CO-OCCURRING DISORDERSIn Substance Abuse

Part 1: THE BRAIN, ADDICTION, and CODs

A Workshop for Alameda County

SUD Providers

January 29, 2016

Rob Lee, MD

Co-Occurring Disorders in SUD:SCOPE OF THE PROBLEM

• CODs are present in 50% of SUD clients

• Often CODs are multiplex: Overlapping CODs, COD + Trauma, etc

• Course and Prognosis are much worse

• Costs and Complications are much higher

• Often CODs are unrecognized or under-treated

Definitions of Addiction

• ASAM: A primary, chronic disease of

brain reward, motivation, memory, and related circuitry.

• NIDA (of the NIH): A chronic, relapsing

brain disease characterized by compulsive drug seeking and use, despite adverse consequences.

A Brief History of Psychiatry

• The Pre-Freud Asylum Era, before 1900

• Freud & the Era of Psychoanalysis, 1900-1950

• Transition to Psychopharmacology, 1950-1975

• The Era of Psychopharmacology, 1975 onwards

• Era of the Brain (and Genetics), 2000 onwards

Philosophy: Views on Mind

Biological View/Bias of Current Psychiatry

• Brain is seen as an intelligent machine

• Mind is seen as a ‘side effect’ of the brain

Spiritual View/Bias (for example 12-Step View)

• Mind is seen as a primary, self-existing entity

• Brain is seen as a tool and/or manifestation of mind

A Pragmatic Approach

Addiction is not adequately approached from any fixed viewpoint. Biological factors as well as Psychological factors (spiritual, cognitive-emotional, social) must be considered in each case, though the relative power of each factor may vary enormously over the range of unique individuals.

How We Know the Brain

Anatomical Study and Surgery

Animal Research

Observations from Drug Effects

Imaging the Brain– [Xray and EEG]

– CT Scan (since ~1980)

– MRI Scan (since ~1990)

– functional-MRI (since ~2000)

– PET Scans and SPECT Scans

The Human Brain

• Brainstem: Automatic Body Functions, Sleep & Wakefulness, [Non-Learning ?]

• Limbic Brain: Emotional Thinking and Learning, Memory, Instincts

• Neocortex Brain: Verbal Thinking and Learning, Judgment, Voluntary Movement, Sensory Processing

Brain Schematic Cross-section

ANATOMICAL HUMAN BRAIN IN CROSS-SECTION

Brainstem within Limbic Brain withinNeocortex Brain

Microscopic Brain• 100 Billion Nerve Cells, called Neurons, often

clustered in functional units: ‘Nuclei’ or ‘Areas’

• >100 Trillion Neuron Interconnections, called

Synapses

• Synapses work by chemical, rather than electrical signal

• Chemical signal molecules are called

Neurotransmitters

• >100 different neurotransmitters are known

NEURONS AND SYNAPSES

SHOWING NEUROTRANSMITTER RELEASE AND BINDING

The Neurotransmitters of Emotion(Monoamines)

• SEROTONIN: Stress Stabilization, Emotional-Cognitive Deactivation

• NOREPINEPHRINE: Focus/Attention, Emotional-Cognitive Activation

• DOPAMINE: Thinking (and Psychosis), Motivation (and Craving), Movement (Parkinsons if deficient)

NEUROTRANSMITTERS OF EMOTION

Dopamine and Serotonin(Norepinephrine Paths are Similar to Serotonin)

Neurotransmitters of Addiction

• DOPAMINE: The primary NT of addiction

• ENDORPHINS: Widespread natural opioids that regulate reward, pain, and other brain functions

• GABA: Calming (Anti-Anxiety), regulates Dopamine

• ANANDAMIDES: Natural cannabinoids, brain deactivators localized mainly to the limbic system

• [GLUTAMINE]: Activation, Learning

• [ACETYLCHOLINE ]: Movement, Cognition, Target Receptor for Nicotine

Biology of Addiction

• Ventral Tegmental Area (VTA) of midbrain• Dopamine (activation) and Endorphin

(reward, pleasure) neurotransmitters• GABA neurotransmitter regulation of

dopamine and endorphin activity• Nucleus Accumbens of the Cingulate Gyrus (in

the Limbic Brain)• Activation of Nuclear Factors (for example

DeltaFosB) that alter DNA Function• Long-term (months to years) Downregualtion

of Reward Circuit Activity

The Dopamine Theory of Addiction

• All known addictive drugs stimulate dopamine release, directly or indirectly

• All known substances that release dopamine in the brain are addictive

• After continued dopamine stimulation, the brain becomes resistant to dopamine

• This produces a functional dopamine deficit and causes craving and compulsive use

