Transcript Structural Changes in the Brain of Addicts

Structural Changes in the Brain of Addicts
Waden E. Emery III M.D. FAAN
Asst. Clinical Professor Neurology University of Miami
Emery Neuroscience Center
5340 N Federal Hwy, Ste. 205
Lighthouse Point, FL 33064
Tel: 954-771-8300
Recovery and Community: It Takes a Village
September 27th 2013
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Brain Imaging Techniques
• Structural Magnetic Resonance Imaging (MRI)
• Functional Magnetic Resonance Imaging
(fMRI)
• Magnetic Resonance Spectroscopy (MRS)
• Positron Emission Tomography (PET)
• Single Photon Emission Computed
Tomography (SPECT)
Structural MRI (MRI)
• Map Tissue morphology and composition
Functional MRI (fMRI)
• Visualize changes in oxygenation and blood
flow associated with brain activities
Magnetic resonance spectroscopy
(MRS)
• Measure cerebral metabolism, physiological
processes involving specific brain chemicals;
detect drug metabolites
Positron emission tomography (PET)
• Quantify biochemical and pharmacological
processes
• Glucose metabolism
• Drug distribution and kinetics
• Receptor ligand interaction
• Enzyme Targeting
Single photon emission computed
tomography (SPECT)
•
•
•
•
Measure receptor ligand interaction
Measure physiological function
Measure biochemical processes
Measure pharmacological processes
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Anatomical Regions Involved in
Addiction
•
•
•
•
•
•
•
•
•
•
Orbitofrontal Cortex (OFC)
Ventral Tegmental Area (VTA)
Prefrontal Cortex
Frontal Cortex
Parietal Cortex
Basal Ganglia
Cingulate Gyrus
Nucleus Accumbens (NAc)
Amygdala
Hippocampus
Anatomical Regions Involved in
Addiction
Functional Correlates
• The Ventral Tegmental Area (VTA) & Nucleus
Accumbens (NAc) are key components of the
brain’s reward system
• The VTA, NAc, amygdala, and hippocampus
are major components of the limbic system,
which coordinates drives, emotions, and
memories
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Structural MRI Changes
• Addictive drugs cause volume and tissue
composition changes in the Frontal cortex
• These changes are likely associated with
abusers’ cognitive and decision making
problems.
• Frontal Lobes and Prefrontal Lobes are
decreased size in drug users
Structural MRI Changes
• Cocaine dependent individuals have enlargement
of the basal ganglia compared to normals
• Methamphetamine abusers had severe gray
matter deficits in the cingulate, limbic, and
paralimbic cortices.
• Methamphetamine abusers had smaller
hippocampi than normals (hippocampi are a key
site for memory storage and volume decrements
correlated with poorer performance on a word
recall test
Structural MRI Changes
• The amygdala, a brain structure that helps
shape our emotional responses to experiences
is relatively small in children of alcoholics
Structural MRI Changes
• Methamphetamine Reduces Grey Matter
Functional MRI (fMRI) Changes
• fMRI studies reveal changes resulting from the
ratio of oxygenated to deoxygenated hemoglobin
(During a task, Oxygen consumption is raised in
specific areas of the brain and therefore the ratio
of oxygenated to deoxygenated hemoglobin
changes)
• When given cocaine in a fMRI machine, the drug
rush correlates with higher activity (Oxygen
consumption) in the caudate, cingulate, and
lateral prefrontal cortex
Functional MRI (fMRI) Changes
• Reports of craving commenced when the euphoria
subsided and persisted as long as a different set of
brain areas including the NAc remained activated
• Other studies suggested higher activation in the NAc,
inferior frontal/orbitofrontal gyrus and anterior
cingulate
• Activation of the anterior cingulate cortex, an area
associated with emotional processing persisted while
cocaine-addicted subjects watched videotapes
containing cocaine-accociated cues
Functional MRI(fMRI) Changes
• The Brains Response to Cocaine Cues-Anterior
Cingulate activated in Cocaine users
Magnetic Resonance Spectroscopy
(MRS) Changes
• MRS scans reveal the location and concentrations
of target chemicals in brain tissue
• Two that have been studied are NAcetylaspartate (NAA) which has been used as a
gauge of neuronal cell health and myoinositol,
which is present in support cells, glia
• Choline compounds which are involved in
turnover of cell membranes and creatinine
compounds which are important for cells’ energy
maintenance
Magnetic Resonance Spectroscopy
(MRS) Changes
• Methamphetamine users have reduced NAA
concentrations in basal ganglia and frontal
white matter—measures of NAA have
correlated with measures of cognitive function
• Cocaine users have decreased NAA levels,
suggesting neuron damage, as well as
elevated creatine and myoinositol levels
reflecting increased glial cell activity or
inflammation
PET & SPECT Changes
• PET & SPECT scans display the distribution of a
labeled compound, called a radiotracer
• PET & SPECT vary with respect to the type of
tracer
• Dopamine is highly concentrated in the striatum,
which forms part of the brain’s reward system—
its levels determine how much pleasure we
derive from our experiences and helps us focus
our attention on what is important
PET & SPECT Changes
• PET & SPECT studies have established that
cocaine, amphetamine, and methylphenidate,
when given intravenously produce their highs by
massively increasing the volume of dopamine in
the striatum
• Further studies have shown that any drug’s abuse
liability depends both on the size of the
dopamine spike it produces and the rapidity with
which dopamine rises and falls back to normal
levels
PET & SPECT Changes
• The “high” experienced correlates with uptake
of cocaine in the striatum
• Cocaine leads to a build up of dopamine in the
synaptic cleft
PET & SPECT Changes
• Chronic exposure reduces the availability of
dopamine transporters, suggesting a loss of
dopamine cells
• Cocaine and methamphetamine reduce cellular
activity in the orbitofrontal cortex (OFC) a brain
area used to make strategic rather than impulsive
decisions
• Traumatic brain injuries to the OFC lead to
aggressiveness, poor judgment of future
consequences and the inability to inhibit
inappropriate responses
PET & SPECT Changes
• Cocaine abusers have decreased metabolism
in the OFC (Right) compared to normals (Left)
PET & SPECT Changes
• striatum of the healthy control (left) is largely
red, indicating the highest level of receptor
availability, while that of the cocaine abuser
has little red.
