Basic Physiology and Neurochemistry of Three Psychiatric Diseases, Including Drug Dependence

1
Basic Physiology and Neurochemistry of Three
Psychiatric Diseases, Including Drug Dependence

• Carlton Erickson, Ph.D.
• Director, Addiction Science Research and
  Education Center
• University of Texas at Austin, USA
• 
  APIA-Singapore, 2004

2
Brain Disorders That Co-occur with Dependence

• Probably Probably Not
• PTSD Alzheimers
• ADHD Parkinsons
• ASP/Conduct Tourettes
• Eating Disorders
• Aggression Compare today
• Mood disorders depression
• Schizophrenia? OCD

3
Common Abbreviations

• BZ - benzodiazepine (tranquilizer)
• CD - chemical dependence
  
• DA - dopamine
• DAT - dopamine transporter
  
• GAD - generalized anxiety disorder
• MAO(I) - monamine oxidase (inhibitor)
• MFB - medial forebrain bundle MH - mental
  health
• NT - neurotransmitter
• OCD - obsessive-compulsive disorder
• SRI - serotonin reuptake inhibitor
• TCA - tricyclic antidepressant
• WNL - within normal limits

4
Research Validity Estimate (RVE)
(A Thoughtful Appraisal of High-Quality
Scientific Research)

• High RVE
• many large, well-controlled studies
• replicable results
• much peer-reviewed, published literature
• Low RVE
• few replicable studies
• highly speculative results
• little peer-reviewed, published literature

100 - 0
5
Neurophysiology 101

• (.made simple)

6
(No Transcript)
7
Drug Receptors

70
8
Major Chemical Messengers of the Mind

• Acetylcholine (ACh)
• Dopamine (DA)
• Serotonin (SER)
• Gamma aminobutyric acid (GABA)
• Endorphins (END)
• Glutamate (GLU)

9
Neurophysiology and Function

• Neurotransmitters (NTs)
• allow nerve cells to talk to one another and to
  other tissues.
• function can be disrupted by disease and by
  drugs.
• allow normal behaviors, emotions, and
  cognition, when WNL.

10
Neurophysiology and Function (cont)

• Receptors
• are the binding sites for NT in the brain.
• when activated, cause nerve cells to be excited
  or inhibited.
• can be dysfunctional in brain disease states.

11
NT Receptor Subtypes

• ACh nicotinic and muscarinic
• DA 5 different subtypes
• SER 16 different subtypes
• GABA 3 different subtypes
• END 5 different opiate Rs
• GLU 16 different subtypes

80
12
Neurochemistry and Brain Areas

• Depression - (SER, NE, DA) in limbic system
• OCD - (SER) in orbitofrontal cortex, cingulate
  cortex, caudate nucleus
• CD - (DA, SER, END, GABA, GLU, ACh functional
  dysregulation) in mesolimbic dopamine system

60
13
Neurotransmitter (NT) involvement in brain
illness is inferred from observed effects of
therapeutic drugs on the illness, plus indirect
NT measurements.
14
For example.

• Anti-depressant drugs such as Prozac increase
  brain SER function in animal studies.
• It is inferred that decreased brain SER
  function is one of the causes of depression in
  humans.
• Indirect evidence supports this.

50
15
(No Transcript)
16
Brain Area Functions

• cerebral cortex - intelligence, judgment, and
  inhibitory control
• prefrontal cortex - planning and reasoning,
  decision-making
• hippocampus - cognitive learning and memory
• amygdala - emotional memory
• involved in the limbic system

70
17
Brain Area Functions (cont)

• basal ganglia - reaction time, fine motor
  control
• nucleus accumbens - compulsions, locomotor
  activity
• thalamus - way station for incoming
• sensory signals
• hypothalamus - instinctive and appetitive
  systems
• brainstem - alerting, stimulus
• filtering, sleep, autonomic control
• involved in the limbic system

70
18
Psychotherapy

• drug therapy is often necessary to access
  psychotherapy
• drug therapy sets baseline psychotherapy
  fine-tunes
• psychotherapy can help get at the primary cause
  of the disorder, drugs cannot

40
19
Brain Disease 1

• Mood Disorders
• (ex Depression)

20
Major Depressive Disorders

• a.k.a. affective or mood disorders
•  Types mild, moderate, severe w/o
• psychotic features, severe with
• psychotic features, in partial remission, in
  full remission, chronic, with postpartum onset,
  with melancholic features, etc.

