RESUMO
Introduction: In the US, women are one of the fastest-growing segments of the prison population and more than a quarter of women in state prison are incarcerated for drug offenses. Substance use criminal diversion programs can be effective. It may be beneficial to identify individuals who are most likely to complete the program versus terminate early as this can provide information regarding who may need additional or unique programming to improve the likelihood of successful program completion. Prior research investigating prediction of success in these programs has primarily focused on demographic factors in male samples. Methods: The current study used machine learning (ML) to examine other non-demographic factors related to the likelihood of completing a substance use criminal diversion program for women. A total of 179 women who were enrolled in a criminal diversion program consented and completed neuropsychological, self-report symptom measures, criminal history and demographic surveys at baseline. Model one entered 145 variables into a machine learning (ML) ensemble model, using repeated, nested cross-validation, predicting subsequent graduation versus termination from the program. An identical ML analysis was conducted for model two, in which 34 variables were entered, including the Women's Risk/Needs Assessment (WRNA). Results: ML models were unable to predict graduation at an individual level better than chance (AUC = 0.59 [SE = 0.08] and 0.54 [SE = 0.13]). Post-hoc analyses indicated measures of impulsivity, trauma history, interoceptive awareness, employment/financial risk, housing safety, antisocial friends, anger/hostility, and WRNA total score and risk scores exhibited medium to large effect sizes in predicting treatment completion (p < 0.05; ds = 0.29 to 0.81). Discussion: Results point towards the complexity involved in attempting to predict treatment completion at the individual level but also provide potential targets to inform future research aiming to reduce recidivism.
RESUMO
BACKGROUND: Dysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes. METHODS: 195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-). RESULTS: MDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp2 = 0.02), dorsolateral prefrontal cortex (ηp2 = 0.01) and dorsal anterior/mid cingulate cortex (ηp2 = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD. LIMITATIONS: Limitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants. CONCLUSIONS: AnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group.
Assuntos
Transtornos de Ansiedade , Condicionamento Clássico , Transtorno Depressivo Maior , Medo , Giro do Cíngulo , Imageamento por Ressonância Magnética , Humanos , Masculino , Medo/fisiologia , Feminino , Giro do Cíngulo/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Adulto , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Condicionamento Clássico/fisiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/epidemiologia , Córtex Insular/fisiopatologia , Córtex Insular/diagnóstico por imagem , Pessoa de Meia-Idade , Comorbidade , Lobo Frontal/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Adulto Jovem , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Ansiedade/fisiopatologia , Ansiedade/psicologiaRESUMO
Background: Sensitivity to threat with dysregulation of fear learning is thought to contribute to the development of psychiatric disorders, including anxiety disorders (AD) and major depressive disorder (MDD). However, fewer studies have examined fear learning in MDD than in AD. Nearly half of individuals with MDD have an AD and the comorbid diagnosis has worse outcomes. The current study used propensity matching to examine the hypothesis that AD+MDD shows greater neural correlates of fear learning than MDD, suggesting that the co-occurrence of AD+MDD is exemplified by exaggerated defense related processes. Methods: 195 individuals with MDD (N = 65) or AD+MDD (N=130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Results: MDD and AD+MDD showed significantly different patterns of activation for [CSplus-CSminus] in the medial amygdala (ηp2=0.009), anterior insula (ηp2=0.01), dorsolateral prefrontal cortex (ηp2=0.002), dorsal anterior cingulate cortex (ηp2=0.01), mid-cingulate cortex (ηp2=0.01) and posterior cingulate cortex (ηp2=0.02). These differences were driven by greater activation to the CS+ in late conditioning phases in ADD+MDD relative to MDD. Conclusions: AD+MDD showed a pattern of increased sustained activation in regions identified with fear learning. Effects were consistently driven by the threat condition, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, and self-relevant processing.These findings help to elucidate the fear signaling mechanisms involved in the pathophysiology of comorbid anxiety and depression, thereby highlighting promising treatment targets for this prevalent treatment group.
