Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury

Abstract

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms “gender” and “men/women” are used in this article in place of “sex” or “males/females” given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n ² = 0.018–0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n ² = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n ² = 0.032–0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n ² = 0.024–0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

Introduction

Women are more directly involved in combat operations today than ever before. In 2015, the secretary of defense rescinded the Direct Group Combat Definition and Assignment Rule that limited women from combat roles. This policy change opened >200,000 new jobs to women in the armed forces, which included roles with special operators and infantry units. Women currently make up 18.6% of officers and 16.8% of enlisted personnel in the United States military.¹ This increase in women's role in combat operations also increases their chances of traumatic brain injury (TBI). Despite this increase, women continue to be under-represented in military research.²

In civilian populations, it has been found that women, in comparison with men, report greater depression, anxiety, stress, and fatigue, but less substance abuse and impulsivity, following mild to moderate TBI. ^3
–5 There is also evidence of greater physical symptoms such as headaches and dizziness in women following mild to moderate TBI.^6,7 At 6 months after mild TBI (mTBI), women reported decreased functional outcome and women in the age range of 30–39 reported greater PTSD symptomatology⁸ as well as loss of confidence, perceived need for supervision, difficulty setting goals, and lack of initiative.⁹

There is a limited number of studies that have investigated differences in outcomes from TBI between men and women in military populations. In a series of studies by Iverson and colleagues, women injured during the conflicts in Iraq and Afghanistan reported greater levels of depression, generalized anxiety, and post-traumatic stress, as well as a range of neurobehavioral symptoms after an mTBI compared with men.¹⁰ Similarly, veterans who were women were more likely to report depression following a history of mTBI even in the absence of PTSD. MTBI was strongly associated with all health symptoms for women, whereas it was only associated with anxiety and physical health symptoms for men.¹¹

MTBI and PTSD have a high rate of comorbidity, and the presence of PTSD is known to impact TBI outcomes. Systematic reviews have found the comorbidity rate of PTSD and TBI to be double for service members and veterans compared with the general population, reaching near 50%.^12,13 In a study with 1540 former and current military personnel, >40% had comorbid TBI and PTSD.¹⁴ Additionally, the combination of PTSD and depression have been shown to be one of the most powerful predictors of problems with long-term functioning in service members and veterans as many as 10 years after the TBI.¹⁵ There are only a limited number of studies accounting for the role of PTSD in TBI outcomes. A matched group comparison of 86 women and men to control for key variables including TBI severity, mechanism of injury, bodily injury severity, age, and number of deployments found that women reported significantly more post-concussive and post-traumatic stress symptoms than men.¹⁶ When controlling for PTSD and symptom validity in this sample, it was found that women reported more somatosensory and vestibular symptoms than men under specific conditions related to whether they had PTSD, and alterations of consciousness associated with the mTBI, and to the severity of bodily injury.¹⁷

Studies investigating the differences in outcomes between men and women following TBI primarily compare differences without controlling for other factors not related to TBI. Non-TBI factors can potentially be driving the differences between men and women found in the TBI studies. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. For example, differences between men and women have been reported for pain sensitivity and analgesic response, in both acute and chronic reporting of pain,¹⁸ with women reporting greater symptoms. A large epidemiological study across multiple geographic regions found that pain is reported more frequently by women than by men.¹⁹ In the mental health literature, women are almost twice as likely to experience major depression as men,²⁰ and these differences are stated to represent a major health disparity.²¹ A meta-analysis examining differences in the effects of TBI between men and women concluded that mTBI is associated with worse outcomes in women in clinical studies but that there are mixed results in animal studies; whereas moderate to severe TBI is associated with better outcomes for women.²² The researchers suggest that the difference in outcome measures may be what accounts for this finding, as human studies of mTBI rely primarily on self-report measures, on which men and women may evidence different response styles.

This study presents a unique opportunity to incorporate an injured control group. Although it is already unique for military TBI research to include a control group, having a control group that has sustained physical injury excluding a TBI is particularly informative. This opportunity to investigate gender effects in symptom reporting for mTBI, injured and uninjured (healthy) control groups allows for more definitive conclusions regarding gender effects in TBI recovery. Given the prevalence of co-occurring TBI and PTSD, we plan to evaluate the role of PTSD in symptom reporting. It should be noted that the terms “gender” and “men/women” are used in this article in place of “sex” or “males/females” given we are not discussing biological attributes.

