more:
• Persistent concern or worry about panic attacks
• Change in behavior to avoid attacks
Panic Disorder
• Median age: 24 years
• Twice as common in women vs. men
• Risk factors
• Genetic component: 1st degree relative with PD: ↑ risk
• History of physical or sexual abuse
• Life stress
• Treatments:
• CBT
• Antidepressants (SSRIs)
• Benzodiazepines
Generalized Anxiety Disorder
• Chronic, persistent anxiety
• About many different events/activities
• Lasts > 6 months
• More days than not for at least six months
Generalized Anxiety Disorder
• Three or more of the following:
• Restlessness
• Fatigue
• Difficulty concentrating
• Irritability
• Muscle tension
• Sleep disturbance
Specific Phobias
• Fear of a specific object or situation
• Leads to avoidance behavior
• Persists for > 6 months
• Common: flying, dental procedures, blood draw
Specific Phobias
• Social anxiety disorder
• Specific phobia of social settings
• Excessive fear of embarrassment in social settings
• Fear of being humiliated or judged
• Agoraphobia
• Agora = public space (Greek)
• Fear of leaving a safe place (home) for public setting
• Fear of needing to flee with no help available
• NOT fear of scrutiny and embarrassment
• Example: Fear of empty bus (no people)
• Often co-occurs with panic disorder
• Often patients fear panic attack in public setting
Specific Phobias
Treatments

• Medications
• Benzodiazepines for infrequent exposure
• Beta blockers (blunt physical symptoms)
• SSRIs for frequent exposure
Specific Phobias
Treatments

• Often responds to behavioral therapy

• Systematic desensitization
• Imagining exposure to feared stimulus
• Relaxation
• Exposure therapy
• Confrontation of feared stimulus in safe/controlled manner
• Fear reduced over time (extinction learning)
OCD
Obsessive-Compulsive Disorder

• Obsessions
• Recurrent, persistent thoughts, urges, or images
• Intrusive and unwanted
• Patient attempts to ignore or suppress
• Causes distress
• Compulsions
• Repetitive behaviors or mental acts
• Done to relieve obsessions
• Hand washing, checking stove
• Praying, counting, repeating words
• Patient feels driven to perform in response to obsessions
OCD
Obsessive-Compulsive Disorder

• Ego
• Mediates id (desire) and super-ego (rules, society)
• Egosyntonic
• Behaviors that achieve goals of the ego
• Obsessions/compulsions used to achieve goals
• Seen in obsessive-compulsive personality disorder
• Egodystonic
• Behaviors that conflict with goals of the ego
• Obsessions/compulsions are barriers to goals
• Seen in obsessive-compulsive disorder
OCD
Obsessive-Compulsive Disorder

• Commonly co-occurs with:

• Schizophrenia or schizoaffective disorder
• Bipolar disorder
• Eating disorders (anorexia/bulimia)
• Tourette’s disorder
• Treatment: CBT
• “Exposure and response” therapy
• Expose patient to obsessive thoughts/image
• Respond with non-compulsive behavior
• Also SSRIs and clomipramine (TCA)
Body Dysmorphic Disorder
• Occurs in physically normal patients
• Preoccupation with physical appearance
• Focus on nonexistent or minor defects
• Patient believes they look abnormal, ugly, deformed
• Leads to repetitive behavior
• Checking mirror
• Combing hair
• Treatment: CBT plus SSRIs
PTSD
Post Traumatic Stress Disorder

• Follows traumatic event

• Rape, physical assault
• Thoughts, nightmares, flashbacks
• Avoidance of reminders
• Hypervigilance (anxious, alert, scanning)
• Sleep problems (restless, can’t fall or stay asleep)
• Leads to social dysfunction
PTSD
Diagnosis

• Exposure to traumatic event

• Trauma persistently re-experienced
• Thoughts, nightmares, flashbacks
• Avoidance of trauma-related stimuli
• Negative thoughts or feelings after trauma
• Trauma-related arousal and reactivity
• Symptoms last for more than 1 month
PTSD
Treatments

• CBT
• SSRIs
• Prazosin
• Alpha-1 blocker
• Reduces nightmares and improves sleep
• May cause orthostatic hypotension
Acute Stress Disorder
• Exposure to threatened death, injury, sexual assault
• Recurrent, intrusive memories
• Recurrent distressing dreams
• Dissociative symptoms
• Altered sense of reality
• In a daze, time is slow
• Cannot remember aspects of trauma (dissociative amnesia)
• Lasts less than one month
• Treatment: CBT (no drugs)
Separation Anxiety Disorder
• Childhood anxiety disorder
• Distress when separating home/parents
• Refusal to leave home
• Refusal to go to school
• Worry about losing major attachment figures
• Persistent reluctance/refusal to go out
Separation Anxiety Disorder
• Nightmares about separation
• Repeated complaints of physical symptoms
• Headaches, upset stomach, nausea
• Occurs with separation or in anticipation
• Treated with therapy
• Goal: teach children coping skills
• Cognitive behavioral therapy
• Parent-child interaction therapy

D Sharon Pruitt/Wikipedia
Eating
Disorders
Jason Ryan, MD, MPH
Eating Disorders
• Abnormal eating patterns
• Disrupt health or psychosocial functioning
• More common in women
• Usually present adolescence or young adulthood
• DSM-V Disorders
• Anorexia nervosa
• Bulimia nervosa
• Binge eating disorder
Anorexia Nervosa
• Diet and exercise that leads to low body weight
• World Health Organization: BMI <18.5 kg/m2
• Intense fear of gaining weight
• Distorted perception of body weight
• Increased mortality from malnutrition

Wikipedia/Public Domain
Anorexia Nervosa
• Often co-exists with other disorders
• Depression
• Anxiety
• Obsessive-compulsive disorder
• Posttraumatic stress disorder
• Substance abuse
• Often secondary to eating disorder
• Improve with weight restoration
• Especially depression
Anorexia Nervosa
Endocrine Effects

• ↓ GnRH secretion
• ↓ LH/FSH
• Amenorrhea
• “Functional hypothalamic amenorrhea”
Anorexia Nervosa
Electrolytes

• Inability to concentrate urine

• Free water loss
• Hyponatremia
• Volume depletion
• ↓ GFR
• Creatinine low (↓ muscle mass)
• If purging: hypokalemia
Anorexia Nervosa
Bones

• ↓ bone density
• Low estrogen
• High cortisol
• Loss of cortical and trabecular bone
• Osteopenia
• Osteoporosis

