Drugs and the Developing Brain – Study Notes (Markdown)

CADS Pregnancy and Parental Service (PPS) – Overview

• Assertive MDT outreach service for pregnant clients or parents of children < $3$ years who:
  • Experience issues related to alcohol and/or drug use
  • Are disconnected from health and/or social services
• Service goals:
  • Provide evidence-based education and interventions
  • Co-ordinate/support engagement with other services
  • Reduce potential harm to unborn children or infants

Why is parental substance use important?

• Parental substance use can cause harm to children at any age:
  • Direct harm from exposure to substances in utero and/or during breast-feeding
  • Indirect harm via effects on parenting, home environment, and related risks
• Harm can persist across the lifespan and may be intergenerational
• The first $1000$ days of a child’s life lay the foundations for their future
  • Key point: early development is critical for long-term outcomes

Blame it on your mother.

• Slogan/reference from the slide highlighting prenatal origins of risk

Lecture Outline (from slides)

• Why parental substance use is important
• Prevalence of prenatal substance use
• Aetiological/risk factors for substance use
• Impact on fetal/brain development (including alcohol-focused effects)
• Effects of parental substance use on children’s physical, emotional, and social well-being
• Impact of alcohol and other drugs on adolescent development

Substance Use in Women – Key factors

• Gender gap is narrowing in some contexts
• Telescoping: shorter interval from first use to problem use to dependence
• Increased vulnerability to adverse effects, craving, and relapse
• Association with disadvantage and trauma (e.g., IPV, sex work)
• Co-morbid mental health difficulties
• Unique physical health risks
• Greater barriers to effective care

Prevalence of Substance Use: Pregnancy

• Alcohol use:
  • NZ Health Survey (NZHS) 2012/2013: $19$% when pregnant
  • NZHS 2022/2023: $73$% of women reported alcohol use in the past year
  • Growing recognition of alcohol exposure around pregnancy
• Tobacco use (smoking):
  • GuINZ (Growing Up in NZ) 2009/2010: $20$% pre-pregnancy/pregnancy awareness; $9.9$% during pregnancy
  • Maternal rates at 2 weeks postnatal: from $13.7$% in 2009 to $9.4$% in 2018
• Illicit substance use (Australia, 2019):
  • Cannabis: $5.4$%
  • Other illicit drugs: $1.8$%

Impact of Prenatal Substance Use – Mechanisms of Effect (Overview)

• Direct exposure via the placenta (teratogens: chemicals or factors that disturb growth/development when exposure occurs during pregnancy)
• Indirect pathways including effects on uterus/placenta and maternal physiology
• Altered maternal health behaviours linked to substance use
• Altered maternal stress response and neuroendocrine changes (e.g., cortisol) can affect fetal development

Teratogens and Timing

• Periods of dividing zygote, implantation, embryonic period (weeks), fetal period (weeks to full term)
• Common sites of teratogenic action include: brain/CNS, eyes, heart, teeth, ears, palate, external genitals, upper/lower limbs
• Timing and dose of exposure are critical for outcomes
• Example: different organs show susceptibility at different windows

Teratogens: Thalidomide (as an example of teratogenicity)

• Historical example illustrating organ-specific vulnerability depending on timing
• Highlights importance of exposure windows for limb development and other organ systems

Mechanisms of Effect on the Developing Fetus (Summary)

1) Direct exposure via placenta
2) Impact on uterus and/or placenta
3) Altered maternal physiology
4) Altered maternal health behaviours

• Toxin exposure leads to detrimental effects on biological systems

Altered Maternal Physiology: Maternal Stress

• Maternal stress can affect multiple biological systems:
  • Neuroendocrine: increased cortisol
  • Vascular and immune systems
• Consequences for offspring:
  • Increased sensitivity to adverse experiences
  • Risk of emotional/behavioral/cognitive problems (e.g., anxiety, ADHD, language delay)
  • Long-term mental health issues and cardiovascular disease risk

Impact of Prenatal Substance Use – Summary of Mechanisms

• Mechanisms of effect on developing fetus:
  1. Direct exposure via placenta
  2. Impact on uterus and/or placenta
  3. Altered maternal physiology
  4. Altered maternal health behaviours
• Toxin effects on biological systems

Prenatal Substance Use and Fetal Brain Development – Brain Changes

• Brain Structure: reduced brain volume, especially frontal lobe
• Altered growth patterns: lateral temporal and parietal cortices
• Neurobiology: impaired neuronal growth, differentiation, dendritic complexity, synaptic density, neurotransmitter signaling
• Brain Function: deficits in executive function, attention, memory, language, self-regulation

