Neonatal temperament and neuromotor differences are predictive of adolescent alcohol intake in rhesus monkeys (Macaca mulatta)

Abstract

Identifying predictors of teenage alcohol use disorder (AUDs) is a major health initiative, with studies suggesting that there are distinct personality-related traits that underlie patterns of alcohol intake. As temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. As such, we hypothesized that neonatal temperament traits would predict anxiety-mediated adolescent alcohol consumption. To test this, N = 145 rhesus macaque (Macaca mulatta) infants (14 days of age), reared in a neonatal nursery (n = 82) or in a control condition with their mothers (n = 63) were assessed with a widely used standardized nonhuman primate testing battery, the Infant Behavioral Assessment Scale (IBAS), modeled after the Brazelton Neonatal Assessment Scale, evaluating visual orienting, temperament, motor maturity and, more recently, sensory sensitivity. As adolescents (3–4 years of age), these same subjects were allowed unfettered access to a sweetened-alcohol solution for 1 hr/day, 4 days/week, over 5–7 weeks. Subjects were allowed to self-administer alcohol while housed alone (n = 70) or socially in their home cage (n = 55). Linear regressions showed that alcohol intake was predicted by neonatal orienting ability (β = −.35; p = .01), state control (β = −.19; p = .04), and motor maturity (β = −.24; p = .01). Poor neonatal orienting, state control (ease of consolability), and motor maturity were associated with higher adolescent alcohol intake in rhesus monkeys. These findings suggest that neonatal temperament is predictive of patterns of adolescent alcohol intake. To the extent that these results generalize to humans, they provide evidence that early-life temperament and neurodevelopment may be important risk factors for adolescent AUDs and that the IBAS may be used as an assessment tool for identifying such risk.

1 |. INTRODUCTION

Most of the research on identifying risk factors for alcohol use disorders (AUDs) has focused on understanding the underlying differences in individuals who tend to misuse alcohol. These differences are thought to lead to different types of AUDs. One of these, type-1 alcoholism, sometimes termed anxiety-mediated alcoholism (Cloninger, 1987), is associated with internalizing behavioral traits, and is thought to be related to attempts to reduce anxiety by consuming alcohol for its anxiolytic properties (Goldberg, 1984; Spanagel et al., 1995; Turner, Mota, Bolton, & Sareen, 2018). As certain aspects of internalizing behaviors may reflect temperament traits, we investigate whether alcohol intake is predicted from early-life temperament traits that are related to anxiety before the initiation of alcohol consumption.

Temperament is defined as a group of biologically based behavioral and personality traits that are identifiable early in life and are stable across time and situation (Chess & Thomas, 1977; Gartstein & Rothbart, 2003). Anxiety is one such temperament trait, identifiable early in life (Mian, Carter, Pine, Wakschlag, & Briggs-Gowan, 2015), and stable across development (Caspi, Moffitt, Newman, & Silva, 1996; Lovibond, 1998; Schwartz, Wright, Shin, Kagan, & Rauch, 2003). In line with Cloninger’s (1987) type-1 alcoholism, the comorbidity of AUDs and anxiety and anxiety disorders is well-established in adults (Burns & Teesson, 2002; Chavarria et al., 2015; Gierski et al., 2017; Grant et al., 2004) and in adolescents (Blumenthal, Ham, Cloutier, Bacon, & Douglas, 2016; Blumenthal, Leen-Feldner, Frala, Badour, & Ham, 2010). However, while it is recognized that temperament traits are stable and that antecedents of personality characteristics can be ascertained from infant and toddler temperament, and while adolescents can be diagnosed with AUDs (National Institute on Alcohol Abuse and Alcoholism, 2017), longitudinal data on early temperament styles as foundational aspects of adolescent alcohol use patterns are lacking.