Hellerhoff/Wikipedia
Anorexia Nervosa
Hematology

• Bone marrow suppression

• Anemia
• Leukopenia
• Thrombocytopenia

Keith Chambers/Wikipedia
Anorexia Nervosa
Physical Exam

• Low body mass index (<18.5 kg/m2)

• Mild: 17 to 18.5
• Moderate: 16 to 16.99
• Severe: 15 to 15.99
• Extreme: <15

Public Domain
Anorexia Nervosa
Physical Exam

• Bradycardia
• Hypotension
• ↓ bowel sounds
• Dry, scaly skin (xerosis)
• Hair loss
• Lanugo hair growth
• Soft, fine hair

Wikipedia/Public Domain
Anorexia Nervosa
Treatment

• Nutritional rehabilitation
• Structured meals with observation
• Calorie goals
• Psychotherapy
• SSRIs
Refeeding Syndrome
• Hallmark: hypophosphatemia
• Low PO4 from poor nutrition Phosphate
• Glucose → ↑ insulin → ↑ metabolism
• Further ↓ PO4 from cellular uptake
• Loss of ATP → cardiac and respiratory failure
• Most fatalities: cardiac
• Poor contractility, low stroke volume
• Heart failure, arrhythmias
• Prevention: slow refeeding (gentle ↑ calorie intake)
Bulimia Nervosa
• Binge eating
• Inappropriate compensation to avoid weight gain
• Vomiting (purging)
• Laxatives, diuretics, enemas
• Excessive exercise
• Fasting
• Severely restrictive diets
Bulimia Nervosa
• Occurs at least once a week for three months
• Weight usually normal (contrast with anorexia)
• Commonly coexists with other disorders
• Anxiety
• Depression
• Posttraumatic stress disorder
• Substance abuse
Bulimia Nervosa
Purging Complications

• Contraction alkalosis
• Loss of K+
• Urinary chloride is low (<20)
Urinary Chloride
• Useful in metabolic alkalosis unknown cause
• Low (<10-20) in vomiting
• Loss of Cl in gastric secretions
• High (>20) in many other causes alkalosis
• Classic scenario:
• Young woman with unexplained metabolic alkalosis
• Urinary chloride low
Bulimia Nervosa
Purging Complications

• Parotid swelling
• “Parotid gland hypertrophy”
• Sialadenosis
• Erosion of dental enamel

BruceBlaus/Wikipedia
Russell’s Sign
• Scars on knuckles from induced-vomiting

Wikipedia/Public Domian
Bulimia Nervosa
Treatment

• Nutritional rehabilitation
• Psychotherapy
• SSRIs
Binge Eating Disorder
• Binge eating
• Compulsive overeating
• Excessively large amounts of food
• Often eaten quickly
• Patient feels they lack control
• Patient feels shame/embarrassment
• No inappropriate compensation
• Weight gain
• Occurs at least once a week for three months
Binge Eating Disorder
• Often occurs with other disorders
• Anxiety, depression
• Studies show high risk of type II diabetes
• First line treatment: Psychotherapy (CBT)
• Large clinical effect in trials
• Greater than medication effect
• SSRIs used but less effective
Binge Eating Disorder
• Lisdexamfetamine
• ADHD stimulant
• Topiramate
• Seizure medication
• Clinical trials: ↑ abstinence from binge episodes
• Both lead to reduced weight
Sleep Disorders
Jason Ryan, MD, MPH
Sleep Physiology
• Several stages
• Non-REM sleep (N1, N2, N3)
• REM
• Unique EEG findings to each phase

Image courtesy of Der Lange

Sleep Physiology
• Awake, eyes open
• Beta waves
• “Low amplitude, high frequency”
• Awake, eyes closed
• Alpha waves
• Increased amplitude, more synchronous
Beta

Alpha
Sleep Physiology Theta

• N1
• Theta waves
• Lightest sleep (easy to wake)
• Smallest percentage (5-10%) sleep time
• N2
• Theta waves
• K complexes: Sudden ↑ amplitude
• Sleep spindles: Sudden ↑ frequency
• Largest percentage (50%) sleep time
• Teeth grinding (bruxism)

Wikipedia/Public Domain
Sleep Physiology
• N3
• Last phase before REM sleep
• Delta waves
• “Slow waves”
• Lowest frequency, highest amplitude
• Deepest sleep (hardest to wake sleeper)
• Sleep walking, sleep talking, bed wetting

Delta
REM Sleep
• Rapid eye movements
• PPRF (paramedian pontine reticular formation)
• Low voltage pattern
• Often appears “saw-toothed”
REM Sleep
• Loss of motor tone (muscle paralysis)
• Dreaming, nightmares
• Penile tumescence
Sleep Physiology
• Sleep goes through “cycles” during the night
• NREM → REM → NREM → REM
• Repeated during the night
• One cycle from NREM to REM about 90 minutes
• Length of REM increases during cycles
• Length of N3 decreases during cycles
Hypnogram
Drugs
• Many drugs alter “sleep architecture”
• N3 and REM sleep % decreased by sedative drugs
• Alcohol
• Benzodiazepines
• Barbiturates
• Nonbenzodiazepine hypnotics
• Zolpidem, zaleplon, eszopiclone
• Activate benzodiazepine (GABA) receptor
• High affinity for BZ1 receptor
• Decrease time to fall asleep (sleep latency)
• Less effect on sleep cycle than benzodiazepines
Depression
• REM starts quicker after sleep onset
• ↓ REM latency
• ↑ total REM sleep
• ↓ slow-wave (N3) sleep
• Sleep rhythms normalize on anti-depressant drugs
Hypnogram

Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5

Awake
REM
N1
N2
N3

Time during night

Parasomnias
• Occur during sleep
• Undesirable physical events (movements, behaviors)
• Unwanted experiences (emotions, dreams)
• Non-rapid eye movement (NREM)-related
• Rapid eye movement (REM)-related
• Sleep paralysis (wake but cannot move)
• Nightmare disorders
NREM Disorders
• Disorders of arousal during sleep
• Occur during non-REM sleep
• Usually occur in N3 (deepest sleep)
• Usually occur earlier in night (more N3 sleep)
• Patient does not recall arousal activities
• Sleepwalking
• Sleep terrors (sitting up, screaming)
• Sleep-related eating disorder
• Treatment: benzodiazepines (↓ N3 sleep)
Narcolepsy
• Neurologic disorder of sleep-wake cycles
• Sleep during wakefulness
• Wakefulness during sleep
• Causes excessive daytime sleepiness
• Caused by ↓ neuropeptides in lateral hypothalamus
• Orexin-A (also called hypocretin-1)
• Orexin-B (also hypocretin-2)
• Rarely CSF tested for diagnosis
• Orexin-A/hypocretin-1 levels

