Mental illness and the risk of self- and other-directed aggression: Results from the National Survey on Drug Use and Health

Ghossoub, Elias; Cherro, Michele; Akil, Carla; Gharzeddine, Yara

doi:10.1016/j.jpsychires.2020.10.010

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Dysregulated social behavior, including aggression, can result from changes to neural circuits that participate in the execution of social actions, or dysregulation can affect neural mechanisms that determine whether highly motivated states will be initiated or reinitiated. Many diverse psychiatric disorders with varied etiologies can result in dysregulated aggression 1,2 , further suggesting that aggression may have multiple types of "brakes'' that can go awry. While several brain regions have been previously identified as broadly participating in the gating of aggressive behavior [3][4][5][6] , it is currently unclear whether these brakes have separable functions on aggressive motivation and action.…”

Section: Introductionmentioning

confidence: 99%

Independent inhibitory control mechanisms for aggressive motivation and action

Minakuchi,

Guthman,

Acharya

et al. 2024

Nat Neurosci

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Social behaviors, like other motivated behaviors, frequently consist of a flexible motivatedseeking or approach phase followed by social action. Dysregulated social behavior may arise from changes to motivation, wherein individuals fail to enter a motivated seeking state, or may be in the execution of the social action itself. However, it is unclear how the brain generates and gates this flexible motivation-to-action sequence, and whether aggressive motivation and action are controlled by separate circuit mechanisms. Here, we record populations of neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of male mice at cellular resolution during "free" aggression and also during an aggression operant task, where the behaviors that precede attack are stereotyped. We find that this population encodes the temporal sequence of aggressive motivation to action and that the temporal selectivity of neurons is invariant to differences in motivated behavior. To test whether motivation and action could be independently regulated, we focused on two key inhibitory inputs to the VMHvl: a source of local . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made inhibition (VMHvl shell) and the primary source of long-range inhibition (the medial preoptic area, MPO). While we find that the VMHvl receives broad monosynaptic inhibitory input from both inputs, optogenetic perturbation of these inputs during recording reveals temporal selectivity during aggressive motivation and action, suggesting specificity of function. Encoding models applied to population calcium recordings of these inhibitory inputs during naturalistic social interactions and during the social operant task further reveal that these inputs have different temporal dynamics during aggression: VMHvl shell vgat+ activity peaks at the start of aggressive interactions, while MPO-VMHvl vgat+ activity peaks at behaviorally aligned endpoints of aggressive interactions. Finally, using closed-loop optogenetic stimulation timed to specific phases of the aggression-operant task, we find a double-dissociation of the effects on aggressive motivation and action: activation of MPO-VMHvl vgat+ , even briefly and temporally distant from the initiation of aggression, produces long-lasting motivational deficits, delaying the initiation of aggression and generating behaviors consistent with an unmotivated state. In contrast, activation of VMHvl shell vgat+ produces acute action-related deficits, causing an exit from an attack state. Fitting a Hidden Markov Model (HMM) to behavior further corroborates these findings by showing that MPO-VMHvl vgat+ stimulation prolongs a low motivation state and VMHvl shell vgat+ promotes exit from an attack state. Together, these data demonstrate how separable inhibitory circuits in the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of c...

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Section: Introductionmentioning

confidence: 99%

Independent inhibitory control mechanisms for aggressive motivation and action

Minakuchi,

Guthman,

Acharya

et al. 2024

Nat Neurosci

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show abstract

“…There are multiple risks associated with mental illness which include, but are not limited to, a lack of social connectedness which manifests as isolation or loneliness (Kiely et al , 2021), decreased quality of life (Radicke et al , 2021) and shorter life expectancy than those not suffering from mental illness (Stevenson et al , 2022). Fundamentally, the disadvantage of mental illness is that it not only predisposes individuals to dying by suicide, with almost 90% of those dying from suicide having suffered from a mental illness (Ghossoub et al , 2021), but it also increases their susceptibility to a range of physical health conditions (Launders et al , 2022). The aforementioned dichotomous presentation of wellbeing and mental illness, consequences of experience of mental illness and increased risk of poor mental wellbeing triggered by the COVID-19 pandemic (Campion et al , 2020), suggests the potential benefit in exploring interventions aimed at improving mental wellbeing and strengthening its protective capabilities.…”

Section: Introductionmentioning

confidence: 99%

Research protocol for a preliminary evaluation of a gamified tool for adult wellbeing

