Publications by authors named "Susan Andersen"

106 Publications

Single-molecule fluorescence detection of a tricyclic nucleoside analogue.

Chem Sci 2020 Dec 28;12(7):2623-2628. Epub 2020 Dec 28.

Department of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University San Diego CA 92182 USA

Fluorescent nucleobase surrogates capable of Watson-Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics, but their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Aiming to improve on these properties, we designed a new tricyclic pyrimidine nucleoside analogue with a push-pull conjugated system and synthesized it in seven sequential steps. The resulting -linked 8-(diethylamino)benzo[][1,8]naphthyridin-2(1)-one nucleoside, which we name ABN, exhibits = 20 000 M cm and = 0.39 in water, increasing to = 0.50-0.53 when base paired with adenine in duplex DNA oligonucleotides. Single-molecule fluorescence measurements of ABN using both one-photon and two-photon excitation demonstrate its excellent photostability and indicate that the nucleoside is present to > 95% in a bright state with count rates of at least 15 kHz per molecule. This new fluorescent nucleobase analogue, which, in duplex DNA, is the brightest and most red-shifted known, is the first to offer robust and accessible single-molecule fluorescence detection capabilities.
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http://dx.doi.org/10.1039/d0sc03903aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179283PMC
December 2020

Reducing smoking in youth by a smoke-free school environment: A stratified cluster randomized controlled trial of Focus, a multicomponent program for alternative high schools.

Tob Prev Cessat 2021 2;7:42. Epub 2021 Jun 2.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Youth smoking remains a major challenge for public health. Socioeconomic position influences the initiation and maintenance of smoking, and alternative high school students are at particularly high risk. The school environment is an important setting to promote health, however there is a lack of evidence-based school intervention programs. This article presents the Focus study, which aims to test the implementation and effectiveness of a school-based intervention integrating a comprehensive school smoking policy [i.e. smoke-free school hours (SFSH)], a course for school staff in short motivational conversations, school class-based teaching material, an edutainment session5, a class-based competition, and6 access to smoking cessation support. Together these intervention components address students' acceptability of smoking, social influences, attitudes, motivation, and opportunities for smoking. The setting is alternative high schools across Denmark, and the evaluation design is based on a stratified cluster randomized controlled trial comparing the intervention group to a control group. Outcome data is collected at baseline, midway, and at the end of the intervention period. Moreover, a detailed process evaluation, using qualitative and quantitative methods, is conducted among students, teachers, and school principals. The results from this trial will provide important knowledge on the effectiveness of a smoke-free school environment. The findings will lead to a better understanding of which policies, environments, and cognitions, contribute to preventing and reducing cigarette use among young people in a diverse and high-risk school setting, and illuminate which complementary factors are significant to achieve success when implementing SFSH.
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http://dx.doi.org/10.18332/tpc/133934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171329PMC
June 2021

Academic Tenure: Perceptual Variations Among Tenured, Tenure-seeking and Non-tenure Faculty.

J Prof Nurs 2021 May-Jun;37(3):578-587. Epub 2021 Mar 5.

School of Nursing, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430, MS 6264, United States of America. Electronic address:

Background: Tenure is a hallmark of higher education, but its value and relevance is questioned.

Purpose: This study examined faculty perceptions of the value of tenured and non-tenured nursing faculty appointments.

Methods: A descriptive correlational design using an anonymous survey was sent to members of the American Association of College of Nursing. Participants (N = 542) from 44 states completed the survey.

Results: Significant differences in workload were found in teaching, administrative responsibilities, scholarship, and academic service. Compared to non-tenured faculty, tenured faculty had higher scores on Career Opportunities (p < 0.001), lower Life Balance scores (p = 0.001) and higher Academic Support scores (p = 0.014). Non-tenured faculty were less likely to agree than tenured faculty that tenure improves quality of education (χ2 = 86.48, p < 0.001) or is relevant to the modern university (χ2 = 75.20, p < 0.001). Narrative responses revealed six themes about tenure. Faculty on both tracks questioned the value of tenure.

Conclusions: Faculties in schools of nursing nationwide need to re-evaluate the purpose of tenure and the tenure criteria in light of each institution's unique mission and expectations to determine how they are meeting the needs of both academic institution and nursing faculty. Although the idea of tenure is institutional, implementation is initiated at the school level. Our study revealed naivete about tenure among nursing faculty at the school level.
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http://dx.doi.org/10.1016/j.profnurs.2021.03.002DOI Listing
June 2021

Building nurse resilience in the workplace.

Appl Nurs Res 2021 06 14;59:151433. Epub 2021 Apr 14.

Texas Tech University Health Sciences Center School of Nursing, 3601 4th St., MS 6264, Lubbock, TX 79430, USA. Electronic address:

Aims: The aims of the study were 1) to replicate the research based on the pilot study; 2) to increase resilience in nurses working on all units at four hospitals and 3) to determine which interventions were preferred and most effective.

Background: Work stress mediates resilience and resilience moderates work stress. Resilience building activities in the literature are often time consuming, complex and done outside work hours. This study investigated use of portable, accessible and brief interventions by nurses to decrease stress and increase resilience during work hours.

Methods: This study used a cross sectional, longitudinal, repeated measures survey design. The study took place in October 2018 to January 2019. Toolkits included written instructions for completing the study protocol, and six activities. Nurses completed surveys at baseline, at 10 time points over a four- to six-week period, and at study conclusion.

Results: Connor-Davidson Resilience Scale-10 instrument scores showed resilience increased significantly at four weeks and the effect continued at three months (p < .02). Self-reported stress levels decreased over the study period and nurses self-selected to continue use of the interventions.

Conclusion: The interventions used during work hours decreased self-reported stress and increased resilience. Nurse leaders may easily adopt these options to promote a less stressed workforce. Resilience can increase the ability of nurses to tolerate high stress in the workplace, which may decrease burnout and turnover. In the pandemic, resilience is even more important as hospitals struggle to retain nurses.
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http://dx.doi.org/10.1016/j.apnr.2021.151433DOI Listing
June 2021

Exploring Strategies to Build Resiliency in Nurses During Work Hours.

