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Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders.
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Depressão , Mania , Humanos , Adulto Jovem , Adulto , Cognição , Imageamento por Ressonância Magnética/métodos , Encéfalo , Mapeamento Encefálico/métodos , Vias NeuraisRESUMO
BACKGROUND: Offspring of parents with bipolar disorder (BD-I/II) are at increased risk to develop the disorder. Previous work indicates that bipolar spectrum disorder (BPSD) is often preceded by mood/anxiety symptoms. In school-age offspring of parents with BD, we previously built a risk calculator to predict BPSD onset, which generates person-level risk scores. Here, we test whether preschool symptoms predict school-age BPSD risk. METHODS: We assessed 113 offspring of parents with BD 1-3 times during preschool years (2-5 years old) and then approximately every 2 years for a mean of 10.6 years. We used penalized (lasso) regression with linear mixed models to assess relationships between preschool mood, anxiety, and behavioral symptoms (parent-reported) and school-age predictors of BPSD onset (i.e., risk score, subthreshold manic symptoms, and mood lability), adjusting for demographics and parental symptomatology. Finally, we conducted survival analyses to assess associations between preschool symptoms and school-age onset of BPSD and mood disorder. RESULTS: Of 113 preschool offspring, 33 developed new-onset mood disorder, including 19 with new-onset BPSD. Preschool irritability, sleep problems, and parental factors were lasso-selected predictors of school-age risk scores. After accounting for demographic and parental factors, preschool symptoms were no longer significant. Lasso regressions to predict mood lability and subthreshold manic symptoms yielded similar predictors (irritability, sleep problems, and parental affective lability), but preschool symptoms remained predictive even after adjusting for parental factors (ps < .005). Exploratory analyses indicated that preschool irritability univariately predicted new-onset BPSD (p = .02) and mood disorder (p = .02). CONCLUSIONS: These results provide initial prospective evidence that, as early as preschool, youth who will develop elevated risk scores, mood lability, and subthreshold manic symptoms are already showing symptomatology; these preschool symptoms also predict new-onset BPSD. While replication of findings in larger samples is warranted, results point to the need for earlier assessment of risk and development of early interventions.
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Transtorno Bipolar , Filho de Pais com Deficiência , Transtornos do Sono-Vigília , Adolescente , Humanos , Pré-Escolar , Estudos Prospectivos , Transtornos do Humor , Pais/psicologia , Filho de Pais com Deficiência/psicologiaRESUMO
OBJECTIVE: This study (NIMH RO1 MH095750; ClinicalTrials.gov Identifier: NCT02543359) evaluated the effectiveness of three training models to implement a well-established evidence-based treatment, Parent-Child Interaction Therapy (PCIT). METHOD: Fifty licensed outpatient clinics, including 100 clinicians, 50 supervisors, and 50 administrators were randomized to one of three training conditions: 1) Learning Collaborative (LC), 2) Cascading Model (CM) or 3) Distance Education (DE). Data to assess training and implementation outcomes were collected at 4 time points coinciding with the training period: baseline, 6- (mid), 12- (post), and 24-months (1-year follow-up). RESULTS: Multi-level hierarchical linear growth modeling was used to examine changes over time in training outcomes. Results indicate that clinicians in CM were more likely to complete training, reported high levels of training satisfaction and better learning experiences compared to the other training conditions. However, supervisors in the LC condition reported greater learning experiences, higher levels of knowledge, understanding of treatment, and satisfaction compared to supervisors in other conditions. Although clinicians and supervisors in the DE condition did not outperform their counterparts on any outcomes, their performance was comparable to both LC and CM in terms of PCIT use, supervisor perceived acceptability, feasibility, system support, and clinician satisfaction. CONCLUSIONS: Through the use of a randomized controlled design and community implementation, this study contributes to the current understanding of the impact of training design on implementation of PCIT. Results also indicate that although in-person training methods may produce more positive clinician and supervisor outcomes, training is not a one-size-fits-all model, with DE producing comparable results on some variables.
