Individual Differences 2023 - Developmental and Behavioural Teratology

Teratology: Definition and Etymology

Teratology is defined as the science of congenital developmental disorders, including overt or latent defects resulting from internal and external factors affecting developmental processes (Ujházy et al, 2012). The word originates from:

• Terat: sign sent by the gods, portent, marvel, monster.
• Ology: doctrine, theory, science of (Mirriam-Webster).

Psychology and Teratology

This lecture focuses on the impact of prenatal exposures on fetal and child development, leading to individual differences in cognitive, social, behavioral, and emotional functioning.

Nature vs. Nurture

The question of whether our characteristics are primarily determined by genetics (nature) or environment (nurture) is addressed. The answer acknowledges the contribution of both, while also considering that:

• Environment is to some extent hereditary, as we inherit our parents' environment.
• Biological inheritance includes epigenetic changes reflecting parental experiences.
• Prenatal experiences are a significant factor.

Epigenetic Changes

Epigenetics involves molecules and processes that control gene activation without altering the DNA sequence itself.

• Changes to the epigenome can affect gene activation, and these changes can be inherited.
• The Överkalix study (2002) demonstrated that grandparents' diet influenced grandchildren's physical health (e.g., cardiovascular disease and diabetes).
• Teratogens can affect developmental outcomes through epigenetic changes

Timing of Exposures and Vulnerability

The timing of exposure during prenatal development is critical in determining the type and severity of birth defects. A diagram illustrates the vulnerability of different organs at different stages of development (Period of the Ovum (1-2 weeks), Period of the Embryo (3-8 weeks), Period of the Fetus (12-38 weeks)).

• The central nervous system (CNS) is vulnerable throughout much of the pregnancy.
• The heart is most vulnerable during weeks 3-6.
• Arms and legs are most susceptible to damage during weeks 4-7.
• Alcohol is highlighted as a leading cause of fetal death.

Signal to Noise Ratio

• High signal to noise ratio means it is easier to detect the signal
• Low signal to noise ratio means it is harder to detect the signal

Bradford Hill Criteria for Causality

These criteria are used to assess the plausibility of a causal relationship between a factor and an outcome:

1. Temporality: Cause precedes the outcome.
2. Strength: Strong relationship between variables.
3. Biological gradient: Dose-response effect (more exposure, more outcome).
4. Consistency: Relationship is consistent across studies and populations.
5. Specificity: Single cause for a single effect.
6. Plausibility: Biological rationale for the relationship.
7. Coherence: Consistent with existing knowledge.
8. Analogy: Similar to other known relationships.
9. Experiment/intervention: Randomly assigned treatment alters the outcome.

Known Teratogens

Examples of known teratogens are categorized:

• Medications: Anticonvulsants, Thalidomide, SSRIs, Statins
• Drugs: Alcohol, Tobacco, Cocaine, Amphetamines/meth/MDMA, Opiates (e.g., Heroin)
• Conditions and infections: Hypotension, Toxoplasmosis, Rubella, Diabetes, Stress
• Environmental exposures: Heavy metals, Radiation, Pesticides, Fluoride, Industrial chemicals

The Placenta

The placenta serves as a barrier between the mother and fetus, facilitating the exchange of oxygen, nutrients, and waste products.

• While it blocks some harmful substances, smaller and lipid-soluble molecules can pass through, including certain teratogens.

Toxoplasmosis

Toxoplasmosis is a bacterial infection transmitted through cats and other animals.

• Infected mice lose their fear of cats.
• During pregnancy, toxoplasmosis can cause hydrocephalus, microcephaly, intracranial calcifications, blindness, epilepsy, psychomotor difficulties, learning disabilities, and anemia in infants.

Medications with Teratogenic Effects

A list of medications with known teratogenic effects or contraindications during pregnancy is provided. (van Gelder et al, 2014)

Thalidomide

Thalidomide was initially developed as an anti-nausea drug in the 1950s and was used to treat morning sickness.

• It was later found to cause severe birth defects, leading to damage to limbs, internal organs, and the brain.

Accutane (Isotretinoin)

Prenatal exposure to isotretinoin can result in severe birth defects, including learning disabilities (IQ<70), attention deficits, motor skill impairments, and executive function difficulties.
Health authorities recommend two forms of contraception and regular pregnancy tests for women taking isotretinoin.