J Nurs Adm 2021 Apr;51(4):185-191

Author Affiliations: Associate Professor (Drs Mintz-Binder and Andersen), School of Nursing, Texas Tech University Health Sciences Center, Lubbock; Director of Magnet Program and Centralized Nursing (Ms Sweatt), Methodist Mansfield Medical Center, Mansfield; and Health Science Center Senior Research Associate (Dr Song), School of Nursing, Texas Tech University Health Sciences Center, Lubbock.

Objective: This pilot study investigated increasing nurse resiliency utilizing a toolkit of stress-reducing interventions on medical-surgical units at 4 hospitals.

Background: Resiliency-building activities are time consuming and undertaken outside work hours. Although the activities show a positive impact on resilience, researchers investigated whether similar results could be achieved where nurses experience work stress.

Methods: This quasi-experimental pretest and posttest interventional study used a within-subjects design. Provided toolkits included written instructions to carry out the study. Nurses completed surveys at baseline, at 10 time points over a 6-week period, and at study conclusion.

Results: The Connor-Davidson Resilience Scale-10 scores increased significantly at follow-up (P < .02). Self-reported stress levels decreased over the 10 shifts with continued use of the interventions.

Conclusion: Using stress-reducing interventions during work decreased stress and increased resiliency, thereby offering nurse leaders additional options to promote a healthy workforce at the bedside.
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http://dx.doi.org/10.1097/NNA.0000000000000996DOI Listing
April 2021

Assessing Differences in the Implementation of Smoke-Free Contracts-A Cross-Sectional Analysis from the School Randomized Controlled Trial X:IT.

Int J Environ Res Public Health 2021 02 23;18(4). Epub 2021 Feb 23.

Steno Diabetes Center, Hedeager 3, 8200 Aarhus, Denmark.

Objective: The X:IT study is a school-based smoking preventive intervention that has previously been evaluated in a large randomized controlled trial (RCT) with good effects. However, the actual effect for participating students depends on the individual implementation. The aim of this study was to examine the implementation of smoke-free contract, which is one of the three main intervention components. Specifically, we examined whether it was implemented equally across family occupational social class (OSC), separately for boys and girls, the joint effect of OSC and gender, and the participants' own reasons for not signing a contract.

Results: Overall, the smoke-free contract was well implemented; 81.8% of pupils (total N = 2.015) signed a contract (girls 85.1, boys 78.6%). We found a social gradient among girls; more than 90% were in OSC group I vs. 75% in group VI. Among boys, however, we found no difference across OSC. Boys in all the OSC groups had about half the odds (i.e., medium OSC boys: OR = 0.48 (95% CI: 0.32-0.72) of having a smoke-free contract compared to girls from a high OSC.

Conclusion: future interventions should include initiatives to involve families from all OSC groups and allow for different preferences among boys and girls.
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http://dx.doi.org/10.3390/ijerph18042163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926470PMC
February 2021

Novelty preferences and cocaine-associated cues influence regions associated with the salience network in juvenile female rats.

Pharmacol Biochem Behav 2021 04 6;203:173117. Epub 2021 Feb 6.

McLean Hospital, Department of Psychiatry, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, United States of America. Electronic address:

Preferences for novel environments (novelty-seeking) is a risk factor for addiction, with little known about its underlying circuitry. Exposure to drug cues facilitates addiction maintenance, leading us to hypothesize that exposure to a novel environment activates a shared neural circuitry. Stimulation of the D1 receptor in the prelimbic cortex increases responsivity to drug-associated environments. Here, we use D1 receptor overexpression in the prelimbic cortex to probe brain responses to novelty-preferences (in a free-choice paradigm) and cocaine-associated odors following place conditioning. These same cocaine-conditioned odors were used to study neural circuitry with Blood Oxygen Level Dependent (BOLD) activity. D1 overexpressing females had deactivated BOLD signals related to novelty-preferences within the insula cortex and amygdala and activation in the frontal cortex and dopamine cell bodies. BOLD responses to cocaine cues were also sensitive to D1. Control females demonstrated a place preference for cocaine environments with no significant BOLD response, while D1 overexpressing females demonstrated a place aversion and weak BOLD responses to cocaine-conditioned odor cues within the insula cortex. For comparison, we provide data from an earlier study with juvenile males overexpressing D1 that show a strong preference for cocaine and elevated BOLD responses. The results support the use of a pharmacological manipulation (e.g., D1 overexpression) to probe the neural circuitry downstream from the prelimbic cortex.
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http://dx.doi.org/10.1016/j.pbb.2021.173117DOI Listing
April 2021

Estimating future smoking in Danish youth - effects of three prevention strategies.

Scand J Public Health 2020 Aug 14:1403494820942678. Epub 2020 Aug 14.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Preventing smoking and aiding cessation among youth and young adults carries the possibility of reducing future smoking prevalence significantly. This paper estimates the impact on future smoking prevalence of 25 year olds by increasing tobacco prices, securing indoor smoke-free homes and implementing school-based multi-tiered interventions. Utilizing a multi-state Markov model, a status quo projection of the smoking prevalence from years 2017 to 2030 were compared with projections of the smoking prevalence in 2030 considering the impact of the three prevention strategies. In a status quo projection, 27.0% of Danish 25-year-old females are expected to be smokers in 2030, while 13.2% would be smokers in 2030 were all three prevention strategies in effect from 2019. By itself, increasing tobacco prices by 50% reduced the prevalence of smokers among 25-year-old females to 14.8% in 2030, a relative reduction of 47.5%. For 25-year-old males in 2030 the reductions were similar, with a prevalence of 16.6% when all three prevention strategies were in effect, a relative reduction of 51.5%.
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http://dx.doi.org/10.1177/1403494820942678DOI Listing
August 2020

This is your teen brain on drugs: In search of biological factors unique to dependence toxicity in adolescence.

