Dendrites differ from axons in patterns of microtubule stability and polymerization during development

BACKGROUND: Dendrites differ from axons in patterns of growth and development, as well as in morphology. Given that microtubules are key structural elements in cells, we assessed patterns of microtubule stability and polymerization during hippocampal neuron development in vitro to determine if these aspects of microtubule organization could distinguish axons from dendrites. RESULTS: Quantitative ratiometric immunocytochemistry identified significant differences in microtubule stability between axons and dendrites. Most notably, regardless of developmental stage, there were high levels of dynamic microtubules throughout the dendritic arbor, whereas dynamic microtubules were predominantly concentrated in the distal end of axons. Analysis of microtubule polymerization using green fluorescent protein-tagged EB1 showed both developmental and regional differences in microtubule polymerization between axons and dendrites. Early in development (for example, 1 to 2 days in vitro), polymerization events were distributed equally in both the anterograde and retrograde directions throughout the length of both axons and dendrites. As development progressed, however, polymerization became biased, with a greater number of polymerization events in distal than in proximal and middle regions. While polymerization occurred almost exclusively in the anterograde direction for axons, both anterograde and retrograde polymerization was observed in dendrites. This is in agreement with predicted differences in microtubule polarity within these compartments, although fewer retrograde events were observed in dendrites than expected. CONCLUSION: Both immunocytochemical and live imaging analyses showed that newly formed microtubules predominated at the distal end of axons and dendrites, suggesting a common mechanism that incorporates increased microtubule polymerization at growing process tips. Dendrites had more immature, dynamic microtubules throughout the entire arbor than did axons, however. Identifying these differences in microtubule stability and polymerization is a necessary first step toward understanding how they are developmentally regulated, and may reveal novel mechanisms underlying neuron maturation and dendritic plasticity that extend beyond the initial specification of polarity

Cigarette Smoking Progression Among Young Adults Diagnosed With ADHD in Childhood: A 16-year Longitudinal Study of Children With and Without ADHD.

INTRODUCTION:Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for smoking cigarettes, but there is little longitudinal research on the array of smoking characteristics known to be prognostic of long-term smoking outcomes into adulthood. These variables were studied into early adulthood in a multisite sample diagnosed with ADHD combined type at ages 7-9.9 and followed prospectively alongside an age- and sex-matched local normative comparison group (LNCG). METHODS:Cigarette smoking quantity, quit attempts, dependence, and other characteristics were assessed in the longitudinal Multimodal Treatment Study of Children with ADHD (MTA) eight times to a mean age of 24.9 years: ADHD n = 469; LNCG n = 240. RESULTS:In adulthood, the ADHD group had higher rates of daily cigarette smoking, one or more quit attempts, shorter time to first cigarette of the day, and more severe withdrawal than the LNCG. The ADHD group did not appear to have better smoking cessation rates despite a higher proportion quitting at least once. Smoking quantity and nicotine dependence did not differ between groups. The ADHD group reported younger daily smoking onset and faster progression from smoking initiation to daily smoking across assessments. Finally, ADHD symptom severity in later adolescence and adulthood was associated with higher risk for daily smoking across assessments in the ADHD sample. CONCLUSIONS:This study shows that ADHD-related smoking risk begins at a young age, progresses rapidly, and becomes resistant to cessation attempts by adulthood. Prevention efforts should acknowledge the speed of uptake; treatments should target the higher relapse risk in this vulnerable population. IMPLICATIONS:Although childhood ADHD predicts later smoking, longitudinal studies of this population have yet to fully characterize smoking behaviors into adulthood that are known to be prognostic of long-term smoking outcome. The current study demonstrates earlier and faster progression to daily smoking among those with a childhood ADHD diagnosis, as well as greater risk for failed quit attempts. Prevention efforts should address speed of smoking uptake, while treatments are needed that address smoking relapse risk. The current study also demonstrates ADHD symptom severity over development increases daily smoking risk, implicating the need for continuous ADHD symptom management

Corrigendum: Cigarette smoking progression among young adults diagnosed with ADHD in Childhood: A 16-year longitudinal study of children with and without ADHD (Nicotine and Tobacco Research (2018) DOI: 10.1093/ntr/nty045)