One difficulty in conducting longitudinal studies assessing early-life anxiety and later alcohol use in humans is the long-term time commitment, as well as the numerous extraneous variables that can intervene across test periods. While some longitudinal studies in humans suggest that there is a relationship between early behavior, temperament, and alcohol use (Birrell, Newton, Teesson, Tonks, & Slade, 2015; Blumenthal et al., 2010, 2016; Woodward & Fergusson, 2001), these studies typically utilize self-reported alcohol use, a methodological choice that tends to be limited by recall, which can result in significant under-reporting (Bailey, Flewelling, & Rachal, 1992; Bertol et al., 2017; Ismail & Seneviratne, 2010; Popham & Schmidt, 1981; Smith, McCarthy, & Goldman, 1995), as well as the social desirability bias (Davis, Thake, & Vilhena, 2010), a particularly salient limitation when participants are teenagers self-reporting alcohol use. An additional difficulty in studying infant predictors of adolescent AUDs is that it is unethical to administer alcohol to teenagers, leading researchers to rely on retrospective data and/or on self-reported alcohol use.

Because of these difficulties, nonhuman primate models are useful for the study of alcohol abuse. Rhesus macaques (Macaca mulatta) possess many genetic (Gibbs et al., 2007) and temperament-related (Kay, Marsiske, Suomi, & Higley, 2010; Weinstein & Capitanio, 2008; Wood, Higley, Marsiske, Suomi, & Kay, under review) similarities to humans. Their rate of development is approximately 3–4 times faster than humans (Roth et al., 2004), progressing through comparable developmental periods and allowing for the assessment of longitudinal outcomes in a relatively short period of time. Furthermore, the rearing and environmental conditions during development can be closely controlled. Importantly, rhesus monkeys show similarities in patterns of alcohol consumption that parallel those observed in humans, with about 10–20% of normally-reared subjects routinely drinking to excess (Barr, Schwandt, Newman, & Higley, 2004; Higley & Linnoila, 2002; Higley, Hasert, Suomi, & Linnoila, 1991).

Early work from our laboratory (Fahlke et al., 2000; Higley & Linnoila, 2002; Higley et al., 1991) demonstrated that stress-induced plasma cortisol levels in rhesus monkey infants strongly predicted their alcohol consumption in adolescence. The present study seeks to extend these findings by assessing neonatal temperament and observing adolescent alcohol consumption patterns 4 years later. We utilize the Infant Behavioral Assessment Scale (IBAS), a standardized primate neurodevelopmental battery specifically designed to test nonhuman primate infants (Schneider & Suomi, 1992b). The instrument is an adaptation of the Neonatal Behavioral Assessment Scale (Brazelton, 1973) and is sensitive to a variety of intrinsic and environmental factors in primate neonates (Champoux et al., 2002; Champoux, Schneider, & Suomi, 1994; Schneider & Suomi, 1992b; Schneider, Coe, & Lubach, 1992; Schneider, Moore, Suomi, & Champoux, 1991). The IBAS includes items measuring the orientation, state control, motor maturity, and activity. The IBAS also includes rhesus infant temperament ratings which studies show congruence with the four human temperament clusters (See Table 1 for a description of these clusters) (Kay et al., 2010; Wood et al., under review). Moreover, it includes variables related to behavioral inhibition and anxiety, and it is ideally suited to measure the foundations of type-1-like alcohol intake. To measure adolescent alcohol intake, we use a well-validated paradigm which allows subjects to freely consume alcohol for 1 hr/day, 4 days/week, for a consecutive period of 5–7 weeks (see Higley & Linnoila, 2002, for a detailed description of the methodology). We hypothesize that lower scores on the IBAS will predict higher than average alcohol consumption in adolescence, specifically that those IBAS scores related to an anxious-like temperament and impaired neurodevelopment will together increase the risk for higher alcohol intake later in life.

TABLE 1.

