Mood and Behaviors of Adolescents With Depression in a Longitudinal Study Before and During the COVID-19 Pandemic.

OBJECTIVE: To investigate whether, compared to pre-pandemic levels, depressive and anxiety symptoms in adolescents with depression increased during the pandemic. METHOD: We used data from National Institute of Mental Health Characterization and Treatment of Depression (NIMH CAT-D) cohort, a longitudinal case-control study that started pre-pandemic. Most of the participants are from the states of Maryland and Virginia in the United States. We compared depressive symptoms (1,820 measurements; 519 measurements pre-pandemic and 1,302 during the pandemic) and anxiety symptoms (1,800 measurements; 508 measurements pre-pandemic and 1,292 ratings during the pandemic) of 166 adolescents (109 girls, 96 adolescents with depression) before and during the pandemic. Data were collected during yearly clinical visits, interim 4-month follow-up visits, inpatient stays, and weekly outpatient sessions, with additional data collection during the pandemic. Pre-pandemic, healthy volunteers (HVs) had a median of 1 depressive and anxiety rating (range, 1-3), and adolescents with depression had a median of 2 ratings (anxiety rating range, 1-25; depressive rating range, 1-26). During the pandemic, HVs had a median of 8 anxiety ratings and 9 depressive ratings (range, 1-13), and adolescents with depression had a median of 7 anxiety and depressive ratings (range, 1-29). We also analyzed adolescent- and parent-reported behaviors in the CoRonavIruS Health Impact Survey (CRISIS), totaling 920 self-reported measures for 164 adolescents (112 girls, 92 adolescents with depression). HVs had a median of 7 surveys (range, 1-8), and adolescents with depression had a median of 5 surveys (range, 1-8). RESULTS: Pre-pandemic, adolescents with depression had a mean depressive score of 11.16 (95% CI = 10.10, 12.22) and HVs had a mean depressive score of 1.76 (95% CI = 0.40, 3.13), a difference of 9.40 points (95% CI = 7.78, 11.01). During the pandemic, this difference decreased by 22.6% (2.05 points, 95% CI = 0.71, 3.40, p = .003) due to 0.89 points decrease in severity of scores in adolescents with depression (95% CI = 0.08, 1.70, p = .032) and 1.16 points increase in HVs' depressive symptoms (95% CI = 0.10, 2.23, p = .032). Compared to their pre-pandemic levels, adolescents with depression reported overall lower anxiety symptoms during the pandemic. Parent-on-child reports also were consistent with these results. CONCLUSION: Contrary to our hypothesis, we found that both depressive and anxiety symptoms were lower for adolescents with depression during the pandemic compared to before. In contrast, the depression scores for the HVs were higher during the pandemic relative to their pre-pandemic ratings; these scores remained much lower than those of adolescents with depression. CLINICAL TRIAL REGISTRATION INFORMATION: Characterization and Treatment of Adolescent Depression; https://clinicaltrials.gov/; NCT03388606.

Correction: Ntakolia et al. An Explainable Machine Learning Approach for COVID-19's Impact on Mood States of Children and Adolescents during the First Lockdown in Greece. Healthcare 2022, 10, 149.

Argyris Stringaris was initially included as an author in the original publication [...].

An Explainable Machine Learning Approach for COVID-19's Impact on Mood States of Children and Adolescents during the First Lockdown in Greece.