OpenStax College/Wikipedia
Narcolepsy
• Daytime sleepiness
• Fall asleep during day often at inappropriate times
• “Sleep attacks”: sudden dozing
• Not tired when waking in morning
Cataplexy
• Sudden loss of muscle tone
• Usually affecting face, neck, or knees
• Muscle weakness
• May lead to collapse
• No loss of consciousness (contrast with syncope)
• Triggered by strong emotions
• Classically laughter or excitement
• Sometimes anger or grief
Hallucinations
• Visual, tactile, or auditory
• Usually hypnagogic: occur when falling asleep
• Rarely hypnopompic: occur when awakening

Nevit Dilmen/Wikipedia
Sleep Paralysis
• Inability to move after awakening for 1-2 minutes
• Caused by REM sleep while awake
• Limited movement during REM sleep activity
• May also occur just before falling asleep
• May occur with hallucinations (scary for patient!)
Narcolepsy
Epidemiology and etiology

• Begins in teens and early twenties

• Men = women
• Usually occurs sporadically (rarely in families)
• Autoimmune hypothesis
• Orexin neurons killed by autoimmune process
• Narcolepsy strongly associated HLA DQB1
Narcolepsy
Treatment

• Modafinil
• Controlled substance
• Promotes wakefulness
• Poorly understood mechanism
• Effects on dopamine, NE, GABA
Narcolepsy
Treatment

• Methylphenidate and amphetamines

• Indirect sympathomimetics
• ↑ dopamine and norepinephrine CNS levels in synapses
• Also used in ADHD
Narcolepsy
Treatment

• Sodium oxybate
• Salt form of gamma-hydroxybutyrate (GHB)
• GABA metabolite
• Mechanism of action not known
• CNS depressant (similar to anesthetic)
• Main benefit: reduces cataplexy
• Also improves nocturnal sleep, reduces daytime sleepiness
• Illegal version GHB: “date rape drug”
• One dose at bedtime
• Repeat dose 2.5 to 4 hours later (set alarm)
• Many patients learn to wake on their own
Alcohol &
CNS Depressants
Jason Ryan, MD, MPH
Substance Use Disorder
• DSM-V: Two or more during 12 month period
• Tolerance
• Withdrawal
• Taken in larger amounts or over a longer period
• Unsuccessful efforts to cut down or control use
• Lots of time spent to obtain, use, or recover from
• Craving or a strong desire or urge to use
• Failure to fulfill obligations at work, school, home
• Continued use despite social or interpersonal problems
• Social/occupational activities given up or reduced
• Use in situations in which it is physically hazardous
• Use despite knowledge of having a problem
Stages of Change

Toddatkins
Stages of Change
• Precontemplation
• No intention of behavior change
• May not recognize/acknowledge problem
• Contemplation
• Aware problem exists
• Not yet willing to change
• Preparation
• Intending to take action
• Action
• Maintenance
• Relapse
Alcohol
Ethanol
• “Alcohol” = ethyl alcohol = ethanol
• Found in alcoholic beverages
• Commonly abused substance
• Metabolize by liver
• Numerous biochemical effects

Wikipedia/Public Domain
Alcohol Intoxication
• CNS depressant
• Slurred speech
• Incoordination
• Unsteady gait
• Stupor
• Coma

Pixabay/Public Domain
Alcohol Intoxication
• Serum blood alcohol concentration (BAC)
• Most US states: legal limit 80 mg/dL
• “0.08 g/dL” or “0.08” or “8%”
• Number of drinks to reach limit varies with size

Jeffrey Smith/Flikr
Alcohol Biomarkers
• Markers of liver damage
• Used to screen for heavy, chronic use

Also seen in chronic use: ↑ MCV and hypertension

Alcohol Poisoning
• Very high BAC → respiratory depression
• Can be fatal
• Treatment is supportive
• May require ICU care

Pixabay/Public Domain
Alcohol Withdrawal
• Heavy drinkers after abrupt cessation
• 6 to 24 hours after last drink
• Tremors
• Anxiety
• GI upset
• Headache
• Sweating
• Palpitations
• Mental status intact
Alcohol Seizures
• 6 to 48 hours after last drink
• Generalized tonic-clonic seizures
• Single or in clusters of two to three

RobinH
Alcohol Hallucinosis
• 12 to 48 hours after last drink
• Often visual hallucinations
• Seeing insects or animals
• Hearing voices
• Tactile sensations

Steve Jurvetson/Flikr
Delirium Tremens
• 72 and 96 hours after last drink
• Most severe withdrawal manifestation
• 20% mortality in some studies

Pixabay/Public Domain
Delirium Tremens
• Delirium
• Markedly altered mental status
• Agitation
• Fever
• Drenching sweats
• Autonomic hyperactivity
• Tachycardia, hypertension
• Death from:
• Hyperthermia
• Arrhythmias
• Fluid/electrolyte abnormalities
Alcohol Withdrawal
Treatment

• Benzodiazepines
• Improve agitation
• Prevent progression
• Symptom-triggered therapy
• CIWA scale
• Clinical Institute Withdrawal Assessment for Alcohol
• Point system for assessing withdrawal symptoms
• Regular assessment of patent
• Benzodiazepine given if score is high
Alcoholism Therapy
• Support groups (Alcoholics Anonymous)
• Three FDA approved drugs
• Reduce risk of relapse
• Disulfiram (Antabuse)
• Naltrexone
• Acamprosate
Disulfiram
Anatabuse

• Inhibits aldehyde dehydrogenase

• Acetaldehyde accumulates
• Triggers catecholamine release
• Sweating, flushing, palpitations, nausea, vomiting

NAD+ NADH NAD+ NADH

Alcohol Aldehyde
Dehydrogenase Dehydrogenase

Ethanol Acetaldehyde Acetate

Naltrexone
• Long acting opioid antagonist
• Endogenous opioids reinforce alcohol effects
• Given orally to prevent relapse
• Also used in opioid abuse

Naltrexone
Acamprosate
• Mechanism incompletely understood
• Modulates NMDA receptors
• Alcohol disrupts CNS equilibrium
• Excitatory glutamate activity (NMDA receptor)
• Inhibitory GABA activity
• Common side effect (~15%): diarrhea

