Neurodevelopmental Impact of Prenatal Methamphetamine Exposure Michael Brinker, Psyd Northwest Neurobehavioral Health

Topics What is methamphetamine How does meth use impact functioning? How does PME impact neurodevelopment? NNH research on the impact of PME on cognitive, memory, adaptive, and emotional skills Intervention considerations

Methamphetamine CNS stimulant which serves as a aphrodisiac & euphoriant Low doses can elevate mood, increase alertness, concentration, and energy, reduce appetite and promote intial weight loss High does can produce psychosis, rhabdomyolysis, & cerebral hemorrhage Highly addictive and is associated with dangerous sexual behaviors

Meth use history Created in Germany in 1887 Made more potent in Japan in 1919 Wide use in WWII to help keep troops awake Kamikaze pilots were given high doses 1950’s prescribed as diet aid and to address depression 1960’s developed injectable form 1990’s Mexican cartel’s began mass producing

Chemicals used in meth

PME Research Neuroimaging Mouse models CT & MRI for structural impact Functional neuroimaging (fMRI, DTI) to assess functional changes Mouse models Generalizability??? Assessing abusers of methamphetamine Cross-sectional models Longitudinal models in the future

Difficulty of PME research Meth is an uncontrolled substance Often polysubstance exposure Exposure history often based off parent- report Do not necessarily have information on timing of abuse Often exposed to environmental neglect

Physical impact of Meth exposure Reduces resistance to illness & damages liver Weight loss Kidney damage Difficulty regulating body temperature Meth mouth

Cerebral impact of Meth exposure Floods synapses with dopamine, produces initial euphoric rush Overwhelms and drowns out Dopa receptors Requires more dopamine to produce equivalent levels of pleasure Meth abuse impacts brain structures Reduction of gray matter in the PFC Differences in white matter hypertrophy Some suggestion brain structures can sustain some recover after abuse

Prenatal Meth Exposure Meth crosses the placenta What mother experiences the child experiences PME can produce fetal difficulties Placenta abruption Intrauterine growth restriction Abnormal brain metabolism Pre-term birth

Gestational development Prenatal development varies in rate Exposure at different times may have variable impacts

Structural impact of PME Reduced subcortical volumes Limbic system vulnerable

Structural impact of PME Reductions in cortical volume Damage to fronto-striatal network Abnormalities in the frontal white matter

Functional impact of PME Fronto-striatal networks play significant role in executive skills Selection & perception of important information Working memory Organization & planning Behavioral control & decision-making Adapting to changes Frontal lobes are heavily myelinated

Functional impact of PME Visual-motor integration Sustained attention Memory recall Hyperactivity Inhibitory control Working memory Planning and organization

Developmental impact of PME Functional skills do not “come online” until underlying brain area develops Brain areas do not all develop at uniform rate May not see immediate deficits Especially notable in frontal lobes skills

Prefrontal Cortex Development PFC plays significant role in social interactions Social inhibition, social awareness, planning, organization, self-awareness PFC undergoes rapid growth and development during adolescence

Functional change of adolescence Limbic system regulates emotional processing and reward processing In childhood limbic system over-rules inhibition Decrease in medial PFC growth in adolescence Increases efficiency of PFC’s ability to regulate limbic system

Presenting kids all have struggles Parent-report of PME NNH research on PME Clinical database Presenting kids all have struggles Parent-report of PME Often abuse and neglect are present Mostly preliminary results at this time

Areas of focus NNH database Cognitive skills Adaptive skills Specific WISC indices impacted Adaptive skills Learning and memory Emotional regulation

Common presenting concerns Most common presenting problems of PME (n=103) 87% attention span 81% disobedience 67% aggression 67% anxiety 62% lying and stealing 61% irritability 59% hyperactivity 57% tantrums

IQ performance Mean FSIQ ADHD: 98.16 PME: 87.60

Regression analysis of IQ & age IQ performance Regression analysis of IQ & age Significant at .05 Suggested loss of .86 IQ points per year VCI: ADHD (97) – PME (89) PRI: ADHD (101) – PME (95) WMI: ADHD (94) – PME (86) PSI: ADHD (91) – PME (87)

Regression for VCI, PRI, & WMI non- significant IQ index regression Regression for VCI, PRI, & WMI non- significant Regression significant for PSI @ .01 Loss of approximately 1.8 points per year

IQ results summary PME found to have significantly lower IQ Results consistent when controlling for alcohol exposure Regression significant for FSIQ & PSI All scores were lower, but FISQ & PSI showed relational link with age

Memory Results Significant lower performances (WRAML2) Verbal Memory Composite (.002) ADHD: 95.24 PME: 89 Contextual Verbal Learning (WRAML2 – story memory) Initial encoding (.000), Free Recall (.000), Recognition Recall (.000)

Unstructured Verbal Learning (WRAML2 – verbal memory) Initial encoding (.004) Free recall & Recognition recall were non-significant Visual Encoding (WRAML2 – Design memory & Picture completion) Encoding unstructured information significant (.01) Encoding structured information was non significant

Emotional Regulation Results Increased levels of: Externalized problems (.004) Hyperactivity, Aggression, Conduct Problems Behavioral problems (.005) Atypicality, Withdrawal, Attention Problems Adaptive Skills (.029) Adaptability, Leadership, Functional Communication, Social Skills, Acts of Daily Living

Adaptive Skill Results Increased Levels of: Conceptual Composite (.004) Practical Composite (.037)

Significant differences in IQ Summary of NNH Results Significant differences in IQ Discrepancy increases over time, especially for processing speed Trouble with verbal memory & executive mediated memory skills Initial encoding Free recall Learning unstructured information

Summary of NNH Results Increased levels of externalized problems, & behavioral problems Hyperactivity, attention problems, aggression conduct problems, atypicality, withdrawal Deficits in adaptive skills Conceptual adaptive skills Practical adaptive skills

Summary of NNH Results Present with symptoms consistent with ADHD More functional deficits than ADHD Cognitive impact increases as children age Likely better conceptualized as FAE/FAS and not ADHD

Intervention considerations No PME handbook Adapting current intervention strategies to developmental model Consider age and brain development

Implementing pre-emptive executive and emotional interventions Need patience Organic impact, learning and adaptation can be challenging Deficits similar to ADHD, but likely more persistent & severe