Method

Participants

Participants were 966 United States military service members and veterans (SMVs) prospectively enrolled in a larger study designed to examine the natural history of recovery from TBI (i.e., Defense and Veterans Brain Injury Center [DVBIC]/Traumatic Brain Injury Center of Excellence [TBICoE] 15-Year Longitudinal TBI Study). Participants were recruited and classified into three broad injury groups: uncomplicated mTBI (n = 501 [455 men, 46 women]), injured controls (IC, n = 316 [284 men, 31 women), and non-injured controls (NIC, n = 149 [111 men, 38 women]). Participants were targeted for recruitment using hospital-based and community-based recruitment strategies from three United States medical treatment facilities: Walter Reed National Military Medical Center (WRNMMC), Naval Hospital Camp Pendleton (NHCP), and Naval Medical Center San Diego (NMCSD). The classification of men/women was based on the pronouns used in the medical record review, unless corrected by the SMV.

Participants were enrolled in the larger study if they were (1) male or female; (2) ≥ 18 years of age (3) active-duty service member or other “DEERS-eligible” veteran (i.e., an individual who is eligible for military healthcare benefits administered via the Defense Enrollment Eligibility Reporting System), and (4) able to read and understand English. General exclusion criteria included (1) a lack of proficiency in conversational English, (2) a history of a neurological condition unrelated to the injury (e.g., meningioma, pre-injury seizure disorder, pre-injury hypoxic event, multiple sclerosis), (3) a history of a psychiatric condition unrelated to the injury event or deployment (e.g., bipolar disorder, pre-military major depressive disorder, childhood-related PTSD), or (4) a history of a significant developmental or medical condition that may compromise neurological functioning (e.g., chemotherapy for cancer, attention-deficit/hyperactivity disorder [ADHD]).

Participants were included in the mTBI group if they had sustained a brain injury as indicated by the following criteria: (1) loss of consciousness (LOC) ≤30 min, post-traumatic amnesia (PTA) ≤24 h, Glasgow Coma Scale (GCS) score ≤15 (if available), and/or the presence of a period of alteration of consciousness (AOC) that was directly attributable to head trauma; and (2) no trauma-related intracranial abnormality (ICA) on computed tomography (CT) or magnetic resonance imaging (MRI). Participants were included in the IC group if they had sustained an orthopedic and/or soft-tissue injury; there was no evidence of intracranial abnormality or an altered state of consciousness (e.g., GCS <15, AOC, LOC, or PTA) as a result of the injury, the presenting complaint was not the result of a neurological condition/disorder (e.g., cerebrovascular accident), and they had no history of TBI. Participants were included in the NIC group if they had no history of an orthopedic and/or soft-tissue injury, and no history of TBI. The interested reader is directed to the study by Lange and coworkers²³ for more details.

For the purposes of this study, participants were selected from a larger sample of patients who had been enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI study. Participants were selected for inclusion in the final sample if they (1) had completed a battery of neurobehavioral measures, (2) had scored below the recommended cutoff on a measure designed to evaluate symptom exaggeration (see Measures section), and (3) were evaluated ≥12 months post-injury (MTBI and IC groups only).

TBI evaluation and severity classification

Diagnosis and classification of TBI was based on a medical record review and a comprehensive lifetime TBI history interview. The lifetime TBI history interview was completed by masters-level clinical research personnel who were specifically trained (by R.T.L. and S.M.L.) to evaluate the presence and severity of TBI. The TBI history interview consisted of the Ohio State University TBI identification method²⁴ and an extended semi-structured clinical interview designed to (1) extract more detailed information to estimate the presence/duration of LOC, PTA, AOC, and retrograde amnesia, and (2) gather military-specific information regarding injury circumstances. Final determination and classification of TBI severity was undertaken by consensus, giving consideration to all information, during case conferencing with the interviewer and a PhD-level clinician/scientist trained in neuropsychology and TBI diagnostic interviewing (R.T.L. or S.M.L.).