Acamprosate
Barbiturates
Phenobarbital, pentobarbital

• Anti-seizure drugs
• GABA activators
• Used as sedatives in past Wikipedia/Public Domain

• Now largely replaced benzodiazepines

• Similar effects to alcohol (CNS depressants)
• Narrow therapeutic index
• Dangerous used together with alcohol
Barbiturates
Phenobarbital, pentobarbital

• Overdose: respiratory depression

• No antidote
• Supportive care
• Heavy users must be weaned
• Abrupt withdrawal:
• Delirium
• Hallucinations
• Seizures
• Cardiovascular collapse → death
Benzodiazepines
Diazepam, oxazepam, lorazepam

• Many medical uses (anxiety, alcohol withdrawal)

• Classic overdose presentation:
• CNS depression with normal vitals
• Altered mental status
• Slurred speech
• Ataxia
• Rarely cause respiratory depression (safer drugs)
Flumazenil
• Antagonist of benzodiazepine receptor
• Use to treat overdose controversial
• Overdose has low mortality rate
• Flumazenil may cause withdrawal seizures

Flumazenil
Benzodiazepine Withdrawal
• Occurs with abrupt cessation in chronic user
• Timing depends on drug
• Long acting BZD → longer washout
• Tremors
• Anxiety
• Depressed mood (“dysphoria”)
• Hypersensitivity to sensations (noise, touch)
• Psychosis
• Seizures
• Can be life-threatening
• Treatment: benzodiazepines
Opioids
Jason Ryan, MD, MPH
Endorphins
• Peptides activators of opioid receptors
• Three families: endorphins, enkephalins, dynorphins

Dynorphin A Beta-endorphin
Opioid Receptors
• Central and peripheral nervous system (neurons)
• Activated by endorphins
• Three key subtypes
• Mu (μ) receptor: highest affinity endorphins
• Delta (δ) receptor: enkephalins
• Kappa (κ) receptor: dynorphins
Opioid Receptors
Nerve Effects

• Coupled to G-proteins
• Closes Ca2+ channels on presynaptic nerves
• Reduce neurotransmitter release
• Open K+ channels postsynaptic neurons
• Leads to hyperpolarization
• Less signal transmission
• Decreased activity of neurotransmitters
• Glutamate (excitatory)
• Acetylcholine, norepinephrine, serotonin, substance P
Pre-synaptic
Neuron

NT
X

NT Ca2+

K+
Post-synaptic
+
Neuron
Opioid Drugs
• Activate opioid receptors
• Prototype: morphine
• Also hydromorphone, meperidine, fentanyl, codeine
• Drug of abuse: heroin (diamorphine)

Morphine Heroin
Heroin
• Usually injected into vein
• Dirty needle or contaminated drugs:
• Bacteremia → tricuspid endocarditis
• Hepatitis B & C
• HIV

Psychonaught/Wikipedia
Opioids
Central nervous system effects

• Mostly mediated through mu receptor

• Pain relief (analgesia)
• Euphoria
• Sedation
Opioids
Central nervous system effects

• Respiratory depression
• Cough suppression
• Miosis (small pupils)
• Exception: meperidine

Wikipedia/Public Domain
Opioids
Peripheral nervous system effects

• Constipation
• Skin warmth and flushing

John Johnson/Pexels
Opioids
Clinical Uses

• Pain control
• Acute pulmonary edema (IV morphine)
• Cough suppression (codeine)
• Diarrhea (loperamide)
• Shivering: (meperidine/Demerol)
Addiction & Tolerance
• Highly addictive
• Tolerance develops
• Less effect of drugs over time
• Higher dosages required to achieve effects
• No tolerance to miosis and constipation

Wikipedia/Public Domain John Johnson/Pexels

Acute Intoxication
• Opioids: most common cause drug overdose death
• Euphoria to depressed mental status
• Decreased respiratory rate
• Decreased bowel sounds
• Miotic (constricted) pupils
• Seizures
• Commonly with tramadol or meperidine
Acute Intoxication
Treatment

• Naloxone
• Short-acting opioid antagonist
• May cause withdrawal if dose too high (“overshoot”)

Morphine Naloxone
Withdrawal
• Occurs in opioid-dependent individuals
• Usually starts 6-12 hours after last dose
• Reversal of CNS, eye, skin, GI effects
• Restlessness
• Yawning
• Rhinorrhea and lacrimation
• Piloerection
• Nausea, vomiting, abdominal cramps
• Diarrhea
Withdrawal/Addiction
Treatment

• Buprenorphine
• Partial agonist (agonist and antagonist effects)
• Long duration of action
• Sublingual tablet
• Not regulated/controlled like methadone
• May cause withdrawal (like naloxone)
• Combined with naloxone
• Prevents abuse
• Naloxone not absorbed sublingually
• Crushed pill → IV injection → no effect

Buprenorphine
Withdrawal/Addiction
Treatment

• Methadone
• Long-acting oral opiate
• Reduces cravings
• Maintenance
• Strictly regulated/controlled

Methadone
Withdrawal/Addiction
Treatment

• Naltrexone
• Long acting opioid antagonist
• Blocks effects of opioids if taken
• Administered to detoxified patients to prevent relapse
• Some data show prevention of relapse
• Also used in alcohol abuse

Naltrexone
Stimulants
Jason Ryan, MD, MPH
Stimulants
• Cocaine
• Amphetamines
• Caffeine
• Nicotine
Cocaine
Norepinephrine
• Two key physiologic effects
• #1: Local anesthetic (Na channel blocker)
• #2: Inhibits monoamine reuptake
• Monoamines: Dopamine, serotonin (5HT), NE
• Sympathetic activation

Lidocaine Cocaine
Adrenergic Synapses

Tyrosine

Dopa

Dopamine

Norepinephrine

- α2
-
Cocaine Amphetamine
Amphetamines
NE +

α or β
Receptor
Cocaine Intoxication
• Increased energy
• Decreased need for sleep
• Alertness
• Euphoria

Wikipedia/Public Domain
Cocaine Intoxication
• Hallucinations
• Classically tactile
• “Bugs crawling on my skin”
• Fever
• Increased muscle activity
• Central dopamine release
• Anxiety
• Paranoia
Michael "BuZZeR" Kadykov
• May mimic psychosis
• Treatment: benzodiazepines
Cocaine Intoxication
Signs

• Sympathetic nervous system activation

• Stimulation of alpha and beta receptors
• Dilated pupils
• Tachycardia and increased blood pressure