RESUMO
Background: Adolescents have experienced increases in anxiety, depression, and stress during the COVID-19 pandemic and may be at particular risk for suffering from long-term mental health consequences because of their unique developmental stage. This study aimed to determine if initial increases in depression and anxiety in a small sample of healthy adolescents after the onset of the COVID-19 pandemic were sustained at follow-up during a later stage of the pandemic. Methods: Fifteen healthy adolescents completed self-report measures at three timepoints (pre-pandemic [T1], early pandemic [T2], and later pandemic [T3]). The sustained effect of COVID-19 on depression and anxiety was examined using linear mixed-effect analyses. An exploratory analysis was conducted to investigate the relationship between difficulties in emotion regulation during COVID-19 at T2 and increases in depression and anxiety at T3. Results: The severity of depression and anxiety was significantly increased at T2 and sustained at T3 (depression: Hedges' g [T1 to T2] = 1.04, g [T1 to T3] = 0.95; anxiety: g [T1 to T2] = 0.79, g [T1 to T3] = 0.80). This was accompanied by sustained reductions in positive affect, peer trust, and peer communication. Greater levels of difficulties in emotion regulation at T2 were related to greater symptoms of depression and anxiety at T3 (rho = 0.71 to 0.80). Conclusion: Increased symptoms of depression and anxiety were sustained at the later stage of the pandemic in healthy adolescents. Replication of these findings with a larger sample size would be required to draw firm conclusions.
RESUMO
Recent studies have demonstrated the promise of psilocybin therapies in creating positive changes for those with poor mental health across multiple diagnostic categories, including major depressive disorder (MDD), end-of-life anxiety, and obsessive-compulsive disorder (OCD). While there may be a large population that is eligible to participate in psilocybin therapy based on psychiatric diagnosis and medical clearance, little attention has been given to intrapersonal and interpersonal factors that might influence patient's readiness (i.e., eligibility and capacity) for psychedelic interventions. This paper proposes that readiness assessment includes both intrapersonal and interpersonal factors in order to improve safety, patient care, and treatment outcomes. While at the present time a reliable and valid instrument has not been developed, we propose that three specific areas of focus - patient presentation, therapeutic alliance, and patient safety - may be used to establish a patient's readiness for psilocybin therapy, thus increasing therapy optimization and personalization.
Assuntos
Transtorno Depressivo Maior , Alucinógenos , Transtorno Obsessivo-Compulsivo , Humanos , Psilocibina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Alucinógenos/efeitos adversos , Transtorno Obsessivo-Compulsivo/psicologia , AnsiedadeRESUMO
INTRODUCTION: Repetitive negative thinking (RNT) is a cognitive process focusing on self-relevant and negative experiences, leading to a poor prognosis of major depressive disorder (MDD). We previously identified that connectivity between the precuneus/posterior cingulate cortex (PCC) and right temporoparietal junction (rTPJ) was positively correlated with levels of RNT. OBJECTIVE: In this double-blind, randomized, sham-controlled, proof-of-concept trial, we employed real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) to delineate the neural processes that may be causally linked to RNT and could potentially become treatment targets for MDD. METHODS: MDD-affected individuals were assigned to either active (n = 20) or sham feedback group (n = 19). RNT was measured by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after the intervention. RESULTS: Individuals in the active but not in the sham group showed a significant reduction in the RRS-B; however, a greater reduction in the PCC-rTPJ connectivity was unrelated to a greater reduction in the RRS-B. Exploratory analyses revealed that a greater reduction in the retrosplenial cortex (RSC)-rTPJ connectivity yielded a more pronounced reduction in the RRS-B in the active but not in the sham group. CONCLUSIONS: RtfMRI-nf was effective in reducing RNT. Considering the underlying mechanism of rtfMIR-nf, the RSC and rTPJ could be part of a network (i.e., default mode network) that might collectively affect the intensity of RNT. Understanding the relationship between the functional organization of targeted neural changes and clinical metrics, such as RNT, has the potential to guide the development of mechanism-based treatment of MDD.