Measures and procedure

Participants completed a 2.5 h battery of self-report neurobehavioral measures that included the PTSD Checklist-Civilian version (PCL-C),²⁵ Neurobehavioral Symptom Inventory (NSI),²⁶ Validity-10,²⁷ Traumatic Brain Injury Quality of Life (TBI-QOL),²⁸ and Combat Exposure Scale (CES),²⁹ and a brief structured interview.

The majority of participants (65.4%) completed these measures using a Web-based assessment portal while proctored via telephone. For a smaller proportion of the sample (34.6%), participants completed these measures as part of a larger test battery that was undertaken in person, over a 2-day period, which also included neurocognitive, neuroradiological, and sensory/motor measures, as well as a blood sample.

The PCL-C is a 17-item measure designed to evaluate self-reported PTSD symptoms, patterned specifically after the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)³⁰ symptom criteria for PTSD. The PCL-C requires the test taker to rate the presence/severity of each symptom on a five-point scale. A total score was obtained by summing the ratings for the 17 items (range = 17–85) as well as three cluster scores (Re-experiencing, Avoidance, and Hyper-arousal). Participants' responses were also used to classify DSM-IV-TR symptom criteria for PTSD. A participant was classified into the PTSD-Present category based on the affirmation of mild or higher-severity symptoms for (1) one or more Criterion B symptoms, (2) three or more Criterion C symptoms, and (3) two or more Criterion D symptoms.

The NSI is a 22-item measure designed to evaluate self-reported post-concussion symptoms rated on a five-point scale. A total score was obtained by summing the ratings for the 22 items (range = 0–88) as well as four cluster scores (Vestibular, Somatosensory, Cognitive, and Affective).³¹

The CES is a seven-item measure designed to evaluate wartime stressors rated on a five-point scale. A total score (range = 0–41) was calculated using the sum of weighted scores as outlined by the test developers.²⁹

The Validity-10 is a symptom validity test (SVT) designed to detect symptom exaggeration when administering the NSI. Clinical validation studies have supported its use for this purpose.^32

–37 The Validity-10 scale consist of ten items from the NSI that are considered atypical and infrequently experienced after TBI. As recommended by Vanderploeg and colleagues,²⁷ a cutoff score of >22 was used to classify symptom exaggeration. Participants were not included in the study if they failed this SVT.

The TBI-QOL is a measure designed to provide a comprehensive evaluation of health-related QOL after TBI. For the purposes of this study, eight TBI-QOL scales were included (i.e., Anger, Anxiety, Depression, Emotional and Behavioral Dyscontrol, Fatigue, Headaches, Pain Interference, and Cognitive Concerns-General). The TBI-QOL was administered using static short forms that consisted of 8–10 items in each scale. For each scale, the test taker is required to respond to each item on a five-point scale. A total raw score for each scale was calculated by summing the responses to all items within each scale and converting them to T-scores (mean [M] = 50, standard deviation [SD] = 10). For seven of the scales, high T-scores reflect worse functioning (i.e., Anxiety, Depression, Anger, Headache, Emotional and Behavioral Dyscontrol, Fatigue, Pain Interference). For the Cognitive Concerns-General scale, high T-scores reflect better functioning.

A brief structured interview was designed to gather basic demographic and injury-related information (e.g., number of combat deployments, age, level of education, blasts,). In addition, lifetime blast exposure was evaluated by a single-item measure that was designed to briefly quantify the number of blast exposures a person has experienced across their lifetime. Each participant was asked “In your life, how many times have you been close enough to an explosion in which you felt the blast wave?”

The protocol under which these data were collected was approved by the Institutional Review Board of WRNMMC, Bethesda, MD. This study was completed in accordance with the guidelines of the Declaration of Helsinki.

Statistical analysis plan

Statistical analysis was undertaken using SPSS 27.0. Group comparisons for six select demographic and injury variables (i.e., age, education, number of combat deployments, number of lifetime blast exposures, time since injury, and combat exposure) by gender, in each of the three injury groups separately (MTBI, IC, NIC), was undertaken using t tests (continuous variables) or Mann–Whitney U tests (categorical variables) where appropriate. In order to examine the influence of the select demographic and injury variables on the neurobehavioral measures, Pearson correlation coefficients were calculated between the six demographic/injury variables and all neurobehavioral measures in each of the three injury groups separately (mTBI, IC, NIC). Any demographic or injury variable that was significantly correlated (p < 0.01) with the neurobehavioral measures were used as a covariate in subsequent analyses.

