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Attentional Dysfunction in Psychiatric Disorder
Martin H. Teicher, M.D., Ph.D.
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Attention and Psychopathology
Virtually all major psychiatric disorders are characterized by disturbances in attention or concentration.
Attention-Deficit/Hyperactivity Disorder
Complex Post-Traumatic Stress Disorder -- Secondary to Childhood Trauma
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Attention-Deficit/Hyperactivity Disorder
ADHD is recognized world-wide as one of the most common neuropsychiatric disorders of childhood. It has been estimated to affect between 2% and 9% of school-age children -- with most recent studies indicating a prevalence of approximately 6%.
ADHD accounts for 30% - 50% of child referrals to mental health services.
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Hyperactivity
Inattention
Impulsivity
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Diagnostic Criteria - DSM IV
A. Either (1) or (2):(1) Six (or more) of the following symptoms of inattentionhave persisted for at least 6 months to a degree that ismaladaptive and inconsistent with developmental level
(2) Six (or more) of the following symptoms of hyperactivity -impulsivity have persisted for at least 6 months to a degree thatis maladaptive and inconsistent with developmental level:
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Diagnostic Criteria - DSM IV
1. Often fails to attend to details2. Often has difficulty sustaining attention3. Often does not seem to listen4. Often fails to finish tasks5. Often has difficulty organizing tasks6. Often avoids sustained mental effort7. Often looses things necessary for tasks8. Is often distracted by extraneous stimuli9. Is often forgetful
Inattention - 6 or more
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Diagnostic Criteria - DSM IV
1. Often fidgets with hands or feet2. Leaves seat in classroom when expected to stay seated3. Often runs about or climbs excessively4. Often has difficulty playing quietly5. Often “on the go” or “driven by a motor”6. Often talks excessively7. Often blurts out answers8. Often has difficulty awaiting turn9. Often interrupts or intrudes
Hyperactivity & Impulsivity - 6 or more
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Placebo
0.2 mg/kg bid
0.4 mg/kg bid
0.75 mg/kg bid
Effects of Methylphenidate
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MMAT: Fluctuations in Attention
Computerized vigilance tasks using a GO/NO-GO strategy have been used as laboratory tests to provide composite measures of attention. However, attention is not a static parameter, but a dynamic and fluctuant process. Throughout the course of a 15 minute test there can be many shifts in attention and mental state.
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MMAT: Fluctuations in Attention
Better insight into the nature of the attention disturbance in ADHD, and understanding of the effects of drugs on the disorder may arise from the assessment of attention as a dynamic temporal process.
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MMAT: Fluctuations in Attention
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Imaging studies have identified key brain regions implicated in the pathophysiology of ADHD.
Brain Imaging
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These include the striatum (caudate and putamen), prefrontal cortex, and most recently the cerebellar vermis
Brain Imaging
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Brain Imaging
Initial findings of brain-based differences between individuals with ADHD and healthy controls were established using measures of basal blood flow or metabolism.
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T2-RelaxometryIm
age
Inte
nsity
Time (msec)T2 intensity decay curve from single pixel in the putamen
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T2-Relaxometry & Dynamic Susceptibility Contrast MRI
T2-relaxometry provides a non-invasive indirect measure of resting relative cerebral blood volume.
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T2-Relaxometry
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Logistic Regression Analysis: Using Left-Putamen and Right Dorsolateral Prefrontal Cortex Distinguishes 11/11 ADHD from 6/6 controls.
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ADHD - Circuit Diagram
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Complex PTSD
Developmental Trauma Disorder
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Physical, sexual, and psychological trauma in childhood may lead to psychiatric difficulties that show up in childhood, adolescence, or adulthood.
Introduction
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Hypothesis
We have proposed that early childhood maltreatment acts as a severe stressor, that produces a cascade of physiological and neurohumoral responses which leads to enduring alterations in the patterns of brain development, and that alterations in brain function set the stage for the emergence of psychiatric disorders.
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}SexualAbuse
PhysicalAbuse
WitnessDomesticViolence
VerbalAbuse
Common consequencesrelating to the effectsof stress, fear, anxiety,humiliation, etc. on thedeveloping brain
Hypothesis
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}SexualAbuse
PhysicalAbuse
WitnessDomesticViolence
VerbalAbuse
Hypothesis
+
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SexualAbuse
PhysicalAbuse
WitnessDomesticViolence
VerbalAbuse
Hypothesis
Unique effects relatingto sensory systemsactivated, and ways inwhich specific eventsare processed
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Example of Unique Effects Related to Type of Abuse
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Study consisted of 23 females (mean age, 19.1 ± 1.1 years) with repeated episodes of childhood sexual abuse (CSA) but no exposure to other forms of trauma, and to 14 female controls (mean age, 20.1 ± 1.3 years) with complete MRI scans.
Effects of Childhood Sexual Abuse
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Effects of Childhood Sexual Abuse
CSA was associated with 14.1% reduction in gray matter volume of left primary and secondary visual cortex.
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Results confirmed using cortical surface-based segmentation and parcellation analyses (FreeSurfer)
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Verbal Abuse*!#$^&@
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Study consisted of 17 females (18-22 years) with high degree of exposure to parental verbal aggression, but no history of sexual or significant physical abuse. There were 17 female controls of comparable age and SES.
Effects of Childhood Verbal Abuse
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Effects of Childhood Verbal Abuse
Exposure to high levels of parental verbal abuse was associated with 11.3% reduction in GMV of right superior temporal gyrus..
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Effects of Childhood Verbal Abuse
Exposure to high levels of parental verbal abuse was associated with significant thinning of a portion of the right superior temporal gyrus (FreeSurfer).
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Sensitive Periods
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Index Age of Abuse (years)
Effe
ct S
ize (e
ta s
quar
ed)
Hippocampus
** *****
Hippocampal volume reduced 13.2% in subjects who experienced abuse atage 4 (n=7).
**** * * * *
Abused at index age vs cntl
3 5 7 9 11 13 15 17
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Index Age of Abuse (years)
Effe
ct S
ize (e
ta s
quar
ed)
Corpus Callosum - Rostral Body
* *
CC area reduced 22.4% in subjects who experienced abuse at age 10 (n=5).
Abused at index age vs abused at other ages
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Index Age of Abuse (years)
Effe
ct S
ize (e
ta s
quar
ed)
Prefrontal Cortex
* *
Abused at index age vs abused at other ages
PFC GMV reduced 5.8% in subjects who experienced abuse at age 14 (n=4).
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Density Abuse
6-8 years
Densit y Abuse
11-13 years
Density Abuse
9-10 years
Density Abuse
3-5 years
Density Abuse
14-16 years
HippocampalVolume
-0.69(p<10- 7)
-0.25 (p<0.05)
0.41(p<0.005)
0.58(p<0.0001)
0.44(p<0.005)
Area Rostral BodyCorpus Callosum
Frontal CortexGray Matter Vol.
-0.44(p<0.005)
-0.48(p<0.005)
Composite Path Analysis