Table 1.

List of selected neuroimaging studies of genetic and environmental influences on early brain development discussed in this review.

1. Studies of infants at high familial risk for psychiatric disorders
Article	Population	N	Main Findings
Gilmore et al., 2010	Neonatal offspring of mothers with schizophrenia or schizoaffective disorder and matched comparison mothers without psychiatric illness	26 offspring of mothers with schizophrenia or schizoaffective disorder and 26 matched controls	The high-risk neonates had non-significantly larger intracranial, cerebral spinal fluid (CSF), and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects.
Shi et al., 2012	Same as Gilmore et al., 2010	Same as Gilmore et al., 2010	The brain structural associations of the high-risk neonates tended to have globally lower efficiency, longer connection distance, and less number of hub nodes and edges with relatively higher betweenness. Subgroup analysis showed that male neonates were significantly disease-affected, while the female neonates were not.
Li et al., 2016	Same as Gilmore et al., 2010	21 offspring of mothers with schizophrenia or schizoaffective disorder and 26 matched controls	Female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. High-genetic-risk neonates had marginally different cortical thickness in a number of other brain areas.
Wolf et al., 2015	Infants at high risk for autism spectrum disorder (ASD, having an older sibling with a community diagnosis of ASD) and control groups.	270 infants at high familial risk for ASD and 108 low-risk controls at 6, 12 and 24 months of age	Significantly increased corpus callosum area and thickness in children with ASD starting at 6 months of age followed by a declining in growth rate, resulting diminished differences at 2 years of age.
Shen et al., 2017	Same as Wolf et al., 2015	221 infants at high risk for ASD and 122 low risk controls at 6, 12 and 24 months of age	Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with comparison groups
Lewis et al., 2017	Same as Wolf et al., 2015	260 infants at 6 and 12 months of age with our without known risk for ASD	Inefficiencies in high-risk infants later classified as ASD were detected from 6 months onward in regions involved in low-level sensory processing.
Hazlett et al., 2017	Same as Wolf et al., 2015	106 infants at high familial risk of ASD and 42 low-risk infants	Hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain surface area information of 6–12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months.
Emerson et al., 2017	Same as Wolf et al., 2015	59 6-month-old infants with a high familial risk for ASD	Functional connectivity magnetic resonance imaging features measured at 6 months of age correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age.
2. Studies of candidate genes
Knickmeyer et al., 2014	Neonates with or without parental psychiatric history.	272 neonates.	Local variation in gray matter volume was significantly associated with polymorphisms in DISC1 (rs821616), COMT, NRG1, APOE, ESR1 (rs9340799), and BDNF. Neonates homozygous for the DISC1 (rs821616) serine allele exhibited reduced GM in the frontal lobes, and neonates homozygous for the COMT valine allele exhibited reduced GM in the temporal cortex and hippocampus.
Dean et al., 2014	Healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders	162 infants at 2–25 months of age.	Infant apolipoprotein E (APOE) ε4 allele carriers had lower myelin water fraction (MWF) and gray matter volume (GMV) measurements than non-carriers in areas preferentially affected by AD. They also showed greater MWF and GMV measurements in extensive frontal regions.
Krishnan et al., 2017	Preterm infants	Two independent cohorts of preterm infants (cohort 1: n = 70; cohort 2: n = 271)	Common genetic variation in DLG4 (rs17203281) is associated with fractional anisotropy in preterm infants
3. Genome-wide association studies (GWAS)
Xia et al., 2017	Infants (300 male, 261 female) between 0 and 24 weeks of age, including 295 singletons or unpaired twins, 17 sibling pairs and 232 twins.	561 infants	An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume (P=4.15 × 10–10). An intronic SNP in WWOX (rs10514437) neared genome-wide significance for white matter volume (P=1.56 × 10–8).
Krishnan et al., 2016	Preterm infants (mean gestational age (GA) 28 + 4 weeks, mean postmenstrual age (PMA) at scan 40 + 3 weeks)	72 preterm infants.	Significant relationships between lipid pathways, peroxisome proliferator-activated receptor (PPAR) signaling particularly, and variability in preterm white matter development, measured by fractional anisotropy were detected. Five genes were found to be highly associated with the phenotype: aquaporin 7 (AQP7), malic enzyme 1, NADP(+)-dependent, cytosolic (ME1), perilipin 1 (PLIN1), solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1), and acetyl-CoA acyltransferase 1 (ACAA1).
4. Studies of prenatal maternal mood disorders
Qiu et al., 2013	Full term infants	175 neonates with 35 of them having repeated MRI scans at 6 months	Children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life.
Qiu et al., 2015a	Full term infants	24 infants at 6 months of age	Infants born to mothers with higher prenatal maternal depressive symptoms showed greater functional connectivity of the amygdala with the left temporal cortex and insula, as well as the bilateral anterior cingulate, medial orbitofrontal and ventromedial prefrontal cortices.
Rifkin-Graboi et al., 2013	Full term neonates	157 neonates	Significantly lower fractional anisotropy and axial diffusivity, but not volume, were detected in the right amygdala in the infants of mothers with high compared with those with low depression scores.
Wen et al., 2017a	4.5-year-old children	235 children	Greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys.
5. Studies of prenatal drug exposures
Grewen et al., 2014	Full term neonates with or without prenatal drug exposure	33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine.	Reduced prefrontal and frontal gray matter volume and enhanced whole brain CSF volumes in neonates with prenatal cocaine exposure (PCE) compared with drug-free newborns and those with exposure to similar other drugs but not cocaine.
Salzwedel et al., 2015	Same as Grewen et al., 2014	Same as Grewen et al., 2014	Drug-common effects were detected within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. A prenatal cocaine exposure (PCE)-specific effect was detected within a sub-region of the amygdala–frontal network.
Grewen et al., 2015	Same as Grewen et al., 2014	20 with prenatal marijuana exposure (PME) co-morbid with other drugs, 20 drug-free controls and 20 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without marijuana.	Both marijuana-specific and drug-common alterations in functional connectivity were detected among a range of functional circuits associated with the amygdala, hippocampus, putamen, anterior/posterior insula, caudate, and anterior/posterior thalamus.
Salzwedel et al., 2016	Same as Grewen et al., 2014	Same as Grewen et al., 2014	PCE-related hyper-connectivity between the thalamus and frontal regions and a drug-common hypo-connective signature between the thalamus and motor-related regions were detected. PCE-specific neonatal thalamo-frontal connectivity was inversely related to cognitive and fine motor scores and thalamo-motor connectivity showed a positive relationship with composite motor scores. Moreover, cocaine by selective-serotonin-reuptake-inhibitor (SSRI) interactions were detected, suggesting the combined use of these drugs during pregnancy could have additional consequences on fetal development.
6. Studies of interactions between environmental and genetic effects
Qiu et al., 2015b	Same as Qiu et al., 2013	146 neonates	Individual COMT SNPs modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Specifically, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus.
Qiu et al., 2017	Same as Qiu et al 2013	168 and 85 mother–infant dyads from Asian and United States of America cohorts, respectively	A genomic profile risk score for major depressive disorder (GPRSMDD) moderated the association between antenatal maternal depressive symptoms and the right amygdala volume in neonates.