Rhesus Monkey Neonatal Assessment Item Definitions

Orientation cluster
Visual orientation	Eyes oriented toward toy (plastic Mickey Mouse face) held in four positions in infant’s periphery (0: no orient, 1: direct brief contact, 2: direct prolonged contact)
Visual following	Eyes following moving toy (same as above) in both horizontal and vertical directions (0: contact but no following, 1: starts to follow, 2: complete following)
Duration of looking	Examiner rating of length of looks on previous items (0: no looking, 1: brief looks, 2: 1–2 s looks)
Attention	Examiner rating of attention on previous items (0: lack of attention on all items, 1: attention 25% of the time, 2: attentive 75% of the time)
State control cluster
Irritability	Amount of distress noted during the entire examination (0: distress noted continuously, 1: distress apparent 50% of the examination, 2: distress not apparent during the examination)
Consolability	Ease of consoling infant following distress (0: impossible to soothe or console infant, 1: infant is consoled with difficulty using holding, swaddling, rocking, and/or stroking, 2: infant is easy to console simply by picking up)
Struggle during testing	Amount of squirming (0: squirming 25% of the time, 1: squirming 50% of the time, 2: continuous squirming)
Predominant state	State of infant during examination (0: alert, awake, and aware, 1: alert but somewhat agitated, 2: extremely agitated)
Motor maturity cluster
Head posture prone	Ability to hold head up when held in prone position in air (0: flaccid tone with head hanging down, 1: head lifted but not maintained for three seconds, 2: head lifted and sustained for at least three seconds)
Head posture supine	Assessed exactly as above, but infant held in supine position
Coordination	Quality of movement rated (0: clumsy movements, 1: adequate movements, 2: agile movements)
Response speed	Examiner rating of speed of responding (0: 25% of responses are rapid, 1: 75% of responses are rapid, 2: all responses are rapid)
Labyrinthian righting	Realignment of head when body is tilted 45 degrees sideways (0: head and body in same plane, 1: head partially right, 2: head lines up with the vertical plane)
Activity cluster
Motor activity	Observation of motor activity during the examination (0: infant in motion 25% of the time, 1: infant in motion 50% of the time, 2: continuous motion)
Coordination	Quality of movement rated (1: clumsy movements, 1: adequate movements, 2: agile movements)
Spontaneous locomotion	Quality of locomotion rated (0: none, 1: weak attempt, 2: coordinated crawling)
Passive	Duration of time spent inactive (0: none, 1: inactive 50% of the time, 2: inactive 75 or more of the time)

Note: Adapted from Schneider et al. (1991).

2 |. METHODS

Subjects were N=145 laboratory-born rhesus macaques (M. mulatta—81 males and 64 females), housed at the Laboratory of Comparative Ethology, National Institute of Child Health and Human Development colony as part of an ongoing, longitudinal study investigating genetic and environmental influences on neurobiology and behavior as they relate to alcohol consumption. Seven birth cohorts born between 1991 and 1997 were included in this study. All procedures were conducted in compliance with the Institutional Animal Care and Use Committee of the National Institutes of Health and with the American Society of Primatology’s Principles for the Ethical Treatment of Nonhuman Primates.

Rearing and housing conditions are described in detail elsewhere see (Shannon, Champoux, & Suomi, 1998). Briefly, mother-reared (MR) animals (n = 63) were housed in indoor-outdoor pens in social groups consisting of six to eight adult females, two adult males, and six to eight age-mates. Nursery-reared (NR) animals (n = 82) were separated from their mothers 1–3 days following birth and reared in a neonatal nursery according to procedures described elsewhere (see Ruppenthal, 1979). While in the nursery, subjects were provided a fleece covered, heated, spring-loaded, surrogate mother and a cloth blanket. They were weighed and handled daily.

At 37 days of age, NR infants were assigned to either a peer-only rearing (PR) condition or to a surrogate-peer rearing condition (SPR). PR subjects were placed into a permanent social group consisting of three other age-mates from the same birth cohort. SPR subjects were allowed 3–4 hr a day of social interaction with other age-mates and then returned to their home cage with their surrogate mothers. When subjects reacheed 6–7 months of age, the MR animals were permanently removed from their mothers and housed in large indoor pens with the NR animals from the same birth cohort to form a larger social group. Following group formation, all animals received identical treatment. Before 30 days of age, the peer-reared and surrogate-peer were treated identically, and there were no differences between the surrogate-peer-and peer-reared subjects in mean alcohol intake. Therefore, the two groups were combined for subsequent analyses, hereafter, NR.

