Association of War Zone–Related Stress With Alterations in Limbic Gray Matter Microstructure

Kaufmann, Elisabeth; Rojczyk, Philine; Sydnor, Valerie J.; Guenette, Jeffrey P.; Tripodis, Yorghos; Kaufmann, David; Umminger, Lisa; Seitz-Holland, Johanna; Sollmann, Nico; Rathi, Yogesh; Bouix, Sylvain; Fortier, Catherine B.; Salat, David H.; Pasternak, Ofer; Hinds, Sidney; Milberg, William; McGlinchey, Regina E.; Shenton, Martha E.; Koerte, Inga K.

doi:10.1001/jamanetworkopen.2022.31891

Cited by 3 publications

(4 citation statements)

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“…To date, findings on gray matter diffusion in psychiatric samples are limited. We previously showed an association between higher FA of the amygdalahippocampus complex and greater war zone-related stress (23) and PTSD symptoms (24), suggesting that stress-related experiences alter limbic microstructural integrity. Similarly, increased diffusion in several regions (including the amygdala and hippocampus) was shown in individuals with persistent post-concussive symptoms following mTBI compared to controls (26).…”

Section: Associations Between Limbic Microstructure and Ipv Perpetrationmentioning

confidence: 94%

“…War zone-related stress (23), post-deployment psychiatric disorders (24,25), and mTBI (26) are associated with alterations in brain structure. While brain research in the population of IPV perpetrators is relatively scarce, magnetic resonance imaging (MRI) studies report altered brain function and structure associated with aggressiveness.…”

Section: Ipv Perpetration and Neuroimagingmentioning

confidence: 99%

“…Diffusion-weighted MRI (dMRI) provides information on even subtle brain microstructural alterations by quantifying the motion of water molecules in tissue (44). Associations between altered limbic gray matter microstructure and war zone-related stress (23), psychiatric disorders (24,25), and mTBI (26) have previously been reported, while findings on IPV perpetration are lacking.…”

Section: Ipv Perpetration and Neuroimagingmentioning

confidence: 99%

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Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure

Rojczyk,

Heller,

Seitz-Holland

et al. 2024

Front. Neurol.

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BackgroundIntimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration.MethodsStructural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA.ResultsVeterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r = 0.400, p = 0.005).ConclusionVeterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.

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Section: Associations Between Limbic Microstructure and Ipv Perpetrationmentioning

confidence: 94%

Section: Ipv Perpetration and Neuroimagingmentioning

confidence: 99%

Section: Ipv Perpetration and Neuroimagingmentioning

confidence: 99%

See 1 more Smart Citation

Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure

Rojczyk,

Heller,

Seitz-Holland

et al. 2024

Front. Neurol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…As previously shown, the Free-Water imaging model fits a bi-tensor model [ 47 , 75 ] to the diffusion-weighted images with the first compartment modeling isotropic, unrestricted diffusion in the extracellular space (free water, FW). We extracted averaged FW values for the left and right hippocampus, following previous studies that applied this model to gray matter [ 76 , 77 ].…”

Section: Methodsmentioning

confidence: 99%

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

Seitz-Holland,

Alemán-Gómez,

Cho

et al. 2024

Neuropsychopharmacol.

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Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.

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The formidable challenges faced by surgeons in war zones

Omari

2024

The Surgeon

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Association of War Zone–Related Stress With Alterations in Limbic Gray Matter Microstructure

Abstract: This cohort study evaluates the association between war zone–related stress and alterations in limbic gray matter microstructure in a group of veterans from the US.

Cited by 3 publications

References 105 publications

Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure

Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

The formidable challenges faced by surgeons in war zones

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