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1.
Psychol Med ; : 1-12, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246282

RESUMO

BACKGROUND: Adolescence is a critical period for brain development, consolidation of self-understanding, and onset of non-suicidal self-injury (NSSI). This study evaluated the RDoC (Research Domain Criteria) sub-construct of Self-Knowledge in relation to adolescent NSSI using multiple units of analysis. METHODS: One hundred and sixty-four adolescents assigned female at birth (AFAB), ages 12-16 years with and without a history of NSSI entered a study involving clinical assessment and magnetic resonance imaging (MRI), including structural, resting-state functional MRI (fMRI), and fMRI during a self-evaluation task. For imaging analyses, we used an a priori defined Self Network (anterior cingulate, orbitofrontal, and posterior cingulate cortices; precuneus). We first examined interrelationships among multi-level Self variables. We then evaluated the individual relationships between NSSI severity and multi-level Self variables (self-report, behavior, multi-modal brain Self Network measures), then conducted model testing and multiple regression to test how Self variables (together) predicted NSSI severity. RESULTS: Cross-correlations revealed key links between self-reported global self-worth and self-evaluation task behavior. Individually, greater NSSI severity correlated with lower global self-worth, more frequent and faster negative self-evaluations, lower anterior Self Network activation during self-evaluation, and lower anterior and posterior Self Network resting-state connectivity. Multiple regression analysis revealed the model including multi-level Self variables explained NSSI better than a covariate-only model; the strongest predictive variables included self-worth, self-evaluation task behavior, and resting-state connectivity. CONCLUSIONS: Disruptions in Self-Knowledge across multiple levels of analysis relate to NSSI in adolescents. Findings suggest potential neurobiological treatment targets, potentially enhancing neuroplasticity in Self systems to facilitate greater flexibility (more frequently positive) of self-views in AFAB adolescents.

2.
Dev Psychopathol ; : 1-13, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363720

RESUMO

Dante Cicchetti propelled forward the field of developmental psychopathology by advancing this framework and championing new methods, including emphasizing the central role that multilevel analysis holds for explicating pathways of risk and resilience. His work continues to change the face of existing science. It has also paved the way for the formation of new projects, like the Research Domain Criteria initiative. This paper uses our laboratory's work on multilevel approaches to studying adolescent depression, non-suicidal self-injury, and suicidal thoughts and behaviors to shine a spotlight on Dr Cicchetti's contributions. In addition, we review recent developments, ongoing challenges, and promising future directions within developmental psychopathology as we endeavor to carry on the tradition of growth in the field.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39412694

RESUMO

Depression is a serious public health problem that often emerges during adolescence. Many adolescents do not respond to standard treatments, necessitating the development of novel interventions. We conducted a preliminary study to assess the impact of a novel creative arts intervention on depression and well-being in adolescents. In this quasi-experimental study, 69 adolescents 12-17 years completed an 8-day "Creativity Camp" intervention encompassing multiple creative activities. Self-report questionnaires to measure depression, anxiety, and well-being were administered at five time points to allow examination of change across multiple temporal segments: the 2 weeks before the intervention, the 2 weeks during the intervention, the 2 weeks after the intervention, and the 6 months after the intervention. Adolescents were assigned to one of two groups to compare changes observed during the 2 week before-intervention period (Group A) to the changes observed during the intervention period (pre-post intervention) (Group B). According to both parent and child reports, pre-to-post-intervention, mean adolescent depressive symptoms significantly decreased, and these changes were sustained 2 weeks after the intervention and (according to parents) at the 6-month follow-up. There was preliminary evidence for improved well-being at post-intervention. Comparison of Group A's changes during the before-intervention period to Group B's changes pre-post intervention was significant for parent-reported depression. Preliminary evidence suggests that the Creativity Camp intervention may positively impact adolescent depression and well-being. This evidence highlights the importance of investigating and implementing treatment approaches focusing on creative arts for adolescents with depression.

