Childhood Trauma, ADHD, and Autism

Question 1

What is the eco-biodevelopmental model?

Answer 1

Genetics and neurobiology interact with relational experiences and culture to affect the brain, mind, and body and influence behavior and physical, social, and mental well-being. Many different factors predict developmental health trajectory (genetic, prenatal, neurodevelopment, attachment, socioeconomics, etc.)

Question 2

What can traumatic experiences cause in children?

Answer 2

Dysregulation of neurophysiological, psychological, and cognitive functioning which actually change brain structure and can potentially cause brain injury.

Traumatic experiences can cause PTSD, substance dependence, depression, and separation anxiety. It is rarely the result of a single incident.

Question 3

Describe the stress circuit.

Answer 3

The stress circuit is the hypothalamus-pituitary-adrenal axis. The hypothalamus releases CRF which causes the anterior pituitary to release ACTH which signals the adrenals to release cortosol. When the hippocampus detects cortisol, it signals to the hypothalamus to shut down the stress circuit. This circuit can be impaired in anxious rats.

Question 4

How does methylation of the glucocorticoid promoter gene change with stress patterns?

Answer 4

The methyl group decreases the rate of transcription of the gene so fewer glucocorticoid receptors will be present in the hippocampus. This impairs the HPA feedback loop. Increased methylation results in increased stress; decreased methylation results in a more relaxed personality. Methylation is reversible.

Question 5

What epigenetic changes occur at the level of the estrogen receptor? What is the consequence of this?

Answer 5

Changes to the estrogen receptor in the ventromedial nucleus of the hypothalamus alters sexual behaviors, making female offspring of bad rat mother more promiscuous and aggressive (poor environment -> spread genes)

Question 6

How are telomeres affected by neglect?

Answer 6

Those suffering childhood maltreatment had significantly shorter telomeres than those who were not abused (influences cellular aging).

Question 7

What are the cognitive, emotional, physical, and behavioral symptoms of children who have been traumatized?

Answer 7

Cognitive: memory problems, poor concentration, ruminative thinking, poor executive function

Emotional symptoms: anxiety, impulsiveness or aggression, irritability, withdrawal, depression

Physical: aches and pains, bowel problems, nausea, chest pain, increased heart rate, obesity

Behavioral: sleeping more or less, isolating, procrastinating, fighting, sexualized behaviors

Question 8

What are some of the long term outcomes of adverse childhood experiences?

Answer 8

• Alcoholism, alcohol/drug abuse, smoking
• COPD, ischemic heart disease and liver disease
• Unintended pregnancy, fetal death, risky sexual activity, and STD’s
• Intimate partner violence
• Depression and suicide attempts

Question 9

What polymorphisms increase genetic vulnerability?

Answer 9

• Short allele of 5-HTTLRP
• MAO-A polymorphism that codes for low amount of protein

Question 10

What is the neuroanatomical impact of chronic stress and trauma related anxiety or PTSD on the brain?

Answer 10

Children (immature brain): widespread impact on the developing brain

Adults (mature brain): localized impact on the hippocampus and amygdala

Changes include:

• Decreased corpus callosum volume
• Increased hemispheric lateralization
• Decreased rate of myelination
• Decreased medial prefrontal cortex volume
• Decreased total brain volume
• Hippocampus and right temporal gyrus are particularly vulnerable during childhood

Question 11

What are the key variables in how the brain is affected by maltreatment?

Answer 11

Age of maltreatment: the effects of abuse correspond to the region or function developing at that time

Type of abuse: different types of abuse activate different processes that shape the brain

Gender: the effects of sexual abuse are more profound in girls while the effects of neglect are more profound in boys

Question 12

What is resilience? What protective factors exist?

Answer 12

A dynamic process of risk and protective factors that allow people to effectively cope with adversity.

Protective factors: genetics, relationship with a supportive adult, intellectual ability, talen, community involvement

Question 13

What is the impact of early childhood trauma on health outcomes?

Answer 13

More traumatic experiences leads to worse behavioral health, more chronic disease, poorer mental health, and increased disability.

Question 14

What criteria must be met to diagnose with ADHD?

Answer 14

Six or more symptoms of inattention and six or more symptoms of hyperactivity-impulsivity to a degree that is maladaptive and inconsistent with developmental level. Symptoms must be present in at least two settings.

Question 15

Describe the prevalence of ADHD in children and adults.

Answer 15

Prevalence among 8-15 year olds: 8.7%

Prevalence among 18-44 year olds: 4.4%

Only about a third of children and 10% of adults are receiving treatment.

Question 16

Describe the heritability of ADHD.

Answer 16

Mean heritability is about 0.75 and candidate genes include primarily serotonin and dopamine related enzymes or receptors.

Question 17

What factors may cause ADHD?

Answer 17

Heterogeneous neurobehavioral disorder with multiple possible causes: environmental factors, CNS insults, neuroanatomical/neurochemical changes, genetic origins

Question 18

Describe the posterior system of attention.

Answer 18

The posterior system orients to and engages novel stimuli. It is localized in the superior parietal cortex, the superior colliculus, and the pulvinar. It receives norepinephrine innervation from the locus ceruleus which inhibits spontaneous activity of the postsynaptic neurons by increasing the signal to noise ratio of target neurons.

It makes the person alert and oriented

Question 19

Describe the anterior system of attention.

Answer 19

The anterior system is located in the posterior frontal cortex and anterior cingulate gyrus and is modulated by dopamine fibers from the ventral tegmental area. Dopamine suppresses spontaneous activity of target neurons and reduces responsivity to new inputs.

Question 20

Describe the neuropsychological deficits in ADHD.

