Identifying high school risk factors that forecast heavy drinking onset in understudied young adults.

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.

Acceptability, Validity, and Engagement With a Mobile App for Frequent, Continuous Multiyear Assessment of Youth Health Behaviors (mNCANDA): Mixed Methods Study.

BACKGROUND: Longitudinal studies of many health behaviors often rely on infrequent self-report assessments. The measurement of psychoactive substance use among youth is expected to improve with more frequent mobile assessments, which can reduce recall bias. Researchers have used mobile devices for longitudinal research, but studies that last years and assess youth continuously at a fine-grained, temporal level (eg, weekly) are rare. A tailored mobile app (mNCANDA [mobile National Consortium on Alcohol and Neurodevelopment in Adolescence]) and a brief assessment protocol were designed specifically to provide a feasible platform to elicit responses to health behavior assessments in longitudinal studies, including NCANDA (National Consortium on Alcohol and Neurodevelopment in Adolescence). OBJECTIVE: This study aimed to determine whether an acceptable mobile app system could provide repeatable and valid assessment of youth's health behaviors in different developmental stages over extended follow-up. METHODS: Participants were recruited (n=534; aged 17-28 years) from a larger longitudinal study of neurodevelopment. Participants used mNCANDA to register reports of their behaviors for up to 18 months. Response rates as a function of time measured using mNCANDA and participant age were modeled using generalized estimating equations to evaluate response rate stability and age effects. Substance use reports captured using mNCANDA were compared with responses from standardized interviews to assess concurrent validity. Reactivity was assessed by evaluating patterns of change in substance use after participants initiated weekly reports via mNCANDA. Quantitative feedback about the app was obtained from the participants. Qualitative interviews were conducted with a subset of participants who used the app for at least one month to obtain feedback on user experience, user-derived explanations of some quantitative results, and suggestions for system improvements. RESULTS: The mNCANDA protocol adherence was high (mean response rate 82%, SD 27%) and stable over time across all age groups. The median time to complete each assessment was 51 s (mean response time 1.14, SD 1.03 min). Comparisons between mNCANDA and interview self-reports on recent (previous 30 days) alcohol and cannabis use days demonstrate close agreement (eg, within 1 day of reported use) for most observations. Models used to identify reactivity failed to detect changes in substance use patterns subsequent to enrolling in mNCANDA app assessments (P>.39). Most participants (64/76, 84%) across the age range reported finding the mNCANDA system acceptable. Participants provided recommendations for improving the system (eg, tailoring signaling times). CONCLUSIONS: mNCANDA provides a feasible, multi-year, continuous, fine-grained (eg, weekly) assessment of health behaviors designed to minimize respondent burden and provides acceptable regimes for long-term self-reporting of health behaviors. Fine-grained characterization of variability in behaviors over relatively long periods (eg, up to 18 months) may, through the use of mNCANDA, improve our understanding of the relationship between substance use exposure and neurocognitive development.

Prospective changes in neural alcohol cue reactivity in at-risk adolescents.

Adolescence represents an ideal time for elucidating the etiology of cue reactivity profiles. This study examined the influence of three risk factors consistently associated with heavy adolescent drinking on alcohol cue reactivity. Youth were first assessed while still naïve to alcohol (12-14 years old) and followed after transitioning into alcohol use (17-21 years old). The effects of family history of substance use disorder, sex, and history of early of dating (i.e., before 14 years of age) on BOLD response contrast to alcohol picture cues were examined in a linear mixed model, controlling for age and alcohol use patterns at follow-up. Activation to alcohol picture cues differed as a function of risk factor and time. At baseline, family history positive youth showed greater activation to alcohol cues than family history negative peers in the right middle occipital and anterior cingulate gyri. Youth with a history of early-dating showed greater activation to alcohol cues, compared to non-early daters, in the left anterior cingulate/white matter region. Girls showed greater activation to alcohol than boys at baseline in left middle frontal gyrus. At follow-up, after drinking started, patterns reversed for each risk factor. These results indicate that even prior to initiating alcohol use, adolescents showed differences in activation to alcohol cues based on their family history, dating history, and sex.

Striatopallidal regulation of affect in bipolar disorder.