2.1 |. Infant Behavioral Assessment Scale

Infants were assessed using the IBAS on D-14 of life (Schneider & Suomi, 1992b). Raters were trained to an interrater reliability criterion of 0.90 before collecting data. All testing was performed in a predetermined sequence between 11:00 and 13:00. The test consists of four clusters (orientation, state control, motor maturity, and activity), each consisting of between four and five items (see Table 1). These clusters emerged from an exploratory factor analysis with extracted factor loadings ranging between 0.33 and 0.90 for the items within each cluster, with an average absolute factor loading of 0.73 (Schneider, Moore et al., 1991). To perform the IBAS testing, the infant was wrapped in a cloth, leaving the arms free to move while orientation abilities and attention to visual and auditory stimuli were measured. Second, motor maturity, including a variety of reflex and sensorimotor functions were assessed. Third, temperament ratings for state control were obtained during the orientation and motor maturity assessment. The temperamental measurements of state control included fearfulness, tendency to struggle, consolability, irritability, ability to self-soothe, cuddliness, and overall state of arousal. Lastly, the infant was placed in a small cage (51 × 38 × 43 cm) for a 6-min assessment of the infant’s activity. To prevent distractions, the testing cage was empty except for an absorbent liner pad and the stimulus used for visual orienting. While measuring orientation, the number of vocalizations emitted by the infant was recorded over the 1st min. Then a 5-min focal observation of immobility, fine and gross motor activity, and coordination was assessed. With the exception of the 60-s vocalization count, all items were scored on a scale of 0–2, with scores of 0.5 and 1.5 allowed. Scores for items under each of the four clusters were added together to create the overall cluster scores of the orientation, state control, motor maturity, and activity.

2.2 |. Alcohol consumption paradigm

When subjects reached adolescence (M_age = 46 ± 7 months) they were tested for their propensity to voluntarily consume alcohol. The procedure used to train the subjects to consume alcohol and the data collection methods have been described elsewhere (see Higley & Linnoila, 2002). Briefly, subjects were trained to drink from nipple-like spouts by giving them a period of exposure to an aspartame-sweetened vehicle (30 mg/100 ml of water), ending when each subject had consumed >50 ml of the vehicle. Subsequently, ethanol was added to the vehicle until an 8.4% v/v alcohol solution was produced. The ethanol solution was available each day between 13:00 and 15:30 for 1 hr/day, 4 days a week (Monday through Thursday), for total of between 5 and 7 consecutive weeks. To control for the possibility that subjects were consuming the ethanol solution for its gustatory value, during each drinking session the aspartame-sweetened vehicle was also available. An average daily absolute alcohol consumption value (g/kg body weight) was calculated for each monkey based on the daily intake of the alcohol solution averaged over the duration of the study.

As the assement of alcohol intake occurred over a period of 7 years, housing conditions during the alcohol consumption paradigm differed somewhat across birth cohorts. Quantities of ethanol intake were measured using one of the following procedures:

• Single-cage testing: for n = 70 subjects (comprised of cohorts 1, 2, 3, 4-males-only, 5-males-only, and 7-males-only), subjects were singly housed in adjoined cages (2.44 × 3.0 × 2.33 m). To assure that the subjects were drinking alcohol for its pharmacological effects and not for its gustatory properties, two standard water bottles, each containing 500 ml of one of the two solutions ([a] the sans-alcohol sweetened vehicle and [b] the alcohol + sweetened vehicle) were hung on the sides of each single cage, and bottles were marked to measure the amount consumed every 15 min. The total volume of consumed sweetened-alcohol solution was measured after 1 hr had elapsed, with drippage caught by a funnel and measured to increase accuracy. Water was also available for the subjects during the testing period. At the end of the testing period, subjects were reunited with cage-mates. The side of the cage on which the two solutions were placed was switched at the half-way point of the testing weeks.

• Social-group testing: for n = 55 subjects, (comprised of cohorts 4-females-only, 5-females-only, and 6), subjects were group-housed in an indoor-outdoor run (indoor: 2.44 × 3.05 × 2.21 m, outdoor: 2.44 × 3.0 × 2.44 m) equipped with the automated fluid delivery apparatuses. The apparatus is a closet-like, clear Plexiglas^™-enclosed perch that subjects could enter from the bottom to drink. The apparatus allowed subjects to drink without interference from other animals as it was an enclosed perch, in which only one monkey could fit at a time. Subjects were fitted with collars that contained sensors that the computer detected and used to identify which subject was drinking. The number of drinking bouts and volume of solution dispensed during each drinking session was also recorded by the computer. Two standard water bottles containing 500 ml of the two solutions were hung on the side of the cage and were accessible from each apparatus, and the total volume of consumed sweetened-alcohol solution was measured after 1 hr had elapsed. The side of the cage was switched for each birth cohort. To preclude water satiation at the time of testing, cage water was turned off for 1 hr before the solutions were available. Water was freely available at all other times, including the period when the solutions were available.