Group comparisons for all neurobehavioral measures by gender, in each of the three injury groups separately (MTBI, IC, NIC), was undertaken using analysis of covariance (ANCOVA) (by including any relevant covariates identified previously here) and effect sizes were calculated using partial eta squared. Given the known influence of PTSD¹⁵ and the interaction between PTSD and gender¹⁷ on overall neurobehavioral functioning, further analyses were undertaken by examining the influence of PTSD and gender in the mTBI and IC groups separately (note that the prevalence of PTSD in the NIC group was too small [i.e., n < 10] to include in these analyses). Participants were divided into four PTSD/gender subgroups as follows: (1) PTSD-present/men (mTBI, n = 267; IC, n = 118], (2) PTSD-present/women (mTBI, n = 23; IC, n = 13], (3) PTSD-absent/men (mTBI, n = 188; IC, n = 167), and (4) PTSD-absent/women (mTBI, n = 23; IC, n = 18). Group comparisons for all neurobehavioral measures by gender was undertaken using ANCOVA (including relevant covariates) and effect sizes were calculated using partial eta squared. Only two select pairwise comparisons were undertaken designed to isolate the influence of gender in participants with high PTSD symptoms (i.e., Subgroups 1 vs. 2) and in participants with no/low PTSD symptoms (i.e., Subgroups 3 vs. 4).

It is acknowledged that the probability of Type 1 error increases when multiple statistical comparisons are made, and an adjusted p value should be employed to determine statistical significance. For the purposes of this study, p < 0.01 was used to establish statistical significance for all comparisons.

Results

Demographic and injury variables

Descriptive statistics and group comparisons for select demographic and injury variables by gender, in each of the three injury groups separately (mTBI, IC, NIC), are presented in Table 1. In all three groups, men had a significantly (p < 0.01) higher number of combat deployments, lifetime blast exposures, and higher CES total scores than women. In addition, women had a significantly higher level of education than men in the IC and NIC group, but not the mTBI group. There were no significant differences for age or time since injury in any group.

Table 1.

Descriptive Statistics and Group Comparisons for Demographic Variables by Gender Per Injury Group

	Men		Women			Summary (p <0.01)
	Mean/ Median	SD/ IQR	Mean/ Median	SD/ IQR	T-test/ M-W (p)	Summary (p <0.01)
Uncomplicated mTBI
Age (in years)	36.5	8.9	33.3	11.4	0.025	-
Education (in years)	14.4	2.1	15.2	2.4	0.027	-
#Combat deployments	2.0	1-8	1.0	0-3	<0.001	M > W
#Lifetime blasts	6.0	1-200	0	0-10	<0.001	M > W
Time since injury (in months)	95.0	36-187	41.0	12-337	0.011	-
CES total	19.8	11.9	7.2	9.6	<0.001	M > W
Injured controls
Age (in years)	37.2	9.1	37.7	12.6	0.810	-
Education (in years)	14.6	2.2	15.8	2.6	0.005	W > M
#Combat deployments	3.0	1-8	1.0	0-2.8	<0.001	M > W
#Lifetime blasts	5.0	1-200	0	0-5.8	<0.001	M > W
Time since injury (in months)	73.0	35-146	40.0	17-153.4	0.012	-
CES total	18.0	11.3	4.6	7.2	<0.001	M > W
Non-injured Controls
Age (in years)	39.6	10.2	38.0	9.7	0.411	-
Education (in years)	15.4	2.5	16.9	2.0	0.001	W > M
#Combat deployments	2.0	1-5.8	1.0	0-3	0.002	M > W
#Lifetime blasts	1.0	0-75	0	0-2.1	<0.001	M > W
Time since injury (in months)	-	-	-	-	-	-
CES total	9.6	9.5	3.7	5.5	<.001	M > W

n = 966 (uncomplicated mTBI = 501 [455 men, 46 women]; injured controls = 316 [285 men, 31 women]; non-injured controls = 149 [111 men, 38 women])

mTBI, mild traumatic brain injury; CES, Combat Exposure Scale; M, men; W, women; IQR, interquartile range; SD, standard deviation; M-W = Mann–Whitney U test.

