scholarly journals 3520 Neural connectivity mechanisms linking off-time pubertal development and depression risk in adolescence

2019 ◽  
Vol 3 (s1) ◽  
pp. 17-18
Author(s):  
Rajpreet Chahal ◽  
Scott Marek ◽  
Veronika Vilgis ◽  
David Weissman ◽  
Paul Hastings ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Earlier pubertal timing has been associated with risk for depression, particularly in girls (e.g., Keenan etal., 2014). Evidence suggests pubertal timing in girls also relates to alterations in the microstructural properties of brain white matter tracts in late adolescence (Chahal etal., 2018), and structural connectivity of cingulate and frontal regions (Chahal etal., in prep), though differences in pubertal development in both boys and girls have not been examined in the context of brain functional connectivity (FC). Individual differences in the course of puberty may have enduring effects on functional coupling among brain regions that may contribute to the risk for psychopathology. To address this question, we explored the relation between pubertal timing and tempo with depression symptoms (age 16). Then, we examined whether brain network FC (age 16) associates with pubertal indices and predicts concurrent and later depressive symptoms (age 18). METHODS/STUDY POPULATION: Sixty-eight adolescents (37 females) completed the Mini-Mood and Anxiety Symptom Questionnaire (MASQ; Clark & Watson, 1995) at ages 14-18. Gompertz growth curve modelling of pubertal development (age 10-15; Waves 1-6) was used to estimate pubertal timing and tempo per individual, separately for males and females (e.g., Chahal etal., 2018). Resting-state MRI data (age 16) were parcellated into 264 cortical and subcortical regions to create region-to-region FC matrices based on correlations of time-series. Individual matrices were fed to the GraphVar program (Kruschwitz etal., 2015) to assess the interaction of pubertal timing and pubertal tempo with functional network connectivity using Network-based statistic (NBS; Zalesky etal., 2010). Subnetworks showing alterations in relation to pubertal timing and tempo were then examined in association with concurrent (age 16) symptoms and used to predict future depressive symptoms (age 18). RESULTS/ANTICIPATED RESULTS: In all youth, earlier pubertal timing was associated with higher depressive symptoms at age 16 (p<.018). This association was stronger in girls with slower pubertal tempo (p<.039). Interregional connectivity analyses revealed that the interaction of earlier pubertal timing and slower tempo was associated with lower FC between the left cingulate gyrus and right precuneus (p<.0001), regions implicated in emotion processing (i.e., Affective Processing Network) and self-referential thinking (i.e., Default Mode Network). FC of the three other emotion- and self-referential processing network regions (i.g., left insula, superior parietal lobule, and precuneus) was lower in youth with greater age 16 depressive symptoms (p<.0001). Finally, lower FC of of the left and right inferior parietal lobule predicted greater depressive symptoms at age 18 (p<.0001). In summary, FC of overlapping affective and default mode network areas was related to earlier pubertal timing and higher concurrent and future depressive symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings demonstrate individual differences in pubertal maturation are associated with depressive symptoms and differences in brain connectivity in mid-adolescence. Early pubertal development was associated with greater depression symptoms and lower FC of brain regions involved in emotion regulation and self-referential processing. Further, FC between these regions predicted higher depression symptoms two years later. These neurobiological mechanisms may, in part, underlie the link between off-time pubertal development and the risk for depression. These findings also have important implications for precision psychiatry, as we show that a risk-factor of depression (early pubertal timing) may manifest in developing neurobiology in region-specific ways. Previous network models of depression (e.g., Li etal., 2018) implicated affective network connectivity in sustained negative mood and the default mode/ self-referential network in rumination. Other networks implicated in these past models include the reward network, which may be involved in anhedonia and loss of pleasure. Our study only found associations between affective and self-referential regional connectivity, pubertal maturation, and depression, suggesting that pubertal risk factors may relate more closely with emotion-regulation and self-referential processing deficits.

2010 ◽  
Vol 46 (5) ◽  
pp. 1341-1353 ◽  
Author(s):  
Jane Mendle ◽  
K. Paige Harden ◽  
Jeanne Brooks-Gunn ◽  
Julia A. Graber

Neurology ◽  
2018 ◽  
Vol 91 (23 Supplement 1) ◽  
pp. S15.1-S15
Author(s):  
Lezlie Espana ◽  
William McCuddy ◽  
Lindsay Nelson ◽  
Birn Rasmus ◽  
Andrew Mayer ◽  
...  