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Aprendizagem , Relações Pais-Filho , HumanosRESUMO
Both social support and social stress can impact adolescent physiology including hormonal responses during the sensitive transition to adolescence. Social support from parents continues to play an important role in socioemotional development during adolescence. Sources of social support and stress may be particularly impactful for adolescents with social anxiety symptoms. The goal of the current study was to examine whether adolescent social anxiety symptoms and maternal comfort moderated adolescents' hormonal response to social stress and support. We evaluated 47 emotionally healthy 11- to 14-year-old adolescents' cortisol and oxytocin reactivity to social stress and support using a modified version of the Trier Social Stress Test for Adolescents that included a maternal comfort paradigm. Findings demonstrated that adolescents showed significant increases in cortisol and significant decreases in oxytocin following the social stress task. Subsequently, we found that adolescents showed significant decreases in cortisol and increases in oxytocin following the maternal comfort paradigm. Adolescents with greater social anxiety symptoms showed higher levels of cortisol at baseline but greater declines in cortisol response following maternal social support. Social anxiety symptoms were unrelated to oxytocin response to social stress or support. Our findings provide further evidence that mothers play a key role in adolescent regulation of physiological response, particularly if the stressor is consistent with adolescents' anxiety. More specifically, our findings suggest that adolescents with higher social anxiety symptoms show greater sensitivity to maternal social support following social stressors. Encouraging parents to continue to serve as a supportive presence during adolescent distress may be helpful for promoting stress recovery during the vulnerable transition to adolescence.
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We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Vias Neurais/fisiopatologia , Adolescente , Adulto , Ansiedade/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Biomarcadores , Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Depressão/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/fisiopatologia , Prognóstico , Escalas de Graduação Psiquiátrica , Fatores de Risco , Lobo Temporal/fisiopatologia , Adulto JovemRESUMO
OBJECTIVES: To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. METHOD: Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). RESULTS: After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. CONCLUSION: BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.
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Transtorno Bipolar/psicologia , Transtornos Psicóticos/psicologia , Adolescente , Transtorno Bipolar/epidemiologia , Criança , Comorbidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Transtornos Psicóticos/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Youth anxiety interventions have potential to reduce risk for depression and suicidality. METHODS: This naturalistic follow-up of the multi-site, comparative treatment trial, inking and behavior, and depressive symptoms 3-11 years (mean 6.25 years) following 12-week evidence-based youth anxiety treatment. Participants (N = 319; 10-26 years, mean 17 years) completed semiannual questionnaires and annual diagnostic interviews for 4 years. RESULTS: One-fifth (20.4%) of the sample met DSM-IV criteria for a mood disorder, 32.1% endorsed suicidal ideation, and 8.2% reported suicidal behavior. Latent class growth analysis yielded two linear trajectories of depressive symptoms, and 85% of the sample demonstrated a persistent low-symptom course over seven assessments. Child/Adolescent Anxiety Multimodal Study (CAMS) 12-week treatment outcome (positive response, remission) and treatment condition (cognitive behavior therapy [CBT], medication, CBT + medication, pill placebo) were not associated with subsequent mood disorder or suicidal thinking. CAMS remission predicted absence of suicidal behavior, and treatment response and remission predicted low depressive symptom trajectory. Greater baseline self-reported depressive symptoms predicted all long-term mood outcomes, and more negative life events predicted subsequent mood disorder, depressive symptom trajectory, and suicidal ideation. CONCLUSIONS: Effective early treatment of youth anxiety, including CBT, medication, or CBT + medication, reduces risk for subsequent chronic depressive symptoms and suicidal behavior. Attention to (sub)clinical depressive symptoms and management of negative life events may reduce odds of developing a mood disorder, chronic depressive symptoms, and suicidality. Findings contribute to evidence that early intervention for a primary disorder can serve as secondary prevention.