OpenStax College/Wikipedia
Cocaine Chest Pain
• Common among cocaine users
• ↑ O2 demand (tachycardia, elevated BP)
• ↓ O2 supply (coronary vasoconstriction)
• O2 mismatch → angina
• May lead to thrombosis → myocardial infarction

Freestocks.org
Cocaine Chest Pain
• Treatment: benzodiazepines
• Sedating/calming
• Diminish cocaine-related stimulating effects
• Aspirin
• Avoid beta blockers
• Increased alpha effects
• Worsening of hypertension and chest pain
Cocaine Withdrawal
• Occurs with stopping after chronic, heavy use
• Usually not life-threatening
• Depression
• Fatigue
• Difficulty concentrating
• Increased sleep
Amphetamines
• Contain modified phenethylamines
• Stimulants
• Indirect sympathomimetics
• Increase synaptic dopamine/NE levels

Phenethylamine
Amphetamine Intoxication
• Hyper-alert state
• Decreased need for sleep
• Sympathetic stimulation
• Tachycardia, hypertension
• Pupillary dilation
• Fever
• Agitation
• May cause chest pain
• Rarely causes seizures
• Treatment: benzodiazepines
Caffeine
• Methylxanthine
• Antagonist of adenosine receptors
• Leads to release of dopamine/NE
• Renal adenosine blockade → diuresis

Adenosine Caffeine
Chemical Stress Tests
• Intravenous adenosine used as a vasodilator
• Induces coronary steal for chemical stress testing
• Effects blocked by caffeine
• Also blocked by theophylline (COPD drug)

Adenosine Caffeine Theophylline

Nicotine
• Addictive substance found in tobacco
• Acts on nicotinic acetylcholine receptors
• CNS stimulant
• Activates sympathetic nervous system

Nicotine
Autonomic Nervous System

Use with permission, Katzung BG, Basic and Clinical Pharmacology, 10th ed. New York, McGraw Hill, 2007
Nicotine Withdrawal
• Increased appetite
• Weight gain
• Depression
• Insomnia
• Irritability
• Anxiety Pixabay/Public Domain

• Difficulty concentrating
• Restlessness
• Peak in first three days after cessation
• Subside in 3-4 weeks
Smoking Cessation
• Primary barrier is nicotine addiction
• Assess barriers to quitting
• Discuss benefits of quitting
• Address patient concerns
• Set a quit date
• Often a few weeks in the future
• Stop smoking completely on this date
• Begin supportive therapies
Smoking Cessation
• Nicotine replacement therapy
• Nicotine patches
• Nicotine gum
• Bupropion
• Antidepressant
• Blocks reuptake of NE and dopamine
Smoking Cessation
• Varenicline
• Partial nicotinic receptor agonist
• Agonist effects: limit withdrawal symptoms
• Antagonist effects: block nicotine
• Adverse effects:
• Nausea
• Sleep disturbance (insomnia, abnormal dreams)
Other Drugs
Jason Ryan, MD, MPH
PCP
Phencyclidine

• “Angel dust”
• Antagonist of NMDA receptor in CNS
• N-methyl-D-aspartate
• Glutamate receptor
• Blockade: hallucinations and psychosis
• Inhibits reuptake of dopamine, NE, 5HT
• Increases sympathetic activity
PCP
Phencyclidine

• Stimulant
• Altered mental status
• Psychosis (with hallucinations)
• “Psychomotor agitation” Pxhere/public domain

• Classically agitated, violent behavior

• Tachycardia, hypertension
• Nystagmus (repetitive involuntary eye movements)
• Rarely coma and seizures
PCP
Phencyclidine

• Fatalities most commonly from trauma

• Psychosis plus loss of pain/sensation
• Patients may dissociate
• Walk into traffic
• Jump from buildings
• Treatment:
• Benzodiazepines
Alisha Vargas/Flikr
• Haloperidol (rapid-acting anti-psychotic)
LSD
Lysergic acid diethylamide

• Hallucinogen
• Exact mechanism unknown
• Binds serotonin 5-HT2A receptors
• Not a stimulant (contrast with PCP)

LSD
LSD
Lysergic acid diethylamide

• Causes LSD “trip”

• Feeling of expanded consciousness
• Can sense things beyond usual reality
• Synesthesia (a blending of the senses)
• “Hearing" colors or "seeing" sounds
• Depersonalization
• Feeling disconnected or detached from body
• “Bad trip”
• Paranoia, anxiety
LSD
Lysergic acid diethylamide

• May causes “flashbacks”

• Return of hallucinogen effects after stopping drug
• May occur days, weeks, even months later
• Intoxication management: supportive

Pariroxy/Wikipedia
Ecstasy
Methylenedioxy-methamphetamine (MDMA)

• Amphetamine
• Structurally similar to serotonin
• Major effects on serotonin
• Increased release of serotonin
• Inhibition of serotonin reuptake

Serotonin MDMA
Adrenergic Synapses

Tyrosine

Dopa

Dopamine

Norepinephrine

- α2
-
Cocaine Amphetamine
Amphetamines
NE +

α or β
Receptor
Ecstasy
Methylenedioxy-methamphetamine (MDMA)

• Euphoria
• Alertness
• Bruxism (grinding teeth)

Wikipedia/Public Domain
Ecstasy
Methylenedioxy-methamphetamine (MDMA)

• Tachycardia and hypertension

• Hyperthermia
• Hyponatremia
• Increased fluid intake
• Secretion of antidiuretic hormone
• Reports of seizures and death
• Hepatotoxicity
• RUQ pain
• Increased AST/ALT
Serotonin Syndrome
• Classic triad: Three As
• #1: Mental status changes Cyproheptadine
• Agitation, restlessness, and disorientation
• #2: Autonomic hyperactivity
• Diaphoresis, tachycardia, hyperthermia
• #3: Neuromuscular hyperactivity
• Tremor, clonus, hyperreflexia, bilateral Babinski sign
• Treatment: cyproheptadine
• 5 –HT antagonist
Ecstasy Withdrawal
• “Crash” after being high on MDMA
• Depression and anxiety
• Fatigue and lethargy
• Difficulty concentrating
• Loss of appetite
• Jaw soreness (from grinding teeth while high)
Marijuana
• Derives from cannabis (plant)
• Psych activity from tetrahydrocannabinol (THC)
• Also called Dronabinol
• Stimulates cannabinoid receptors in CNS
• Euphoria
• Increased appetite
• Ataxia
• Slurred speech
• Impaired judgement, cognition
• Rarely anxiety or panic attacks
Wikipedia/Public Domain
Synthetic Cannabinoids
• Pharmaceutical forms of dronabinol
• Available in capsule form
• Two FDA-approved uses
• #1: Chemotherapy-induced nausea and vomiting
• #2: Appetite stimulation in wasting illnesses
• Often end stage HIV/AIDS patients
Antidepressants
Jason Ryan, MD, MPH
Antidepressants
• Tricyclics
• MAO inhibitors
• SSRIs
• SNRIs
• Others
Depression
• Associated with:
• ↓ serotonin
• ↓ norepinephrine
• ↓ dopamine
• Improved symptoms with increased CNS levels
• Most antidepressants → increase levels
• Ways to increase levels
• Block re-uptake → higher levels in synapses
• Inhibit breakdown
 Pre-synaptic
Neuron