The global spread of COVID-19 led the World Health Organization to declare a pandemic on 11 March 2020. To decelerate this spread, countries have taken strict measures that have affected the lifestyles and economies. Various studies have focused on the identification of COVID-19's impact on the mental health of children and adolescents via traditional statistical approaches. However, a machine learning methodology must be developed to explain the main factors that contribute to the changes in the mood state of children and adolescents during the first lockdown. Therefore, in this study an explainable machine learning pipeline is presented focusing on children and adolescents in Greece, where a strict lockdown was imposed. The target group consists of children and adolescents, recruited from children and adolescent mental health services, who present mental health problems diagnosed before the pandemic. The proposed methodology imposes: (i) data collection via questionnaires; (ii) a clustering process to identify the groups of subjects with amelioration, deterioration and stability to their mood state; (iii) a feature selection process to identify the most informative features that contribute to mood state prediction; (iv) a decision-making process based on an experimental evaluation among classifiers; (v) calibration of the best-performing model; and (vi) a post hoc interpretation of the features' impact on the best-performing model. The results showed that a blend of heterogeneous features from almost all feature categories is necessary to increase our understanding regarding the effect of the COVID-19 pandemic on the mood state of children and adolescents.

Great Expectations: A Critical Review of and Suggestions for the Study of Reward Processing as a Cause and Predictor of Depression.

Both human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Given the great promise of this research line, we scrutinized those findings and the theoretical claims that underlie them. To achieve this, we applied the framework provided by classical work on causality as well as contemporary approaches to prediction. We identified a number of conceptual, practical, and analytical challenges to this line of research and used a preregistered meta-analysis to quantify the longitudinal associations between reward processing abnormalities and depression. We also investigated the impact of measurement error on reported data. We found that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the available evidence does not preclude a possible causal role in depression.

Reward Processing in Adolescent Depression Across Neuroimaging Modalities.

Depressive symptoms have long been associated with abnormalities in neural processing of reward. However, no review has yet consolidated evidence of such deficits in adolescent depression, integrating findings across neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The current review found consistent evidence of reduced striatal responses in anticipation and upon receipt of rewards, and blunted feedback-related negativity (FRN) potentials associated with depression in adolescence, consistent with the adult literature. Furthermore, while these occurred in currently depressed adolescents, they were also found to be predictive of the onset of depressive symptoms in longitudinal studies with community-based adolescent samples. This paper makes recommendations for future work to continue to elucidate this relationship, a greater understanding of which may lead to more targeted and efficacious treatments for depression in adolescence.

Modulation of anterior cingulate cortex reward and penalty signalling in medication-naive young-adult subjects with depressive symptoms following acute dose lurasidone.

BACKGROUND: Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression. METHODS: We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0-43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest. RESULTS: Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF. CONCLUSIONS: Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.

Reward Processing in Depression: A Conceptual and Meta-Analytic Review Across fMRI and EEG Studies.

OBJECTIVE: A role for aberrant reward processing in the pathogenesis of depression has long been proposed. However, no review has yet examined its role in depression by integrating conceptual and quantitative findings across functional MRI (fMRI) and EEG methodologies. The authors quantified these effects, with an emphasis on development. METHOD: A total of 38 fMRI and 12 EEG studies were entered into fMRI and EEG meta-analyses. fMRI studies primarily examined reward anticipation and reward feedback. These were analyzed using the activation likelihood estimation method. EEG studies involved mainly the feedback-related negativity (FRN) event-related potential, and these studies were analyzed using random-effects meta-analysis of the association between FRN and depression. RESULTS: Analysis of fMRI studies revealed significantly reduced striatal activation in depressed compared with healthy individuals during reward feedback. When region-of-interest analyses were included, reduced activation was also observed in reward anticipation, an effect that was stronger in individuals under age 18. FRN was also significantly reduced in depression, with pronounced effects in individuals under age 18. In longitudinal studies, reduced striatal activation in fMRI and blunted FRN in EEG were found to precede the onset of depression in adolescents. CONCLUSIONS: Taken together, the findings show consistent neural aberrations during reward processing in depression, namely, reduced striatal signal during feedback and blunted FRN. These aberrations may underlie the pathogenesis of depression and have important implications for development of new treatments.

Tactile-to-Visual Cross-Modal Transfer of Texture Categorisation Following Training: An fMRI Study.