Relationship among neurobehavioral, demographic, and injury measures

In order to examine the influence of select demographic and injury variables on neurobehavioral functioning (i.e., age, education, number of deployments, number of lifetime blast exposures, time since injury, and combat exposure), Pearson correlation coefficients are presented in Table 2 (note that data are only provided for those groups/variables in which two or more significant coefficients were found. Complete data can be found in Supplementary Tables S1–S3).

Table 2.

Summary of Pearson Correlation Coefficients Between Neurobehavioral Measures and Select Demographic, Injury, and Military Variables

	mTBI		IC	NIC
	Education	CES	CES	Deploy	CES	Age	Blast
PCLC Total	-0.21^*	0.31^*	0.30^*	0.35^*	0.31^*	0.22^*	0.19
NSI Total	-0.16^*	0.26^*	0.28^*	0.43^*	0.32^*	0.22^*	0.29^*
NSI Vestibular	-0.06	0.12^*	0.16^*	0.31^*	0.21^*	0.10	0.26^*
NSI Somato-Sensory	-0.09	0.21^*	0.29^*	0.36^*	0.32^*	0.22^*	0.32^*
NSI Cognitive	-0.16^*	0.24^*	0.23^*	0.42^*	0.35^*	0.22^*	0.29^*
NSI Affective	-0.18^*	0.25^*	0.24^*	0.33^*	0.18	0.20	0.12
QOL Anger	-0.23^*	0.24^*	0.21^*	0.30^*	0.16	0.06	0.14
QOL Anxiety	-0.18^*	0.19^*	0.14	0.26^*	0.10	0.14	0.07
QOL Depression	-0.16^*	0.14^*	0.12	0.12	0.06	0.07	0.04
QOL EBDYS	-0.16^*	0.22^*	0.11	0.35^*	0.28^*	0.25^*	0.20
QOL Fatigue	-0.14^*	0.17^*	0.26^*	0.22^*	0.14	0.14	0.03
QOL Headache	-0.10	0.13^*	0.22^*	0.20^*	0.16	0.09	0.29^*
QOL Pain	-0.07	0.25^*	0.30^*	0.28^*	0.17	0.25^*	0.18
QOL Cog Concerns-Gen	0.11	-0.21^*	-0.26^*	-0.30^*	-0.24^*	-0.19	-0.22^*

n = 966 (uncomplicated mTBI = 501; injured controls = 316; non-injured controls = 149).

p < 0.01

mTBI, uncomplicated mild traumatic brain injury; IC, injured controls; NIC, non-injured controls; CES, Combat Exposure Scale; blast, lifetime blast exposure; PCL-C, Post-Traumatic Stress Disorder Checklist-Civilian version; NSI, Neurobehavioral Symptom Inventory; QOL, Traumatic Brain Injury Quality of Life; EBDYS, Emotional and Behavioral Dyscontrol; Cog-Gen, Cognitive Concerns-General.

In the mTBI group, the majority of neurobehavioral measures had significant correlations (p < 0.01) with the CES total score (14 measures), followed by years of education (9 measures) and age (1 measure). CES and education were used as covariates in subsequent analyses in this group. In the IC group, the majority of neurobehavioral measures also had the significant correlations (p < 0.01) with CES total scores (11 measures). CES was used as a covariate in subsequent analyses in this group. In the NIC group, the majority of neurobehavioral measures had significant correlations with number of combat deployments (13 measures), followed by CES total scores (6 measures), age (6 measures), and number of lifetime blast exposures (6 measures). CES, age, number of combat deployments, and number of lifetime blast exposures were used as covariates in subsequent analyses in this group.

Influence of gender

Descriptive statistics and group comparisons for all neurobehavioral measures by gender, in each of the three injury groups separately (MTBI, IC, NIC) are presented in Table 3. In the mTBI group, women had significantly worse scores than men on NSI total and NSI Somatosensory and Affective clusters and on the TBI-QOL Anxiety, Fatigue, and Headache scales. Effect sizes ranged from small (n ² = 0.018) to small-medium (n ² = 0.032). There were no significant differences for the other measures. In the IC group, women had significantly worse scores than men on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales. Effect sizes ranged from small (n ² = 0.024) to small-medium (n ² = 0.042). There were no significant differences for the other measures. In the NIC group, there were no significant differences for the measures.

