Julian G. Simmons

Responsiveness to Drug Cues and Natural Rewards in Opiate Addiction: Associations With Later Heroin Use

CONTEXT Although drug cues reliably activate the brains reward system, studies rarely examine how the processing of drug stimuli compares with natural reinforcers or relates to clinical outcomes. OBJECTIVES To determine hedonic responses to natural and drug reinforcers in long-term heroin users and to examine the utility of these responses in predicting future heroin use. DESIGN Prospective design examining experiential, expressive, reflex modulation, and cortical/attentional responses to opiate-related and affective stimuli. The opiate-dependent group was reassessed a median of 6 months after testing to determine their level of heroin use during the intervening period. SETTING Community drug and alcohol services and a clinical research facility. PARTICIPANTS Thirty-three opiate-dependent individuals (mean age, 31.6 years) with stabilized opiate-substitution pharmacotherapy and 19 sex- and age-matched healthy non-drug users (mean age, 30 years). MAIN OUTCOME MEASURES Self-ratings, facial electromyography, startle-elicited postauricular reflex, and event-related potentials combined with measures of heroin use at baseline and follow-up. RESULTS Relative to the control group, the opiate-dependent group rated pleasant pictures as less arousing and showed increased corrugator activity, less postauricular potentiation, and decreased startle-elicited P300 attenuation while viewing pleasant pictures. The opiate-dependent group rated the drug-related pictures as more pleasant and arousing, and demonstrated greater startle-elicited P300 attenuation while viewing them. Although a startle-elicited P300 amplitude response to pleasant (relative to drug-related) pictures significantly predicted regular (at least weekly) heroin use at follow-up, subjective valence ratings of pleasant pictures remained the superior predictor of use after controlling for baseline craving and heroin use. CONCLUSIONS Heroin users demonstrated reduced responsiveness to natural reinforcers across a range of psychophysiological measures. Subjective rating of pleasant pictures robustly predicted future heroin use. Our findings highlight the importance of targeting anhedonic symptoms within clinical treatment settings.

Orbitofrontal Volumes in Early Adolescence Predict Initiation of Cannabis Use: A 4-Year Longitudinal and Prospective Study

BACKGROUND There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex. METHODS Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%]). RESULTS Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippocampus, and anterior cingulate cortex) did not predict later cannabis use. CONCLUSIONS These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances.

Emotional inertia prospectively predicts the onset of depressive disorder in adolescence.

Emotional inertia refers to the degree to which a persons current emotional state is predicted by their prior emotional state, reflecting how much it carries over from one moment to the next. Recently, in a cross-sectional study, we showed that high inertia is an important characteristic of the emotion dynamics observed in psychological maladjustment such as depression. In the present study, we examined whether emotional inertia prospectively predicts the onset of first-episode depression during adolescence. Emotional inertia was assessed in a sample of early adolescents (N = 165) based on second-to-second behavioral coding of videotaped naturalistic interactions with a parent. Greater inertia of both negative and positive emotional behaviors predicted the emergence of clinical depression 2.5 years later. The implications of these findings for the understanding of the etiology and early detection of depression are discussed.

Parental Behaviors During Family Interactions Predict Changes in Depression and Anxiety Symptoms During Adolescence

This study investigated the prospective, longitudinal relations between parental behaviors observed during parent-adolescent interactions, and the development of depression and anxiety symptoms in a community-based sample of 194 adolescents. Positive and negative parental behaviors were examined, with negative behaviors operationalized to distinguish between observed parental expressions of aggression and dysphoria. Results showed that higher levels of parental aggression prospectively predicted higher levels of both depression and anxiety symptoms in adolescents over two-and-a-half years, whereas higher levels of positive parental behaviors prospectively predicted lower levels of depression symptoms only. Parental dysphoric behavior was not related to changes in either symptom dimension. These results suggest that patterns of parental behaviors may be differentially associated with depressive versus anxious outcomes in adolescents, and highlight the potential role for family-focused prevention or treatment interventions aimed at reducing an escalation of depression and anxiety symptoms in adolescence.

Positive parenting predicts the development of adolescent brain structure: a longitudinal study.

Highlights • Positive parenting predicts development of adolescent amygdala and prefrontal cortex.• Positive parenting has a unique influence on adolescent brain development.• Positive and negative parenting are not opposite sides of a continuum.• Parenting interventions may promote healthy adolescent brain development.

