Infant Inhibited Temperament in Primates Predicts Adult Behavior, is Heritable, and is Associated with Anxiety-Relevant Genetic Variation

Fox, Andrew S.; Rosso, Laura Del; Raveendran, Muthuswamy; Kamboj, Shawn; Kinnally, EL; Capitanio, JP; Rogers, Jeffrey

doi:10.1101/2020.10.30.361477

Cited by 5 publications

(7 citation statements)

References 84 publications

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“…The relationships between infant‐assessed temperament and later behavioral and health outcomes provide evidence that the temperament measures are in fact assessments of traits, and not simply transient states. Moreover, because genetic variation has been related to variation in these temperament measures (heritability estimates ranged from 0.2 to 0.4, a range similar to that seen in human studies [Blomquist et al, 2021; Fox et al, 2021]), it seems reasonable that our two candidate genes of interest might influence temperament.…”

Section: Introductionsupporting

confidence: 63%

“…Animals not satisfying these criteria were considered not inhibited. More information about this measure of BI can be found in Capitanio (2019) and Fox et al (2021).…”

Section: Methodsmentioning

confidence: 99%

“…The fifth measure, behavioral inhibition (BI), was derived from focal animal observations taken on the animals at the beginning and the end of the 25‐h period. Importantly, all five measures have been shown to be related to behavioral and/or health outcomes assessed many years after the initial assessments: these include diarrhea (Elfenbein et al, 2016; Gottlieb et al, 2018), asthma (Capitanio, Miller, et al, 2011; Chun et al, 2013), and various behavioral outcomes (Capitanio, 2019; Capitanio et al, 2017; Chun & Capitanio, 2016; Fox et al, 2021; Gottlieb et al, 2013; Vandeleest et al, 2011). The relationships between infant‐assessed temperament and later behavioral and health outcomes provide evidence that the temperament measures are in fact assessments of traits, and not simply transient states.…”

Section: Introductionmentioning

confidence: 99%

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The relationship of maternal rank, 5‐HTTLPR genotype, and MAOA‐LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta)

Capitanio

Sommet

Rosso

2022

American J Primatol

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Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3-to 4-month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half-acre cages.Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA-LPR and 5-HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014-3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5-repeat allele for MAOA-LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5-HTTLPR associated with behavioral inhibition, and MAOA-LPR associated with ratings-based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a doseresponse: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA-LPR that show functional equivalence based on in vitro tests, and our data for 5-HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the

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Section: Introductionsupporting

confidence: 63%

“…Animals not satisfying these criteria were considered not inhibited. More information about this measure of BI can be found in Capitanio (2019) and Fox et al (2021).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The relationship of maternal rank, 5‐HTTLPR genotype, and MAOA‐LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta)

Capitanio

Sommet

Rosso

2022

American J Primatol

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“…Temperament types impact how parents treat infants in a "goodness-of-fit" fashion [40], thus affecting the mother-child relationship quality. Inherited temperament and childhood experiences are strong predictors of adulthood personality and psychiatric behaviors with other events and potential trauma [41]. Later in childhood, attachment is created between the child and the caregiver.…”

Section: The Uniqueness and Advantages Of Neuropsychodynamicsmentioning

confidence: 99%

Precision Medicine: Neuropsychodynamic Psychiatry Model of Major Depressive Disorder

Huang¹

2021

Advances in Social Science, Education and Humanities Research

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Major Depressive Disorder (MDD) is one of the most extensive types of psychiatric disorders. It refers to various symptoms and considerable rates of relapse, where episodes rarely resolve completely even with intensive psychiatric care. There has been growing concern over the ineffectiveness in treating MDD in reductionist domination in the psychiatry domain. The recent development of neuropsychodynamics offers an integrative model incorporating a holistic understanding of the human mind in terms of neuroscience and psychoanalytic theories and provides a potentially effective cure for MDD. In this review, MDD in the neuropsychodynamic model is manifested as an abnormal operation of the self. The chief feature refers to the increasing inward focus of the self and decreasing outward direction of the environment. To argue for the necessity of utilizing neuropsychodynamic methodology in assessing and treating MDD, the advantages of the model were discussed.

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“…Investigations into the neural substrates of anxiety disorders and BI in humans 10,[41][42][43][44][45][46] , as well as inhibited temperament and BI in NHPs 35,38,[47][48][49][50][51][52] , have implicated a distributed network of brain regions. Notably, this network includes the central extended amygdala (EAc): a neuroanatomical concept that encompasses the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST).…”

Section: Introductionmentioning

confidence: 99%

Rhesus Infant Nervous Temperament Predicts Peri-Adolescent Central Amygdala Metabolism & Behavioral Inhibition Measured by a Machine-Learning Approach

Holley

Campos

Zhang

et al. 2022

Preprint

Self Cite

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Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc), a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders, and how this relationship is mediated by alterations in the EAc, could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.

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Infant Inhibited Temperament in Primates Predicts Adult Behavior, is Heritable, and is Associated with Anxiety-Relevant Genetic Variation

Cited by 5 publications

References 84 publications

The relationship of maternal rank, 5‐HTTLPR genotype, and MAOA‐LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta)

The relationship of maternal rank, 5‐HTTLPR genotype, and MAOA‐LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta)

Precision Medicine: Neuropsychodynamic Psychiatry Model of Major Depressive Disorder

Rhesus Infant Nervous Temperament Predicts Peri-Adolescent Central Amygdala Metabolism & Behavioral Inhibition Measured by a Machine-Learning Approach

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