Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Adolescent neurocognitive development and impacts of substance use: Overview of the adolescent brain cognitive development (ABCD) baseline neurocognition battery.

Adolescence is characterized by numerous social, hormonal and physical changes, as well as a marked increase in risk-taking behaviors. Dual systems models attribute adolescent risk-taking to tensions between developing capacities for cognitive control and motivational strivings, which may peak at this time. A comprehensive understanding of neurocognitive development during the adolescent period is necessary to permit the distinction between premorbid vulnerabilities and consequences of behaviors such as substance use. Thus, the prospective assessment of cognitive development is fundamental to the aims of the newly launched Adolescent Brain and Cognitive Development (ABCD) Consortium. This paper details the rationale for ABC'lected measures of neurocognition, presents preliminary descriptive data on an initial sample of 2299 participants, and provides a context for how this large-scale project can inform our understanding of adolescent neurodevelopment.

Differential behavioral effects of plasma tryptophan depletion and loading in aggressive and nonaggressive men.

Preliminary findings indicate that men with high trait hostility may be prone to aggression increases following plasma tryptophan (Trp) depletion. We measured laboratory aggression in men selected for presence (n = 12) or absence (n = 12) of aggressive histories. Testing occurred before and after plasma Trp depletion, Trp loading, and under a food-restricted control condition. Subjects were provoked by subtractions of money, and aggression was measured as the responses the subject made to ostensibly subtract money from the instigator of the subtractions. When subjects were highly provoked, there was a significant Trp condition x aggression history interaction effect on aggressive responding. In particular, laboratory aggression in aggressive men was elevated under Trp-depleted conditions relative to Trp-loaded conditions, whereas the opposite occurred in nonaggressive men. Moreover, plasma total Trp levels after Trp loading were significantly higher in nonaggressive men, and plasma free (but not total) Trp levels after Trp loading correlated negatively with aggressive responses in the aggressive men. These data corroborate earlier findings that aggressive men may be more prone to aggression induced by reductions in plasma Trp.

Low dose zolmitriptan as a 5-HT neuroendocrine challenge agent in humans.

The 5-HT1B/D agonist sumatriptan has been used in a number of studies as a neuroendocrine challenge agent. Whether its neuroendocrine effects are centrally mediated is unclear, however, since sumatriptan shows minimal penetration of the central nervous system. Zolmitriptan shows a greater penetration into the central nervous system than sumatriptan, and has recently been shown to be an effective challenge agent. In order to determine the neuroendocrine, temperature and side effects of a 2.5 mg oral dose of zolmitriptan, 17 healthy volunteers underwent a placebo controlled, repeated measures, double blind neuroendocrine challenge. Zolmitriptan or placebo were administered, and cortisol, growth hormone, prolactin, blood pressure and temperature, were measured over four hours after the dose of zolmitriptan. Zolmitriptan at this dose was well tolerated by all subjects, with minimal side effects and only minor effects on blood pressure. There was a significant increase in serum growth hormone after zolmitriptan compared to placebo, however there were no significant effects on cortisol, prolactin or oral temperature. The neuroendocrine effects of 2.5 mg of orally administered zolmitriptan are similar to previously reported effects of sumatriptan, with minimal side effects.

The effects of tryptophan depletion and loading on laboratory aggression in men: time course and a food-restricted control.

Some studies have shown that sharp reduction of L-tryptophan (Trp) concentration in plasma results in increases in laboratory-measured aggression. Conversely, raising plasma Trp has blunted aggression. These effects are presumably due to impaired or enhanced serotonin synthesis and neurotransmission in the brain. In this study, the laboratory-measured aggressive behavior of eight men under both Trp depletion (T-) and Trp loading (T+) conditions was compared to their aggressive behavior under food-restricted control conditions (overnight fast without an amino acid beverage). Subjects were provoked by periodic subtraction of money which was attributed to a fictitious other participant, and aggression was defined as the number of retaliatory responses the subject made ostensibly to reduce the earnings of the (fictitious) other participant. Following ingestion of the T- beverage, aggressive responding was significantly elevated relative to the food-restricted control condition, and this increased aggressive behavior became more pronounced across behavioral testing sessions on a time-course which paralleled previously documented decreases in plasma Trp concentrations. In contrast, no changes were observed in aggressive responding under T+ conditions relative to food-restricted conditions. These within-subject behavioral changes under depleted plasma Trp conditions support earlier indications of a role of serotonin in regulating aggression.