Neuroanatomical Correlates of Temperament in Early Adolescents

OBJECTIVE Temperament refers to enduring behavioral characteristics that underpin individual differences in human behavior, including risk for psychopathology. Research attempting to investigate the neurobiological basis of temperament represents an important step toward elucidating the biological mechanisms underlying these individual differences. In the present study, we examined the relation between four core temperament dimensions and anatomically defined regions of the limbic and prefrontal cortices. METHOD We used a cross-sectional design to examine a large sample (N = 153; mean age 12.6 years, SD 0.4, range 11.4-13.7) of healthy early adolescents who were selected from a larger sample to maximize variation in temperament. The main outcome measures were psychometric measures of temperament (four factors: effortful control, negative affectivity, surgency, and affiliativeness) based on the Early Adolescent Temperament Questionnaire-Revised, and volumetric measures of a priori brain regions of interest (anterior cingulate cortex [ACC], orbitofrontal cortex, amygdala, and hippocampus). RESULTS We found regional brain volumes to account for small but significant amounts of the variance in self-reported temperament scores. Specifically, higher effortful control was associated with larger volume of the left orbitofrontal cortex and hippocampus. Higher negative affectivity was associated with smaller volume of the left dorsal paralimbic relative to limbic portion of the ACC. Higher affiliativeness was associated with larger volume of the right rostral/ventral limbic portion of the ACC. Affiliativeness and surgency also showed a number of female-specific associations, primarily involving the rostral/ventral ACC. CONCLUSIONS Our results provide support for a neuroanatomical basis for individual differences in temperament and have implications for understanding the neurobiological mechanisms underlying the development of a number of psychiatric disorders.

Childhood Maltreatment and Psychopathology Affect Brain Development During Adolescence

OBJECTIVE The hippocampus and amygdala have received much attention with regard to the deleterious effects of childhood maltreatment. However, it is not known if and when these effects emerge during adolescence and whether comorbid psychopathology is more likely to explain these effects. This study investigated whether childhood maltreatment was associated with hippocampal and amygdala development from early to midadolescence and whether the experience of psychopathology during this period mediated the relation. METHOD One hundred seventeen (60 male) adolescents, recruited as part of a broader adolescent development study, participated in magnetic resonance imaging assessments during early and midadolescence (mean age at baseline 12.62 years, SD 0.44 years; mean follow-up period 3.78 years, SD 0.20 years), and completed self-report measurements of childhood maltreatment and diagnostic interviews assessing DSM-IV mental disorders. RESULTS Childhood maltreatment was associated with larger baseline left hippocampal volumes and retarded growth of the left amygdala over time and was indirectly associated, through the experience of psychopathology, with retarded growth of the left hippocampus and accelerated growth of the left amygdala over time. Exploratory cortical analysis showed that maltreatment influenced thickening of the superior parietal region through the experience of psychopathology. CONCLUSIONS Childhood maltreatment was associated with altered brain development during adolescence. The experience of Axis I psychopathology during adolescence may be one mechanism by which childhood maltreatment has continuing effects on brain development during the adolescent years. These findings highlight the importance of early intervention for individuals who have experienced childhood maltreatment.

Hippocampal volume and sensitivity to maternal aggressive behavior: A prospective study of adolescent depressive symptoms

It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.

Brain development during adolescence: A mixed-longitudinal investigation of cortical thickness, surface area, and volume

What we know about cortical development during adolescence largely stems from analyses of cross‐sectional or cohort‐sequential samples, with few studies investigating brain development using a longitudinal design. Further, cortical volume is a product of two evolutionarily and genetically distinct features of the cortex ‐ thickness and surface area, and few studies have investigated development of these three characteristics within the same sample. The current study examined maturation of cortical thickness, surface area and volume during adolescence, as well as sex differences in development, using a mixed longitudinal design. 192 MRI scans were obtained from 90 healthy (i.e., free from lifetime psychopathology) adolescents (11‐20 years) at three time points (with different MRI scanners used at time 1 compared to 2 and 3). Developmental trajectories were estimated using linear mixed models. Non‐linear increases were present across most of the cortex for surface area. In comparison, thickness and volume were both characterised by a combination of non‐linear decreasing and increasing trajectories. While sex differences in volume and surface area were observed across time, no differences in thickness were identified. Furthermore, few regions exhibited sex differences in the cortical development. Our findings clearly illustrate that volume is a product of surface area and thickness, with each exhibiting differential patterns of development during adolescence, particularly in regions known to contribute to the development of social‐cognition and behavioral regulation. These findings suggest that thickness and surface area may be driven by different underlying mechanisms, with each measure potentially providing independent information about brain development. Hum Brain Mapp 37:2027–2038, 2016.

The lifetime experience of traumatic events is associated with hair cortisol concentrations in community-based children

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal axis (HPAA) and increase risk for negative health outcomes. Recent research suggests that cortisol in scalp hair represents a promising measure of HPAA function. However, little is known about the relationship between early exposure to traumatic events and hair cortisol concentrations (HCC) in childhood, a critical period of HPAA development. The current study measured HCC in scalp hair samples collected from 70 community-based children (14 males, mean age=9.50) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study (iCATS). Data were also collected on lifetime exposure to traumatic events and current depressive symptoms. Lifetime exposure to trauma was associated with elevated HCC; however, HCC was not associated with current depressive symptoms. Consistent with some prior work, males were found to have higher HCC than females, although results should be treated with caution due to the small number of males who took part. Our findings suggest that hair cortisol may represent a biomarker of exposure to trauma in this age group; however, further study is necessary with a particular focus on the characterization of trauma and other forms of adversity.