Answer 20

Impaired executive functions including:

• Vigilance
• Reaction time
• Response inhibition
• Perceptual motor speed
• Verbal learning
• Working memory
• Planning

Question 21

Describe the neuroimaging findings of ADHD brains.

Answer 21

Smaller, less active, less developed brain regions–size of network is correlated with ADHD symptoms

Reduced volume: orbital prefrontal cortex, basal ganglia, cerebellum

Underactivity: anterior cingulate, cortex

Delayed: brain growth and cortical maturation lags by about three years but catches up to normal by age 16

Question 22

What difference in neural pathway activation are evident in the counting stroop task in ADHD subjects?

Answer 22

The anterior cingulate cortex activates in normal controls while the frontostriato-insular-thalamic network (laterally located) activates in ADHD individuals. Anterior cingulate is underactive so the brain has to use more distant structures to do the same job.

Question 23

What is the action of methylphenidate?

Answer 23

Methylphenidate activates the dorsal anterior midcingulate cortex which improves functioning of midline circuits.

Question 24

What difference is seen in the nucleus accumbens in people with ADHD?

Answer 24

Lower density of dopamine transporters

Question 25

What class of neurotransmitters appears to be altered in individuals with ADHD?

Answer 25

The catecholamines (norepinephrine, dopamine) are important modulators of the attentional system as well as cognitive functions in the prefrontal cortex, basal ganglia, and cerebellum. Too much or too little catecholamine release impaires prefrontal cortex functioning.

Question 26

What are the pharmacological treatments available for ADHD?

Answer 26

Primary: stimulants, atomoxetine, alpha-adrenergic agonists all increase neurotransmission in attentional circuits

Secondary: bupropion, modafanil, tricyclic antidepressants

Adjunctive agents: mood stabilizers, anxiolytics, SSRI’s, neuroleptics, combination regimens

Question 27

How do stimulants work? How do they affect ADHD?

Answer 27

Amphetamine releases dopamine from vesicle and blocks reuptake into the vesicle and pre-synaptic terminal and inhibits MAO (degradation pathway). Methylphenidate works by blocking reuptake of dopamine into pre-synaptic terminal.

Medication alone was found to be nearly equally effective to medication management with behavioral treatment and superior to both behavioral treatment alone or community based treatment.

Stimulants improve attention, impulsivity, hyperactivity, compliance, aggression, social interactions, academic efficiency, and academic accuracy.

Decreased activity level, improved motor performance, increased cognitive performance, decreased conduct problems. Few adverse side effects, well tolerated.

Question 28

What are some of the side effects and health risks of stimulants?

Answer 28

Side effects: reduced appetite, GI symptoms, difficulty falling asleep, mild increase in HR and BP, jitteriness, motor tics, dysphoria, moodiness, rebound effects

Health risks: cardiovascular, psychiatric, stimulant intoxication or withdrawal, interactions with other substances

Question 29

What is the prevalence of autism spectum disorder? Autism proper? Is it heritable?

Answer 29

ASD: 1%

Autism: 0.25%

It is heritable but not by simple Mendelian genetics.

Question 30

What are the diagnostic criteria for autism? How homogenous is the disorder?

Answer 30

Onset by 3 years of age with early language and communication impairment, impairments in reciprocal social interaction, and restricted interests, repetitive, and stereotyped behavior.

Autism is very heterogeneous–it is probably hundreds of separate disorders.

Asperger disorder is specifically autism without the communication impairment.

Question 31

What is the problem with the DSM IV subtypes of autism?

Answer 31

They lack external validity–they are not predicted by biology or treatment response.

They are hard to implement in practice

Social and communicative disorder load onto a common factor so they predict each other

Language delays are not unique–communication is impaired not language use

Subgroups are not stable over time and overlap

Question 32

Describe the heritability of autism.

Answer 32

Sibling recurrence risk: 20%

Concordance in monozygotic twins: 65%

Concordance in dizygotic twins 30%

Heritability estimated to be 34%

Multifactorial, clear role for non genetic factors

Question 33

Describe the environmental factors that may contribute to autism.

Answer 33

Prenatal exposures: thalidomide, valproic acid, maternal rubella infection, possibly engine exhaust, PCB’s, misoprostol, brominated flame retardants, organophosphates, and other pesticides

Question 34

Why is it important to identify autism early?

Answer 34

Early prediction may allow for intervention and better outcomes. It also may permit gene therapy and drug development. Brain size diverges from normal in the second year of life which is when symptoms begin to appear. Before that, diffusion tensor imaging shows different axonal wiring at 6 months.

Question 35

What regions of the brain are hypoactive in autism?

Answer 35

Fusiform gyrus: involved in person perception (underside of temporal gyrus)

Superior temporal sulcus: involved in facial expression (lateral side of temporal lobe)

Amygdala: involved in social arousal, attention/salience and is in sync with the fusiform gyrus

Superior frontal gyrus: involved in predicting what other people are thinking which is important in frontal behavior

Ventral striatum: reward/motivation system for social involvement

There is a lack of synchronicity between regions in kids with autism

Question 36

What does the heuristic model of autism focus on?

Answer 36

The heuristic model focuses on an early lack of social motivation and interest which deprives the child of adequate social learning experiences. The drive to engage others is a basic human motivation–autistic children have a preference for repeating geometric lines and objects over social experiences.

Question 37

What circuit is underactive in ASD?

Answer 37

The reward/reinforcement circuit is underactive. Normally there is activation of the ventral striatum and nucleus accumbens when anticipating “social approval or smiling face.” Receiving social approval stimulates the orbital frontal cortex and anterior cingulate gyrus. The lack of desire/anticipation for social approval causes them to not seek it out.