BACKGROUND: Evidence from the neuroimaging literature suggests that the basal ganglia plays an important role in the regulation of affect. This conclusion stems almost exclusively from group comparisons and it remains unclear whether previous findings can be confirmed from a longitudinal study of mood change. The aim of this study was to increase our understanding of the functional role of the basal ganglia and thalamus in relation to change in affect in patients with bipolar disorder. METHODS: Ten bipolar disorder subjects participated in a functional MRI study. We used a simple motor reaction time task to probe subcortical regions bilaterally. Subjects were scanned twice, once when their self-reported mood ratings indicated hypomania or euthymia and then again when they were in depressed states. RESULTS: Subjects in their euthymic or hypomanic states exhibited increased caudate activity bilaterally and the globus pallidus of the left hemisphere. Longitudinal analyses revealed a significant association between an increase in severity of depression and a decrease in activity in the external segment of the right globus pallidus. CONCLUSIONS: Our findings suggest that the globus pallidus is less responsive during a simple motor task in the depressed compared to the normal or euthymic states in patients with bipolar disorder. These results are consistent with current physiologic models of basal ganglia circuitry in which an increase in caudate activity results in an increase in inhibitory GABAergic outflow to the external globus pallidus and subsequent decrease in thalamocortical excitation and may underlie the clinical manifestations of depression in bipolar disorder. LIMITATIONS: The findings of this study need to be interpreted with caution as correlation coefficients may be overestimated in this small study sample.

A functional magnetic resonance imaging study of cortical asymmetry in bipolar disorder.

OBJECTIVES: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the study was to examine effects of psychotropic medications on blood volume changes in the motor cortices. METHODS: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks. RESULTS: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects. CONCLUSIONS: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

A quantitative neuromotor predictor of antidepressant non-response in patients with major depression.

Predicting response to antidepressant medication has been a challenge to clinicians and researchers for decades. Attention has been paid to the role of motor retardation as a putative indicator of treatment response, yet previous findings have been mixed. One reason for this inconsistency may be related to the subjective nature of motor retardation and how it is assessed. In the present study, we adopted a measure of motor programming previously shown to characterize parkinsonian bradykinesia to test whether neuromotor function could predict response to antidepressant treatment. Twenty-eight patients (14 males and 14 females with a mean age of 42.0 years) meeting DSM-IV criteria for a depressive disorder were randomized to receive 8 weeks of treatment with one of three antidepressant medications (sertraline, phenelzine, or bupropion). Treatment outcomes were assessed using the 17-item version of the Hamilton Rating Scale for Depression (HRSD). Patients were considered asymptomatic if their post-treatment HRSD total score was equal to or less than 7. Treatment responders (n=15) had significantly less baseline impairment (P=0.01) on the neuromotor measure than non-responders (n=13). There was a significant relationship between amount of improvement on the HRSD and severity of baseline neuromotor function (r=-0.51; P=0.006). No significant group effects were found for baseline psychomotor slowing or clinical ratings of motor retardation. These results demonstrate that a quantitative measure of motor programming may be a useful predictor of antidepressant non-response.

An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder.

Structural neuroimaging studies have identified abnormalities in the basal ganglia in patients with bipolar disorder. Findings have been mixed with regard to affective state and have not elaborated on the role of medication on functional brain activity. The aims of the present study were to use functional magnetic resonance imaging (fMRI) to test whether depressed and manic bipolar disorder patients differ in terms of activity in cortical and subcortical brain areas and to examine the effects of psychotropic medication. Twenty-four bipolar disorder subjects and 13 healthy comparison subjects participated in an fMRI study of manual reaction time. Both manic and depressed subjects exhibited abnormally elevated blood oxygen level dependent BOLD responses in cortical and subcortical areas. Manic bipolar subjects had significantly higher BOLD responses in the left globus pallidus and significantly lower BOLD responses in the right globus pallidus compared with depressed bipolar patients. Correlational analyses revealed significant relationships between the severity of mania and activity within the globus pallidus and caudate. Patients off antipsychotic or mood-stabilizing medication exhibited significantly higher BOLD responses throughout the motor cortex, basal ganglia and thalamus compared with patients on these medications. These results suggest that affective state in bipolar disorder may be related to a disturbance of inhibitory regulation within the basal ganglia and that antipsychotics and/or mood stabilizers normalize cortical and subcortical hyperactivity.