4.
J Relig Health ; 63(2): 1017-1037, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38190059

RESUMO

The contributions of religion to reduced suicide risk have been studied in adults and adolescents, though to our knowledge no comprehensive investigation has been conducted in early adolescents, at a time coinciding with emergence of suicide risk trajectories. In this largest study to date on this topic, we aimed to characterise the contributions of various measures of "private" and "public" religiosity to early adolescent suicide ideation (SI) and suicide attempt (SA) histories using information from a large, epidemiologically informed U.S. sample of adolescents (N = 7068; mean age = 12.89 years, 47% female) and their parents. In all youth, parent-reported adolescent religious importance was associated with reduced odds of SA (OR = 0.75, CI = 0.61-0.92, P = .005). Muslim youth were more likely (OR = 1.52, CI = 1.02-2.22, P = .033), and Catholic youth were less likely (OR = 0.80, CI = 0.67-0.95, P = .014), to report SI. A variety of sex differences were noted, with significant protective associations of adolescent self-reported religiosity on SI and SA, religious service attendance on SI, and religious importance on SI, in female-but not male-youth; and significant protective associations of religious importance on SA in male-but not female-youth. Against expectations, there was no evidence that parent religiosity moderated the link between youth religiosity and SI or SA. These results shed light on the roles of cultural and familial context in youth suicide risk, which may ultimately be targeted in screening and interventional approaches.


Assuntos
Religião , Tentativa de Suicídio , Adulto , Humanos , Masculino , Adolescente , Feminino , Estados Unidos/epidemiologia , Criança , Ideação Suicida , Pais , Autorrelato
5.
Psychol Med ; 53(5): 2164-2173, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37310327

RESUMO

BACKGROUND: Suicide is the second-leading cause of death in youth. Understanding the neural correlates of suicide ideation (SI) in children is crucial to ongoing efforts to understand and prevent youth suicide. This study characterized key neural networks during rest and emotion task conditions in an epidemiologically informed sample of children who report current, past, or no SI. METHODS: Data are from the adolescent brain cognitive development study, including 8248 children (ages 9-10; mean age = 119.2 months; 49.2% female) recruited from the community. Resting-state functional connectivity (RSFC) and activation to emotional stimuli in the salience (SN) and default mode (DMN) networks were measured through fMRI. Self-reported SI and clinical profiles were gathered. We examined the replicability of our model results through repeated sub-sample reliability analyses. RESULTS: Children with current SI (2.0%), compared to those without any past SI, showed lower DMN RSFC (B = -0.267, p < 0.001) and lower DMN activation in response to negative as compared to neutral faces (B = -0.204, p = 0.010). These results were robust to the effects of MDD, ADHD, and medication use. Sub-sample analysis further supported the robustness of these results. We did not find support for differences in SN RSFC or in SN activation to positive or negative stimuli for children with or without SI. CONCLUSIONS: Results from a large brain imaging study using robust statistical approaches suggest aberrant DMN functioning in children with current suicide ideation. Findings suggest potential mechanisms that may be targeted in suicide prevention efforts.


Assuntos
Encéfalo , Emoções , Adolescente , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Ideação Suicida , Cognição
6.
Psychol Med ; 53(16): 7902-7912, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37609891

RESUMO

BACKGROUND: Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI. METHODS: Adolescent females (N = 109, ages 12-17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models. RESULTS: Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged. CONCLUSION: Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.


Assuntos
Depressão , Comportamento Autodestrutivo , Humanos , Adolescente , Feminino , Tentativa de Suicídio/psicologia , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Estresse Psicológico , Fatores de Risco
7.
Mol Psychiatry ; 27(11): 4550-4560, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36071108

RESUMO

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.


Assuntos
Ideação Suicida , Tentativa de Suicídio , Adolescente , Humanos , Encéfalo , Neuroimagem/métodos , Transtornos do Humor
8.
Dev Psychopathol ; 35(5): 2384-2401, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37434505

RESUMO

Resilience promotes positive adaptation to challenges and may facilitate recovery for adolescents experiencing psychopathology. This work examined concordance across the experience, expression, and physiological response to stress as a protective factor that may predict longitudinal patterns of psychopathology and well-being that mark resilience. Adolescents aged 14-17 at recruitment (oversampled for histories of non-suicidal self-injury; NSSI) were part of a three-wave (T1, T2, T3) longitudinal study. Multi-trajectory modeling produced four distinct profiles of stress experience, expression, and physiology at T1 (High-High-High, Low-Low-Low, High-Low-Moderate, and High-High-Low, respectively). Linear mixed-effect regressions modeled whether the profiles predicted depressive symptoms, suicide ideation, NSSI engagement, positive affect, satisfaction with life, and self-worth over time. Broadly, concordant stress response profiles (Low-Low-Low, High-High-High) were associated with resilient-like patterns of psychopathology and well-being over time. Adolescents with a concordant High-High-High stress response profile showed a trend of greater reduction in depressive symptoms (B = 0.71, p = 0.052), as well as increased global self-worth (B = -0.88, p = 0.055), from T2 to T3 compared to the discordant High-High-Low profile. Concordance across multi-level stress responses may be protective and promote future resilience, whereas blunted physiological responses in the presence of high perceived and expressed stress may indicate poorer outcomes over time.