Few studies have examined the physiologic correlates of depressive symptoms following sport-related concussion (SRC), despite the prevalence of these symptoms following brain injury. We hypothesized that concussed athletes would have disrupted resting-state functional connectivity in emotional processing regions compared to controls, and that this disruption would be associated with greater post-concussion symptoms of depression. Forty-three concussed athletes at approximately 1 day (N = 34), 1 week (N = 34), and 1 month (N = 30) post-concussion were evaluated along with 51 healthy athletes assessed at a single visit. Resting-state fMRI was collected on a 3T GE scanner (TR = 2s); depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Emotional processing regions of interest (ROI) were defined using an automated meta-analysis of brain regions associated with the term “emotion”. Fisher-Z transformed correlations were calculated between each ROI. A multivariate approach assessed connectivity by analyzing ROI as simultaneous response variables. Concussed athletes had significantly higher depressive symptoms relative to controls at all time points but showed partial recovery by 1-month post-concussion relative to earlier visits (p's< 0.05). Functional connectivity did not differ between controls and concussed athletes at 1 day or one-week post-concussion. However, concussed athletes had significantly different connectivity in regions associated with emotional processing at 1 month relative to 1 day post-concussion (p = 0.002), and relative to controls (p = 0.003). Follow-up analyses showed that increased connectivity between attention and default mode networks at 1-month post-concussion was common across both analyses. In addition, functional connectivity of emotional processing regions was significantly associated with depressive symptoms at 1 day (p = 0.003) and one-week post-concussion (p = 7 × 10-8), with greater HAM-D scores correlating with decreased connectivity between attention and default mode networks. These results suggest that intrinsic connectivity between default mode and attention regions following SRC may be compensatory in nature.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
D. M. Lydon-Staley ◽  
C. Kuehner ◽  
V. Zamoscik ◽  
S. Huffziger ◽  
P. Kirsch ◽  
...  

Abstract Repetitive negative thinking (RNT) is a maladaptive response to sadness and a transdiagnostic risk-factor. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency for RNT remain uncharacterized. From the perspective of the impaired disengagement hypothesis, we examine between-person differences in blood-oxygen-level-dependent (BOLD) functional networks underlying cognitive conflict signaling, self-referential thought, and cognitive flexibility, and the association between sadness and RNT in daily life. We pair functional magnetic resonance imaging with ambulatory assessments deployed 10 times per day over 4 consecutive days measuring momentary sadness and RNT from 58 participants (40 female, mean age = 36.69 years; 29 remitted from a lifetime episode of Major Depression) in a multilevel model. We show that RNT increases following sadness for participants with higher than average between-network connectivity of the default mode network and the fronto-parietal network. We also show that RNT increases following increases in sadness for participants with lower than average between-network connectivity of the fronto-parietal network and the salience network. We also find that flexibility of the salience network’s pattern of connections with brain regions is protective against increases in RNT following sadness. Our findings highlight the importance of functional brain networks implicated in cognitive conflict signaling, self-referential thought, and cognitive flexibility for understanding maladaptive responses to sadness in daily life and provide support for the impaired disengagement hypothesis of RNT.


2013 ◽  
Vol 25 (2) ◽  
pp. 455-471 ◽  
Author(s):  
Amelie Benoit ◽  
Eric Lacourse ◽  
Michel Claes

AbstractThis longitudinal study examined personal-accentuation and contextual-amplification models of pubertal timing. In these models, individual and contextual risk factors during childhood and adolescence can magnify the effects of early or late puberty on depression symptoms that occur years later. The moderating role of prepubertal individual factors (emotional problems in late childhood) and interpersonal factors (deviant peer affiliation, early dating, perceived peer popularity, and perceived parental rejection during adolescence) were tested. A representative sample of 1,431 Canadian adolescents between 10–11 and 16–17 years of age was followed biannually. In line with the personal-accentuation model, early puberty has been shown to be a predictor for depression in both girls and boys who presented emotional problems in childhood. This effect was also noted for late maturing boys. Consistent with the contextual-amplification model, early puberty predicted later depression in youth who perceived greater parental rejection. Interpersonal experiences such as early dating in girls and deviant peer affiliation in boys predicted depression in early maturers as well. For girls, early dating was also found to be amplified by childhood emotional problems. In line with biopsychosocial models, results indicate that the effect of pubertal timing on depressive symptoms must be conceptualized through complex interactions between characteristics of adolescents' interpersonal relationships and prepubertal vulnerabilities.