The influence of menstrual-cycle phase on the relationship between testosterone and aggression.

Plasma testosterone levels and aggressive behavior were measured in 12 women with and without perimenstrual affective symptomatology (e.g., depression, irritability) during the menstrual, midfollicular, ovulatory, and premenstrual phases of the menstrual cycle. The Point Subtraction Aggression Paradigm was used to quantify aggressive response to provocation. Subjects had two response options: a point-maintained option (100 presses earned a point worth 10 cents) and an aggressive response option (10 presses ostensibly subtracted a point from a fictitious partner's counter). Subjects were provoked by the periodic subtraction of a point that was attributed to the responding of a fictitious opponent. Although plasma testosterone levels (determined by radioimmunoassay) increased significantly during the ovulatory phase, aggressive response to provocation remained unchanged across the menstrual cycle. Plasma testosterone did not differ between the 2 groups during any phase. A relationship between plasma testosterone levels and use of the aggressive response option was seen only during the midfollicular phase (Spearman r = .673, p = .017). These preliminary data suggest that: 1. The relationship in female subjects between endogenous testosterone and aggressive behavior is inconsistent; 2. self-report of perimenstrual symptomatology is a more consistent predictor of aggressive behavior across the menstrual cycle than plasma testosterone; and 3. perimenstrual emotional symptomatology is not related to testosterone levels.

Endogenous plasma testosterone levels and commission errors in women: A preliminary report.

A correlation between elevated testosterone and aggressive behavior has been demonstrated in animals and to a lesser degree in humans, primarily in the context of dominance. Some aggression, namely non-premeditated aggression, is characterized by impaired impulse control. Real-world aggressive histories and self-reported impulsivity have correlated with commission errors (failures to withhold responses to nontarget stimuli) in versions of the continuous performance test (CPT). To begin exploring whether testosterone may play a role in aggression due more to a direct relationship with impaired impulse control, we related plasma total testosterone concentrations of 27 psychiatrically healthy women to commission errors in two variants of the CPT - with and without interstimulus distracters. Controlling for age and IQ, testosterone did not relate to rates of correct detections in either task, but correlated positively with commission errors in the distracter CPT variant. In light of the fact previous studies find commission errors on the CPT are associated with impulsivity, the results of this study support a positive relationship between testosterone and impulsivity.

A positive correlation between self-ratings of depression and laboratory-measured aggression.

Aggression and depressive symptoms have been linked using self-rating scales as measures of aggression. In order to study this relationship using an objective measure of aggression, we studied normal controls (42 women and 23 men) with the Point Subtraction Aggression Paradigm (PSAP) and the Beck Depression Inventory (BDI). There was a significant positive correlation (r = 0.442, P = 0.003) between the level of aggressive responding on the PSAP and the level of depressive symptoms on the BDI in women but not in men (r = 0.064, P = 0.773). This study provides some evidence of a link between aggressive behavior and depressive symptoms in a non-clinical population, possibly due to a common neurochemical etiology.

Laboratory measures of aggression and impulsivity in women with borderline personality disorder.

To characterize how severe negative affect in women is reflected in objective measures of aggression and impulsivity, the aggressive and impulsive behavior of 14 hospitalized women with borderline personality disorder (BPD) was compared with that of 17 controls. In an impulsivity task, subjects experienced two sets of 50 trials during which they could choose a smaller, immediate monetary reward or a larger but progressively delayed reward. In a separate task (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money which was blamed on a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). While selection frequency of the short-delay responses was similar in patients and controls, BPD patients responded to avoid longer delay of reward across trials, and had higher Barratt Impulsiveness Scale total scores and attentional subscale scores. BPD patients responded to the money losses with roughly three times as many aggressive responses as controls and had higher Buss-Durkee Hostility Inventory (BDHI), Brown History of Violence, and Retrospective Overt Aggression Scale scores than controls. Aggressive responding rates correlated positively with BDHI scores. These results extend previous findings that negative affect in women is reflected in laboratory behavioral measures.

Influence of trait hostility on tryptophan depletion-induced laboratory aggression.