Assuntos
Resiliência Psicológica , Comportamento Autodestrutivo , Humanos , Adolescente , Estudos Longitudinais , Ideação Suicida , Psicopatologia , Fatores de Risco
9.
J Clin Child Adolesc Psychol ; : 1-15, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37318235

RESUMO

OBJECTIVE: Native American adolescents are disproportionately burdened by suicidality. Here, we examine patterns of reporting of suicide ideation and suicide attempt among Native American youth compared to those from other ethnoracial backgrounds, as this data is important for grounding commonly subscribed to frameworks of suicide risk (e.g., ideation-to-action). METHOD: Data are from the Youth Risk Behavior Surveillance Survey (N = 54,243; grades 9-12; 51.0% female) and Minnesota Student Survey (N = 335,151; grades 8, 9, 11; 50.7% female). Comparing Native American youth to peers from other ethnoracial backgrounds, we examined two suicide reporting patterns: 1) odds of reporting suicide attempt among those who reported ideation and 2) odds of reporting suicide ideation among those who reported an attempt. RESULTS: Across both samples, when reporting suicide ideation, youth from other ethnoracial backgrounds were 20-55% less likely than Native American youth to also report attempt. While few consistent differences were observed between Native American youth and those from other racial minority backgrounds in patterns of co-reporting suicide ideation and attempt across samples, White youth were between 37% and 63% less likely than Native American youth to report a suicide attempt without also reporting ideation. CONCLUSIONS: The increased odds of engaging in a suicide attempt with or without reporting ideation question the generalizability of widely held frameworks of suicide risk to Native American youth and have important implications for suicide risk monitoring. Future research is needed to illuminate how these behaviors unfold over time and the potential mechanisms of risk for engaging in suicide attempts in this disproportionately burdened group.Abbreviations: YRBSS: Youth Risk Behavior Surveillance Survey; MSS: Minnesota Student Survey.

10.
Psychopathology ; 56(6): 473-477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36889291

RESUMO

Apophenia is the tendency to falsely detect meaningful relationships and may indicate susceptibility to more extreme expressions on the psychotic spectrum. This pilot investigated the fragmented ambiguous object task (FAOT), a new measure designed to assess apophenia behaviorally in a sample of adolescents with and without mood disorders using an image recognition task. Our primary hypothesis was that increased image recognition would be associated with PID-5 psychoticism. Participants were 33 (79% female) adolescents with (n = 18) and without (n = 15) mood disorders. Consistent with predictions, increased recognition of ambiguous images correlated positively with psychoticism. There was also moderate evidence for long-term stability of FAOT apophenia scores over time (mean interval of approximately 10 months). These findings offer preliminary evidence that the FAOT may be reflective of underlying psychoticism in our target population.


Assuntos
Transtornos do Humor , Transtornos Psicóticos , Adolescente , Feminino , Humanos , Masculino , Transtornos do Humor/complicações , Transtornos do Humor/diagnóstico , Transtornos Psicóticos/complicações
11.
Mol Psychiatry ; 26(9): 5124-5139, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32424236

RESUMO

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.


Assuntos
Transtorno Depressivo Maior , Adolescente , Adulto , Idoso , Envelhecimento , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Mol Psychiatry ; 26(9): 4839-4852, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467648

RESUMO

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.


Assuntos
Transtorno Depressivo Maior , Idoso , Encéfalo/diagnóstico por imagem , Córtex Cerebral , Transtorno Depressivo Maior/genética , Humanos , Imageamento por Ressonância Magnética , Obesidade/genética , Fatores de Risco
13.
Mol Psychiatry ; 25(7): 1511-1525, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31471575

RESUMO

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.


Assuntos
Transtorno Depressivo Maior/patologia , Substância Branca/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Estudos de Coortes , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Adulto Jovem
14.
Depress Anxiety ; 38(12): 1234-1244, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34110070

RESUMO

METHODS: In a 2-year longitudinal study of 220 families, we examined how youth gender and adrenocortical and parasympathetic activity moderated reciprocal, bidirectional relations between parent and youth anxiety and depression problems. RESULTS: Maternal anxiety predicted subsequent youth anxiety and depression. Maternal depression predicted youth anxiety and, for daughters and youth with low adrenocortical reactivity, youth depression. Youth depression predicted maternal depression only for youth with high adrenocortical reactivity. There were no associations between paternal and youth psychopathology. DISCUSSION: Examining youth gender and psychophysiological characteristics that shape the nature of bidirectional influences may inform efforts to identify families at heightened risk for intergenerational transmission of psychopathology.