Prenatal Exposure to Medications

• Studies on antidepressants show mostly null results regarding neurodevelopmental impacts, but some evidence suggests impaired motor function (Gentile & Galbally, 2011).
• A review of psychotropic medications found antidepressants linked to reduced IQ and impaired language performance, but cautioned that research is limited (Gentile, 2021).
• There is a weak possible link between prenatal paracetamol exposure and neurodevelopmental outcomes, and the NHS advises that paracetamol is safe to use in pregnancy.

Sodium Valproate

Sodium valproate is an anticonvulsant medication used for epilepsy, bipolar disorder, and migraines.

• It is contraindicated in pregnancy due to the risk of Foetal Valproate Spectrum Disorder (FVSD), which includes physical birth defects and developmental problems.
• The risk of FVSD is dose-dependent.

Foetal Valproate Spectrum Disorder (FVSD)

FVSD is characterized by:

• Facial features: Hypotelorism, flat midface, small upturned nose, shallow philtrum, low set ears, small mouth.
• Developmental features: Cognitive delay / low IQ, academic delay, sensory processing difficulties, motor control / movement difficulties, language and communication difficulties; autism is common.

Stress in Pregnancy

All pregnancies involve some degree of stress. Unusually high levels of stress can impact the fetus.
When experiencing stress:

• Stress hormones (adrenaline, cortisol, CRH, ACTH) are released into the bloodstream.
• These hormones can cross the placenta and enter the fetal bloodstream.

Impact of Maternal Prenatal Stress

Maternal stress during pregnancy is associated with increased risk of:

• Spontaneous abortion.
• Structural malformations.
• Preeclampsia.
• Preterm birth.
• Low birth weight.

Animal Models of Prenatal Stress

Animal studies (rats and monkeys) show that prenatal stressors can lead to:

• Delayed motor development.
• Reduced exploration and adaptive behavior.
• Increased emotional and anxious reactions to unfamiliar stimuli.
• Impaired cognitive function.
• Alterations in social and sexual behavior (Mulder et al, 2002; Beydoun & Saftlas, 2008).

Human Studies of Prenatal Stress

Human studies correlate prenatal stress with:

• Externalizing behavioral problems
• Anxiety
• Low mood / emotional problems
• ADHD symptoms (Beydoun & Saftlas, 2008; Talge et al, 2007)
• Motor difficulties
• Low IQ
• Speech and language difficulties
• Impulsivity

Heavy Metals

Heavy metals are elements with an atomic number greater than 20 and a density above 5 g/cm3.

• Studies focus on lead, mercury, cadmium, chromium, arsenic, zinc, selenium, manganese, and copper.
• Exposure sources include food, air, pesticides, tobacco smoke, and lead-based paint.

Prenatal Exposure to Heavy Metals

Heavy metals can cross the blood-brain barrier and:

• Interact with neurotransmitters, receptors, ion pumps, enzymes, and amino acids.
• Alter brain development.

Specific Heavy Metals and Neurodevelopment

• Arsenic, cadmium, lead, manganese, and mercury are all associated with neurodevelopmental changes.
• Lead exposure is linked to poor academic achievement, low IQ, externalizing behavioral problems, and difficulties with memory, motor skills, language, and visual-spatial ability (Heng et al, 2022).

Other Environmental Teratogens

• Organophosphate pesticides may be linked to Autism and ADHD.
• Zika virus infection in pregnancy is linked to microcephaly.
• Ionising radiation is linked to an increase in schizophrenia.

Cocaine

It is difficult to isolate the impact of just cocaine because Cocaine is typically used alongside other substances, hence the low signal-to-noise ratio.

• Prenatal cocaine exposure (PCE) affects visual memory, information processing, executive functions, arousal, and inhibitory control.
• PCE can lead to a heightened stress response, frustration, and disruptive behavior in school, especially in boys.

Internalising and Externalising Behaviours

• Internalising:
  • Withdrawal
  • Avoidance
  • Somatic complaints
  • Anxiety
  • Depression
• Externalising:
  • Temper outbursts
  • Aggression
  • Oppositionality
  • Defiance

Cannabis

Cannabis is typically used alongside tobacco, so it is difficult to isolate the impact of just cannabis and Many studies have investigated them together, effectively treating them as one exposure.

• Prenatal cannabis exposure impacts visual-spatial and motor functioning, early language development, impulsivity, hyperactivity, aggression and attention problems.