Gavin

Barnes

2023

MHSI

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Purpose The purpose of this paper is to outline a research protocol for an initial investigation into the efficacy of an early-development gamified intervention (“Wellbeing Town”) designed with potential end-users with the aim of improving adult wellbeing. Rationale for the proposed research is discussed along with a summary of the planned methodological approach. Design/methodology/approach Preliminary evaluation of “Wellbeing Town” is proposed to begin using a quasi-experiment, pre- vs post-intervention repeated-measures design with follow-up. Evaluation of changes in self-reported wellbeing will be supplemented with an investigation into the extent of self-directed play between post-intervention and follow-up, and its implications for follow-up outcome. Findings As this paper represents a protocol for future evaluation, no data is reported presently. The authors present the protocol for data analysis. Originality/value Once concluded, this study represents an initial evaluation of a gamified tool for adult wellbeing designed in conjunction with potential end-users. Should the game elicit significant improvements to wellbeing when played, proposals for further evaluation and possible future scalability are presented.

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“…Dysregulated social behavior, including 3 aggression, can result from changes to neural circuits that participate in the execution of social actions, or dysregulation can affect neural mechanisms that determine whether highly motivated states will be initiated or reinitiated. Many diverse psychiatric disorders with varied etiologies can result in dysregulated aggression 1,2 , further suggesting that aggression may have multiple types of "brakes'' that can go awry. While several brain regions have been previously identified as broadly participating in the gating of aggressive behavior [3][4][5][6] , it is currently unclear whether these brakes have separable functions on aggressive motivation and action.…”

Section: Introductionmentioning

confidence: 99%

Independent inhibitory control mechanisms for aggressive motivation and action

Minakuchi

Guthman

Acharya

et al. 2022

Preprint

View full text Add to dashboard Cite

Social behaviors, like other motivated behaviors, frequently consist of a flexible motivated-seeking or approach phase followed by social action. Dysregulated social behavior may arise from changes to motivation, wherein individuals fail to enter a motivated seeking state, or may be in the execution of the social action itself. However, it is unclear how the brain generates and gates this flexible motivation-to-action sequence, and whether aggressive motivation and action are controlled by separate circuit mechanisms. Here, we record populations of neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of male mice at cellular resolution during free aggression and also during an aggression operant task, where the behaviors that precede attack are stereotyped. We find that this population encodes the temporal sequence of aggressive motivation to action and that the temporal selectivity of neurons is invariant to differences in motivated behavior. To test whether motivation and action could be independently regulated, we focused on two key inhibitory inputs to the VMHvl: a source of local inhibition (VMHvl shell) and the primary source of long-range inhibition (the medial preoptic area, MPO). While we find that the VMHvl receives broad monosynaptic inhibitory input from both inputs, optogenetic perturbation of these inputs during recording reveals temporal selectivity during aggressive motivation and action, suggesting specificity of function. Encoding models applied to population calcium recordings of these inhibitory inputs during naturalistic social interactions and during the social operant task further reveal that these inputs have different temporal dynamics during aggression: VMHvl shell-vgat+ activity peaks at the start of aggressive interactions, while MPO-VMHvl-vgat+ activity peaks at behaviorally aligned endpoints of aggressive interactions. Finally, using closed-loop optogenetic stimulation timed to specific phases of the aggression-operant task, we find a double-dissociation of the effects on aggressive motivation and action: activation of MPO-VMHvl-vgat+, even briefly and temporally distant from the initiation of aggression, produces long-lasting motivational deficits, delaying the initiation of aggression and generating behaviors consistent with an unmotivated state. In contrast, activation of VMHvl shell-vgat+ produces acute action-related deficits, causing an exit from an attack state. Fitting a Hidden Markov Model (HMM) to behavior further corroborates these findings by showing that MPO-VMHvl-vgat+ stimulation prolongs a low motivation state and VMHvl shell-vgat+ promotes exit from an attack state. Together, these data demonstrate how separable inhibitory circuits in the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.

show abstract

Mental illness and the risk of self- and other-directed aggression: Results from the National Survey on Drug Use and Health

Cited by 6 publications

References 26 publications

Independent inhibitory control mechanisms for aggressive motivation and action

Independent inhibitory control mechanisms for aggressive motivation and action

Research protocol for a preliminary evaluation of a gamified tool for adult wellbeing

Independent inhibitory control mechanisms for aggressive motivation and action

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