Reward Signals, Attempted Suicide, and Impulsivity in Late-Life Depression
TL;DR: Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts.
Abstract: IMPORTANCE—Suicide can be viewed as an escape from unendurable punishment at the cost of any future rewards. Could faulty estimation of these outcomes predispose to suicidal behavior? In behavioral studies, many of those who have attempted suicide misestimate expected rewards on gambling and probabilistic learning tasks.OBJECTIVES—To describe the neural circuit abnormalities that underlie disadvantageous choices in people at risk for suicide and to relate these abnormalities to impulsivity, which is one of the components of vulnerability to suicide.DESIGN—Case-control functional magnetic resonance imaging study of reward learning using are inforcement learning model.SETTING—University hospital and outpatient clinic.PATIENTS—Fifty-three participants 60 years or older, including 15 depressed patients who had attempted suicide, 18 depressed patients who had never attempted suicide (depressed control subjects), and 20 psychiatrically healthy controls.MAIN OUTCOMES AND MEASURES—Components of the cortical blood oxygenation level–dependent response tracking expected and unpredicted rewards.RESULTS—Depressed elderly participants displayed 2 distinct disruptions of control over reward-guided behavior. First, impulsivity and a history of suicide attempts (particularly poorly planned ones) were associated with a weakened expected reward signal in the paralimbic cortex,which in turn predicted the behavioral insensitivity to contingency change. Second, depression was associated with disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted the behavioral over sensitivity to punishment. These results were robust to the effects of possible brain damage from suicide attempts, depressive severity, co-occurring substance use and anxiety disorders, antidepressant and anticholinergic exposure, lifetime exposure to electroconvulsive therapy, vascular illness, and incipient dementia.CONCLUSIONS AND RELEVANCE—Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts. This pattern, also seen in gambling and cocaine use, may reflect a primary deficit in the paralimbic cortex or in its mesolimbic input. The over reactivity to punishment in depression may be caused in part by a disruption of appetitive learning in the corticostriatothalamic circuits.
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TL;DR: Results from a range of studies using diverse designs and post-mortem and in-vivo techniques show impairments of the serotonin neurotransmitter system and the hypothalamic-pituitary-adrenal axis stress-response system in the diathesis for suicidal behaviour.
425 citations
TL;DR: A novel integrative model of neuroplasticity as a multi-domain neurobiological, cognitive, and psychological construct relevant in depression and other related disorders of negative affect is presented.
Abstract: Chronic stress and depressive-like behaviors in basic neuroscience research have been associated with impairments of neuroplasticity, such as neuronal atrophy and synaptic loss in the medial prefrontal cortex (mPFC) and hippocampus. The current review presents a novel integrative model of neuroplasticity as a multi-domain neurobiological, cognitive, and psychological construct relevant in depression and other related disorders of negative affect (e.g., anxiety). We delineate a working conceptual model in which synaptic plasticity deficits described in animal models are integrated and conceptually linked with human patient findings from cognitive science and clinical psychology. We review relevant reports including neuroimaging findings (e.g., decreased functional connectivity in prefrontal-limbic circuits), cognitive deficits (e.g., executive function and memory impairments), affective information processing patterns (e.g., rigid, negative biases in attention, memory, interpretations, and self-associations), and patient-reported symptoms (perseverative, inflexible thought patterns; inflexible and maladaptive behaviors). Finally, we incorporate discussion of integrative research methods capable of building additional direct empirical support, including using rapid-acting treatments (e.g., ketamine) as a means to test this integrative model by attempting to simultaneously reverse these deficits across levels of analysis.
226 citations
TL;DR: In patients with schizophrenia neuroimaging studies have revealed global differences with some brain regions showing focal abnormalities, suggesting that multiple brain circuits are impaired, a neural feature that may be better addressed with network level analyses.
Abstract: In patients with schizophrenia neuroimaging studies have revealed global differences with some brain regions showing focal abnormalities. Examining neurocircuitry, diffusion-weighted imaging studies have identified altered structural integrity of white matter in frontal and temporal brain regions and tracts such as the cingulum bundles, uncinate fasciculi, internal capsules and corpus callosum associated with the illness. Furthermore, structural co-variance analyses have revealed altered structural relationships among regional morphology in the thalamus, frontal, temporal and parietal cortices in schizophrenia patients. The distributed nature of these abnormalities in schizophrenia suggests that multiple brain circuits are impaired, a neural feature that may be better addressed with network level analyses. However, even with the advent of these newer analyses, a large amount of variability in findings remains, likely partially due to the considerable heterogeneity present in this disorder.