NT

Reuptake Breakdown
NT

Post-synaptic
Neuron
Depression
Acetylcholine
• Monoamines
• Serotonin, norepinephrine, histamine, dopamine
• Most drugs affect more than one monoamine
• Anti-histamine effects
• Common: sedation, dry mouth
• NE blockade: hypotension (alpha-1)
• Muscarinic blockade: tachycardia, urinary retention

Serotonin
Norepinephrine Histamine 5-HT
Tricyclic Antidepressants
• Old antidepressants (1970s)
• Blocked re-uptake of 5-HT and norepinephrine
• “Broad spectrum”
• Anti-histamine
• Anti-muscarinic
• Block alpha-1 receptors
• Many side effects

Nortriptyline Imipramine Amitriptyline

Tricyclic Antidepressants
• Anti-histamine
• Sedation, weight gain, confusion (especially elderly)
• Anti-cholinergic (muscarinic)
• Blurry vision, constipation, dry mouth, urinary retention
• Alpha-1 block
• Orthostatic hypotension
Tricyclic Antidepressants
• Tertiary amines (3 nitrogen attachments)
• Amitriptyline, clomipramine, doxepin, imipramine, trimipramine
• More sedating (anti-histamine effects)
• Secondary amines (2 nitrogen attachments)
• Desipramine, nortriptyline, protriptyline
• More activating (norepinephrine effects)

Imipramine Nortriptyline
Tricyclic Antidepressants
Overdose

• Potentially fatal
• Seizures and coma
• TCAs antagonize GABA receptors
• Anticholinergic toxicity
• Hyperthermia (loss of sweating)
• Skin flushing, dilated pupils
• Ileus, urinary retention
• Hypotension (alpha blockade)
• Major cause of death
• Prolongation of QT interval → arrhythmias
Tricyclic Antidepressants
Overdose

• Monitor ECG for increased QRS interval

• Most prominent manifestation of toxicity
• TCAs block cardiac sodium channels
• Treatment: Sodium bicarbonate
• Extra sodium overcomes TCA Na-channel blockade
• Also ↑ pH favors inactive form of drug
Tricyclic Antidepressants
Non-depression uses

• Obsessive-compulsive disorder (clomipramine)

• Diabetic peripheral neuropathy
• Amitriptyline, desipramine
• Chronic pain
• Amitriptyline, doxepin, imipramine, nortriptyline, desipramine
• Prevention of migraine headaches
• Amitriptyline
• Bed wetting (enuresis)
• Not first line therapy (desmopressin)
• Imipramine, amitriptyline, and desipramine
• Insomnia (doxepin)
MAO Inhibitors
Monoamine Oxidase Inhibitors

• Inhibits monoamine oxidase

• ↓ breakdown of monoamines
• Serotonin, norepinephrine, dopamine
• MAO-A
• Dopamine, serotonin, norepinephrine
• MAO-B
• Dopamine

Serotonin
Norepinephrine Dopamine 5-HT
MAO Inhibitors
Monoamine Oxidase Inhibitors

• Non-selective MAO inhibitors

• Tranylcypromine, phenelzine, isocarboxazid
• MAO-b selective: selegiline
• Rarely used in modern era
• Refractory depression
• Anxiety
• Selegiline (selective MAO-B inhibitor) used in Parkinson’s
Serotonin Syndrome
• Classic triad: Three As
• #1: Mental status changes Cyproheptadine
• Agitation, restlessness, and disorientation
• #2: Autonomic hyperactivity
• Diaphoresis, tachycardia, hyperthermia
• #3: Neuromuscular hyperactivity
• Tremor, clonus, hyperreflexia, bilateral Babinski sign
• Treatment: cyproheptadine
• 5 –HT antagonist
Serotonin Syndrome
• Often caused by MAOi plus another serotonin drug
• Any drug that that ↑ serotonin activity
• SSRIs, MAO inhibitors, SNRis, TCAs
• MDMA (ecstasy)
• Ondansetron (nausea; 5-HT3 antagonist)
• Tramadol (weak opioid; inhibits 5-HT reuptake)
• Meperidine (opioid; inhibits 5-HT reuptake)
• Triptans (migraines; 5-HT agonists)
• Linezolid (antibiotic; weak MAO inhibitor)
• Dextromethorphan (cough suppressant; weak SSRI)
• St. John’s wort (herbal supplement; increase 5-HT activity)
• Two week washout (stopping/starting)
Tyramine
Tyramine
• Naturally occurring monoamine
• Sympathomimetic
• Causes sympathetic activation
• Normally metabolized GI tract
• Patients on MAOi → tyramine in blood
• Hypertensive crisis
• “Cheese effect”
• Cheese, red wine, some meats

Pixabay/Public Domain
SSRIs
Selective serotonin reuptake inhibitors

• Inhibits 5-HT reuptake by neurons

• Leads to ↑ 5-HT levels in synaptic cleft Fluoxetine
Fluvoxamine
• Take 4-8 weeks to have effects Paroxetine
• Used in many psychiatric disorders Sertraline
• Depression Escitalopram
• Generalized anxiety disorder Citalopram
• Panic disorder
• Obsessive-compulsive disorder
• Bulimia
• Social anxiety disorder
• PTSD
SSRIs
Selective serotonin reuptake inhibitors

• Common side effect: sexual dysfunction

• Increased serotonin effects in spinal cord
• Decreased libido (54 percent)
• Anorgasmia: difficulty achieving orgasm (36 percent)
• Erectile dysfunction in males (37 percent)
SSRIs
Selective serotonin reuptake inhibitors

• GI upset
• GI serotonin effects
• Nausea, abdominal pain, constipation
• Drowsiness
• Weight gain
• SIADH and hyponatremia (rare)
• QT prolongation (rare)
SNRIs
Serotonin-norepinephrine reuptake inhibitors