Neurotoxicol Teratol 2020 Sep - Oct;81:106916. Epub 2020 Jul 19.

Exponent, Inc. Health Sciences, San Francisco, CA 94114, United States of America.

Response variability across the lifespan is an important consideration in toxicology and risk assessment, and the toxic effects of drugs and chemicals during adolescence need more research. This paper summarizes a workshop presented in March 2019, at the Society of Toxicology Annual Meeting in Baltimore, Maryland, that brought together experts in research on drug dependence and toxicity related to nicotine, cannabis, cocaine, and other illicit drugs during adolescence. The goal of the workshop was to address the following issues: (1) Do the effects of adolescent exposure differ from the same exposure in adults? (2) Are there unique biological markers of adolescent brain development? If so, what are they and how reliable are they? (3) Since multiple factors influence substance use disorder, can we disentangle risk factors for abuse and/or toxicity? What are the underlying biological susceptibilities that lead to dependence and neurotoxicity? What are the social, psychosocial and environmental factors that contribute to abuse susceptibilities? This paper reviews drug policy and national trends in adolescent substance use; the public health consequences of e-cigarettes; rat models of adolescent-onset nicotine self-administration and persisting effects of gestational nicotine; sex-dependent effects of delta-9-tetrahydrocannabinol on adolescent brain-behavior relationships; and translational approaches for identifying adolescent risk factors for transition to drug dependence. There is strong evidence that drug exposure prior to adulthood has longer lasting effects on behavior and the underlying neural circuitry. These effects, which are sex-dependent and influenced by stress, may be candidates as predictors of adolescent vulnerability. A major challenge to determining if adolescents have a unique susceptibility to dependence is whether and to what extent the human data allow distinction between the increased risk due to biological immaturity, an underlying biological susceptibility to dependence, or psychosocial and environmental factors for substance dependence. Factors important to consider for development of animal models include the timing and pattern of exposure as it relates to adolescence; age of assessment, and direct comparison with similar effects following exposures to adults to demonstrate that these effects are unique to adolescence. Here we provide a roadmap for further research into what makes adolescent brain development unique.
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http://dx.doi.org/10.1016/j.ntt.2020.106916DOI Listing
July 2020

Body therapy versus treatment as usual among Danish veterans with PTSD: Study protocol for a randomised controlled trial combined with a qualitative study.

Contemp Clin Trials Commun 2020 Sep 20;19:100596. Epub 2020 Jun 20.

National Institute of Public Health, University of Southern Denmark, Studiestræde 6, DK-1455, Copenhagen, Denmark.

Background: Many veterans suffer from Post-Traumatic Stress Disorder (PTSD) after returning from military missions. This implies complex physical and psychosocial problems for veterans and their families. Treatment options today are primarily medically and psychologically founded but treatment response is incomplete. Body therapy for PTSD is scarcely researched though subject of increased attention. In 2015, a Danish pilot study was conducted exploring body therapy for PTSD. The study showed positive results and formed basis for a randomised controlled trial. This paper outlines the protocol for this trial.

Methods: The intervention will be evaluated in a two-arm randomised controlled trial (1:1). The trial will include 42 veterans with PTSD recruited by the Danish Military Psychiatric Centre. The intervention group receives treatment as usual and weekly body therapy treatment as add-on. The control group receives treatment as usual (TAU). Participants will complete four questionnaires assessing PTSD, depression, quality of life, function level and body awareness: at baseline, and at 3 months, 6 months and 12 months post baseline. Linear regression models and mixed effects models will be used to assess intervention effects. Furthermore, an ethnographic study will examine how the participants experience the treatment and changes in their everyday life. The ethnographic study is based on in-depth interviews, participant observations and focus groups. A mixed method, convergent parallel design will be applied.

Discussion: This study examines the efficacy of body therapy for veterans with PTSD and how the treatment is experienced and affects daily life. The study will contribute with important knowledge on an alternative treatment for PTSD.

Trial Registration: ClinicalTrials.gov Identifier: NCT03777800.
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http://dx.doi.org/10.1016/j.conctc.2020.100596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322676PMC
September 2020

An 1,4-α-Glucosyltransferase Defines a New Maltodextrin Catabolism Scheme in Lactobacillus acidophilus.

Appl Environ Microbiol 2020 07 20;86(15). Epub 2020 Jul 20.

Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark

The maltooligosaccharide (MOS) utilization locus in NCFM, a model for human small-intestine lactobacilli, encodes three glycoside hydrolases (GHs): a putative maltogenic α-amylase of family 13, subfamily 20 (GH13_20), a maltose phosphorylase of GH65 (GH65), and a family 13, subfamily 31, member (GH13_31B), annotated as a 1,6-α-glucosidase. Here, we reveal that GH13_31B is a 1,4-α-glucosyltransferase that disproportionates MOS with a degree of polymerization of ≥2, with a preference for maltotriose. Kinetic analyses of the three GHs encoded by the MOS locus revealed that the substrate preference of GH13_31B toward maltotriose complements the ~40-fold lower of GH13_20 toward this substrate, thereby enhancing the conversion of odd-numbered MOS to maltose. The concerted action of GH13_20 and GH13_31B confers the efficient conversion of MOS to maltose that is phosphorolyzed by GH65. Structural analyses revealed the presence of a flexible elongated loop that is unique for a previously unexplored clade of GH13_31, represented by GH13_31B. The identified loop insertion harbors a conserved aromatic residue that modulates the activity and substrate affinity of the enzyme, thereby offering a functional signature of this clade, which segregates from 1,6-α-glucosidases and sucrose isomerases previously described within GH13_31. Genomic analyses revealed that the GH13_31B gene is conserved in the MOS utilization loci of lactobacilli, including acidophilus cluster members that dominate the human small intestine. The degradation of starch in the small intestine generates short linear and branched α-glucans. The latter are poorly digestible by humans, rendering them available to the gut microbiota, e.g., lactobacilli adapted to the small intestine and considered beneficial to health. This study unveils a previously unknown scheme of maltooligosaccharide (MOS) catabolism via the concerted activity of an 1,4-α-glucosyltransferase together with a classical hydrolase and a phosphorylase. The intriguing involvement of a glucosyltransferase likely allows the fine-tuning of the regulation of MOS catabolism for optimal harnessing of this key metabolic resource in the human small intestine. The study extends the suite of specificities that have been identified in GH13_31 and highlights amino acid signatures underpinning the evolution of 1,4-α-glucosyl transferases that have been recruited in the MOS catabolism pathway in lactobacilli.
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http://dx.doi.org/10.1128/AEM.00661-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376546PMC
July 2020

Sluggish cognitive tempo and exposure to interpersonal trauma in children.