Biology of Addiction: Nucleus Accumbens

• The Nucleus Accumbens is a small structure at the front of the cingulate gyrus

• It is the primary brain center of pleasure and motivation

• It is activated mainly by VTA dopamine, potentiated by endorphins

• How sensitive it is to dopamine, and how quickly it changes due to dopamine stimulation may be genetic

THE NUCLEUS ACCUMBENSAND RELATED BRAIN CIRCUITS

Biology of Addiction: Nuclear Factors

• Nuclear Factors [= Transcription Factors] are proteins in the cell that turn DNA on or off

• Several NFs are increased in the Nucleus Accumbens due to persistent dopamine effect

• One called DeltaFosB (DFB) is crucial in causing addiction: It PHYSICALLY CHANGES the cells of the Nucleus Accumbens

• Once activated, DFB persists for MONTHS

The Five-Year Principleof Addiction Recovery

ADDICTION (=‘SUD’) DIFFERS FROM:

• Dependence: Needing to take the drug to avoid physical or psychological withdrawal

• Tolerance: The decrease of drug effect over an extended period of use

• Abuse: Using a drug to get high, or using an illegal substance

• Misuse: Taking a drug other than as prescribed, or giving it to other persons

• Pseudo-Addiction: Craving a drug because the dose was cut back too quickly

Is Addiction a Brain Disorder?• Addiction Definition (Haight-Ashbury):

– Craving +

– Compulsions (including Continued Use despite harm)

• Craving is conscious painful drug hunger but it arises choicelessly, like food hunger

• Compulsion is unconscious almost uncontrollable motivation towards use: “I wasn’t even thinking, I just started again.”

• Choiceless drug hunger and unconscious behavioral motivation are best considered brain activity, not an intentional mental activity

Is Addiction a Brain Disorder?

• “Heritability” is a measure of the role of genetic factors in a disorder, estimated through studies of twins

• Twin studies suggest that the Heritability of Addiction is roughly 50%, suggesting that half the cause of Addiction is genetic

• So far all identified addiction genes act on the brain

Co-Occurring Disorders (CODs)• DEF= Diagnosable Psychiatric Disorders that

occur along with an SUD (Dual Diagnosis)

• CODs may lead to drug use due to psychic pain, poor judgment, or risk-attraction

• SUDs may worsen or even trigger (cause) Psychiatric Disorders (eg, Psychosis)

• MOST Psych Disorders have COD risk

• Treatment & Recovery are impaired

Common Co-Occurring Disorders

• Bipolar Disorder (Types I and II)

• Psychosis/Schizophrenia

• Depression

• Anxiety Disorders (GAD, Panic, Phobias)

• Trauma & PTSD

• ADHD

• Personality Disorders

• Eating Disorders

Brain Anatomy of Emotion and Thinking

• Amygdala: Scanning & Recognition Memory, Basic Emotional Response

• Hippocampus: Significance, Complex Memory

• Nucleus Accumbens: Craving and Seeking

• Cingulate Gyrus: Complex Motivation, Feeling

• Prefrontal Neocortex:

– Emotional Restraint and Oversight

– Abstract Thinking and Judgment

BRAIN COGNITIVE-EMOTIONAL SYSTEM

‘THE LIMBIC SYSTEM’ OR, ‘THE THINKING MACHINE’

COD: Bipolar Disorder

• DEF= Episodes of mania or hypomania, usually alternating with severe depressions

• Heritability 50-70%

• Addiction is very common, especially alcohol, and greatly worsens prognosis

• Failure in prefrontal limbic regulation?