Assuntos
Transtorno Depressivo Maior , Neurorretroalimentação , Pessimismo , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Neurorretroalimentação/métodos , Depressão , Imageamento por Ressonância Magnética/métodosRESUMO
American Indians (AI) experience disproportionately high prevalence of suicide and substance use disorders (SUD). However, accounting for risk burden (e.g. historical trauma and discrimination), the likelihood of mental health disorders or SUD is similar or decreased compared with the broader population. Such findings have spurred psychological research examining the protective factors, but no studies have investigated its potential neural mechanisms. Inhibitory control is one of the potential neurobehavioral construct with demonstrated protective effects, but has not been examined in neuroimaging studies with AI populations specifically. We examined the incidence of suicidal thoughts and behaviors (STB) and SUD among AI (n = 76) and propensity matched (sex, age, income, IQ proxy and trauma exposure) non-Hispanic White (NHW) participants (n = 76). Among the AI sample, functional magnetic resonance imaging (fMRI) data recorded during the stop-signal task (SST) was examined in relation to STB and SUDs. AIs relative to NHW subjects displayed lower incidence of STB. AIs with no reported STBs showed greater activity in executive control regions during the SST compared with AI who endorsed STB. AI without SUD demonstrated lower activity relative to those individual reporting SUD. Results are consistent with a growing body of literature demonstrating the high level of risk burden driving disparate prevalence of mental health concerns in AI. Furthermore, differential activation during inhibitory control processing in AI individuals without STB may represent a neural mechanism of protective effects against mental health problems in AI. Future research is needed to elucidate sociocultural factors contributing protection against mental health outcomes in AIs and further delineate neural mechanisms with respect to specific concerns (e.g. SUD vs STB).
Assuntos
Indígenas Norte-Americanos , Inibição Psicológica , Saúde Mental , Humanos , Indígenas Norte-Americanos/psicologia , Transtornos Relacionados ao Uso de Substâncias , Ideação SuicidaRESUMO
OBJECTIVE: To identify robust and reproducible factors associated with suicidal thoughts and behaviors (STBs) in college students. METHODS: 356 first-year university students completed a large battery of demographic and clinically-relevant self-report measures during the first semester of college and end-of-year (n = 228). Suicide Behaviors Questionnaire-Revised (SBQ-R) assessed STBs. A machine learning (ML) pipeline using stacking and nested cross-validation examined correlates of SBQ-R scores. RESULTS: 9.6% of students were identified at significant STBs risk by the SBQ-R. The ML algorithm explained 28.3% of variance (95%CI: 28-28.5%) in baseline SBQ-R scores, with depression severity, social isolation, meaning and purpose in life, and positive affect among the most important factors. There was a significant reduction in STBs at end-of-year with only 1.8% of students identified at significant risk. CONCLUSION: Analyses replicated known factors associated with STBs during the first semester of college and identified novel, potentially modifiable factors including positive affect and social connectedness.