Anxiety Stress Coping 2020 01 9;33(1):100-114. Epub 2019 Dec 9.

Department of Psychiatry, McLean Hospital, Belmont, USA.

Childhood adversity has been suggested, but not yet empirically examined, as a factor in sluggish cognitive tempo (SCT) in childhood. This study was an examination of SCT in relation to childhood adversity, and its association with exposure to non-interpersonal and interpersonal trauma. Caregivers ( = 161) and a sub-sample of children, 8-17 years old, were recruited from mental health and pediatric practices/programs and interviewed. SCT was positively associated with interpersonal trauma but not non-interpersonal trauma. Two hierarchical regression analyses revealed that interpersonal trauma exposure was associated with SCT score over and above symptoms of other psychopathologies. Results suggest that SCT is associated with interpersonal trauma exposure in children. Further research is needed to examine the association between SCT and interpersonal trauma exposure, and trauma-related biopsychosocial impairments.
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http://dx.doi.org/10.1080/10615806.2019.1695124DOI Listing
January 2020

Roles of the N-terminal domain and remote substrate binding subsites in activity of the debranching barley limit dextrinase.

Biochim Biophys Acta Proteins Proteom 2020 01 30;1868(1):140294. Epub 2019 Oct 30.

Enzyme and Protein Chemistry, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, building 224, DK 2800 Kgs. Lyngby, Denmark. Electronic address:

Barley limit dextrinase (HvLD) of glycoside hydrolase family 13 is the sole enzyme hydrolysing α-1,6-glucosidic linkages from starch in the germinating seed. Surprisingly, HvLD shows 150- and 7-fold higher activity towards pullulan and β-limit dextrin, respectively, than amylopectin. This is investigated by mutational analysis of residues in the N-terminal CBM-21-like domain (Ser14Arg, His108Arg, Ser14Arg/His108Arg) and at the outer subsites +2 (Phe553Gly) and +3 (Phe620Ala, Asp621Ala, Phe620Ala/Asp621Ala) of the active site. The Ser14 and His108 mutants mimic natural LD variants from sorghum and rice with elevated enzymatic activity. Although situated about 40 Å from the active site, the single mutants had 15-40% catalytic efficiency compared to wild type for the three polysaccharides and the double mutant retained 27% activity for β-limit dextrin and 64% for pullulan and amylopectin. These three mutants hydrolysed 4,6-O-benzylidene-4-nitrophenyl-6-α-d-maltotriosyl-maltotriose (BPNPG3G3) with 51-109% of wild-type activity. The results highlight that the N-terminal CBM21-like domain plays a role in activity. Phe553 and the highly conserved Trp512 sandwich a substrate main chain glucosyl residue at subsite +2 of the active site, while substrate contacts of Phe620 and Asp621 at subsite +3 are less prominent. Phe553Gly showed 47% and 25% activity on pullulan and BPNPG3G3, respectively having a main role at subsite +2. By contrast at subsite +3, Asp621Ala increased activity on pullulan by 2.4-fold, while Phe620Ala/Asp621Ala retained only 7% activity on pullulan albeit showed 25% activity towards BPNPG3G3. This outcome supports that the outer substrate binding area harbours preference determinants for the branched substrates amylopectin and β-limit dextrin.
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http://dx.doi.org/10.1016/j.bbapap.2019.140294DOI Listing
January 2020

Experience during adolescence shapes brain development: From synapses and networks to normal and pathological behavior.

Neurotoxicol Teratol 2019 Nov - Dec;76:106834. Epub 2019 Sep 7.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA, United States of America.

Adolescence is a period of dramatic neural reorganization creating a period of vulnerability and the possibility for the development of psychopathology. The maturation of various neural circuits during adolescence depends, to a large degree, on one's experiences both physical and psychosocial. This occurs through a process of plasticity which is the structural and functional adaptation of the nervous system in response to environmental demands, physiological changes and experiences. During adolescence, this adaptation proceeds upon a backdrop of structural and functional alterations imparted by genetic and epigenetic factors and experiences both prior to birth and during the postnatal period. Plasticity entails an altering of connections between neurons through long-term potentiation (LTP) (which alters synaptic efficiency), synaptogenesis, axonal sprouting, dendritic remodeling, neurogenesis and recruitment (Skaper et al., 2017). Although most empirical evidence for plasticity derives from studies of the sensory systems, recent studies have suggested that during adolescence, social, emotional, and cognitive experiences alter the structure and function of the networks subserving these domains of behavior. Each of these neural networks exhibits heightened vulnerability to experience-dependent plasticity during the sensitive periods which occur in different circuits and different brain regions at specific periods of development. This report will summarize some examples of adaptation which occur during adolescence and some evidence that the adolescent brain responds differently to stimuli compared to adults and children. This symposium, "Experience during adolescence shapes brain development: from synapses and networks to normal and pathological behavior" occurred during the Developmental Neurotoxicology Society/Teratology Society Annual Meeting in Clearwater Florida, June 2018. The sections will describe the maturation of the brain during adolescence as studied using imaging technologies, illustrate how plasticity shapes the structure of the brain using examples of pathological conditions such as Tourette's' syndrome and attention deficit hyperactivity disorder, and a review of the key molecular systems involved in this plasticity and how some commonly abused substances alter brain development. The role of stimulants used in the treatment of attention deficit hyperactivity disorder (ADHD) in the plasticity of the reward circuit is then described. Lastly, clinical data promoting an understanding of peer-influences on risky behavior in adolescents provides evidence for the complexity of the roles that peers play in decision making, a phenomenon different from that in the adult. Imaging studies have revealed that activation of the social network by the presence of peers at times of decision making is unique in the adolescent. Since normal brain development relies on experiences which alter the functional and structural connections between cells within circuits and networks to ultimately alter behavior, readers can be made aware of the myriad of ways normal developmental processes can be hijacked. The vulnerability of developing adolescent brain places the adolescent at risk for the development of a life time of abnormal behaviors and mental disorders.
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http://dx.doi.org/10.1016/j.ntt.2019.106834DOI Listing
May 2020

