Adolescent Nicotine Exposure Induces Dysregulation of Mesocorticolimbic Activity States and Depressive and Anxiety-like Prefrontal Cortical Molecular Phenotypes Persisting into Adulthood

2018 ◽  
Vol 29 (7) ◽  
pp. 3140-3153 ◽  
Author(s):  
Christina L M Jobson ◽  
Justine Renard ◽  
Hanna Szkudlarek ◽  
Laura G Rosen ◽  
Brian Pereira ◽  
...  

Abstract Considerable evidence demonstrates strong comorbidity between nicotine dependence and mood and anxiety disorders. Nevertheless, the neurobiological mechanisms linking adolescent nicotine exposure to mood and anxiety disorders are not known. Disturbances in the mesocorticolimbic dopamine (DA) system, comprising the prefrontal cortex (PFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), are correlates of mood and anxiety-related symptoms and this circuitry is strongly influenced by acute or chronic nicotine exposure. Using a combination of behavioral pharmacology, in vivo neuronal electrophysiology and molecular analyses, we examined and compared the effects of chronic nicotine exposure in rats during adolescence versus adulthood to characterize the mechanisms by which adolescent nicotine may selectively confer increased risk of developing mood and anxiety-related symptoms in later life. We report that exposure to nicotine, selectively during adolescence, induces profound and long-lasting neuronal, molecular and behavioral disturbances involving PFC DA D1R and downstream extracellular-signal-related kinase 1-2 (ERK 1-2) signaling. Remarkably, adolescent nicotine induced a persistent state of hyperactive DA activity in the ventral tegmental area (VTA) concomitant with hyperactive neuronal activity states in the PFC. Our findings identify several unique neuronal and molecular biomarkers that may serve as functional risk mechanisms for the long-lasting neuropsychiatric effects of adolescent smoking behaviors.

2021 ◽  
Vol 226 (4) ◽  
pp. 1155-1167 ◽  
Author(s):  
Anne C. Trutti ◽  
Laura Fontanesi ◽  
Martijn J. Mulder ◽  
Pierre-Louis Bazin ◽  
Bernhard Hommel ◽  
...  

AbstractFunctional magnetic resonance imaging (fMRI) BOLD signal is commonly localized by using neuroanatomical atlases, which can also serve for region of interest analyses. Yet, the available MRI atlases have serious limitations when it comes to imaging subcortical structures: only 7% of the 455 subcortical nuclei are captured by current atlases. This highlights the general difficulty in mapping smaller nuclei deep in the brain, which can be addressed using ultra-high field 7 Tesla (T) MRI. The ventral tegmental area (VTA) is a subcortical structure that plays a pivotal role in reward processing, learning and memory. Despite the significant interest in this nucleus in cognitive neuroscience, there are currently no available, anatomically precise VTA atlases derived from 7 T MRI data that cover the full region of the VTA. Here, we first provide a protocol for multimodal VTA imaging and delineation. We then provide a data description of a probabilistic VTA atlas based on in vivo 7 T MRI data.


2018 ◽  
Vol 50 (3) ◽  
pp. 2146-2155 ◽  
Author(s):  
Lindsay Naef ◽  
Lauren Seabrook ◽  
Jeff Hsiao ◽  
Calvin Li ◽  
Stephanie L. Borgland

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jessica S Jarmasz ◽  
Alexandrea Anderson ◽  
Margaret E Bock ◽  
Yan Jin ◽  
Peter A Cattini ◽  
...  

Abstract BACKGROUND: Pregnant women with obesity are at increased risk for peripartum depression. Maternal obesity is also associated with reduced human placental lactogen (hPL) levels, and decreased hPL transcripts were reported in women with clinical depression. In addition, hPL production may be rescued in women with obesity that were subsequently diagnosed with gestational diabetes and treated with insulin (INS). Objective: Study the effect of INS treatment in pregnancy on the risk for postpartum psychological distress (PPD) in women with and without obesity. Study Design: Using data housed at the Manitoba Centre for Health Policy (2002–2017), cohorts of women (ages 15+) with a single live birth with and without obesity were developed using weight (≥85 and <65.6 kg, respectively) and an average (1.63 m) height. Pre-existing mood and anxiety disorders within 5 years preceding delivery as well as gestational hypertension were excluded. After randomly selecting 1 birth per mother, cohorts were stratified by INS treatment during the gestational period. The risk of PPD within 1 year of delivery was assessed by Poisson regression analysis. Models were adjusted for maternal age and area-level income at delivery. Results: The risk of PPD was 27% greater among women with obesity versus without (adjusted rate ratio (aRR)=1.27, 95% CI 1.16–1.4, p<0.0001). However, women with obesity treated with INS did not have a significantly different risk of PPD compared to women without obesity whether treated with INS (aRR=0.99, 95%CI 0.48–2.02, p=0.974) or not (aRR=1.16, 95%CI 0.86–1.56, p=0.328). This suggests that the risk of PPD among women with obesity may be reduced by INS treatment; however, our ability to detect a significant difference may be limited by small cohort numbers (46 women with obesity received INS in pregnancy) or confounders for receiving INS in pregnancy. Direct comparison of INS treatment within weight groups faced the same limitations but trended toward a reduction in women with obesity who received INS (aRR=0.91, 95%CI 0.68–1.22, p=0.531). The positive association between INS treatment in pregnancy and decreased risk of PPD in women with obesity was lost when pre-existing mood and anxiety disorder was not excluded. Inclusion of pre-existing diabetes in the adjusted models did not improve model fit or contribute significantly to the differences in PPD rates. Conclusions: Maternal obesity increases the risk for PPD but this risk may be reduced by gestational INS treatment in the absence of a pre-existing mood and anxiety disorders. This correlates with the decrease and increase in hPL levels reported previously with maternal obesity without and with INS treatment (for diabetes) in pregnancy, respectively. Thus, hPL levels may serve as a possible indicator of PPD risk and a potential target for gestational INS treatment.