We investigated the neural underpinnings of texture categorisation using exemplars that were previously learned either within modalities (visual training and visual test) or across modalities (tactile training and visual test). Previous models of learning suggest a decrease in activation in brain regions that are typically involved in cognitive control during task acquisition, but a concomitant increase in activation in brain regions associated with the representation of the acquired information. In our study, participants were required to learn to categorise fabrics of different textures as either natural or synthetic. Training occurred over several sessions, with each fabric presented either visually or through touch to a participant. Pre- and post-training tests, in which participants categorised visual images only of the fabrics, were conducted during a functional magnetic resonance imaging (fMRI) scan. Consistent with previous research on cognitive processes involved in task acquisition, we found that categorisation training was associated with a decrease in activation in brain regions associated with cognitive systems involved in learning, including the superior parietal cortex, dorsal anterior cingulate cortex (dACC), and the right dorsolateral prefrontal cortex (DLFC). Moreover, these decreases were independent of training modality. In contrast, we found greater activation to visual textures in a region within the left medial occipital cortex (MOC) following training. There was no overall evidence of an effect of training modality in the main analyses, with texture-specific regional changes associated with both within- (visual) and cross- (touch) modal training. However, further analyses suggested that, unlike categorisation performance following within-modal training, crossmodal training was associated with bilateral activation of the MOC. Our results support previous evidence for a multisensory representation of texture within early visual regions of the cortex and provide insight into how multisensory categories are formed in the brain.

Changes in Regional Brain Grey-Matter Volume Following Successful Completion of a Sensori-Motor Intervention Targeted at Healthy and Fall-Prone Older Adults.

Previous studies have suggested that discrete cross-sensory events could be incorrectly combined in the brain of older adults with a history of falls, possibly undermining motor and balance control. Based on previous findings that multisensory integration is modifiable with practice, even in an ageing population, we designed a serious game, named CityQuest, to train typical, everyday multisensory processes including sensori-motor control, spatial navigation, obstacle avoidance and balance control. Played over several sessions, this game was shown to improve these functions in older adults with and without a history of falls, depending on the specific condition of the game on which they were trained. Here, using voxel-based morphometry analysis of anatomical magnetic resonance imaging (MRI) data, we investigated structural changes in the brain of a smaller group of older adults from those who successfully completed this five-week intervention. A grey-matter (GM) volume increase in the precentral gyrus, and GM volume reduction in the inferior temporal and orbitofrontal gyri, was found for all participants. Changes in GM volume within regions of the cerebellum were differentially associated with fall-prone and healthy older adults. Furthermore, a greater GM volume increase in the precentral gyrus was observed in participants who performed the full CityQuest intervention relative to those required to avoid obstacles only. Our results support previous evidence that multisensory training can affect structural changes in the older brain and have implications for programmes designed for the successful rehabilitation of perceptual and cognitive functions.

Impaired decision making among morbidly obese adults.

OBJECTIVE: The Iowa Gambling Task (IGT) measures affective decision making and has revealed decision making impairments across a wide range of eating disorders. This study aimed to investigate affective decision making in severely obese individuals. METHODS: Forty-two (12 male, 30 female) morbidly obese participants (mean BMI = 41.45) and 50 comparison participants (17 male, 33 female) matched for age, gender and education, completed the IGT. RESULTS: Obese participants performed significantly worse on the IGT compared to the comparison group, with 69% of the obese group demonstrating clinically impaired decision making. There was no evidence of learning across the five trial blocks in obese participants, with significant differences between the groups emerging in blocks 3, 4, and 5. IGT impairment was unrelated to BMI or eating pathology. CONCLUSION: Obese participants were significantly impaired on the IGT. The pattern of performance suggested a potential inability to maximise an immediate reward or program a delayed reward. The findings support the view that common decision making impairments exist across disordered eating populations. Future research is required to specify the source and mechanisms of these decision making deficits. The logical progression of this research is the development of interventions which improve decision making capacity and measure subsequent impact on psychological and physical outcomes.