• Inhibits 5-HT and NE reuptake by neurons

• Take 4-8 weeks to have effects
• Used in many psychiatric disorders
• Depression Venlafaxine
• Generalized anxiety disorder Desvenlafaxine
• Social anxiety disorder Duloxetine
• Panic disorder Levomilnacipran
Milnacipran
• PTSD
• Obsessive-compulsive disorder
• Fibromyalgia (duloxetine)
• Diabetic neuropathy (venlafaxine)
SNRIs
Serotonin-norepinephrine reuptake inhibitors

• May increase blood pressure

• Norepinephrine effects
• Nausea (diminishes with time)
• Sexual dysfunction
• Highest rate: venlafaxine
Bupropion
• Blocks reuptake of NE and dopamine
• Increases presynaptic release of catecholamines
• No effects on serotonin
• Used in depression and smoking cessation
• May improve sexual dysfunction of SSRIs
• Toxicity related to stimulant effects
• Anxiety
• Insomnia
• Seizures
Mirtazapine
• Blocks presynaptic alpha-2 receptors
• More norepinephrine and serotonin release
• Blocks postsynaptic serotonin 5-HT2 and 5-HT3
• More 5-HT1 activity
• Also anti-histamine → side effects
• Sedation
• Dry mouth
• Increased appetite
• Weight gain
 Alpha 2 Receptors
α2 receptors in CNS
Presynaptic receptor Pre-
Feedback to nerve when NE released synaptic
Activation leads to ↓NE release
Neuron

α2
Norepinephrine
NE
Serotonin

Post-synaptic
Neuron
Serotonin Modulators
• Inhibit reuptake of serotonin
• Antagonists and agonists of serotonin receptors
• Minimal effects on norepinephrine or dopamine
• Trazadone
• Vilazodone
• Vortioxetine
Trazadone
• Weak serotonin reuptake inhibitor
• Affects serotonin 5-HT2A and 5-HT2C receptors
• Low doses: serotonin antagonist
• High doses: serotonin agonist
• No longer used as antidepressant
• Main clinic use is insomnia (sedating)

Public Domain
Vilazodone
• Blocks reuptake of serotonin
• Partial agonist at postsynaptic 5-HT1A receptors
• Diarrhea (28%)
• Sexual dysfunction
• Case reports of serotonin syndrome
Vortioxetine
• Blocks reuptake of serotonin
• Various properties on serotonin receptors:
• Antagonist 5-HT3
• Weak antagonist 5-HT7/5-HT1D
• Partial agonist 5-HT1B
• Full agonist 5-HT1A
• Main side effect: nausea
Lithium
Jason Ryan, MD, MPH
Lithium
• Chemical element/cation
• First medical therapy of bipolar disorder (1949)
• Many toxicities
• Narrow therapeutic index
• Serum level monitored to titrate dose
• Low level = subtherapeutic
• High level = risk of toxicity
Lithium
Mechanism

• Incompletely understood
• Inhibits inositol monophosphatase (IMPase)
• Used to regenerate inositol
• Depletes inositol → ↓ intracellular 2nd messenger levels
• Phosphatidylinositol-4,5-bisphosphate (PIP2)
• Inositol trisphosphate (IP3)
• Diacylglycerol (DAG)
Lithium
Elimination

• Primarily renal excretion

• Mostly reabsorbed in proximal tubule (like Na)
• Contraindicated with significant renal impairment

BruceBlaus
Lithium Toxicity
Risk Factors

• Renal insufficiency
• Volume depletion
• Elderly patients (low glomerular filtration rate)

Image courtesy of BruceBlaus

Lithium
Drug Interactions

• Increased lithium level

• Thiazide diuretics
• NSAIDS
• ACE inhibitors
• Decreased lithium level
• Potassium-sparing diuretics
• Varying effects: loop diuretics
Lithium
Adverse Effects

• Acute effects
• Tremor
• Long term effects
• Hypothyroidism
• Nephrogenic diabetes insipidus
• Cardiac
• Fetal effects
• Ebstein’s anomaly
Tremor
• Occurs when drug started or dose increased
• Symmetric
• Usually limited to hands or arms
• Often resolves over time
• Most common symptom of lithium toxicity
Thyroid Effects
• Lithium: goitrogen
• Inhibits hormone release
• Commonly causes goiter (enlarged thyroid)
• 40-50% of patients on lithium
• May cause hypothyroidism

Wikipedia/Public Domain
Diabetes insipidus
• “Chronic tubulointerstitial nephropathy”
• Loss of tubule urine concentrating ability
• Tubules do not respond to ADH
• Dilute urine (low Uosm)
• Polyuria and polydipsia
• Serum sodium normal or increased
Diabetes insipidus
Treatment

• Vasopressin: no response (no change Uosm)

• Nephrogenic DI
• Discontinue lithium (if possible)
• Amiloride
• Potassium-sparing diuretic
• Inhibits Na channels (ENaC) of principal cells
• Blocks lithium entry into renal cells

Amiloride
 Amiloride

Lumen (Urine) Principal Cell Interstitium/Blood

Na+
Na+
Amiloride ATP
K+
K+

H2O
Cardiac Effects
• Suppression of sinus node
• Make cause sinus node dysfunction
• Bradycardia
• Pauses
• Syncope
Maternal Lithium
• Teratogen
• Completely equilibrates across the placenta
• Teratogenic effects primarily involve heart
• Ebstein’s anomaly most common

Øyvind Holmstad/Wikipedia
Antipsychotics
Jason Ryan, MD, MPH
Dopamine
• 1950s: chlorpromazine found to improve psychosis
• Also found to block CNS dopamine receptors
• Dopamine hypothesis

Dopamine
Antipsychotics
First Generation or Typical

• Haloperidol
• Chlorpromazine
• Trifluoperazine
• Fluphenazine
• Thioridazine
• Pimozide
Antipsychotics
First Generation or Typical

• Primary antipsychotic effect: D2 receptor blockade

• Found on post-synaptic CNS neurons
• Limbic system, basal ganglia, prefrontal cortex
• G-protein coupled
• D1: activates adenylyl cyclase → ↑ cAMP
• D2: inhibits adenylyl cyclase → ↓ cAMP
• D2 blockade → ↑ cAMP

Adenosine triphosphate
(ATP) Cyclic-adenosine monophosphate
(cAMP)
Antipsychotics
First Generation or Typical