Table 3.

Descriptive Statistics and Group Comparisons (ANCOVA^b) by Gender

	Uncomplicated mTBI n = 501						Injured controls n = 316						Non-injured controls n = 149
	Men n = 455		Women n = 46				Men n = 285		Women n = 31				Men n = 111		Women n = 38
Measures	Mean	Std. Err	Mean	Std. Err	p	n ²	Mean	Std. Err	Mean	Std. Err	p	n ²	Mean	Std. Err	Mean	Std. Err	p	n ²
PCL-C Total	37.1	0.7	42.2	2.2	0.028	0.010	31.2	0.8	35.3	2.6	0.134	0.008	22.1	0.7	23.5	1.2	0.325	0.007
NSI Total	27.0	0.8	35.2	2.4	0.002	0.020	19.8	0.9	25.6	3.0	0.067	0.011	8.3	0.9	10.4	1.5	0.241	0.010
NSI Vestibular	2.4	0.1	3.1	0.4	0.042	0.009	1.6	0.1	2.0	0.4	0.219	0.005	0.5	0.1	0.5	0.2	0.729	0.001
NSI Somatosens	7.2	0.2	10.4	0.8	<0.001	0.030	5.3	0.3	6.1	0.9	0.415	0.002	2.1	0.3	2.9	0.5	0.180	0.013
NSI Cognitive	5.9	0.2	6.6	0.6	0.238	0.003	4.1	0.2	6.3	0.8	0.009	0.023	1.6	0.2	1.9	0.4	0.568	0.002
NSI Affective	9.5	0.3	12.8	0.9	<0.001	0.026	7.2	0.3	9.9	1.1	0.018	0.019	3.4	0.3	4.6	0.6	0.090	0.021
QOL Anger	53.3	0.5	57.3	1.7	0.024	0.011	49.9	0.6	51.4	1.9	0.460	0.002	44.1	0.7	44.6	1.2	0.763	0.001
QOL Anxiety	54.3	0.5	58.9	1.5	0.003	0.018	51.8	0.6	54.7	1.8	0.139	0.007	46.8	0.8	48.2	1.3	0.390	0.005
QOL Depression	49.1	0.4	50.7	1.4	0.271	0.003	47.3	0.5	47.6	1.6	0.882	0.000	44.6	0.7	43.7	1.1	0.549	0.003
QOL EBDYS	47.8	0.4	50.6	1.4	0.059	0.007	44.9	0.5	46.8	1.7	0.278	0.004	40.4	0.6	41.4	1.0	.413	.005
QOL Fatigue	54.5	0.4	59.0	1.3	0.002	0.021	51.9	0.5	58.4	1.7	<0.001	0.042	47.1	0.7	49.6	1.3	0.095	0.020
QOL Headache	51.6	0.4	56.7	1.2	<0.001	0.032	48.9	0.5	50.8	1.6	0.252	0.004	43.2	0.5	44.7	0.9	0.188	0.012
QOL Pain	56.0	0.4	59.3	1.3	0.015	0.012	52.6	0.5	57.2	1.6	0.007	0.024	45.8	0.7	47.7	1.2	0.169	0.014
QOL Cog-Gen^a	36.2	0.4	34.1	1.3	0.136	0.005	40.0	0.6	37.3	1.8	0.161	0.007	47.0	0.8	47.0	1.3	0.983	0.000

n = 966.

For the majority of measures, high scores reflect worse functioning, with the exception of the measures indicated. For these measures, low scores reflect worse functioning; ²Covariates: mTBI = CES Total and education; IC = CES total; NIC = CES total, age, number of lifetime blast exposures, and number of combat deployments.