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Afeto , Transtornos de Ansiedade/terapia , Ansiedade/terapia , Suicídio/psicologia , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/psicologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/psicologia , Criança , Terapia Cognitivo-Comportamental , Depressão/complicações , Depressão/psicologia , Depressão/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Autorrelato , Ideação Suicida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Prevenção do SuicídioRESUMO
The current study evaluated the interrater reliability of the Child and Adolescent Services Assessment (CASA), a widely used structured interview measuring pediatric mental health service use. Interviews (N = 72) were randomly selected from a pediatric effectiveness trial, and audio was coded by an independent rater. Regressions were employed to identify predictors of rater disagreement. Interrater reliability was high for items (> 94%) and summary metrics (ICC > .79) across service sectors. Predictors of disagreement varied by domain; significant predictors indexed higher clinical severity or social disadvantage. Results support the CASA as a reliable and robust assessment of pediatric service use, but administrators should be alert when assessing vulnerable populations.
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Serviços de Saúde do Adolescente/estatística & dados numéricos , Ansiedade/terapia , Serviços de Saúde da Criança/estatística & dados numéricos , Depressão/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. METHODS: The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. RESULTS: The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (Ps <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). CONCLUSIONS: Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications.
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Transtorno Bipolar , Filho de Pais com Deficiência/psicologia , Depressão , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/etiologia , Transtorno Bipolar/psicologia , Criança , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Saúde da Família/estatística & dados numéricos , Feminino , Humanos , Masculino , Pais/psicologia , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Medição de Risco/métodos , Fatores de Risco , Avaliação de Sintomas/métodos , Estados UnidosRESUMO
OBJECTIVES: Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross-sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with BP compared with non-BP patients and healthy controls. METHODS: Subjects with bipolar I disorder (BP-I)/bipolar II disorder (BP-II) (n = 255), those with non-BP psychopathology (n = 85), and healthy controls (n = 84) (average 38.9 years, 78.7% female, and 84.9% Caucasian) were evaluated at intake and after two and four years of follow-up. Aggression was self-rated using the Aggression Questionnaire (AQ). Comparisons were adjusted for any significant demographic and clinical differences and for multiple comparisons. For subjects with BP, associations of AQ with subtype of BP, current versus past mood episodes, polarity and severity of the current episode, psychosis, and current pharmacological treatment were evaluated. RESULTS: In comparison with subjects with non-BP psychiatric disorders and healthy controls, subjects with BP showed persistently higher total and subscale AQ scores (raw and T-scores) during the four-year follow-up. There were no effects of BP subtype, severity or polarity of the current episode, psychosis, and current pharmacological treatments. Subjects in an acute mood episode showed significantly higher AQ scores than euthymic subjects. CONCLUSIONS: BP, particularly during acute episodes, is associated with increased self-reported verbal and physical aggression, anger, and hostility. These results provide further evidence of the need for treatments to prevent mood recurrences and prompt treatment of acute mood episodes in subjects with BP.
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Agressão/fisiologia , Transtorno Bipolar/fisiopatologia , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The purpose of this study is to compare the dimensional psychopathology, as ascertained by parental report, in preschool offspring of parents with bipolar disorder (BP) and offspring of community control parents. METHODS: 122 preschool offspring (mean age 3.3 years) of 84 parents with BP, with 102 offspring of 65 control parents (36 healthy, 29 with non-BP psychopathology), were evaluated using the Child Behavior Checklist (CBCL), the CBCL-Dysregulation Profile (CBCL-DP), the Early Childhood Inventory (ECI-4), and the Emotionality Activity Sociability (EAS) survey. Teachers' Report Forms (TRF) were available for 51 preschoolers. RESULTS: After adjusting for confounders, offspring of parents with BP showed higher scores in the CBCL total, externalizing, somatic, sleep, aggressive, and CBCL-DP subscales; the ECI-4 sleep problem scale; and the EAS total and emotionality scale. The proportion of offspring with CBCL T-scores ≥ 2 SD above the norm was significantly higher on most CBCL subscales and the CBCL-DP in offspring of parents with BP compared to offspring of controls even after excluding offspring with attention deficit hyperactivity disorder and/or oppositional defiant disorder. Compared to offspring of parents with BP-I, offspring of parents with BP-II showed significantly higher scores in total and most CBCL subscales, the ECI-4 anxiety and sleep scales and the EAS emotionality scale. For both groups of parents, there were significant correlations between CBCL and TRF scores (r = .32-.38, p-values ≤.02). CONCLUSIONS: Independent of categorical axis-I psychopathology and other demographic or clinical factors in both biological parents, preschool offspring of parents with BP have significantly greater aggression, mood dysregulation, sleep disturbances, and somatic complaints compared to offspring of control parents. Interventions to target these symptoms are warranted.