Previous research has indicated that laboratory aggression in men increases after temporarily reducing the synthesis and neurotransmission of serotonin (5-HT) in the brain using the plasma L-tryptophan (Trp) depletion technique. Further research indicates that male subjects selected for high trait hostility are particularly prone to increased aggression following plasma Trp depletion. In a recent study of laboratory aggression in male control subjects, we demonstrated that laboratory aggression increased following ingestion of a Trp-depleting beverage, but not after ingestion of a Trp-containing beverage nor under food-restricted conditions. We report here that the increases in aggression under Trp-depleted conditions were specific to men who scored the highest on the Buss-Perry Aggression Questionnaire. These preliminary data support earlier findings that compared to non-hostile men, hostile men may be more prone to behavior change induced by the perturbation of the 5-HT neurotransmitter system.

Plasma GABA levels correlate with aggressiveness in relatives of patients with unipolar depressive disorder.

Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mania and alcoholism. Medications which increase plasma GABA improve symptoms of mood disorders and can decrease aggression. We examined the relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility Inventory in 77 psychiatrically healthy adults. In subjects selected for having a first-degree relative with primary unipolar depressive disorder (FH+, n=33), plasma GABA was negatively correlated with aggressiveness (beta=-0.338, P=0.036), as was age (beta=-0.483, P=0.005). A relationship between plasma GABA levels and aggressiveness was not observed in subjects with no such family history (FH-, n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations than FH- subjects. These data suggest that low GABA levels may correlate with some aspects of aggressiveness and may be genetically regulated.

The effects of a cumulative alcohol dosing procedure on laboratory aggression in women and men.

OBJECTIVE: This study directly compared the effects of cumulative alcohol dosing procedure on aggression in both women and men. METHOD: Thirteen women and 13 men consumed three beverages 1 hour apart. There were two experimental conditions: (1) a placebo day, when subjects consumed three 240 ml beverages, each containing only 1 ml of alcohol; and (2) an alcohol day, when subjects consumed three 240 ml beverages, each containing 0.35 g/kg of 95% alcohol. Alcohol doses for women were reduced by 8%. Prior to beverage consumption, and periodically after consumption, subjects participated in 25-minute laboratory testing sessions designed to measure aggression. In this paradigm, subjects could earn points by responding on a button, or aggress toward a fictitious opponent who ostensibly subtracted earnings from them. RESULTS: Both women and men showed an increase in aggressive responding after drinking alcohol but not placebo. As a group the greatest increases were observed after consuming the second alcohol drink (BAC = 0.08%). Aggressive responding, however, remained elevated for several hours after alcohol consumption. A post hoc analysis of the data indicated that subjects with high aggression levels under placebo conditions showed the greatest increases in aggression under alcohol conditions. CONCLUSIONS: These results indicate that at least under these conditions, alcohol does increase aggression in both women and men. The aggression-increasing effects of alcohol appear to be long-lasting and specific to individuals with the higher aggressive tendencies while sober.

Plasma L-tryptophan depletion and aggression.

There is a well-established relationship between aggression and lowered serotonin neuro-transmission. Recently developed methodologies for manipulating L-tryptophan levels (and brain serotonin) have been applied to human laboratory studies of aggression. Collectively, these studies provide further evidence for the serotonin-aggression relationship. Two important findings have been made recently: (1) subsets of individuals (e.g., persons self-rating high on aggressive or hostility scales) may differ in their susceptibility to aggression produced through plasma tryptophan depletion; and (2) alcohol in combination with L-tryptophan depletion has an additive effect on aggression. All previous studies have been conducted with men. Extending these studies to women appears to be the much-needed next step given that serotonergic levels appear to vary both as a function of the menstrual cycle phase and menstrual symptomatology.

Self-reported impulsivity is correlated with laboratory-measured escape behavior.

Aggression has been previously correlated with impulsive personality. In the present study, Barratt Impulsiveness Scale (BIS) scores of 40 male controls aged 15-40 years were related to the frequency of free-operant aggressive and escape responses toward a fictitious antagonist. Participants earned "points" worth money with repeated button presses on a fixed-ratio schedule and were provoked by the periodic subtraction of a point. These subtractions were blamed on the behavior of a (fictitious) other participant, and aggressive responses (presses of a separate button) were defined as those emitted by the participant with an intent to subtract earnings from the other (fictitious) participant. BIS scores were not correlated with frequency of point-subtracting (aggressive) responses to the point subtractions, but they were correlated with the frequency of escape responses on a third button, which the participant was told would protect his points from subtraction for an unspecified period of time. These results suggest that among normal controls, impulsivity might be characterized by some sensitivity to aversive stimuli.

Differences in alcohol expectancy between aggressive and nonaggressive social drinkers.