The use of laser capture microdissection to identify specific pathways and mechanisms involved in impulsive choice in rats.

Heliyon 2019 Aug 23;5(8):e02254. Epub 2019 Aug 23.

Laboratory of Developmental Neuropharmacology, McLean Hospital, Harvard Medical School, USA.

Background: Microinjections, lesions, viral-mediated gene transfer, or designer receptors exclusively activated by designer drugs (DREADDs) can identify brain signaling pathways and their pharmacology in research animals. Genetically modified animals are used for more precise assessment of neural circuits. However, only a few of the gene-based pathway modifications are available for use in outbred rat strains.

New Method: Behaviorally characterized Sprague-Dawley rats undergo tract tracing through microinjection of fluorospheres, followed by laser capture microdissection (LCM) and qPCR for detecting mRNA of pathway-associated gene products. Correlations between mRNA expression and behavior identify specific involvement of pharmacologically relevant molecules within cells of interest. Here, we examined this methodology in an impulsive choice paradigm and targeted projections from the orbital and medial prefrontal cortex.

Results: In this proof of concept study, we demonstrate relationships between measures of impulsive choice with distinct neurotransmitter receptor expression in cell populations from four different signaling pathways.

Comparisons With Existing Methods: Combining behavior, tract tracing, LCM, and gene expression profiling provides more cellular selectivity than localized lesions and DREADDs, and greater pharmacological specificity than microinjections and viral-mediated gene transfer due to targeting identified neurons. Furthermore, the assessment of inter-individual pathways provides insight into the complex nature of underlying mechanisms involved in typical and atypical behavior.

Conclusions: The novel combination of behavior, tract tracing, LCM, and single gene or potential whole genome transcriptome analysis allows for a more targeted understanding of the interconnection of neural circuitry with behavior, and holds promise to identify more specific drug targets that are relevant to behavioral phenotypes.
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http://dx.doi.org/10.1016/j.heliyon.2019.e02254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716106PMC
August 2019

Associations of school tobacco policies and legislation with youth smoking: a cross-sectional study of Danish vocational high schools.

BMJ Open 2019 07 24;9(7):e028357. Epub 2019 Jul 24.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Background: In vocational high schools, the prevalence of smoking is high (nearly 40% daily smoking in Danish vocational high schools). Schools are increasingly adopting school tobacco policies (STPs) and a national law on smoke-free school grounds has been implemented. Our objective was to explore the extent of STPs in vocational schools and examine the association of STPs and smoke-free school grounds legislation with student smoking.

Methods: We used data from the cross-sectional Danish National Youth Study 2014, including 5013 vocational high school students (76% male) at 40 campuses. Implementation of STPs was measured by questionnaires to principals and field observations of smoking practices were conducted. Logistic regression models assessed whether STP characteristics were associated with students' current smoking (ie, daily and occasional) compared with non-current smoking. Negative binominal regression models assessed cigarettes per day among daily smokers.

Results: Schools covered by the national law on smoke-free school ground had more comprehensive STPs than schools not covered by the law. Student smoking was observed on 78% of campuses, with less visibility of smoking in schools covered by the national law (69% vs 83%). Current smoking was lower for students attending a school covered by the national law (OR=0.86, 95% CI 0.75 to 0.97). Students who attended schools that allowed teacher-student smoking were more likely to smoke (OR=1.13, 95% CI 1.01 to 1.27).

Conclusions: A law on smoke-free school grounds was associated with less current smoking in vocational high schools, while school norms that are supportive of teacher-student smoking were associated with greater odds of current smoking. Visibility of student smoking was less prevalent at schools covered by the law on smoke-free school grounds; nevertheless, the visibility of smoking was high. Better enforcement or an extension of the current law on smoke-free school grounds is recommended.
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http://dx.doi.org/10.1136/bmjopen-2018-028357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661684PMC
July 2019

Stress, sensitive periods, and substance abuse.

Authors:
Susan L Andersen

Neurobiol Stress 2019 Feb 27;10:100140. Epub 2018 Nov 27.

McLean Hospital and Harvard Medical School, USA.

Research on the inter-relationship between drug abuse and social stress has primarily focused on the role of stress exposure during adulthood and more recently, adolescence. Adolescence is a time of heightened reward sensitivity, but it is also a time when earlier life experiences are expressed. Exposure to stress early in postnatal life is associated with an accelerated age of onset for drug use. Lifelong addiction is significantly greater if drug use is initiated during early adolescence. Understanding how developmental changes following stress exposure interact with sensitive periods to unfold over the course of maturation is integral to reducing their later impact on substance use. Arousal levels, gender/sex, inflammation, and the timing of stress exposure play a role in the vulnerability of these circuits. The current review focuses on how early postnatal stress impacts brain development during a sensitive period to increase externalizing and internalizing behaviors in adolescence that include social interactions (aggression; sexual activity), working memory impairment, and depression. How stress effects the developmental trajectories of brain circuits that are associated with addiction are discussed for both clinical and preclinical studies.
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http://dx.doi.org/10.1016/j.ynstr.2018.100140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288983PMC
February 2019

Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior.