Because previous studies showed that anesthetizing subjects to obtain blood alcohol concentrations during the drinking phase of a study led to reduced alcohol intake over the week following measurement (Higley et al., 1991), subjects were not routinely removed from their home cages to obtain blood alcohol contents (BACs) during the study. Instead, at the end of the study, a representative sample of subjects was removed from their cages to obtain a blood sample for assessment of BAC.

2.3 |. Data analysis

Of the 145 laboratory-reared rhesus monkeys, n = 135 animals participated in the IBAS testing and n = 125 animals were given access to alcohol in the alcohol consumption paradigm. Of the 125 animals given access to alcohol, n = 34 animals drank in single cages and n = 91 animals drank in social groups. Because subjects were given access to alcohol under different conditions in different years, z scores of alcohol intake were calculated within cohort test year and the individual standardized scores were used for all linear regressions.

Descriptive statistics were used to report the typical alcohol intake across subjects, as well as the percentage of subjects showing high rates of alcohol intake, as defined by an individual average alcohol intake in excess of 1.4 g/kg/. A subsequent χ² test was performed to assess whether alcohol intake in excess of 1.4 g/kg was equally distributed across rearing conditions (a known mediator of alcohol intake; See Fahlke et al., 2000; Higley et al., 1991; Higley, Suomi, & Linnoila, 1996).

As IBAS averages for each cluster have not been previously reported in this large of a sample, descriptive statistics were also used to characterize the mean standardized IBAS cluster scores. To statistically test the relationship between the neonatal IBAS scores and adolescent alcohol intake, separate linear regression analyses were conducted for each of the Day-14 neonatal clusters: orientation, state control, motor maturity, and activity, with the specific neonatal cluster as the independent variable and standardized alcohol intake as the independent variable. Preliminary independent t tests assessing sex and rearing differences in alcohol intake showed no significant differences between males and females (t(123) = −0.67; p = .50) or between subjects that were MR or NR (t(123) = −1.05; p = .30). As preliminary independent t tests assessing sex and rearing differences in the orientation, state control, motor maturity, and activity showed significant differences between males and females for the activity cluster (t(133) = 2.09; p = .04) and significant differences between MR and NR subjects for the state (t(132) = 10.01, p < .0001) and activity clusters (t(133) = 4.44, p < .0001), sex and rearing were entered in the regression analyses. However, as neither rearing nor sex were significant contributors to any of the linear regression analyses (p > .37), they were dropped from the final models.

3 |. RESULTS

3.1 |. Typical alcohol intake

Across all of the adolescent subjects, the average alcohol intake was 0.93 ± 0.07 g/kg. Further analyses showed that 25% of the subjects consumed alcohol in excess of 1.4 g/kg, an amount that other studies show results in an average BAC in excess of 0.10% (Higley et al., 1991; Vivian et al., 1999). As this is a somewhat higher percentage of subjects drinking in excess of 1.4 g/kg than that seen in other studies (Higley et al., 1991), a χ² test was performed, showing that the high percentage of individuals that drank to intoxication was, in part, due to the high intake of NR subjects, which were more likely to consume alcohol at rates that produce intoxication when compared with MR subjects (31% of NR subjects consumed over 1.4 g/kg, compared with 12% of MR subjects, χ² = 8.96, p = .003). Consistent with other studies (Fahlke et al., 2000), male subjects drank significantly more alcohol than did female subjects (t(123) = −3.13, p = .002; males: M = 1.20 ± 0.13 g/kg; females: M = 0.73 ± 0.08 g/kg). Also consistent with other studies (Fahlke et al., 2000; Higley et al., 1991, 1996), NR subjects drank significantly more alcohol than did MR subjects (t(123) = −3.17, p = .002); NR: M = 1.13 ± 0.11 g/kg; MR: M = 0.65 ± 0.08 g/kg). On the last day of the study for each cohort, a blood sample was obtained from a representative sample of 25 subjects that consumed more than 1.4 g/kg. There was a significant, positive correlation between the amount of alcohol consumed and BAC (r = 0.55, p = .0001), with a mean BAC of 125 mg/dl. As in other studies using this paradigm, subjects showed a binge-like rapid intake, with about two-thirds of the available alcohol consumed in the first 15 min (Higley et al., 1991).