Corrections have been made throughout the article to clarify how daily smoking during the 12- through 16-year assessments was defined in the original report. In this corrigendum, daily smoking during these assessments was defined by participant's responding either (a) once a day or more in response to In the past year, how often did you smoke cigarettes? or (b) responding yes to Are you currently a daily smoker? The authors repeated their analyses and this updated definition of daily smoking did not change findings in terms of statistical significance for Aims 1, 2, or 3 with one exception. In Aim 2, the initiation age (linear) by childhood ADHD status interaction was significant in this correction (p=.025), indicating that progression to daily smoking was faster for LNCG participants who initiated smoking at an older age than ADHD participants. For instance, mean latency was 5.61 years (SD=3.28) for ADHD participants and 5.29 (SD=3.22) for LNCG participants who initiated at 17 year-old or younger, but 2.14 (SD=2.26) for ADHD participants and 1.20 (SD=1.23) for LNCG participants who initiated at 18 years-old and older. This re-analysis did not impact the main findings from this study. This corrigendum includes updated values in the main article and supplemental material based on how we operationalize daily smoking status between 12- through 16-year assessments. The authors also clarify that for the 2- through 10-year assessments, participants were coded as daily smokers if they smoked at least one cigarette per day in response to During the past month, how many cigarettes have you smoked on an average day? The authors also clarify in this correction that weekly smoking in Aim 1 analysis was defined as those who responded once a week or more in response to In the past year, how often did you smoke cigarettes? These two clarifications did not require any re-analysis

Cigarette Smoking Progression Among Young Adults Diagnosed With ADHD in Childhood: A 16-year Longitudinal Study of Children With and Without ADHD

INTRODUCTION: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for smoking cigarettes, but there is little longitudinal research on the array of smoking characteristics known to be prognostic of long-term smoking outcomes into adulthood. These variables were studied into early adulthood in a multisite sample diagnosed with ADHD combined type at ages 7-9.9 and followed prospectively alongside an age- and sex-matched local normative comparison group (LNCG). METHODS: Cigarette smoking quantity, quit attempts, dependence, and other characteristics were assessed in the longitudinal Multimodal Treatment Study of Children with ADHD (MTA) eight times to a mean age of 24.9 years: ADHD n = 469; LNCG n = 240. RESULTS: In adulthood, the ADHD group had higher rates of daily cigarette smoking, one or more quit attempts, shorter time to first cigarette of the day, and more severe withdrawal than the LNCG. The ADHD group did not appear to have better smoking cessation rates despite a higher proportion quitting at least once. Smoking quantity and nicotine dependence did not differ between groups. The ADHD group reported younger daily smoking onset and faster progression from smoking initiation to daily smoking across assessments. Finally, ADHD symptom severity in later adolescence and adulthood was associated with higher risk for daily smoking across assessments in the ADHD sample. CONCLUSIONS: This study shows that ADHD-related smoking risk begins at a young age, progresses rapidly, and becomes resistant to cessation attempts by adulthood. Prevention efforts should acknowledge the speed of uptake; treatments should target the higher relapse risk in this vulnerable population. IMPLICATIONS: Although childhood ADHD predicts later smoking, longitudinal studies of this population have yet to fully characterize smoking behaviors into adulthood that are known to be prognostic of long-term smoking outcome. The current study demonstrates earlier and faster progression to daily smoking among those with a childhood ADHD diagnosis, as well as greater risk for failed quit attempts. Prevention efforts should address speed of smoking uptake, while treatments are needed that address smoking relapse risk. The current study also demonstrates ADHD symptom severity over development increases daily smoking risk, implicating the need for continuous ADHD symptom management

How Substance Users With ADHD Perceive the Relationship Between Substance Use and Emotional Functioning.

ObjectiveAlthough substance use (SU) is elevated in ADHD and both are associated with disrupted emotional functioning, little is known about how emotions and SU interact in ADHD. We used a mixed qualitative-quantitative approach to explore this relationship.MethodNarrative comments were coded for 67 persistent (50 ADHD, 17 local normative comparison group [LNCG]) and 25 desistent (20 ADHD, 5 LNCG) substance users from the Multimodal Treatment Study of Children with ADHD (MTA) adult follow-up (21.7-26.7 years-old).ResultsSU persisters perceived SU positively affects emotional states and positive emotional effects outweigh negative effects. No ADHD group effects emerged. Qualitative analysis identified perceptions that cannabis enhanced positive mood for ADHD and LNCG SU persisters, and improved negative mood and ADHD for ADHD SU persisters.ConclusionPerceptions about SU broadly and mood do not differentiate ADHD and non-ADHD SU persisters. However, perceptions that cannabis is therapeutic may inform ADHD-related risk for cannabis use