21
Clinical Features of Depression

• excess sadness in response to loss, failure, or
  disappointment
• dysphoria loss of interest and anhedonia
• loss of appetite, sleep disorders, crying,
  fatigue, loss of ambition
• 7-15 commit suicide

22
Dysthymic Disorder

• a.k.a. depressive neurosis
• chronically depressed mood most of each day for
  2 years
• prevalence is 6 of population
• best treated with tricyclic antidepressants and
  psychotherapy

23
Therapy of Depression

• First choice SSRIs (e.g. Prozac) - new, few side
  effects (impotence?)
• Second choice new generation - e.g., Effexor,
  Remeron, Edronax
• Third choice tricyclics (e.g. desipramine) -
  many choices, very effective
• (Main NT?)

70
24
Therapy of Depression (continued)

• Fourth choice MAO Inhibitors (e.g., Nardil) -
  major interaction with tyramine-containing foods
• Fifth choice Electroconvulsive shock - in
  patients who are drug-resistant or who are
  suicidal

70
25
Some Off-Label Uses of Antidepressants

• ADHD Insomnia
• PTSD Panic disorder
• Social phobia Enuresis
• Chronic pain Anxiety
• Smoking cessation
• Anorexia and bulimia
• Premenstrual dysphoric disorder

25
26
Brain Disease 2

• Obsessive-Compulsive Disorder (OCD)

27
Clinical Features of OCD

• obsessions (thinking about things all the time,
  which causes anxiety or distress) and compulsions
  (doing things all the time, which tend to
  neutralize anxiety)
• OCD adults recognize symptoms as excessive or
  unreasonable

28
Treatment of OCD

• SSRIs - esp. fluoxetine (Prozac), fluvoxamine
  (Luvox), Zoloft (kids)
• clomipramine (Anafranil) - 4-10 week onset
• behavioral therapy is also useful in some
  patients

20
29
Brain Disease 3

• Chemical Dependence
• (addiction)

30
Two Critical Definitions

• abuse - intentional overuse in cases of
  celebration, anxiety, despair, self-medication,
  or ignorance. Tends to decline with adverse
  consequences.
• (a problem to solve)
• dependence - impaired control over drug use,
  probably caused by a dysfunction of the medial
  forebrain bundle, pleasure pathway
• (a disease to conquer)
• Based on the Diagnostic and Statistical
  Manual-IV (DSM-IV)

31
Neurotransmitters of Addiction

• Dopamine (DA)
• Serotonin (SER)
• Endorphins (END)
• Gamma-aminobutyric acid (GABA)
• Glutamate (GLU)
• Acetylcholine (ACh)
• (emphasis on dysregulations)

32
(No Transcript)
33
A Brain Chemistry Disease!

• addicting drugs seem to match the transmitter
  system that is not normal
• this is not a will power or poor judgment
  disease (frontal cortex)
• impaired control is caused by brain chemistry
  malfunction
• abstinence is the first step in the total
  treatment process, but new studies on reducing
  drinking are available

70
34
Is Chemical Dependency a Mental Disorder?
35
Impaired Control Problems

• problems with controlling behavior Tourettes
  pts, schizophrenics, manic pts, OCD pts, addicts
• are the following OCD or addiction?
• - pathological gambling
• - compulsive shopping
• - hypersexual behavior
• - overeating
• impulse control disorders?

36
Are Addictions an Obsessive-compulsive Disorder
Subtype?

• drug dependence satisfies all DSM OCD criteria
• are all pts in recovery always abstinent of all
  drugs?
• addiction, a compulsive disease Volkow
  Fowler, 2000
• OCD pts and heroin addicts have impairment in
  prefrontal areas
• Papageorgiou et al. 2003

60
37
Todays Treatment

• 12 step programs (abstinence)
• inpatient/outpatient/aftercare (insurance?)
• new meds to enhance abstinence
• harm reduction, MM, methadone
• brief motivational counseling, CBT, MET,
  SO-involved therapy, vouchers, vaccines
• (MM Moderation Management, CBT cognitive
  behavioral therapy,
• MET motivational enhancement therapy, SO
  significant other)

60
38
Final Thoughts

• Brain diseases
• - caused by disrupted neurochemistry
• - have a significant genetic component
• - environment plays a lesser role
• - are best treated with pharmacotherapy
• - but talk therapy is also powerful
• and can increase quality of life

39
Remember the Best Academic Website in the World!

• www.utexas.edu/research/asrec