3.2 |. IBAS and adolescent alcohol intake

The average for each of the IBAS clusters was similar to that seen in other studies (orientation, M = 0.93 ± 0.05; state control, M = 0.73 ± 0.06; motor maturity, M = 1.31 ± 0.05; activity, M = 0.96 ± 0.06; Schneider & Suomi, 1992b). Results showed that subjects with lower scores on the orientation cluster on Day-14 of life had significantly higher voluntary adolescent alcohol intake (β = −.35; p = .01; overall R = 0.23, F(1,114) = 6.47, p = .01, see Figure 1). Subjects with lower scores on the state control cluster on Day-14 of life exhibited significantly higher voluntary adolescent alcohol intake (β = −.19; p = .04; overall R = 0.19, F(1,115) = 4.24, p = .04, see Figure 2), and subjects with lower scores on the motor maturity cluster on Day-14 of life exhibited significantly higher voluntary adolescent alcohol intake (β = −.24; p = .01; overall R = 0.24, F(1,115) = 6.82, p = .01, see Figure 3). No significant effects were found for the activity cluster on adolescent alcohol intake (p > .05).

FIGURE 1.

Graphical depiction of significant relationship (β = −.35; p = .01) between the orientation cluster score at Day-14 of life and adolescent alcohol intake. Female subjects are depicted in black; male subjects are depicted in white. MR subjects are depicted by circles; NR subjects are depicted by triangles

FIGURE 2.

Graphical depiction of significant relationship (β = −.19; p = .04) between the state control cluster score at Day-14 of life and adolescent alcohol intake. Female subjects are depicted in black; male subjects are depicted in white. MR subjects are depicted by circles; NR subjects are depicted by triangles

FIGURE 3.

Graphical depiction of significant relationship (β = −.24; p = .01) between the motor maturity cluster score at Day-14 of life and adolescent alcohol intake. Female subjects are depicted in black; male subjects are depicted in white. MR subjects are depicted by circles; NR subjects are depicted by triangles

4 |. DISCUSSION

In support of our hypothesis, we found that lower scores on a standardized neonatal assessment of temperament and neurobehavioral development were associated with higher adolescent alcohol consumption. Lower cluster scores on items assessing attention (orienting), emotion regulation (state control), and motor immaturity on Day-14 of life were predictive of higher alcohol consumption approximately 4 years later. While some longitudinal studies in humans have shown relationships between adolescent alcohol intake and maternal ratings of infant temperament (Dick et al., 2013) and other studies have demonstrated a relationship between adolescent temperament and adolescent alcohol use (Birrell et al., 2015; Blumenthal et al., 2010, 2016; Woodward & Fergusson, 2001), such studies assessed teenage alcohol intake using self-report and retrospective methods. The present study is, to our knowledge, the first prospective study to use neonatal measures of temperament as predictors of adolescent alcohol intake. Moreover, it utilizes a translational nonhuman primate model that directly measures adolescent alcohol consumption, reducing extraneous variables inherent to studies of teenage drinking. These findings represent an important step in early identification of temperamental profiles that are risk factors for deleterious patterns of alcohol intake and adolescent AUDs.

Studies in humans show that when teenagers drink, they consume the majority of their alcohol in the form of binge-drinking (Office of Juvenile Justice and Delinquency Prevention, 2005; Substance Abuse and Mental Health Services Administration, 2018). This pattern is associated with a number of high-risk behaviors, including accidents (Hicks, Morris, Bass, Holcomb, & Neblett, 1990), sexual assaults (Champion et al., 2004), violence (Buydens-Branchey, Branchey, & Noumair, 1989), alcohol poisoning, and other physical consequences (De Bellis et al., 2000). The nonhuman primate translational model used to evaluate adolescent alcohol intake in this study shows rapid rates of alcohol intake paralleling the drinking patterns of human teenagers who binge drink. A subset of the sample also showed chronic patterns of intake that other studies show leads to BACs in excess of 0.10% in rhesus monkey adolescents (Higley et al., 1991). The overall percentage of subjects that chronically consume alcohol to a point of attaining BACs in excess of 0.10% is similar to that found in other studies of rhesus monkey alcohol consumption (Vivian et al., 1999) and other species of nonhuman primates (i.e., vervet monkeys—Ervin, Palmour, Young, Guzman-Flores, & Juarez, 1990), and parallels alcohol consumption patterns found in human teenagers (National Institute on Alcohol Abuse and Alcoholism, 2017). Furthermore, the majority of the subjects that consumed alcohol at this high rate were those that were separated from their mothers at birth (NR) and reared without parents in peer-groups or with only three-to-four hours of daily interactions with other peers, and both are known risk-factors for an anxiety-like temperament, as well as future high alcohol intake in rhesus monkeys (Higley et al., 1991).