• Often exacerbated by trauma or sleep deficit

• “Kindling”: Mania begets more mania

COD: Psychosis/Schizophrenia

• DEF= Delusional thinking +/- Hallucinations• Misperceptions (“positive” symptoms) and

Cognitive deficits (“negative” symptoms)• Heritability ~80%• Frontal/Temporal Lobe damage/dysfunction• Over-activation of dopamine system plays a

major role in positive symptoms• Drugs of Abuse may exacerbate psychosis OR

induce a temporary psychosis OR initiate a psychosis that then persists

COD: Depression

• DEF= Persistent low mood +/- anhedonia

• Mild (dysthymia) and Major (MDD) types

• Heritability for MDD is 30-40%

• Exacerbations often from acute or chronic stress

• Strong evidence of reversible damage and shrinking of emotional brain structures (hippocampus especially)

• Role of serotonin and norepinephrine, at least in treatment

COD: Anxiety Disorders

• DEF= Excessive Worry, or Panics, or Phobia

• Heritability of GAD is ~30%

• Modestly increased SUD risk—generally out of attempts to ‘medicate’ anxiety

• Amygdala may be over-sensitized, genetically or due to trauma

• Role of norepinephrine flooding, at least in Panic Attacks

COD: Trauma & PTSD

• PTSD= Failure to process and appropriately “dis-remember” a severe trauma

• Amygdala and Hippocampus are “overwhelmed”

• PTSD is accompanied by SUD risk and persistent (>1 month) emotional and cognitive dysregulation: Necessary for diagnosis

• Stress (universal) vs Trauma vs Catastrophic Trauma

• Severe trauma leads to PTSD in “only” 10-50%

• PTSD worsens SUD craving and all other CODs

COD: ADHD

• DEF= Difficulty with focus tasks, often also with impulsivity and restlessness (less in adults)

• ADHD is strongly heritable, ~75%

• A “spectrum” disorder, over-diagnosis possible

• Decreased norepinephrine effect in Prefrontal Lobe leads to impulsivity and impaired focus (?)

• Alcohol and MJ addictions are common

• Risk of other addictions is variable

COD: Personality Disorders

• DEF= Persistent early-onset ‘abnormal’ levels of social instability or insensitivity or oddness or discomfort/anxiety

• Moderate heritability, ~50%

• Genetic or physical factors may alter the prefrontal lobe and/or amygdala

• Variable addiction risk, but high in Antisocial PD and Borderline PD and Schizotypal PD

• Medical treatments are relatively ineffective

COD: Eating Disorders• Binge, Bulimia, Anorexia, and Mixed types

• Heritability estimates range 40-70%, more common in women than men

• Very common (10%?, 20%?) as a transient disorder in adolescence/youth

• Persistent or severe types 1-2% prevalence

• Higher risk of SUD especially in Mixed type

• Similar to SUD in many ways, but the “addictive substance” is an eating behavior

BRAIN CIRCUITS WITHIN THE LIMBIC BRAIN

Special Issue: Chronic Pain

• Chronic Pain is increasingly common, and frequently leads to SUD

• Though CP is not a Psychiatric Diagnosis (in the DSM), its effect on the brain resembles a hybrid of Depression and Addiction

• Hippocampus is atrophied

• Reward circuit, especially Nucleus Accumbens, is downregulated

Special Issue: The Teenage Brain

• The brain develops “from back to front” and the Prefrontal Lobes are the last to mature

• Full PFL maturity not until age 25-30

• Prior to maturation the PFL is undergoing critical and permanent ‘programming’ towards it role regulating emotion and reward

• Drugs (especially alcohol and nicotine) clearly inhibit and distort this process

• Teenage risk of addiction is 2x higher

A Word of Humility: Brain Complexity

• 3 pounds of tissue, ~2% of body weight

• Uses 20% of body energy at rest

• ~100 billion nerve cells (neurons)

• 100-500 billion support cells (glia cells)

• The most complicated known natural object, ounce for ounce

Taking Care of the Brain

• Issue of sleep

• Issue of chronic inflammation

• Exercise

• Diet

• Supplements

• Social Connection

• Cultivating Awareness

Treatments for CODs, and other Brain Disorders

• Recognizing and treating MEDICAL ISSUES

• Cognitive psychotherapy, working with education and thinking habits

• Social psychotherapy, working with relatedness and emotional experiences

• Complementary approaches: Acupuncture, etc

• Medications

• Neuromodulation