Opiates

Studies into prenatal opiate exposure are difficult and tend to be of low quality with a high risk of bias (small sample sizes, little control of confounding variables, cross sectional design).
Neurobehavioural studies have shown differences in general cognition, language and motor functioning but the risk of bias is high – overall findings in humans are inconclusive.

• Brain studies, including animal models, do show an effect on basal ganglia, thalamus, and cerebellar white matter – which are linked to deficits in motor control and sensory function.

Tobacco

• Prenatal tobacco exposure leads to difficulties with emotional and cognitive functioning, especially in executive functioning.
• Children show reduced volume in the frontal lobe, lateral ventricular system, and cerebellum.
• They are more likely to suffer from low mood and heightened stress response, especially in boys.
• Older children and teens have higher rates of antisocial behaviour, conduct disorder, and addictions.

Caffeine

• Caffeine has been identified as a potential cause of developmental problems when consumed in pregnancy, however, the findings in human epidemiological studies are inconsistent because of lots of confounding variables and low signal to noise ratio.
• Experiments using animals do show birth defects but not the same ones reported in human studies and only at very high doses

Alcohol

Alcohol is one of the more well-understood teratogens:

• Leads to fetal alcohol spectrum disorder (FASD)

PAE – mechanisms of damage

• Alcohol passes though placenta into amniotic fluid
• Fetus does not metabolise alcohol
• Alcohol can kill cells via a number of mechanisms
• Can disrupt or reduce cell division and migration
• Can disrupt foetal sleep cycle
• Can alter functioning of neurotransmitter systems, especially glutamate and serotonin
• Can disrupt gene expression and these changes can be inherited – transgenerational epigenetics

Genetic differences in PAE impact

• Hemmingway et al (2018) compared FASD diagnoses in monozygotic twins (who share 100% DNA), dizygotic twins (50% DNA), full siblings (50% DNA), and half-siblings (25% DNA)
• Twins obviously will have the exact same exposure to PAE, and the other siblings had similar exposures
• Despite the same or very similar PAE, shared DNA made the biggest difference to FASD diagnosis, birth defects and neurodevelopmental outcomes
  • 100% DNA (twins) à 0% discordance
  • 50% DNA (siblings) à 59% discordance
  • 50% DNA (twins) à 44% discordance
  • 25% DNA (half siblings) à 78% discordance

Presentation of FASD

Physical and neurodevelopmental signs of FASD include:

• Low birthweight
• Small head/brain – microcephaly
• Small stature
• Craniofacial anomalies including 3-4 facial features
• Problems with organs, joints
• Compromised immune system
• Poor academic achievement
• Sensory dysfunction
• Problems with emotional regulation / arousal
• Executive dysfunction (planning, attention)
• Hyperactivity, impulsivity
• Difficulty with mathematics and other abstract reasoning
• Difficulty with daily living, adaptive functioning
• Problems with social communication

Estimated prevalence of FASD

• Problem with quality of evidence in UK
• Best data from analysis of longitudinal cohort – McQuire et al (2018)
• Estimates prevalence of FASD somewhere between 6% and 17%
• Active case ascertainment (ACA) – gold standard
• Study by University of Salford found about 2-4%
  • Small scale – Greater Manchester only
• ACA in other countries:
  • USA 3-4%
  • Croatia 4-6%
  • South Africa 6-20%
  • Italy 2-4%
  • Norway 3%
  • Canada 3%

Developmental-Transactional Model

• Prenatal Substance Exposure, Prenatal nutrition, stress, illness, infection
• Maternal prenatal brain and endocrine responses
• Fetal Development: Fetal stress (reduced blood flow: oxygen and nutrients)
• Brain structure and function
• Peripheral autonomic pathways
• Neonatal Period: Birth weight, gestational age, head circumference
• Ability to maintain homeostasis
• Soothability/arousal
• Physical changes (e.g., facial dysmorphia, cleft lip/palate)
• Infancy: Reactivity/regulation (adrenocortical, autonomic, behavior)
• Cognitive difficulties
• Childhood: Self-regulation and social competence
• School readiness and academic competence
• Behavioral and cognitive difficulties
• Adolescence: Behavioral difficulties
• Risk behaviors including substance use (onset, frequency, problems, disorder)
• Brain structure and function
• Genetic Variations and Epigenetic Modifications
• Parenting And Caregiving Environment
• Context: Strengths and Risks