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Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno Bipolar/psicologia , Transtornos do Comportamento Infantil/psicologia , Filho de Pais com Deficiência/psicologia , Adulto , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Transtornos do Comportamento Infantil/etiologia , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Objective: Existing neuroimaging studies of psychotic and mood disorders have reported brain activation differences (first-order properties) and altered pairwise correlation-based functional connectivity (second-order properties). However, both approaches have certain limitations that can be overcome by integrating them in a pairwise maximum entropy model (MEM) that better represents a comprehensive picture of fMRI signal patterns and provides a system-wide summary measure called energy. This study examines the applicability of individual-level MEM for psychiatry and identifies image-derived model coefficients related to model parameters. Method: MEMs are fit to resting state fMRI data from each individual with schizophrenia/schizoaffective disorder, bipolar disorder, and major depression (n=132) and demographically matched healthy controls (n=132) from the UK Biobank to different subsets of the default mode network (DMN) regions. Results: The model satisfactorily explained observed brain energy state occurrence probabilities across all participants, and model parameters were significantly correlated with image-derived coefficients for all groups. Within clinical groups, averaged energy level distributions were higher in schizophrenia/schizoaffective disorder but lower in bipolar disorder compared to controls for both bilateral and unilateral DMN. Major depression energy distributions were higher compared to controls only in the right hemisphere DMN. Conclusions: Diagnostically distinct energy states suggest that probability distributions of temporal changes in synchronously active nodes may underlie each diagnostic entity. Subject-specific MEMs allow for factoring in the individual variations compared to traditional group-level inferences, offering an improved measure of biologically meaningful correlates of brain activity that may have potential clinical utility.
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The number of young adults seeking help for emotional distress, subsyndromal-syndromal mood/anxiety symptoms, including those associated with neuroticism, is rising and can be an early manifestation of mood/anxiety disorders. Identification of gray matter (GM) thickness alterations and their relationship with neuroticism and mood/anxiety symptoms can aid in earlier diagnosis and prevention of risk for future mood and anxiety disorders. In a transdiagnostic sample of young adults (n = 252;177 females; age 21.7 ± 2), Hypothesis (H) 1:regularized regression followed by multiple regression examined relationships among GM cortical thickness and clinician-rated depression, anxiety, and mania/hypomania; H2:the neuroticism factor and its subfactors as measured by NEO Personality Inventory (NEO-PI-R) were tested as mediators. Analyses revealed positive relationships between left parsopercularis thickness and depression (B = 4.87, p = 0.002), anxiety (B = 4.68, p = 0.002), mania/hypomania (B = 6.08, p ≤ 0.001); negative relationships between left inferior temporal gyrus (ITG) thickness and depression (B = - 5.64, p ≤ 0.001), anxiety (B = - 6.77, p ≤ 0.001), mania/hypomania (B = - 6.47, p ≤ 0.001); and positive relationships between left isthmus cingulate thickness (B = 2.84, p = 0.011), and anxiety. NEO anger/hostility mediated the relationship between left ITG thickness and mania/hypomania; NEO vulnerability mediated the relationship between left ITG thickness and depression. Examining the interrelationships among cortical thickness, neuroticism and mood and anxiety symptoms enriches the potential for identifying markers conferring risk for mood and anxiety disorders and can provide targets for personalized intervention strategies for these disorders.