Assuntos
Depressão , Relações Pais-Filho , Adolescente , Ansiedade/epidemiologia , Depressão/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pais , Psicofisiologia
15.
Dev Psychopathol ; 33(4): 1156-1169, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32672147

RESUMO

Growing evidence suggests that emotion socialization may be disrupted by maternal depression. However, little is known about emotion-related parenting by mothers with bipolar disorder or whether affective modeling in early childhood is linked to young adults' recollections of emotion socialization practices. The current study investigates emotion socialization by mothers with histories of major depression, bipolar disorder, or no mood disorder. Affective modeling was coded from parent-child interactions in early childhood and maternal responses to negative emotions were recollected by young adult offspring (n = 131, 59.5% female, M age = 22.16, SD = 2.58). Multilevel models revealed that maternal bipolar disorder was associated with more neglecting, punishing, and magnifying responses to children's emotions, whereas maternal major depression was associated with more magnifying responses; links between maternal diagnosis and magnifying responses were robust to covariates. Young adult recollections of maternal responses to emotion were predicted by affective modeling in early childhood, providing preliminary validity evidence for the Emotions as a Child Scale. Findings provide novel evidence that major depression and bipolar disorder are associated with altered emotion socialization and that maternal affective modeling in early childhood prospectively predicts young adults' recollections of emotion socialization in families with and without mood disorder.


Assuntos
Mães , Socialização , Adulto , Pré-Escolar , Emoções , Feminino , Humanos , Masculino , Transtornos do Humor , Poder Familiar , Adulto Jovem
16.
Dev Psychopathol ; 33(5): 1774-1792, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34486502

RESUMO

Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala-mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala-mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.


Assuntos
Comportamento Autodestrutivo , Adolescente , Humanos , Feminino , Estudos Transversais , Tentativa de Suicídio , Tonsila do Cerebelo/diagnóstico por imagem , Hidrocortisona
17.
Int J Mol Sci ; 22(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34830395

RESUMO

The NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome is a node of intracellular stress pathways and a druggable target which integrates mitochondrial stress and inflammatory cascades. While a body of evidence suggests the involvement of the NLRP3 inflammasome in numerous diseases, a lack of reliable measurement techniques highlights the need for a robust assay using small quantities of biological samples. We present a literature overview on peripheral activation of the NLRP3 inflammasome in mood disorders, then outline a process to develop and validate a robust assay to measure baseline and activated intracellular levels of "apoptosis-associated speck-like protein containing a CARD" (ASC) as a key component of an inflammatory profile in peripheral blood mononuclear cells (PBMC). A consistent association between high NLRP3 mRNA levels and relevant cytokines was seen in the literature. Using our method to measure ASC, stimulation of PBMC with lipopolysaccharide and nigericin or adenosine triphosphate resulted in microscopic identification of intracellular ASC specks, as well as interleukin 1 (IL-1) beta and caspase-1 p10 in the periphery. This was abolished by dose-dependent pre-treatment with 100 nM MCC950. We also report the use of this technique in a small pilot sample from patients with bipolar disorder and depressive disorders. The results show that levels of intracellular ASC and IL-1 beta are sensitive to change upon activation and maintained over time, which may be used to improve the detection of NLRP3 activation and guide personalized therapeutic strategy in the treatment of patients.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/sangue , Inflamação/sangue , Interleucina-1beta/sangue , Transtornos do Humor/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Adolescente , Animais , Apoptose/genética , Caspase 1/sangue , Feminino , Humanos , Inflamassomos/sangue , Inflamassomos/genética , Inflamação/genética , Inflamação/patologia , Leucócitos Mononucleares/metabolismo , Masculino , Mitocôndrias/genética , Transtornos do Humor/genética , Transtornos do Humor/patologia
18.
Stress ; 23(1): 105-115, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418329

