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AN4017 > L4 DOHAD > Flashcards

L4 DOHAD Flashcards

1
Q

What is a teratogen?

A

Any agent that causes an abnormality following fetal exposure during pregnancy

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2
Q

Most sensitive period for teratogen-induced limb malformations

A

4th and 5th developmental week

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3
Q

What is fetal/prenatal programming?

A

A concept that suggests certain events (exposures) occurring during critical points of pregnancy may cause permanent effects on the fetus and the infant long after birth

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4
Q

Some of the most commonly studied exposures during pregnancy

A
  • maternal hormonal changes e.g. stress
  • maternal inflammation e.g. PE
  • alterations in nutritional status
  • exposure to toxins e.g. Thalidomide
  • infection e.g. Zika virus
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5
Q

Risk factors for schizophrenia

A
  • genetics (e.g. if a monozygotic twin develops schizophrenia, the other twin has a 50% chance of developing it too)
  • children born during late winter/early spring: seasonality effect (higher risk of infections like RSV, depression, stress, nutrition status)
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6
Q

Example of a cytokine that affects axonal growth

A

IL-1β

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7
Q

What is psychoneuroimmunology?

A

Branch of neuroscience involved with interactions between environmental stimuli, nervous system & immune system

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8
Q

One line of research in neuroimmune interactions during nervous system development has focused on the impact of prenatal maternal infection on the development of childhood and adult neuropsychiatric disorders, particularly…

A

schizophrenia and ASD

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9
Q

2 extensively used models of maternal immune activation

A
  1. Maternal exposure to LPS (mimics G- bacterial infection)
  2. Maternal exposure to poly I:C (mimics acute-phase inflammatory response to viral infection)
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10
Q

What is the name of the first comprehensive study that investigated the interaction between genetic and environmental factors that influence ASD development?

A

The CHARGE Study (enrolled >500 children)

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11
Q

Dutch Famine Birth Cohort Study findings

A
  • famine exposure associated with glucose intolerance in the children
  • increased risk of CHD & obesity
  • increased risk of brain disorders
  • prenatal undernutrition permanently affected brain size
  • prenatal undernutrition associated with premature brain aging during late adulthood
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12
Q

How is prenatal maternal stress measured?

A
  • Objective stress (amount of hardship faced e.g. no. of days exposed to stressor)
  • Subjective stress (personal reaction to stressor)
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13
Q

Which is easier to study: objective or subjective stress?

A

Objective, as it is more defined and can be quantified (objective measurements)

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14
Q

Prenatal maternal stress is associated with an increased risk of which brain disorders?

A

ASD and ADHD, but significant heterogeneity

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15
Q

How does the placenta protect the fetus from excessive cortisol exposure?

A

Blood is carried to the chorionic villi (composed of syncytiotrophoblast & cytotrophoblast) of placenta. HSD11β2, highly expressed in syncytiotrophoblast, converts maternal cortisol to inactive cortisone.

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16
Q

Cortisol stimulates fetal…

A

lung maturation and placental CRH

17
Q

How is psychological stress measured?

A

using the 10-item Perceived Stress Scale (PSS)

18
Q

How is maternal anxiety measured?

A

using the 6-item version of the State Trait Anxiety Inventory (STAI)

19
Q

How are depressive symptoms assessed?

A

using the Edinburgh Postnatal Depression Scale (EPDS)

20
Q

What effect did high levels of maternal stress have on placental HSD11β2 levels?

A

They had significantly lower levels of HSD11β2, thereby increasing cortisol exposure to the fetus

21
Q

How does the placenta synthesise serotonin?

A

from maternally-derived tryptophan during pregnancy

22
Q

How do alterations in 5-HT expression during development affect the brain?

A

patterns of brain wiring are affected, which could subsequently lead to impairment of neurodevelopmental processes

23
Q

What is considered one of the most common gestational complications, affecting 3-10% of pregnancies?

A

Hypertensive disorders of pregnancy (HDP) - association between HDP exposure and neurodevelopmental disorders

24
Q

Why doesn’t everyone who is exposed to prenatal perturbations develop a brain disorder?

A

Genetics

25
Q

What is at the interface of the interaction between genes and the environment?

A

The epigenome

26
Q

What is the name given to spontaneous base pair differences between individuals?

A

Single nucleotide polymorphisms (SNPs)

27
Q

SNPs in coding regions cause…

A

missense mutations or silent mutations

28
Q

How many SNPs does the average gene have?

A

4

29
Q

A single base change in which gene is associated with a higher risk for Alzheimer’s?

A

APOE

30
Q

What is 5-HTTLPR (serotonin transporter-linked polymorphic region)

A

A repeat polymorphism in the SLC6A4 gene that encodes the 5-HT transporter. This polymorphism occurs in the promoter region, thereby affecting gene function.

31
Q

Individuals with the 5-HTTLPR long allele express…

A

high levels of the 5-HT transporter

32
Q

How does the 5-HTTLPR genotype affect the amygdala?

A

by affecting its reactivity to environmental threat

33
Q

The 5-HTTLPR short allele is associated with…

A

lower 5-HT transporter expression & function, as well as neuropsychiatric disorders such as anxiety in healthy individuals

34
Q

How does 5-HTTLPR allelic variation affect ACTH levels?

A

Animals with short alleles had higher ACTH levels when exposed to stress, compared to animals with only long alleles.

35
Q

How is 5-HTTLPR allelic variation associated with ASB?

A

Short allele carriers were more sensitive to a lack of parental support in predicting later ASB, which was not seen in the long/long genotype.

AN4017 (8 decks)

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