functional and structural ( mri ) brain data for each animal were co - registered to a standard space based on an age - appropriate rhesus monkey brain template .
whole - brain linear regression analyses examined the relations between fdg uptake and at . to account for potential confounds , age and sex
gray matter probability was also included as a voxelwise covariate to account for the possibility that structural differences affected the relation between brain metabolic activity and at .
the resulting 3d t - map was corrected for multiple comparisons using the idk equation ( 1  ( 1  )1 / n ) , which is similar to the bonferroni method and determined the statistical threshold of p=0.05 , corrected ( t > 5.47 ) . to estimate the heritability of at , phenotypic covariance / correlation amongst pairs of relatives was modeled as a function of expected pairwise kinship values to estimate the magnitude of additive genetic variance relative to that of the observed phenotypic variance .
age , age and sex were included in the mean effects model as covariates to control for these potential confounds .
the resulting heritability data were corrected for multiple comparisons based on the total volume of all the clusters correlated with at using a false discovery rate ( fdr ; q - value = 0.05 ) .
measured genotype analyses use the same variance components approach as the heritability analyses , and were implemented using solar .
measured genotype analyses simultaneously estimate the effect of specific genotypic differences among animals and the overall effect of pair - wise kinship , thus testing for the effect of a single polymorphism while accounting for background allele sharing across the genome due to genealogical relatedness .
 anxious temperament ( at ) in human and non - human primates is a trait - like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli 14 . 
 studies in children demonstrate that at is an important risk factor for the later development of anxiety disorders , depression , and comorbid substance abuse 5 . despite its importance as an early predictor of psychopathology , little 
 is known about the factors that predispose vulnerable children to develop at and the brain systems that underlie its expression . to characterize the neural circuitry associated with at and the extent to which the function of this circuit is heritable 
 , we performed a study in a large sample of rhesus monkeys phenotyped for at . using 238 young monkeys from a multigenerational single - family pedigree , we simultaneously assessed brain metabolic activity and at while monkeys were exposed to the relevant ethological condition that elicits the phenotype . 
 high - resolution 18f - deoxyglucose positron emission tomography ( fdg - pet ) was selected as the imaging modality since it provides semi - quantitative indices of absolute glucose metabolic rate , allows for simultaneous measurement of behaviour and brain activity , and has a time course suited to assess temperament - associated sustained brain responses . 
 results demonstrated that the central nucleus region of amygdala and the anterior hippocampus are key components of the neural circuit predictive of at . 
 quantitative genetic analysis demonstrated significant heritability of the at phenotype . 
 additionally , a voxelwise analysis revealed significant heritability of metabolic activity in at - associated hippocampal regions . however , activity in the amygdala region predictive of at was not significantly heritable . 
 furthermore , the heritabilities of the hippocampal and amygdala regions significantly differed from each other . 
 even though these structures are closely linked , the results suggest differential influences of genes and environment on how these brain regions mediate at and the ongoing risk to develop anxiety and depression . 
METHODS SUMMARY
Supplementary Material