To the extent that our findings generalize to humans, they suggest that temperament, which is stable across development (Chess & Thomas, 1977; Gartstein & Rothbart, 2003), and widely held to be the foundation of personality, appears to play a role in the development of patterns of adolescent alcohol intake. Furthermore, the results of our study suggest that a standardized neonatal assessment of temperament like the NBAS (Brazelton, 1973), a tool routinely used to study human infants, may be useful in identifying individuals at risk for engaging in problematic alcohol use behavior (i.e., binge-drinking) later in life. Based on the high rates of comorbidity between anxiety and AUDs in human populations (Burns & Teesson, 2002; Chavarria et al., 2015; Gierski et al., 2017; Grant et al., 2004), we hypothesized that temperament variables related to future anxiety and fearfulness would be positively associated with alcohol intake, and indeed, neonatal state control (consolability, irritability, predominant state, etc.) was associated with higher adolescent alcohol intake. In addition, two other clusters (orientation and motor maturity) were also related to adolescent alcohol intake. One interpretation of our findings is that low orienting abilities and attentional control, in addition to reductions in motor maturity, are foundational temperamental components of future anxiety and fearfulness, which are related to type-1, anxiety-mediated alcohol intake. A growing literature suggests that temperament and personality traits are not completely orthogonal (Digman, 1997; McCrae & Costa, 2003). Rothbart’s restructuring of infant temperament (Rothbart & Bates 2006), shows some overlap of these clusters with later negative affectivity, including anxiety, which may explain, in part, why the orienting and motor abilities also predicted alcohol intake. On the other hand, low values on these two clusters likely also represent variation in central development that may be suggestive of difficulties in sensory processing and attention, which are known risk factors for developmental delays and deviant developmental pathways (Boyd et al., 2010; Yochman, Ornoy, & Parush, 2006). To our knowledge, outside of the present study, the long-term developmental outcomes for the IBAS have not yet been assessed, but other studies show that attention and sensory deficits are related to AUDs (Monnig et al., 2013; Wilens, Biederman, Mick, Faraone, & Spencer, 1997). This latter explanation, however, does not explain why the other temperament clusters were similar in relational strength.

A number of researchers have shown that deviations from averages in temperament, particularly extreme deviations in temperament, are risk factors for other forms of psychopathology (Goldsmith et al., 1987; Kagan, Reznick, & Snidman, 1988; Schmidt et al., 2013), some of which lead to risk for developing AUDs (Gierski et al., 2017). As AUDs have multiple pathways (Oreland et al., 2018; Pombo & Lesch, 2008), with high intake as the final common pathway, an alternative, but not inconsistent, explanation, is that early developmental delays and deviations may each represent individual contributions to alcohol intake and lead to future risk for excessive alcohol intake. For example, scores on the motor maturity cluster reflect speed of responding on test items, motor coordination, and ability to make postural adjustments, with deviations from developmental norms potentially indicating delays in development. Such deviations may also be related to propensities for alcohol intake in adolescence. In one longitudinal study conducted in humans, comparisons of postural sway in controls and children at risk for alcohol-related problems later in life indicated that the high-risk children exhibited developmental delays in the maturation of postural control (Hill et al., 2000). Other studies in humans show that those at risk for developing an alcohol-related disorder show less pronounced static ataxia and postural sway when compared with controls, suggesting that early measures of the motor maturity may serve as psychobiological markers for future motor or sensory problem (Hegedus, Tarter, Hill, Jacob, & Winsten, 1984; Hill & Steinhauer, 1993; Lipscomb, Carpenter, & Nathan, 1979) as well as disordered alcohol consumption later in life. Our findings lend support to this hypothesis, and further suggest that early motoric delays may be assessed early in life and serve as a predictor or marker of biological risk AUDs.

