Reward Signals, Attempted Suicide, and Impulsivity in Late-Life Depression

Dombrovski, Alexandre Y.; Szántó, Katalin; Clark, Luke; Reynolds, Charles F.; Siegle, Greg J.

doi:10.1001/jamapsychiatry.2013.75

Cited by 211 publications

(192 citation statements)

References 91 publications

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“…Possibly, these changes are associated with reduction of BDNF, since this factor is responsible for neurogenesis and neuroplasticity of the central nervous system (Kimpton, 2012). In addition, playing an important role in the progression of depression, BDNF deficiency is implicated as a cause of the dysfunction observed in depressive disorders that are associated with the prefrontal cortex, for example, loss of concentration and attention, compulsion, cognitive deficits and suicidal ideation (Miller and Cohen, 2001;Yuen et al, 2012;Dombrovski et al, 2013). Thus, as the combination of ALA and DVS shown to be effective in reversing the low concentrations of BDNF, treatment with both drugs shows promise in reducing symptoms associated with prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

Sousa

Meneses

Vasconcelos

et al. 2015

Psychiatry Research

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Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression.

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Section: Discussionmentioning

confidence: 99%

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

Sousa

Meneses

Vasconcelos

et al. 2015

Psychiatry Research

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“…This particular deficit in risk-sensitive decision making appears to reflect a minimization of negative outcomes in the face of uncertainty, and has been associated with deficits in the orbitofrontal prefrontal cortex (Fellows and Farah 2005;Jollant et al 2010). In previous adult studies, suicide attempts were associated with a style of decision processing that discounted past consequences in favor of immediate loss or gain ( Jollant et al 2005;Dombrovski, et al 2010Dombrovski, et al , 2013. The authors concluded that suicide attempters were vulnerable to a specific type of executive dysfunction, such that learning from past events was more challenging for attempters than for nonattempters.…”

Section: Decision-making Of Teen Suicide Attemptersmentioning

confidence: 98%

“…Prior studies using adult samples have linked suicidal behavior to specific neurocognitive factors including executive dysfunction and decision-making deficits ( Jollant et al 2005;Dour et al 2011;Chamberlain et al 2013;Keilp et al 2013) in the context of relatively unimpaired global brain functioning (Marzuk et al 2005). Behavioral and neuroimaging data have increasingly implicated prefrontal cortex (PFC) deficits, and associated reward-sensitive pathways in the expression of suicidal behavior among at-risk individuals (Mann 2003;Oquendo et al 2003;Monkul et al 2007;Jollant et al 2010;Dombrovski et al 2013). Relative to adults, adolescents are vulnerable to decision-making deficits because of an underdeveloped ability to judge long-term risk (Blakemore and Robins 2012).…”

mentioning

confidence: 99%

Risk-Sensitive Decision-Making Deficit in Adolescent Suicide Attempters

Ackerman

McBee-Strayer

Mendoza

et al. 2015

Journal of Child and Adolescent Psychopharmacology

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Objective: Suicide among adolescents is a major public health problem. Decision-making deficits may play an important role in vulnerability to suicidal behavior, but few studies have examined decision-making performance in youth at risk for suicide. In this study, we seek to extend recent findings that adolescent suicide attempters process risk evaluations differently than adolescents who have not attempted suicide. Methods:We assessed decision-making in 14 adolescent suicide attempters and 14 non-attempter comparison subjects, ages 15-19, using the Cambridge Gambling Task (CGT). Each participant was also administered a diagnostic interview (MiniInternational Neuropsychiatric Interview [MINI]), structured suicide severity measures, and a brief intelligence quotient (IQ) measure. Results: After controlling for gender and IQ differences, suicide attempters displayed an elevated risk-taking propensity on the CGT relative to comparison subjects, such that they were more willing to take a large risk with their bank of points, a decision-making style that proves disadvantageous over time. No group differences in the latency or accuracy of decisionmaking were observed. Conclusions: Adolescents with a history of suicide attempt display increased risk-taking and greater difficulty predicting probable outcomes on the CGT. Such deficits have been associated with dysfunction in the orbitofrontal prefrontal cortex, which supports other studies implicating impaired decision-making among individuals with a history of suicide attempt.

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“…Model-based fMRI has also been applied to patients, for example, in depression (Dombrovski et al, 2013;Gradin et al, 2011) and addiction (Harle et al, 2015;Tanabe et al, 2013). Perhaps most notably, model-based fMRI studies of patients with schizophrenia (Gradin et al, 2011;Murray et al, 2008;Romaniuk et al, 2010) have contributed empirical evidence for the long-standing hypothesis that disturbances in PE signalling by dopaminergic neurons in the midbrain might assign "aberrant salience" to environmental events (Heinz, 2002;Kapur, 2003).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Computational neuroimaging strategies for single patient predictions

et al. 2017

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Neuroimaging increasingly exploits machine learning techniques in an attempt to achieve clinically relevant single-subject predictions. An alternative to machine learning, which tries to establish predictive links between features of the observed data and clinical variables, is the deployment of computational models for inferring on the (patho)physiological and cognitive mechanisms that generate behavioural and neuroimaging responses. This paper discusses the rationale behind a computational approach to neuroimaging-based single-subject inference, focusing on its potential for characterising disease mechanisms in individual subjects and mapping these characterisations to clinical predictions. Following an overview of two main approaches - Bayesian model selection and generative embedding - which can link computational models to individual predictions, we review how these methods accommodate heterogeneity in psychiatric and neurological spectrum disorders, help avoid erroneous interpretations of neuroimaging data, and establish a link between a mechanistic, model-based approach and the statistical perspectives afforded by machine learning.

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Reward Signals, Attempted Suicide, and Impulsivity in Late-Life Depression

Cited by 211 publications

References 91 publications

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

Risk-Sensitive Decision-Making Deficit in Adolescent Suicide Attempters

Computational neuroimaging strategies for single patient predictions

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