RESUMO
Objective: Exposure-based therapy (EXP) and behavioral activation (BA) are empirically-supported behavioral intervention techniques that target avoidance and approach behavior to alleviate symptoms. Although EXP is an established treatment for generalized anxiety disorder (GAD), the effectiveness of BA for GAD has not been directly tested or compared with that of EXP. This study examined the efficacy of EXP and BA for adults with GAD. Method: In a randomized clinical trial (clinicaltrials.gov: NCT02807480) with partial blinding in Tulsa, OK, 102 adults with GAD were allocated to manualized, 10-session EXP or BA between April 2016-April 2021. Primary analyses were intention-to-treat and included the 94 (46 EXP, 48 BA) participants who started treatment. The GAD-7 self-report scale was the primary outcome measure. Results: Similar GAD-7 declines were observed at post-treatment for EXP (d=-0.97 [95% CI -1.40 to -0.53]) and BA (d=-1.14 [95% CI -1.57 to -0.70]), and were maintained through 6-month follow-up (EXP: d=-2.13, BA: d=-1.98). Compared to EXP, BA yielded more rapid declines in anxiety and depression scores during therapy (d=0.75-0.77), as well as lower anxiety and depression scores (d=0.13-0.14) and greater participant-rated improvement (d=0.64) at post-treatment. Bayesian analyses indicated 74-99% probability of greater change in BA than EXP at post-treatment. Conclusions: BA and EXP are both effective in treating GAD, and BA may confer greater benefit during treatment. Future research is warranted to inform personalized treatment approaches.
RESUMO
BACKGROUND: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC. METHODS: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures. RESULTS: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27). LIMITATIONS: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference. CONCLUSION: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.
Assuntos
Depressão , Recompensa , Adulto , Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade , Corpo Estriado/diagnóstico por imagem , Depressão/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Objective: Repetitive negative thinking (RNT) is an important symptom in the development and maintenance of eating disorders (EDs). RNT Research on RNT's effect on cognition in EDs is scarce. This investigation focused on associations between RNT and cognition in individuals with EDs. Methods: Ruminative Response Scale (RRS) was used from Tulsa-1000 study (T-1000) data (eating disorders-ED, Major Depressive Disorder-MDD, and healthy subjects) who were propensity matched to examine associations with cognitive performance. RNT was examined across groups and we quantified the associations between scores for RNT, depression, executive function, and learning/memory from the T-1000 study. A linear regression analysis was conducted to determine predictors of disability. Results: RNT was similar in ED and MDD participants, and more intense than in controls. RNT was significantly correlated with verbal learning/memory in the control (r = 0.514, p = 0.006) and ED groups (r = -0.447, p = 0.020), but this relationship had opposite slopes in either group. Increased RNT was associated with decreased verbal learning/memory ability in ED participants while in controls, increased RNT was associated with increased ability. Comorbid depression in the ED group acted as a potential moderator of the above relationship between RNT and EF. Among ED patients, depressive symptom severity was the best predictor of disability. Discussion: The differential association of RNT with cognitive abilities in ED and MDD patients suggests depression is not a mediator of RNT-mediated cognitive dysfunction in EDs. This necessitates a better understanding of the mechanistic relationship between RNT and diverse types of cognitive functioning.
RESUMO
Objective: To further delineate risk and resilience factors contributing to trajectories of mental health symptoms experienced by college students through the pandemic. Participants: n = 183 college students (67.2% female). Methods: Linear mixed models examined time effects on depression and anxiety. Propensity-matched subgroups exhibiting "increased" versus "low and stable" depression symptoms from before to after the pandemic-onset were compared on pre-pandemic demographic and psychological factors and COVID-related experiences and coping strategies. Results: Students experienced worsening of mental health symptoms throughout the pandemic, particularly during Fall 2020 compared with Fall 2019 (Depression scale d = -0.43 [95% CI: -0.65 to -0.21]). The propensity-matched subgroup exhibiting relative resilience ("low and stable" symptoms) reported less alcohol use prior to the pandemic, greater use of active coping strategies, and less of an impact on their college progress. Conclusions: Results point to several potential targets of screening and intervention to decrease residual impacts of the pandemic.