Prenatal Alcohol Use – Key Points

• Direct toxin and teratogen
• Developing brain is affected across pregnancy (eternal exposure window)
• Associated risks: miscarriage, prematurity, IUGR/LBW, congenital heart disease (possible), FASD, SUDI

Fetal Alcohol Spectrum Disorder (FASD) – Overview

• Definition: severe neurodevelopmental impairments in brain and body due to alcohol exposure in pregnancy
• Effects are variable across individuals
• Key factors: timing, pattern, amount of exposure
• Critical period: first $8$ weeks are especially important for organ development (eyes, heart, ears, CNS)
• Life-long effects but vary across the lifespan
• Leading preventable cause of non-genetic intellectual disability
• Often an “invisible disability” that is undetected or misdiagnosed

FASD – Features and Diagnosis

• Classic triad:
  1) Growth deficiency
  2) Facial features (present in < $10$% of cases)
  3) Pervasive neurodevelopmental impairment
• IQ range varies; NZ Criteria includes $9$ domains:
  • General intellectual abilities
  • Attention
  • Communication
  • Executive functioning
  • Motor
  • Emotional/behavioural regulation
  • Literacy/Numeracy skills
  • Adaptive/social functioning
  • Memory

Normal vs FAS Brain (Illustrative)

• Visual comparison shows typical brain development vs brain affected by FASD (image reference)

FASD: Secondary Disabilities

• School disruption: $61$%
• Physical/sexual abuse/ Family violence: $60$%
• Conf confinement: $50$%
• Involvement with Criminal Justice System: $60$%
• Dependent living: $80$%
• Mental health impairment: $94$%
• Substance use disorder (SUD): $35$%

Prenatal Tobacco Use – Key Facts

• Tobacco contains $4000$ compounds
• Nicotine crosses the placenta → direct/indirect effects on neural development
• Tar fetotoxic and teratogenic in animal studies
• CO causes intrauterine hypoxia
• Risks include miscarriage/stillbirth, placental abruption/placenta previa, LBW, SUDI; potential associations with congenital abnormalities, asthma, ADHD, addiction

Prenatal Illicit Substance Use – Highlights

• Cannabis:
  • No clear, consistent link to adverse pregnancy outcomes or congenital malformations
  • Risk factors include poorer prenatal growth and potential developmental problems (memory/verbal performance/hyperactivity)
• Methamphetamine:
  • Vasoconstriction and neurotoxic effects; no definitive congenital abnormalities
  • Associated with pregnancy complications; later effects include delayed motor skills, increased anxiety/depressive symptoms and ADHD symptoms up to age 5
• Opioids:
  • Mixed data on teratogenicity (e.g., club foot, heart defects, neural tube defects, cleft palate)
  • Neonatal dependence risk: Neonatal Abstinence Syndrome (NAS)
  • Maternal risks: overdose/death, LBW/IUGR, hemorrhage, BBV, SUDI
  • Long-term concerns: possible visual-motor impairments, reduced IQ
• Benzodiazepines:
  • Teratogenic potential (e.g., cleft palate)
  • Possible associations with miscarriage, pre-term birth, LBW, C-section/ventilation, Floppy Infant Syndrome, NAS

Impact of Postnatal Substance Use – Brain Development

• Postnatal exposure impacts brain development from birth through early childhood
• Observed progression in risk markers across ages (illustrative data):
  • At birth: $25$%
  • 0-1 year: $70$%
  • 1-3 years: $85$%
  • 0-5 years: $92$%
  • 3-5 years: (not specified here)
• Emphasizes cumulative impact of early postnatal environment on neurodevelopment

Altered Gestational Biology and Postnatal Environment

• Prenatal factors influence postnatal biology (e.g., HPA-axis and immune pathways)
• Consequences include low birth weight and preterm birth
• Early emotional states (depression, anxiety, distress) can affect infant brain development
• Infant outcomes are shaped by linguistic, cognitive, and social stimulation, as well as caregiving quality
• Socioeconomic status and postnatal caregiving quality mediate late-child outcomes

Impact of Postnatal Substance Use – Practical Effects on the Family

• Attachment and caregiving quality affected by parental substance use
• Roles within the family and presence/attentiveness of caregiver
• Modelling of behaviours and potential “parentified” children
• Family breakdown and parent-child separation
• Disrupted routines and rituals; preoccupation with substances can dominate family life