• “Neuroleptics”: depresses nervous system activity

• Schizophrenia (positive symptoms)
• Psychosis
• Mania
• Bipolar disorder
• Obsessive-compulsive disorder
• Delirium (haloperidol)
• Tourette syndrome
• Huntington disease
Parkinson’s Disease
• Motor dysfunction
• Tremors, rigidity
• Associated with ↓ CNS dopamine activity

Wikipedia/Public Domain
Neurotransmitters

Histamine Serotonin
5-HT

Dopamine

Acetylcholine
Epinephrine
(Muscarinic)
Antipsychotics
First Generation or Typical

• Dopamine blockade
• Serotonin blockade
• Histamine blockade
• Acetylcholine (muscarinic) blockade
• Epinephrine (alpha-1) blockade
Antipsychotics
First Generation or Typical

• Dopamine blockade
• Parkinsonian effects (extrapyramidal)
• Hyperprolactinemia
• Amenorrhea
• Galactorrhea
• Gynecomastia
• Anti-emetic (Prochlorperazine/Chlorpromazine)
• ACh muscarinic receptor blockade
• Dry mouth
• Constipation
Antipsychotics
First Generation or Typical

• α1 receptor blockade
• Hypotension
• Histamine receptor blockade
• Sedation
• Constipation
Pyramidal vs. Extrapyramidal
• Pyramidal system
• Corticospinal tract
• Run in pyramids of medulla
• Damage → weakness
• Extrapyramidal system
• Basal ganglia nuclei and associated tracts
• Modulation of movement
• Damage → movement disorders
EPS
Extrapyramidal Symptoms

• Response to dopamine receptor blockade

• Movement side effects
• Dystonia
• Akathisia
• Bradykinesia
• Tardive dyskinesia
Dystonia
Extrapyramidal Symptoms

• Acute side effect

• Occurs within hours/days
• Involuntary contraction of muscles
• Spasms, stiffness
• Treatment: benztropine
• Anticholinergic
• Blocks M1 receptors
• Improves dystonia
Akathisia
Extrapyramidal Symptoms

• Occurs within days

• Most common EPS adverse effect
• Restlessness, urge to move
• Sometimes misdiagnosed as worsening agitation
• Treatment: Lower dose, benzos, propranolol
Bradykinesia
Extrapyramidal Symptoms

• Occurs weeks after starting drug

• “Drug-induced Parkinsonism”
• Slow movements (Parkinson-like)
• Treatment: benztropine
Tardive dyskinesia
Extrapyramidal Symptoms

• Occurs months or years after starting drug

• Choreoathetosis
• Chorea: irregular migrating contractions
• Athetosis: twisting and writhing
• Mouth, tongue, face, limbs
• Smacking lips
• Grimacing
• Often irreversible
• Stopping drug doesn’t help
Antipsychotics
First Generation or Typical

• High potency agents

• Haloperidol, trifluoperazine, fluphenazine
• Lower dose required to achieve effect
• Example: Haldol 1mg
• Little effect on histamine and muscarinic receptors
• Less dry mouth (muscarinic), sedation (histamine)
• Extrapyramidal side effects

Chlorpromazine: α1=5HT> D2
Haloperidol: D2 > α1 > 5HT > H1
Antipsychotics
First Generation or Typical

• Low potency agents

• Thioridazine, chlorpromazine
• Example: Thioridazine 50-100mg
• Less extrapyramidal side effects
• More non-neurologic side effects
• Sedating (“sedatives”)
• Dry mouth
Antipsychotics
First Generation or Typical

High Potency
Low Potency
Haloperidol
Thioridazine
Trifluoperazine
Chlorpromazine
Fluphenazine

Non-EPS Effects EPS Effects

Sedation Movement symptoms
Dry mouth
NMS
Neuroleptic Malignant Syndrome

• Rare, dangerous reaction to neuroleptics

• Usually 7-10 days after treatment started
NMS
Neuroleptic Malignant Syndrome

• Fever and rigid muscles

• Mental status changes (encephalopathy)
• Elevated creatine kinase (muscle damage)
• Myoglobinuria → acute renal failure (rhabdomyolysis)
• Treatment:
• Dantrolene (muscle relaxant)
• Bromocriptine (dopamine agonist)
• Similar to malignant hyperthermia
• Reaction to halothane, succinylcholine
• Same treatment: dantrolene (muscle relaxant)
QT interval
• May block cardiac potassium channels
• Prolongs QT interval
• Strongest association with IV haloperidol

Torsade de Pointes
Ocular Effects
• Chlorpromazine
• May cause corneal deposits
• May accelerate aging of lens
• Thioridazine Christian Hamel

• Retinal deposits
• Advanced cases resemble retinitis pigmentosa
• May cause “browning” of vision
• Uses lower doses to avoid this complication
Antipsychotics
Second Generation or Atypical
• Clozapine
• Olanzapine
• Quetiapine
• Asenapine
• Iloperidone
• Paliperidone
• Risperidone
• Lurasidone
• Ziprasidone
• Aripiprazole
• Defining feature: Less EPS adverse effects
Serotonin
5-hydroxytryptamine (5 HT)

• LSD (lysergic acid diethylamide)

• 5-HT agonist
• Produces hallucinations via 5-HT2A activity
• ↓ 5-HT2A activity seen with many atypicals
• As or more effective 5-HT blockade versus dopamine

Clozapine: α1 > 5HT > D2

Olanzapine: 5HT > H1 > D2 > α1
Antipsychotics
Second Generation or Atypical

• Schizophrenia
• Improve positive and negative symptoms
• Bipolar disorder
• Obsessive-compulsive disorder
• Anxiety disorder
• Depression
• Tourette syndrome
• Fewer EPS and anti-cholinergic effects
• May prolong QT interval
Metabolic Syndrome
• May occur with any antipsychotic
• Common with clozapine and olanzapine
• Weight gain
• Hyperglycemia
• Hyperlipidemia
Clozapine
• Toxic to bone marrow
• May cause agranulocytosis (1-2% of patients)
• Must monitor WBCs during therapy
• Weekly at start
• Every few weeks to monthly thereafter
• Reversible when drug stopped
• May also cause seizures (2-5% of patients)
• Dose related

Dr Graham Beards
Hyperprolactinemia
• Antipsychotics: most common drug-induced cause
• Dopamine blockade → ↑ prolactin
• Amenorrhea in women
• Gynecomastia in men
• Galactorrhea
• Highest rates:
• Haloperidol
• Fluphenazine
• Risperidone
• Paliperidone
Aripiprazole
• D2 partial agonist
• Some blockade, some agonist effects
• Less dopamine blockade adverse effects
• Most common side effect: akathisia