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Transtornos de Ansiedade , Mania , Feminino , Adulto Jovem , Humanos , Adulto , Transtornos de Ansiedade/psicologia , Neuroticismo , Afeto , Emoções , Ansiedade/psicologia , Transtornos do HumorRESUMO
BACKGROUND: Bipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample. METHODS: A prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline). RESULTS: Over a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset. LIMITATIONS: Clinical samples may limit generalizability; the RC does not assess more acute suicide risk. CONCLUSIONS: One-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.
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Transtorno Bipolar , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/diagnóstico , Estudos Prospectivos , Transtornos do Humor , Tentativa de Suicídio , Fatores de RiscoRESUMO
Brain arterioles are active, multicellular complexes whose diameters oscillate at â¼ 0.1 Hz. We assess the physiological impact and spatiotemporal dynamics of vaso-oscillations in the awake mouse. First, vaso-oscillations in penetrating arterioles, which source blood from pial arterioles to the capillary bed, profoundly impact perfusion throughout neocortex. The modulation in flux during resting-state activity exceeds that of stimulus-induced activity. Second, the change in perfusion through arterioles relative to the change in their diameter is weak. This implies that the capillary bed dominates the hydrodynamic resistance of brain vasculature. Lastly, the phase of vaso-oscillations evolves slowly along arterioles, with a wavelength that exceeds the span of the cortical mantle and sufficient variability to establish functional cortical areas as parcels of uniform phase. The phase-gradient supports traveling waves in either direction along both pial and penetrating arterioles. This implies that waves along penetrating arterioles can mix, but not directionally transport, interstitial fluids.
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Circulação Cerebrovascular , Animais , Camundongos , Arteríolas/fisiologia , Circulação Cerebrovascular/fisiologia , Masculino , Córtex Cerebral/fisiologia , Córtex Cerebral/irrigação sanguínea , Camundongos Endogâmicos C57BL , Neocórtex/fisiologia , Neocórtex/irrigação sanguíneaRESUMO
BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance. We hypothesized that 1) HA, not an OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2) HA-specific findings would be robust to comorbid symptoms; and 3) reliable findings would replicate in a holdout testing subsample. METHODS: Using resting-state functional connectivity magnetic resonance imaging, cross-validated elastic net for feature selection, and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample (n = 73; 71.8% female; healthy control group n = 36, OCD group n = 37); robustness to comorbidities; and replicability in a testing subsample (n = 30; 56.7% female; healthy control group n = 15, OCD group n = 15). RESULTS: Stronger inverse connectivity between the right dorsal anterior cingulate cortex and right basolateral amygdala and stronger positive connectivity between the right ventral anterior insula and left ventral striatum were associated with greater HA across groups. Network connections did not discriminate OCD diagnostic status or predict HA-correlated traits, suggesting sensitivity to trait HA. The dorsal anterior cingulate cortex-basolateral amygdala relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. CONCLUSIONS: Stronger inverse dorsal anterior cingulate cortex-basolateral amygdala connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent avoidance-related network to OCD, with implications for precision-based approaches and treatment.