Substance Use and Adolescent Development – Key Concepts

• Adolescence as a second major brain development period
• Significant nerve pruning and myelination; frontal lobe maturation continues into late adolescence (roughly $21-25$ years)
• Brain as a “learning machine”; immature frontal lobe + psychosocial context can increase risk-taking and AOD use during this sensitive period
• Substance use compounds executive function deficits and complicates navigation of developmental tasks

Alcohol Use and the Adolescent Brain

• Alcohol interferes with storing new information as memories
• Brain development is protracted; full maturation occurs around $23-25$ years
• Alcohol disrupts brain wiring by slowing down brain activity and development
• Most individuals who become alcohol-dependent began drinking before age $18$
• Hippocampus (learning and memory center) can be about $10 hpercent$ smaller in underage drinkers

Cannabis Use and the Adolescent Brain

• Cannabinoid receptors are abundant in the brain and regulate higher-order functions, pain, appetite, sleep
• THC exposure disrupts the balance of the brain’s endocannabinoid system
• Associated with deficits in executive function, attention, episodic memory
• Increased risk of dependence and other substances, poorer educational outcomes, and poorer mental health (psychosis, anxiety)
• Physical health can also be affected

Cannabis Use and Psychosis – Harm Reduction

• Large-scale longitudinal studies show adolescents who use cannabis are $2-4$x more likely to develop psychosis
• Greatest risk with early onset, more frequent/high-potency use, plus genetic or environmental vulnerabilities
• Harm reduction message: Delay first use

Case Vignette – Example (NZ Māori wahine in pregnancy)

• Pregnant in the mid- to late-30s range with three children at home
• Pregnant at 36/40 weeks, separated from partner, IPV history, legal and financial challenges, no transport, temporary accommodation
• Sporadic engagement with AOD services around alcohol/MA; prior psychiatric admission for drug-induced psychosis; trauma history
• Previous involvement with MCOT; minimal antenatal care
• Referred to PPS by LMC for relapse to alcohol during pregnancy; concerns around mental well-being
• Current Alcohol use: AX drinking 4-8 standard drinks (SD) per occasion (RTD) 2-3 times per week; goal to cease

Vignette – Adolescent Cannabis and Distress (NZ context)

• 15-year-old NZ Pākehā boy living at home, attending secondary school
• Presenting with being “stoned in class,” underperforming academically (possible ADHD), truancy
• Referred to AHYS by SGC; cannabis use increasing (tinny/day) and alcohol at parties
• Referred for psychiatric review due to increased persecutory concerns and perceptual abnormalities in a party-related incident
• Cannabis used as a means of managing distress

Weighted Harm Contributions (Substance harm profile)

• Harm contributions by substance (illustrative scale ranging from low to high): alcohol, methamphetamine, synthetic cannabinoids, solvents & fuels, non-prescription opioids, cannabis, opioid sub-products, prescription opioids, fentanyls, tobacco products, heroin-type substances, benzodiazepines, cocaine, GHB/GBL, synthetic cathinones, ENDS/vapes, ketamine, inhalants, kava, etc.
• Interpretation: multiple substances contribute to overall harm with varying weights; emphasis on alcohol and stimulants as common contributors

Summary of Key Takeaways

• The developing brain is highly vulnerable to the effects of both parental and personal substance use
• The first $1000$ days and adolescence are critical windows for intervention
• Mechanisms of impact are both direct (teratogenic/toxic effects) and indirect (environmental/parenting factors)
• Alcohol is a known teratogen; no amount or timing is deemed completely safe in pregnancy
• Adolescent cannabis use is associated with a range of adverse outcomes, including increased risk of psychosis

Resources for Further Learning (Videos)

• Brief overview of addiction: https://www.youtube.com/watch?v=VI4KZWtROt0
• Neurobiology of addiction: https://www.youtube.com/watch?v=7VUlKP4LDyQ
• Cannabis effects: https://www.youtube.com/watch?v=FvszaF4vcNY
• Alcohol in adolescence: https://www.youtube.com/watch?v=g2gVzVIBc_g
• Cannabis in adolescence: https://www.youtube.com/watch?v=FvszaF4vcNY

Learning Objectives

• Define teratogens and explain how prenatal exposure to different drugs and alcohol can affect fetal development in general, and brain development specifically
• Describe the effects of parental substance use on children, including physical, emotional, and social consequences
• Discuss the impact of alcohol and other drugs on adolescent development