2018 ◽  
Vol 32 (3) ◽  
pp. 140-155 ◽  
Author(s):  
Daniel Ruivo Marques ◽  
Ana Allen Gomes ◽  
Vanda Clemente ◽  
José Moutinho dos Santos ◽  
Isabel Catarina Duarte ◽  
...  

Abstract. Psychophysiological insomnia (PI) is one of the most frequent sleep disorders. In this study we tested whether differences in terms of neural activation are present between a group of PI patients and a healthy-control group while they are exposed to idiosyncratic ruminations and worries, evoked visually by words, so as to explore their hypothetical link with default-mode network (DMN) dysfunction in PI. We recruited five PI patients diagnosed according to the International Classification of Sleep Disorders, version 2 (ICSD-2) of American Academy of Sleep Medicine (AASM) and five age- and sex-matched healthy controls. Patients were recruited at the outpatient Sleep Medicine Centre of the Coimbra University Hospital Centre. We used a functional magnetic resonance imaging (fMRI) block-design paradigm where the participants visualized lists of words related to past/present and future concerns and also emotionally neutral words. The results suggested that the PI patients showed a failure of the DMN to deactivate. Moreover, when these patients were exposed to words concerning both past/present ruminations and future worries, there was a pronounced and significant over-recruitment of brain areas related to DMN and self-referential processing when they were compared to healthy volunteers. The differences between the patient and control groups were also evident in self-report measures. In sum, despite the relatively small sample size, our study clearly suggests that in PI there is a dysfunction in brain regions pertaining to self-referential processing, which is corroborated by an overall pattern of hyperarousal in brain regions comprising the DMN. These data may be useful in the improvement of pathophysiological models, diagnostic and therapeutic interventions for insomnia.


2013 ◽  
Vol 44 (10) ◽  
pp. 2041-2051 ◽  
Author(s):  
F. Sambataro ◽  
N. D. Wolf ◽  
M. Pennuto ◽  
N. Vasic ◽  
R. C. Wolf

BackgroundMajor depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.MethodHere, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.ResultsWe show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.ConclusionsThese data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets.


2018 ◽  
Author(s):  
David M. Lydon-Staley ◽  
Christine Kuehner ◽  
Vera Zamoscik ◽  
Silke Huffziger ◽  
Peter Kirsch ◽  
...  

Rumination, the perseverative thinking about one’s problems and emotions, is a maladaptive response to sadness and a risk factor for the development and course of depression. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency to ruminate following depressed mood remain uncharacterized. We examine the importance of between-person differences in blood-oxygen-level dependent (BOLD) functional networks underlying cognitive control for the moment-to-moment association between sadness and rumination in daily life. We pair functional magnetic resonance imaging with ambulatory assessments measuring momentary sadness and rumination deployed 10 times per day over 4 consecutive days from 58 participants (40 female, mean age = 36.69 years; 29 remitted from a lifetime episode of Major Depression). Using a multilevel model, we show that rumination increases following increases in sadness for participants with higher than average between-network connectivity of the default mode network and the fronto-parietal network. We also show that rumination increases following increases in sadness for participants with lower than average between-network connectivity of the fronto- parietal network and the salience network. In addition, we find that the flexibility of the salience network’s pattern of connections with brain regions across time is protective against increases in rumination following sadness. Our findings highlight the importance of the neural correlates of cognitive control for understanding maladaptive responses to sadness and also support the value of large-scale functional connectivity networks for understanding cognitive-affective behaviors as they naturally occur during the course of daily life.


2012 ◽  
Author(s):  
Rosemarie Kluetsch ◽  
Tomas Ros ◽  
Jean Theberge ◽  
Paul Frewen ◽  
Christian Schmahl ◽  
...  

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