Previous reports have shown that drinkers with aggressive personalities not only hold the strongest beliefs that alcohol facilitates aggressive behavior, but they also display the greatest increases in laboratory aggression after receiving alcohol. Given that several studies have demonstrated that a portion of the behavioral and subjective effects of alcohol are due to psychological expectancy, this study explored whether aggressive drinkers have elevated intoxication expectancies from laboratory beverages with unknown alcohol content. The rates of aggressive responses emitted in a money subtraction aggression model under baseline conditions were used to select an aggressive group and a nonaggressive group, each with five male and five female participants. Subjects then ingested and rated each of three placebo (1 ml alcohol) beverages administered hourly during a subsequent laboratory visit, and rated a series of three 0.35 g/kg of alcohol beverages the following day. Whereas nonaggressive subjects clearly discriminated the relative alcohol content of alcohol and placebo drinks, aggressive subjects gave progressively elevated shot equivalent ratings to placebo drinks, similar to their ratings of alcohol doses. However, despite similar self-reported drinking histories, aggressive subjects reported anticipating only half the intoxication from the alcohol doses (and in fact achieved a lower peak breath alcohol concentration) than was expected by nonaggressive subjects.

Symptomatology of depression and anxiety in female "social drinkers".

Self-reported alcohol use, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores were obtained during on-site interviews of 172 female applicants for paid participation in behavioral research. Mood symptomatology as reflected in BDI and BAI scores was analyzed as a function of alcohol use and other demographic variables. Women reporting even light alcohol use (up to three drinks per week) were significantly more symptomatic than abstinent women. In contrast, no significant differences in symptomatology were observed due to race or education level. This analysis extends previous findings of depressed mood in women (while sober) whose lifestyle includes moderate alcohol consumption and suggests that even light alcohol use is related to depressed and/or anxious mood.

Behavioral tolerance to and withdrawal from multiple fluoxetine administration.

The objective of this study was to characterize the lasting effects of fluoxetine on the locomotor behavior of rats using a computerized activity-monitoring system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the dark phase resulted in dose-dependent suppression of locomotor activity for 4 h following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine administration for the next five days resulted in decreasing locomotor activity during the multiple-administration period relative to saline control. Circadian activity patterns at the conclusion of the regimen were unchanged in shape, but featured uniform decreases in locomotor activity at every hour which were more significant during the phase. Upon discontinuation, fluoxetine-treated rats showed a significant increase in activity during the first 4 h following the first "missed" dose which was not seen in subsequent washout. Ninety-six h after the final maintenance dose, the initial three dosages were readministered, and the locomotor activity suppression in response to the rechallenge dose of fluoxetine was significantly lessened compared to initial challenge. These findings suggest that tolerance and withdrawal were obtained.

Alcohol increases commission error rates for a continuous performance test.

BACKGROUND: Studying the effects of alcohol on Continuous Performance Test (CPT) performance was of interest for two reasons, i.e., (1) perhaps because of the ease of the task used in previous experiments, alcohol has not been found to impair performance, and (2) CPT commission errors (described below) have been related to impulsive behavior. METHODS: In this study, the CPT featured both an Immediate Memory Task (IMT) and a more difficult Delayed Memory Task (DMT). We compared the performance of 18 subjects under both alcohol and placebo conditions, using a within-subject design. Both the IMT (0.5-sec delay) and the DMT (3.5-sec delay, with distracter stimuli at 0.5-sec intervals) required the subject to respond if a briefly displayed number was identical to the one presented before it. Stimuli included target (identical match), catch (4 of 5 digits matched), and novel (random number) stimuli. On 2 separate days, subjects performed between administrations of three hourly placebo drinks or three hourly drinks containing 0.20 g/kg of alcohol (producing peak breath alcohol concentrations of approximately 0.035%). RESULTS: The main finding was that alcohol consumption increased responses to catch stimuli (i.e., commission errors) in the DMT. In contrast, performance in the IMT (the easier task) was unaffected by alcohol. Commission errors measured during peak breath alcohol concentrations were significantly correlated with scores on the Barratt Impulsivity Scale for both the IMT and DMT. Discriminability (A') between target and catch stimuli was reduced by alcohol for the DMT only. CONCLUSIONS: These data indicate that even small amounts of alcohol can produce measurable changes in CPT performance parameters if the task is of sufficient difficulty and that commission errors can be increased by alcohol consumption.