Psychopharmacology (Berl) 2019 Feb 9;236(2):685-698. Epub 2018 Nov 9.

Laboratory of Developmental Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Rationale: Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females.

Objective: This study aims to determine sex differences and dose-dependent effects of juvenile exposure to MPH or guanfacine on delay-discounting and later cocaine self-administration.

Methods: The dose-dependent effects of vehicle, MPH (0.5, 1, and 2 mg/kg p.o.) or guanfacine (0.003, 0.03, and 0.3 mg/kg, i.p.) on discounting were determined in male and female Sprague-Dawley rats beginning at postnatal day (P)20. At P90, the amount, motivation, and sensitivity to cocaine following early drug exposure were determined with self-administration.

Results: Guanfacine, but not MPH, significantly reduced weight by 22.9 ± 4.6% in females. MPH dose dependently decreased delay discounting in both juvenile males and females, while guanfacine was only effective in males. Discounting was associated with cocaine self-administration in vehicle males (R = -0.4, P < 0.05) and self-administration was reduced by guanfacine treatment (0.3 mg/kg). Guanfacine significantly decreased cocaine sensitivity in both sexes.

Conclusions: These data suggest that MPH is effective in reducing delay discounting in both sexes. Due to both weight loss and ineffectiveness on discounting in females, guanfacine should be used only in males to reduce delay discounting and later cocaine use.
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http://dx.doi.org/10.1007/s00213-018-5096-0DOI Listing
February 2019

Effectiveness of the settings-based intervention Shaping the Social on preventing dropout from vocational education: a Danish non-randomized controlled trial.

BMC Psychol 2018 Sep 12;6(1):45. Epub 2018 Sep 12.

National Institute of Public Health, University of Southern Denmark, Studiestræde 6, DK-1455, Copenhagen, Denmark.

Background: Lack of formal education is an important social determinant of health inequality and represents a public health problem. School dropout is particularly common in vocational education; however few prevention programs targeting dropout in the vocational school setting have been evaluated. The purpose of the present study was to test the effect on school dropout of a settings-based intervention program (named Shaping the Social) that targeted the school organization in order to create social and supportive learning environments.

Methods: A non-randomized controlled design including four large intervention schools and six matched-control schools was used. The target population was students in technical and agricultural vocational education, which is provided to students from age 16. Students were enrolled at school start. Register-based data (n = 10,190) was used to assess the effect on school dropout during a 2-year period. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models, adjusting for age, sex, ethnicity, parental income, prior school dropout and type of basic course. Student survey (n = 2396) at 10-week follow-up was used to examine wellbeing at school (four subscales: school connectedness, student support, teacher relatedness, and valuing the profession) which was the hypothesized proximal intervention effect. As a secondary aim, we examined how the student wellbeing factors were associated with school dropout, independently of the intervention, and we explored whether the student wellbeing factors were potential mediators.

Results: The present study showed an intervention effect on school dropout with dropout rates lower in intervention schools (36%) than control schools (40%) (OR = 0.86, 95% CI: 0.74, 0.99). We had no attrition on the dropout outcome. School connectedness mediated the intervention effect; no significant mediation effects were found for student support, teacher relatedness, and valuing the profession. Independently of the intervention, each student wellbeing factor prevented dropout.

Conclusions: Findings from this study suggest that a comprehensive, multicomponent school-based intervention could prevent dropout from vocational education by promoting school connectedness; nevertheless, the dropout rate remained high. Our results point to the need to explore how to further improve the wellbeing at school among young people in vocational education.

Trials Registration: ISRCTN, ISRCTN57822968 . Registered 16 January 2013 (retrospective registered).
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http://dx.doi.org/10.1186/s40359-018-0258-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134754PMC
September 2018

Anhedonic behavior and γ-amino butyric acid during a sensitive period in female rats exposed to early adversity.

J Psychiatr Res 2018 05 13;100:8-15. Epub 2018 Feb 13.

Laboratory for Developmental Neuropharmacology, McLean Hospital, MA, 02478, United States; Harvard Medical School, United States. Electronic address:

Early life adversity increases depressive behavior that emerges during adolescence. Sensitive periods have been associated with fewer GABAergic interneurons, especially parvalbumin (PV), brain derived growth factor, and its receptor, TrkB. Here, maternal separation (MS) and social isolation (ISO) were used to establish a sensitive period for anhedonic depression using the learned helplessness (LH) paradigm. Female Sprague-Dawley rat pups underwent MS for 4-h/day or received typical care (CON) between postnatal days 2-20; for the ISO condition, separate cohorts were individually housed between days 20-40 or served as controls (CON2). Anhedonia was defined by dichotomizing subjects into two groups based on one standard deviation of the mean number of escapes for the CON group (<14). This approach categorized 22% of CON subjects and 44% of MS subjects as anhedonic (p < 0.05), similar to the prevalence in maltreated human populations. Only 12.5% of ISO rats met criterion versus 28.5% in CON2 rats. Levels of PV and TrkB were reduced in the amygdala and prelimbic prefrontal cortex (PFC) in MS rats with <14 escapes, but elevated in behaviorally resilient MS rats (>13 escapes). The number of escapes in MS subjects significantly correlated with PV and TrkB levels (PFC: r = 0.93 and 0.91 and amygdala: r = 0.63 and 0.81, respectively; n = 9), but not in CON/ISO/CON2 subjects. Calretinin, but not calbindin, was elevated in the amygdala of MS subjects. These data suggest that low levels of PV and TrkB double the risk for anhedonia in females with an MS history compared to normal adolescent females.
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http://dx.doi.org/10.1016/j.jpsychires.2018.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295145PMC
May 2018

Shared reality in interpersonal relationships.

Curr Opin Psychol 2018 10 24;23:42-46. Epub 2017 Nov 24.