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Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Humanos , Masculino , Feminino , Adulto , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto Jovem , Aprendizagem da Esquiva/fisiologia , Redução do DanoRESUMO
OBJECTIVE: We present results from a 2-site, randomized clinical trial to assess the efficacy of a brief intervention (As Safe As Possible [ASAP]), a safety plan phone application (BRITE), and their combination on suicide attempts, suicidal ideation, non-suicidal self-injury, re-hospitalizations. and suicidal events among adolescents. METHOD: Adolescents (n= 240; 12-17 years of age) who were hospitalized for suicidal ideation with plan and/or intent, and/or suicide attempt, were assigned to 1 of 4 treatment conditions in a 2 by 2 design: ASAP+BRITE app+treatment as usual (TAU); (2) BRITE+TAU; (3) ASAP+TAU; and (4) TAU alone. Independent evaluators assessed suicidal ideation and behavior at 4, 12, and 24 weeks using the Columbia-Suicide Severity Rating Scale (C-SSRS) and re-hospitalization using the Child and Adolescent Services Assessment (CASA). RESULTS: No group differences were found on primary outcomes, except that ASAP participants were less likely to be re-hospitalized over 6 months (15.6%, vs 26.5%, p = .046). Participants hospitalized for an attempt and assigned to BRITE had a lower rate of subsequent attempts (odds ratio [OR] = 0.16, p = .01) and a greater time to attempt (hazard ratio [HR] = 0.20, p = .02). ASAP+BRITE, albeit not statistically significant, was most consistently associated with a reduction (60% reduction) in suicide attempts. CONCLUSION: ASAP, BRITE, and their combination are equally effective at decreasing risk for suicidal events 6 months post hospital discharge among suicidal adolescents; the ASAP intervention (with or without BRITE) was associated with lower rates of re-hospitalization. The BRITE app in youth hospitalized for suicide attempt had promising outcomes in regard to future attempts. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The research was performed with permission from the University of Pittsburgh Institutional Review Board and the University of Texas Institutional Review Board. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. CLINICAL TRIALS REGISTRATION INFORMATION: Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE); https://clinicaltrials.gov/study/; NCT03825588.
RESUMO
OBJECTIVES: Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study. METHODS: Forty-one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of 174 BP parents, and 192 offspring of 117 control parents completed a scale that was developed to evaluate mood lability in youth, i.e., the Children's Affective Lability Scale (CALS). RESULTS: A factor analysis of the parental CALS, and in part the child CALS, revealed Irritability, Mania, and Anxiety/Depression factors, with most of the variance explained by the Irritability factor. After adjusting for confounding factors (e.g., parental and offspring non-BP psychopathology), BP offspring of BP parents showed the highest parental and child total and factor scores, followed by the non-BP offspring of BP parents, and then the offspring of the controls. CONCLUSIONS: Mood lability overall and mania-like, anxious/depressed, and particularly irritability symptoms may be a prodromal phenotype of BP among offspring of parents with BP. Prospective studies are warranted to clarify whether these symptoms will predict the development of BP and/or other psychopathology. If confirmed, these symptoms may become a target of treatment and biological studies before BP develops.
Assuntos
Transtorno Bipolar , Filho de Pais com Deficiência/psicologia , Humor Irritável/fisiologia , Relações Pais-Filho , Pais/psicologia , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Escalas de Graduação Psiquiátrica , Características de ResidênciaRESUMO
Hippocampal abnormalities are associated with psychosis-risk states. Given the complexity of hippocampal anatomy, we conducted a multipronged examination of morphometry of regions connected with hippocampus, and structural covariance network (SCN) and diffusion-weighted circuitry among 27 familial high-risk (FHR) individuals who were past the highest risk for conversion to psychoses and 41 healthy controls using ultrahigh-field high-resolution 7 Tesla (7T) structural and diffusion MRI data. We obtained fractional anisotropy and diffusion streams of white matter connections and examined correspondence of diffusion streams with SCN edges. Nearly 89 % of the FHR group had an axis-I disorder including 5 with schizophrenia. Therefore, we compared the entire FHR group regardless of the diagnosis (All_FHR = 27) and FHR-without-schizophrenia (n = 22) with 41 controls in this integrative multimodal analysis. We found striking volume loss in bilateral hippocampus, particularly the head, bilateral thalamus, caudate, and prefrontal regions. All_FHR and FHR-without-SZ SCNs showed significantly lower assortativity and transitivity but higher diameter compared to controls, but FHR-without-SZ SCN differed on every graph metric compared to All_FHR suggesting disarrayed network with no hippocampal hubs. Fractional anisotropy and diffusion streams were lower in FHR suggesting white matter network impairment. White matter edges showed significantly higher correspondence with SCN edges in FHR compared to controls. These differences correlated with psychopathology and cognitive measures. Our data suggest that hippocampus may be a "neural hub" contributing to psychosis risk. Higher correspondence of white matter tracts with SCN edges suggest that shared volume loss may be more coordinated among regions within the hippocampal white matter circuitry.