The findings of this study offer important insight into potential biological risk factors for risky drinking patterns in adolescence, as well as suggest the potential for the use of early measures of temperament as screening tools for developmental risk for adolescent AUDs. As our study investigated adolescent drinking, our drinking model attempted to parallel the acquisition of alcohol consumption and patterns of teenage alcohol intake, which typically involves drinking alcohol in palatable, often sweet, concentrations (Wagenaar et al., 1993). This approach is limited somewhat, however, in its capacity to tease out gustatory versus pharmacological motivating factors for consuming the sweetened-alcohol solution. As our subjects were not offered solutions containing differing concentrations of alcohol, the findings that neonatal temperament is predictive of later adolescent alcohol intake could be attributed to neonatal temperament predicting adolescent propensity to drink liquids overall, irrespective of alcohol content. However, two lines of evidence suggest that the subjects’ motivation to consume alcohol was, in large part, based on the reinforcing effects of alcohol consumption: first, using the same procedures and time of exposure as those described in this study, Vivian et al. (1999) reports that stable drinking rates were established in a group of adolescent monkeys. These subjects were then transferred to another laboratory where they were tested for alcohol preferences and intake using simultaneous, two-spout access to both water and unsweetened ethanol. Even though the context was different, sweetened-alcohol consumption in the first laboratory was strongly correlated with the consumption of the unsweetened alcohol in the new laboratory. (r = 0.86, p = .001), with subjects that consumed the largest volume of unflavored alcohol also consuming the the most flavored alcohol. Second, when unsweetened alcohol intake and water intake were simultaneously measured, those monkeys showing the greatest preference for the alcohol solution over water were the same subjects that consumed the most alcohol. Furthermore, in this study, these monkeys were allowed to consume unsweetened alcohol solutions at eight different concentrations, ranging from 0% to 16%, with raw alcohol fluid volume intake levels highest at lower alcohol concentrations (0.5%, 1%, and 2%). Subjects showed a progressive decline in raw alcohol fluid intake as the concentrations increased (4%, 8%, and 16%), but ml/kg body weight alcohol intake actually increased from 4% to 8% alcohol concentration and remained steady at 16% concentration, producing pharmacologically relevant BACs at higher concentrations (Vivian et al., 1999). Such findings provide evidence that consumption of the sweetened alcohol was primarily motivated by the pharmacological effects of the alcohol and not for its gustatory value or the propensity to consume liquids.

While the IBAS has a long history, most previous studies were performed using smaller sample sizes (Champoux et al., 1994; Schneider, 1984, 1992; Schneider & Suomi, 1992a, 1992b; Schneider et al., 1992; Schneider, Kraemer, & Suomi, 1991; Schneider, Moore et al., 1991); although, see Coe et al. (2010). The current large sample of subjects are from a different laboratory and population than those studied by Coe et al. (2010), and, as such, provide estimates for each of the clusters that others may use to better establish norms. We refer to the neonatal measures as important in the developmental pathway for patterns of alcohol intake. Given the early stage of life in which the subjects’ temperaments were measured, it is not surprising that the correlation between neonatal temperament and alcohol intake were modest. Other studies in humans also show low but significant correlations between early infant temperament and adolescent and young adult personality (see McCrae et al., 2000), suggesting that our findings are in line with other temperament research that shows modest, but positive, correlations between temperament in infancy and personality in adolescence, suggesting therefore, an underlying continuity. This study suggests that temperament appears to play an important, albeit modest, developmental role in the risk for psychopathology, including patterns of adolescent alcohol intake.

These findings of our study suggest that early behavioral capacities may be predictive of alcohol consumption later in life. To the extent that these results generalize to humans, they suggest that decreased attention and orientation abilities, lower emotional regulation abilities, and motor immaturity very early in life may be foundational for the development of traits that lead to increased alcohol consumption in adolescence. They further suggest that, in humans, individual risk for developing an AUD may be identified early in life using an assessment of temperament and neurobehavioral capacities, such as the NBAS (Brazelton, 1973). The results of this study are an important step in understanding the biological origins of AUDs and may ultimately be useful in developing preventative and intervention-related measures for individuals at risk for AUDs.