RESUMO
BACKGROUND: Dysregulation of fear learning has been associated with psychiatric disorders that have altered positive and negative valence domain function. While amygdala-insula-prefrontal circuitry is considered important for fear learning, there have been inconsistencies in neural findings in healthy and clinical human samples. This study aimed to delineate the neural substrates and behavioral responses during fear learning in a large, transdiagnostic sample with predominantly depressive and/or anxious dysfunction. METHODS: Two-hundred and eighty-two individuals (52 healthy participants; 230 participants with depression and/or anxiety-related problems) from the Tulsa 1000 study, an ongoing, naturalistic longitudinal study based on a dimensional psychopathological framework, completed a Pavlovian fear learning task during functional magnetic resonance imaging. Linear mixed-effects analyses examined condition-by-time effects on brain activation (CS+, CS- across familiarization, conditioning, and extinction trials). A data-driven latent profile analysis (LPA) examined distinct patterns of behavioral and neural responses to threat across fear conditioning and extinction, while logistic regression analyses evaluated cognitive-affective predictors of latent profiles. RESULTS: Whole-brain analyses revealed a condition-by-time interaction in the anterior insula, postcentral gyrus, superior temporal gyrus, middle frontal gyrus, and cerebellum but not amygdala. The LPA identified distinct latent profiles across subjective and neural levels of measurement. Anterior insula profiles were characterized by marginal differences in age and state anxiety. CONCLUSIONS: Our findings demonstrate that human fear learning recruits a distributed network of regions involved in interoceptive, cognitive, motivational, and psychomotor processes. Data-driven analyses identified distinct profiles of subjective and neural responses during fear learning that transcended clinical diagnoses, but no robust relationships to demographic or cognitive-affective variable were identified.
Assuntos
Condicionamento Clássico , Extinção Psicológica , Mapeamento Encefálico , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância MagnéticaRESUMO
Mindfulness training (MT) reduces self-referential processing and promotes interoception, the perception of sensations from inside the body, by increasing one's awareness of and regulating responses to them. The posterior cingulate cortex (PCC) and the insular cortex (INS) are considered hubs for self-referential processing and interoception, respectively. Although MT has been consistently found to decrease PCC, little is known about how MT relates to INS activity. Understanding links between mindfulness and interoception may be particularly important for informing mental health in adolescence, when neuroplasticity and emergence of psychopathology are heightened. We examined INS activity during real-time functional magnetic resonance imaging neurofeedback-augmented mindfulness training (NAMT) targeting the PCC. Healthy adolescents (N = 37; 16 female) completed the NAMT task, including Focus-on-Breath (MT), Describe (self-referential processing), and Rest conditions, across three neurofeedback runs and two non-neurofeedback runs (Observe, Transfer). Regression coefficients estimated from the generalized linear model were extracted from three INS subregions: anterior (aINS), mid (mINS), and posterior (pINS). Mixed model analyses revealed the main effect of run for Focus-on-Breath vs. Describe contrast in aINS [R2 = 0.39] and pINS [R2 = 0.33], but not mINS [R2 = 0.34]. Post hoc analyses revealed greater aINS activity and reduced pINS activity during neurofeedback runs, and such activities were related to lower self-reported life satisfaction and less pain behavior, respectively. These findings revealed the specific involvement of insula subregions in rtfMRI-nf MT.
RESUMO
Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).
Assuntos
Atenção Plena , Autocontrole , Adolescente , Estudos de Viabilidade , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Altered interoception, or the processing of bodily signals, has been argued to play a role in the development and maintenance of substance use disorders (SUD). Therefore, interoceptive interventions focusing on bodily awareness, such as mindfulness meditation, may improve treatment outcomes for individuals with SUD. Here we review: (1) subjective, behavioral and brain evidence for altered interoceptive processing in SUD, focusing on insular and anterior cingulate cortices (INS, ACC), key regions for interoceptive processing; (2) research highlighting links between mindfulness and brain function; and (3) extant brain research investigating mindfulness-based interventions in SUD. SUD tend to be characterized by heightened INS and ACC responses to drug cues but blunted interoceptive awareness and attenuated INS and ACC responses during tasks involving bodily attention and/or perturbations. In contrast, mindfulness interventions in healthy individuals are linked to enhanced INS and ACC responses and heightened interoceptive awareness. It is crucial for future research to identify: (1) whether mindfulness-based treatments are efficacious across substance classes; (2) what particular approaches and dosages show the largest effect sizes in enhancing INS and ACC function to non-drug stimuli and reducing responsivity to substance cues, thereby improving SUD treatment outcomes (reducing drug craving and relapse).