University of Pennsylvania, USA. Electronic address:

Close relationships afford us opportunities to create and maintain meaning systems as shared perceptions of ourselves and the world. Establishing a sense of mutual understanding allows for creating and maintaining lasting social bonds, and as such, is important in human relations. In a related vein, it has long been known that knowledge of significant others in one's life is stored in memory and evoked with new persons-in the social-cognitive process of 'transference'-imbuing new encounters with significance and leading to predictable cognitive, evaluative, motivational, and behavioral consequences, as well as shifts in the self and self-regulation, depending on the particular significant other evoked. In these pages, we briefly review the literature on meaning as interpersonally defined and then selectively review research on transference in interpersonal perception. Based on this, we then highlight a recent series of studies focused on shared meaning systems in transference. The highlighted studies show that values and beliefs that develop in close relationships (as shared reality) are linked in memory to significant-other knowledge, and thus, are indirectly activated (made accessible) when cues in a new person implicitly activate that significant-other knowledge (in transference), with these shared beliefs then actively pursued with the new person and even protected against threat. This also confers a sense of mutual understanding, and all told, serves both relational and epistemic functions. In concluding, we consider as well the relevance of co-construction of shared reality n such processes.
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http://dx.doi.org/10.1016/j.copsyc.2017.11.007DOI Listing
October 2018

Working memory and salivary brain-derived neurotrophic factor as developmental predictors of cocaine seeking in male and female rats.

Addict Biol 2018 05 31;23(3):868-879. Epub 2017 Aug 31.

Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Poor working memory is linked to future risk-taking behaviors. Lifelong risk of habitual drug use is highest in individuals who initiate use in early adolescence. We sought to determine in rats whether juvenile traits, specifically poor working memory and low salivary brain-derived neurotrophic factor (BDNF), are related to elevated cocaine taking and relapse in adolescence and adulthood. On postnatal day (P) 20, working memory was assessed using the novel object recognition task in male and female rats. Saliva was assayed at P20 for BDNF before cocaine self-administration on P28 [0.75 or 0.25 mg/kg/infusion for 30 days under a fixed-ratio (FR) 1 to FR5 schedule] and on P94 before relapse after 30-day abstinence in adulthood. A separate cohort of P28 male rats was assayed for object discrimination and BDNF in saliva and the medial prefrontal cortex and dorsolateral striatum. Novel object discrimination correlated positively with salivary BDNF on P20 and dorsolateral striatum levels, but negatively with medial prefrontal cortex BDNF in male rats. In female rats, P20 salivary BDNF negatively correlated with object discrimination. Salivary BDNF positively correlated across age in male rats. Male rats earned more cocaine (0.75 mg/kg) at FR5 and responded more at relapse than did female rats. These elevated relapse rates in male rats were significantly associated with P20 object discrimination and salivary BDNF. Relapse after 0.75 and 0.25 mg/kg in female rats correlated only with object discrimination. In conclusion, poor working memory and low salivary BDNF in juvenile male rats may represent biomarkers for later cocaine use. Further research is needed to identify biomarkers for risk in male rats.
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http://dx.doi.org/10.1111/adb.12535DOI Listing
May 2018

GH62 arabinofuranosidases: Structure, function and applications.

Biotechnol Adv 2017 Nov 29;35(6):792-804. Epub 2017 Jun 29.

Enzyme and Protein Chemistry, Department of Biotechnology and Biomedicine, Technical University of Denmark, Elektrovej, Building 375, DK-2800 Kgs. Lyngby, Denmark. Electronic address:

Motivated by industrial demands and ongoing scientific discoveries continuous efforts are made to identify and create improved biocatalysts dedicated to plant biomass conversion. α-1,2 and α-1,3 arabinofuranosyl specific α-l-arabinofuranosidases (EC 3.2.1.55) are debranching enzymes catalyzing hydrolytic release of α-l-arabinofuranosyl residues, which decorate xylan or arabinan backbones in lignocellulosic and pectin constituents of plant cell walls. The CAZy database classifies α-l-arabinofuranosidases in Glycoside Hydrolase (GH) families GH2, GH3, GH43, GH51, GH54 and GH62. Only GH62 contains exclusively α-l-arabinofuranosidases and these are of fungal and bacterial origin. Twenty-two GH62 enzymes out of 223 entries in the CAZy database have been characterized and very recently new knowledge was acquired with regard to crystal structures, substrate specificities, and phylogenetics, which overall provides novel insights into structure/function relationships of GH62. Overall GH62 α-l-arabinofuranosidases are believed to play important roles in nature by acting in synergy with several cell wall degrading enzymes and members of GH62 represent promising candidates for biotechnological improvements of biofuel production and in various biorefinery applications.
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http://dx.doi.org/10.1016/j.biotechadv.2017.06.005DOI Listing
November 2017

Early life stress and later peer distress on depressive behavior in adolescent female rats: Effects of a novel intervention on GABA and D2 receptors.

Behav Brain Res 2017 07 9;330:37-45. Epub 2017 May 9.

Laboratory for Developmental Neuropharmacology, McLean Hospital, Belmont, MA USA; Harvard Medical School, Belmont, MA USA. Electronic address:

Early life adversity (ELA) increases the risk of depression during adolescence that may result from a decline in parvalbumin (PVB) secondary to increased neuroinflammation. In this study, we investigated depressive-like behavior following exposure to two different types of stressors that are relevant for their developmental period: 1) chronic ELA (maternal separation; MS) and 2) an acute emotional stressor during adolescence (witnessing their peers receive multiple shocks; WIT), and their interaction. We also determined whether reducing inflammation by cyclooxygenase-2 (COX-2) inhibition would prevent the onset of depressive-like behavior. Female Sprague-Dawley rat pups underwent MS for four-hours/day or received typical care (CON) between postnatal days (P) 2 and P20. A COX-2 inhibitor (COX-2I) or vehicle was administered every other day between P30 and P38. Subjects were tested for learned helplessness to assess depressive-like behavior at P40 (adolescence). MS females demonstrated increased escape latency and decreased PVB in the prefrontal cortex (PFC) and dorsal raphe that were attenuated by COX-2I intervention. Helplessness was also associated with an increase in D2 receptors in the accumbens. In contrast, WIT elevated escape latency in CON, but reduced latency in MS females. Furthermore, COX-2I intervention decreased escape latency in both CON and MS after WIT. WIT reduced PVB levels in the basolateral amygdala and increased PFC levels to CON levels. Our data suggest that decreased PVB in the PFC is important for the expression of depressive-like behavior and suggest that COX-2I intervention may provide a novel prevention for depression.
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http://dx.doi.org/10.1016/j.bbr.2017.04.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546234PMC
July 2017

Risks of Stimulant Use for Attention Deficit Hyperactivity Disorder on the Developing Brain: Primum non nocere.

Clin Pediatr (Phila) 2017 08 1;56(9):805-810. Epub 2017 May 1.

6 Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.

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http://dx.doi.org/10.1177/0009922817706148DOI Listing
August 2017

Erratum to "Preventative treatment in an animal model of DHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats" [Eur. Neuropsychopharmacol. 26 (2016) 1496-1506].

Eur Neuropsychopharmacol 2016 11 28;26(11):1843. Epub 2016 Oct 28.

Laboratory for Developmental Neuropharmacology, McLean Hospital, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, USA. Electronic address:

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http://dx.doi.org/10.1016/j.euroneuro.2016.10.001DOI Listing
November 2016

Induced optimism as mental rehearsal to decrease depressive predictive certainty.

Behav Res Ther 2017 03 22;90:1-8. Epub 2016 Nov 22.

New York University, 6 Washington Place, New York, NY, 10003, United States.

The present study examined whether practice in making optimistic future-event predictions would result in change in the hopelessness-related cognitions that characterize depression. Individuals (N = 170) with low, mild, and moderate-to-severe depressive symptoms were randomly assigned to a condition in which they practiced making optimistic future-event predictions or to a control condition in which they viewed the same stimuli but practiced determining whether a given phrase contained an adjective. Overall, individuals in the induced optimism condition showed increases in optimistic predictions, relative to the control condition, as a result of practice, but only individuals with moderate-to-severe symptoms of depression who practiced making optimistic future-event predictions showed decreases in depressive predictive certainty, relative to the control condition. In addition, they showed gains in efficiency in making optimistic predictions over the practice blocks, as assessed by response time. There was no difference in depressed mood by practice condition. Mental rehearsal might be one way of changing the hopelessness-related cognitions that characterize depression.
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http://dx.doi.org/10.1016/j.brat.2016.11.011DOI Listing
March 2017

Sensitive periods of substance abuse: Early risk for the transition to dependence.

Dev Cogn Neurosci 2017 06 29;25:29-44. Epub 2016 Oct 29.

Department of Psychiatry, Mclean Hospital/Harvard Medical School, Belmont, MA 02478, United States.

Early adolescent substance use dramatically increases the risk of lifelong substance use disorder (SUD). An adolescent sensitive period evolved to allow the development of risk-taking traits that aid in survival; today these may manifest as a vulnerability to drugs of abuse. Early substance use interferes with ongoing neurodevelopment to induce neurobiological changes that further augment SUD risk. Although many individuals use drugs recreationally, only a small percentage transition to SUD. Current theories on the etiology of addiction can lend insights into the risk factors that increase vulnerability from early recreational use to addiction. Building on the work of others, we suggest individual risk for SUD emerges from an immature PFC combined with hyper-reactivity of reward salience, habit, and stress systems. Early identification of risk factors is critical to reducing the occurrence of SUD. We suggest preventative interventions for SUD that can be either tailored to individual risk profiles and/or implemented broadly, prior to the sensitive adolescent period, to maximize resilience to developing substance dependence. Recommendations for future research include a focus on the juvenile and adolescent periods as well as on sex differences to better understand early risk and identify the most efficacious preventions for SUD.
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http://dx.doi.org/10.1016/j.dcn.2016.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410194PMC
June 2017

Commentary on the special issue on the adolescent brain: Adolescence, trajectories, and the importance of prevention.

Authors:
Susan L Andersen

Neurosci Biobehav Rev 2016 Nov 14;70:329-333. Epub 2016 Jul 14.

Laboratory of Developmental Neuropharmacology, McLean Hospital, Department of Psychiatry, Harvard Medical School, Mailstop 333, 115 Mill Street, Belmont, MA 02478, United States. Electronic address:

Adolescence as highlighted in this special issue is a period of tremendous growth, synaptic exuberance, and plasticity, but also a period for the emergence of mental illness and addiction. This commentary aims to stimulate research on prevention science to reduce the impact of early life events that often manifest during adolescence. By promoting a better understanding of what creates a normal and abnormal trajectory, the reviews by van Duijvenvoorde et al., Kilford et al., Lichenstein et al., and Tottenham and Galvan in this special issue comprehensively describe how the adolescent brain develops under typical conditions and how this process can go awry in humans. Preclinical reviews also within this issue describe how adolescents have prolonged extinction periods to maximize learning about their environment (Baker et al.), whereas Schulz and Sisk focus on the importance of puberty and how it interacts with stress (Romeo). Caballero and Tseng then set the stage of describing the neural circuitry that is often central to these changes and psychopathology. Factors that affect the mis-wiring of the brain for illness, including prenatal exposure to anti-mitotic agents (Gomes et al.) and early life stress and inflammation (Schwarz and Brenhouse), are included as examples of how exposure to early adversity manifests. These reviews are synthesized and show how information from the maturational stages that precede or occur during adolescence is likely to hold the key towards optimizing development to produce an adolescent and adult that is resilient and well adapted to their environment.
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http://dx.doi.org/10.1016/j.neubiorev.2016.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5268741PMC
November 2016
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