RESUMO

Transcendental meditation (TM) is effective in alleviating stress and anxiety and promoting well-being. While the underlying biological mechanisms of TM are not yet fully explored, the hypothalamic-pituitary-adrenal (HPA) axis represents an index providing important clues embodying the stress system cascade. In this pilot study, young adults were randomly assigned to TM training followed by 8 weeks of meditation practice or a wait-list control condition. TM was conducted over 8 weeks. Thirty-four young adult participants were randomized; 27 participants completed the HPA outcome assessments (41% male). To assess HPA axis functioning, salivary samples to assess cortisol awakening response (CAR) that were collected in the morning, both at baseline and at week-4. Salivary cortisol in the context of a social stressor using the Trier Social Stress Test (TSST) was collected at week-8. The results indicate that participants who were randomly assigned to TM had lower awakening salivary cortisol levels and a greater drop in CAR from baseline to week-4 than the control group. There were no significant differences in HPA axis functioning in the context of the TSST. Primary limitations of this randomized controlled trial were the small sample size, the use of a wait-list as opposed to an active control, and the limited scope of HPA axis assessments. The results of this pilot study provide tentative evidence that TM may impact biological stress system functioning and suggests that this may be a worthwhile avenue to continue to examine. It will also be useful to extend these findings to a broader array of meditative and mindful practices, particularly for those who are experiencing more distress.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Meditação/psicologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/terapia , Ansiedade/psicologia , Feminino , Humanos , Hidrocortisona , Masculino , Atenção Plena , Projetos Piloto , Saliva , Estresse Psicológico/psicologia , Adulto Jovem
19.
J Adolesc ; 84: 45-55, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32853861

RESUMO

INTRODUCTION: While peer delinquency is a known mediator between early pubertal timing and externalizing behaviors, little is known about factors that could protect against the adverse influence of peer delinquency. This study assesses the possible moderating role of cognitive flexibility, which is one index of executive functioning that facilitates flexible and adaptive responses to challenging situations. We assessed the interactive influence of peer delinquency and cognitive flexibility in the association between pubertal maturation and externalizing behaviors in boys and girls. METHOD: Participants were 220 adolescents (111 boys) from the United States, between the ages of 11 and 16 years (M = 13.2, SD = 1.53) who participated in the Adolescent Emotion Study (AES). RESULTS: Findings from the cross-sectional path modeling analyses provided evidence for the mediating role of peer delinquency for boys and girls, indicating that early maturing adolescents tend to affiliate with delinquent peers, which in turn exacerbates externalizing problems. Additionally, the moderating role of cognitive flexibility was also demonstrated for both boys and girls. Region of significance tests revealed that relatively well-developed cognitive flexibility skills could protect against the adverse influences of peer delinquency, whereas lower levels could exacerbate those negative influences. CONCLUSION: These findings suggest that involvement with deviant peers increases vulnerability for both early maturing boys and girls. Additionally, cognitive flexibility was an important moderating factor for adolescents, such that youths with less developed skills would be at a higher risk for psychopathology, whereas those with better development could be protected.


Assuntos
Comportamento do Adolescente/psicologia , Cognição , Delinquência Juvenil/psicologia , Grupo Associado , Maturidade Sexual , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino
20.
Hum Brain Mapp ; 40(2): 652-662, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30251758

RESUMO

Neurobiological disturbances associated with reward and/or habit learning are theorized to maintain symptoms of anorexia nervosa (AN). Although research has investigated responses in brain regions associated with reward and habit to disorder-specific cues (e.g., food) and presumed rewards (e.g., money), little is known about the functional organization of the circuits underlying these constructs independent of stimulus. This study aimed to provide initial data on the synchrony of networks associated with reward and habit in AN by comparing resting-state functional connectivity (RSFC) patterns between AN and healthy control (HC) participants in these circuits and delineating how these patterns relate to symptoms. Using theoretically selected seeds in the nucleus accumbens (NAcc), ventral caudate, and dorsal caudate, reflecting a continuum from reward- to habit- oriented regions, RSFC patterns were compared between AN restricting subtype (n = 19) and HC (n = 19) participants (cluster threshold: p < .01). Exploratory correlations between RSFC z-scores and Eating Disorder Examination (EDE) scores, BMI, and illness duration were conducted. The AN group demonstrated lower RSFC between the NAcc and superior frontal gyrus, between the ventral caudate and frontal and posterior regions, and between the dorsal caudate and frontal, temporal, and posterior regions. In the AN group, lower NAcc- superior frontal gyrus RSFC correlated with greater EDE Global scores (r = -.58, CI: -.83, -.13). These resting-state synchrony disruptions of the ventral and dorsal frontostriatal circuits, considered in context of the broader literature, support the utility of further investigating possible reward and habit disturbances supporting symptoms in AN.


Assuntos
Anorexia Nervosa/fisiopatologia , Núcleo Caudado/fisiopatologia , Córtex Cerebral/fisiopatologia , Conectoma , Hábitos , Rede Nervosa/fisiopatologia , Núcleo Accumbens/fisiopatologia , Recompensa , Adolescente , Adulto , Anorexia Nervosa/diagnóstico por imagem , Núcleo Caudado/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Núcleo Accumbens/diagnóstico por imagem , Adulto Jovem
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