RESUMO
BACKGROUND: Repetitive negative thinking (RNT) is a symptom dimension of depression that is associated with a poorer prognosis in terms of higher recurrence, treatment resistance, residual symptoms, and disability. This investigation examined whether RNT is associated with aberrant reward processing and fear learning. METHODS: Very high RNT (VH-RNT) (n = 60) and high RNT (H-RNT) (n = 60) propensity-matched individuals with depression (age, sex, race/ethnicity, income/employment, body mass index, depressive and anxiety symptom severity) participated in this study along with matched healthy comparison volunteers (n = 30). This propensity-matched sample was selected from the larger Tulsa 1000 study. Participants performed two functional magnetic resonance imaging tasks: the monetary incentive delay task probing reward processing and the fear conditioning task probing aversive learning and extinction. RESULTS: Both VH-RNT and H-RNT groups showed lower neural activity than healthy comparison subjects in reward circuitry, including the inferior frontal gyrus (VH-RNT: ß = -1.24, H-RNT: ß = -1.28) and the cerebellum (VH-RNT: ß = -0.93, H-RNT: ß = -1.14). However, individuals with VH-RNT exhibited lower activation than those with H-RNT in central autonomic network components during fear conditioning (ß = -0.84) and continued conditioned responses during early extinction in the postcentral cortex (ß = 0.71). CONCLUSIONS: VH-RNT showed aberrant processing in fear conditioning during both learning and extinction phases compared with H-RNT. These findings demonstrate that dysfunctions of negative valence associated with RNT may be domain specific, which should be taken into account for identifying potential specific targets of intervention.
Assuntos
Pessimismo , Ansiedade/diagnóstico , Transtornos de Ansiedade/diagnóstico , Medo , Humanos , PensamentoRESUMO
BACKGROUND: An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown. METHODS: Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA). RESULTS: BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy. CONCLUSION: The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
Assuntos
Transtorno Depressivo Maior , Cinurenina , Humanos , Cinurenina/metabolismo , Ácido Quinolínico , Depressão , Triptofano/metabolismo , Ácido Cinurênico/análise , Ácido Cinurênico/metabolismoRESUMO
Computational modelling is a promising approach to parse dysfunctional cognitive processes in substance use disorders (SUDs), but it is unclear how much these processes change during the recovery period. We assessed 1-year follow-up data on a sample of treatment-seeking individuals with one or more SUDs (alcohol, cannabis, sedatives, stimulants, hallucinogens, and/or opioids; N = 83) that were previously assessed at baseline within a prior computational modelling study. Relative to healthy controls (HCs; N = 48), these participants were found at baseline to show altered learning rates and less precise action selection while completing an explore-exploit decision-making task. Here we replicated these analyses when these individuals returned and re-performed the task 1 year later to assess the stability of baseline differences. We also examined whether baseline modelling measures could predict symptoms at follow-up. Bayesian and frequentist analyses indicated that: (a) group differences in learning rates were stable over time (posterior probability = 1); and (b) intra-class correlations (ICCs) between model parameters at baseline and follow-up were significant and ranged from small to moderate (.25 ≤ ICCs ≤ .54). Exploratory analyses also suggested that learning rates and/or information-seeking values at baseline were associated with substance use severity at 1-year follow-up in stimulant and opioid users (.36 ≤ rs ≤ .43). These findings suggest that learning dysfunctions are moderately stable during recovery and could correspond to trait-like vulnerability factors. In addition, computational measures at baseline had some predictive value for changes in substance use severity over time and could be clinically informative.