2002 ◽  
Vol 11 (2) ◽  
pp. 88-99 ◽  
Author(s):  
Paolo Brambilla ◽  
Francesco Barale ◽  
Edgardo Caverzasi ◽  
Jair Constante Soares

RIASSUNTOScopo – Gli studi con Risonanza Magnetica Nucleare (RMN) hanno permesso la valutazione in vivo dell'anatomia cerebrale di vari disturbi psichiatrici e l'approfondimento degli ipotetici circuiti cerebrali disfunzionali coinvolti nella patofisiologia di queste malattie. In questo articolo abbiamo revisionato la letteratura comprendente gli studi con RMN condotti nei disturbi dell'umore e d'ansia. Metodi – Tutti gli studi in Inglese con RMN condotti in pazienti con disturbo dell'umore o d'ansia pubblicati tra il 1966 ed il gennaio 2002 sono stati identificati attraverso una ricerca Medline, completata dall'analisi manuale delle referenze bibliografiche. Risultati – Differenti aree anatomiche cerebrali sembrano essere coinvolte nei diversi sottotipi di disturbo dell'umore. Infatti, l'ippocampo ed i gangli della base sembrano essere anormali nei disturbo unipolare, mentre l'amigdala ed il cervelletto in quello bipolare. Questo suggerisce che le due malattie abbiano un substrata biologico distinto. Per quanto riguarda i disturbi d'ansia, le regioni orbito-frontali ed i gangli della base sembrano avere un'anatomia anormale nei disturbo ossessivo-compulsivo, i lobi temporali nei disturbo da attacchi di panico e l'ippocampo nei disturbo post-traumatico da stress. Conclusioni – I dati della letteratura riassunti in questo articolo suggeriscono che specifiche aree cerebrali siano coinvolte nella patofisiologia dei disturbi dell'umore e d'ansia. Tuttavia, gli studi a tutt'oggi a disposizione sono stati condotti su campioni relativamente piccoli di soggetti, spesso sottoposti a medicamenti psicotropi, e sono in gran parte studi trasversali. Per tale motivo gli studi con RMN in futuro dovranno avere un disegno di tipo longitudinale ed arruolare campioni più ampi di soggetti, possibilmente senza trattamento psicofarmacologico, al primo episodio di malattia o ad alto rischio di sviluppare un disturbo dell'umore o d'ansia. Inoltre, l'associazione di questo tipo di ricerche con studi di tipo genetico potranno essere estremamente utili per separare anomalie anatomiche cerebrali di stato da quelle di tratto e per ulteriormente caratterizzare la patofisiologia di questi disturbi.


2012 ◽  
Vol 43 (7) ◽  
pp. 1487-1497 ◽  
Author(s):  
Z. Sjoerds ◽  
M.-J. van Tol ◽  
W. van den Brink ◽  
N. J. A. van der Wee ◽  
A. Aleman ◽  
...  

BackgroundA family history (FH) of alcohol dependence (AD) not only increases the risk for AD, but is also associated with an increased risk for mood and anxiety disorders. However, it is unknown how a FH of AD affects neural substrates in patients with mood and anxiety disorders. In this study we examined the effects of an alcoholic FH on cognitive and emotional functions in these patients using functional magnetic resonance imaging (fMRI).MethodIn a sample of non-alcoholic patients with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) neuroimaging study, patients with a first-degree FH of AD (FH + ; n = 31) were compared with patients without a FH (FH–; n = 77) on performance and brain activation during visuospatial planning and emotional word encoding. Results were compared with those of healthy controls (HCs) without a FH of AD (n = 31).ResultsFH+ patients performed slower during planning with increasing task load, coupled with stronger blood oxygen level-dependent responses in dorsal prefrontal areas compared with FH− patients and HCs. FH was not associated with performance differences during word encoding, but right insula activation during positive word encoding was present in FH+ patients, comparable with HCs, but absent in FH− patients.ConclusionsThis study demonstrates subtle impairments during planning in FH+ compared with FH− patients and HCs, whereas activation during mood-incongruent stimuli in FH+ patients was similar to HCs but not FH− patients, suggesting that the presence of a FH of AD is a useful marker for the neurophysiological profile in mood/anxiety disorders and possible predictor for treatment success.


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