PET & SPECT Changes
• Cocaine users decreased judgment has
correlated with decreased metabolism in the
OFC
• Abusers of alcohol, cocaine, heroin and
methamphetamine all have reduced levels of
brain dopamine receptors
PET & SPECT Changes
• Smokers have decreased MAO, enzyme that
metabolizes dopamine
PET & SPECT Changes
• Smokers have low levels of MAO (monoamine
oxidase) which breaks down dopamine
• Releases hydrogen peroxide, a potential
source of free radicals that can damage nerve
cells
• MAO-inhibiting chemical compounds have
been isolated from tobacco and shown to
have a protective action in rodent model of
Parkinson’s disease
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Genetic Variations
• Genetic variations have been documented in
individuals with respect to their response to
amphetamine
• Genetic variation could increase sensitivity to
stress and heighten vulnerability to drug abuse
• Current hypothesis is that individuals with low
levels of dopamine receptors, either genetically
or as a result of experiences, have a higher risk of
abuse and addiction.
Genetic Variations
• Individuals with fewer dopamine receptors
obtain less than normal amounts of
dopamine-mediated pleasure from ordinary
activities and accomplishments and therefore
are highly susceptible to wanting to repeat the
euphoria that occurs when drugs massively
increase dopamine in the brain
Overview
• Current Imaging Techniques (primarily research)
• Anatomical Regions believed to be involved in
Addiction
• Anomalies seen in the addicted brains
• Neurotransmitters involved in addiction
• Genetic variations alter anomalies of brain
anatomy
• Treatment strategies
Treatment Strategies
• Medications are being developed that will
produce only a modest dopamine spike
causing susceptible individuals to experience
pleasure normally
• MAO-B inhibitors and other medications
fitting this criterion have been used to treat
smoking addiction
Treatment Strategies
• Compounds that enhance the
neurotransmitter gamma-aminobutyric acid
(GABA) which has been shown to inhibit
dopamine-releasing cells’ response to drug
related cues
• Other drugs are currently under study that
modify the dopamine-receiving cells and
thereby attenuate the reinforcing effects of
abused drugs
Treatment Strategies
• Drugs are currently under study that cause only a
modest dopamine spike instead of a sharp spike--treatment of heroin addiction with methadone and
buprenorphine exemplify this approach
• Functional MRI studies of men entering treatment for
methamphetamine addiction while they made
decisions during a psychological test showed two
patterns and predicted with 90 percent accuracy which
of the men would relapse within 1 to 3 years after
completing treatment---those who relapsed had less
activity in the prefrontal lobe
Summary
• Imaging techniques have defined the regions of
the brain that are altered when exposed to
various chemicals (drugs) in addicted individuals
• Areas of the brain are those involved with
reward, coordination of drives, emotions, and
memories
• The “high” from drug usage correlates with the
neurotransmitter spike dopamine in specific
areas of the brain
Summary
• Medications are currently used and being
developed to alter the dopamine spike
• Genetic variations to the dopamine spike have
been identified
• Imaging techniques may help to predict
potential recidivism rates
Lessons from Neurology
• Dopamine agonists in Parkinson’s Disease can
cause obsessive/compulsive behavior, eg,
gambling, sexual addictions---now carry a
warning from FDA
• Cocaine users have a significantly increased
risk of stroke, cerebral vasculitis
• Alcoholics can develop Wernicke and or
Korsakoff’s Syndromes due to vitamin
deficiency
Lessons from Neurology
• Delerium Tremens from alcohol/drug
withdrawal leads to seizures----my number
one consult while taking call at Broward
Health Imperial Point
• Parkinson’s Disease from ingestion of MPTP, a
synthetic form of heroin
• Polyneuropathy and focal neurapraxia from
drug ingestion
Lessons from Neurology
• Cerebellar Degeneration from long term alcohol
abuse
• Alcohol Dementia
• Fetal Alcohol Syndrome
• Myopathy-Alcohol
• Tremor associated with Amphetamines
• Decrease in Memory/Higher Cortical
Functions/Seizures associated with
benzodiazepines