213 citations
TL;DR: It is proposed that mood represents the overall momentum of recent outcomes, and its biasing influence on the perception of outcomes ‘corrects’ learning to account for environmental dependencies.
209 citations
Cites background from "Reward Signals, Attempted Suicide, ..."
...Moreover, a depressed mood is associated with a reduced effect of rewards on subsequent choices [41,42], an effect that is better explained by reduced valuation of reward than by a reduced rate of learning [43]....
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TL;DR: A comprehensive review of neuroimaging studies of suicidal thoughts and behaviors is presented in this paper, which summarizes the progress achieved on elucidating neurobiological substrates of STBs, with a focus on converging findings across studies.
Abstract: Identifying brain alterations that contribute to suicidal thoughts and behaviors (STBs) are important to develop more targeted and effective strategies to prevent suicide. In the last decade, and especially in the last 5 years, there has been exponential growth in the number of neuroimaging studies reporting structural and functional brain circuitry correlates of STBs. Within this narrative review, we conducted a comprehensive review of neuroimaging studies of STBs published to date and summarize the progress achieved on elucidating neurobiological substrates of STBs, with a focus on converging findings across studies. We review neuroimaging evidence across differing mental disorders for structural, functional, and molecular alterations in association with STBs, which converges particularly in regions of brain systems that subserve emotion and impulse regulation including the ventral prefrontal cortex (VPFC) and dorsal PFC (DPFC), insula and their mesial temporal, striatal and posterior connection sites, as well as in the connections between these brain areas. The reviewed literature suggests that impairments in medial and lateral VPFC regions and their connections may be important in the excessive negative and blunted positive internal states that can stimulate suicidal ideation, and that impairments in a DPFC and inferior frontal gyrus (IFG) system may be important in suicide attempt behaviors. A combination of VPFC and DPFC system disturbances may lead to very high risk circumstances in which suicidal ideation is converted to lethal actions via decreased top-down inhibition of behavior and/or maladaptive, inflexible decision-making and planning. The dorsal anterior cingulate cortex and insula may play important roles in switching between these VPFC and DPFC systems, which may contribute to the transition from suicide thoughts to behaviors. Future neuroimaging research of larger sample sizes, including global efforts, longitudinal designs, and careful consideration of developmental stages, and sex and gender, will facilitate more effectively targeted preventions and interventions to reduce loss of life to suicide.
184 citations
References
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11 Jun 2013
113,134 citations
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
76,181 citations
01 Jan 2002
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Abstract: EXAMINATION of the mental state is essential in evaluating psychiatric patients.1 Many investigators have added quantitative assessment of cognitive performance to the standard examination, and have documented reliability and validity of the several “clinical tests of the sensorium”.2*3 The available batteries are lengthy. For example, WITHERS and HINTON’S test includes 33 questions and requires about 30 min to administer and score. The standard WAIS requires even more time. However, elderly patients, particularly those with delirium or dementia syndromes, cooperate well only for short periods.4 Therefore, we devised a simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely. It is “mini” because it concentrates only on the cognitive aspects of mental functions, and excludes questions concerning mood, abnormal mental experiences and the form of thinking. But within the cognitive realm it is thorough. We have documented the validity and reliability of the MMS when given to 206 patients with dementia syndromes, affective disorder, affective disorder with cognitive impairment “pseudodementia”5T6), mania, schizophrenia, personality disorders, and in 63 normal subjects.
70,887 citations
TL;DR: A package of computer programs for analysis and visualization of three-dimensional human brain functional magnetic resonance imaging (FMRI) results is described and techniques for automatically generating transformed functional data sets from manually labeled anatomical data sets are described.
10,002 citations
TL;DR: The results of the present study suggest that the total score of the BIS-11 is an internally consistent measure of impulsiveness and has potential clinical utility for measuring impulsiveness among selected patient and inmate populations.
Abstract: The purpose of the present study was to revise the Barratt Impulsiveness Scale Version 10 (BIS-10), identify the factor structure of the items among normals, and compare their scores on the revised form (BIS-11) with psychiatric inpatients and prison inmates. The scale was administered to 412 college undergraduates, 248 psychiatric inpatients, and 73 male prison inmates. Exploratory principal components analysis of the items identified six primary factors and three second-order factors. The three second-order factors were labeled Attentional Impulsiveness, Motor Impulsiveness, and Nonplanning Impulsiveness. Two of the three second-order factors identified in the BIS-11 were consistent with those proposed by Barratt (1985), but no cognitive impulsiveness component was identified per se. The results of the present study suggest that the total score of the BIS-11 is an internally consistent measure of impulsiveness and has potential clinical utility for measuring impulsiveness among selected patient and inmate populations.
6,818 citations