ANCOVA, analysis of covariance; mTBI, mild traumatic brain injury; CES, Combat Exposure Scale; PCL-C, Post-Traumatic Stress Disorder Checklist-Civilian version; NSI, Neurobehavioral Symptom Inventory; QOL, Traumatic Brain Injury Quality of Life; EBDYS, Emotional and Behavioral Dyscontrol; Cog-Gen, Cognitive Concerns-General; n ²⁼ partial eta squared (0.01 = small, 0.06 = medium, 0.14 = large).

Influence of gender and PTSD

Descriptive statistics and select pairwise comparisons for all neurobehavioral measures by PTSD/gender subgroups in the mTBI and IC groups is presented in Tables 4 and 5. In the mTBI group (Table 4), select pairwise comparisons designed to examine the influence of gender within the same PTSD categories (i.e., 1. PTSD-present/men vs. women; 2. PTSD-absent/men vs. women) revealed that for participants classified in the PTSD-present category, women had higher scores than men only on the NSI Somatosensory cluster (n ² = 0.029, small-medium effect size). In contrast, for participants classified in the PTSD-absent category, women had elevated scores on the NSI Somatosensory and Affective clusters and the TBI-QOL Anxiety and Headache scales compared with men. Effect sizes ranged from small-medium (n ² = 0.032) to medium (n ² = 0.063). In the IC group (Table 5), there were no significant group differences for all measures.

Table 4.

Descriptive Statistics and Select Pairwise Comparisons (ANCOVA^b) for Neurobehavioral Measures by PTSD/Gender Subgroup: Uncomplicated mTBI Group

	1. PTSD-present men (n = 267)		2. PTSD-present women (n = 23)		3. PTSD-absent men (n = 188)		4. PTSD-absent women (n = 23)		Select pairwise comparisons: Influence of gender within same PTSD classification
	1. PTSD-present men (n = 267)		2. PTSD-present women (n = 23)		3. PTSD-absent men (n = 188)		4. PTSD-absent women (n = 23)		1 v 2 PTSD present			3 v 4 PTSD absent
	Mean	Std. Err	Mean	Std. Err	Mean	Std. Err	Mean	Std. Err	p	n ²	Summary	p	n ²	Summary
NSI Total	36.9	0.8	43.4	2.8	13.8	0.8	20.2	2.4	0.028	0.018	-	0.013	0.031	-
NSI Vestibular	3.2	0.1	4.3	0.5	1.3	0.1	1.4	0.4	0.025	0.018	-	0.841	0.000	-
NSI Som-Sens	9.8	0.3	12.8	1.0	3.8	0.3	6.3	0.9	0.004	0.029	W > M	0.009	0.034	W > M
NSI Cognitive	8.0	0.2	8.3	0.8	3.1	0.2	3.6	0.7	0.671	0.001	-	0.512	0.002	-
NSI Affective	13.1	0.3	15.4	1.0	4.7	0.3	7.8	0.8	0.028	0.017	-	<0.001	0.060	W > M
QOL Anger	59.1	0.6	62.7	2.0	45.6	0.7	48.2	1.9	0.095	0.010	-	0.212	0.008	-
QOL Anxiety	60.0	0.4	62.6	1.5	46.7	0.6	51.3	1.7	0.108	0.009	-	0.010	0.032	W > M
QOL DEP	53.7	0.5	54.4	1.8	42.9	0.5	43.7	1.4	0.713	0.000	-	0.559	0.002	-
QOL EBDYS	52.5	0.5	53.9	1.8	41.4	0.5	44.1	1.6	0.470	0.002	-	0.106	0.013	-
QOL Fatigue	58.9	0.4	62.0	1.5	48.7	0.6	53.0	1.8	0.048	0.014	-	0.023	0.026	-
QOL Headache	54.9	0.4	57.5	1.5	47.1	0.6	53.7	1.7	0.087	0.011	-	<0.001	0.063	W > M
QOL Pain	60.0	0.4	61.9	1.4	50.7	0.6	54.2	1.7	0.226	0.005	-	0.061	0.018	-
QOL Cog-Gen^a	32.4	0.4	30.7	1.5	41.3	0.6	40.1	1.9	0.297	0.004	-	0.542	0.002	-

n = 501.

For the majority of measures, high scores reflect worse functioning, with the exception of the measures indicated. For these measures, low scores reflect worse functioning; ^bCovariates = CES Total and education.

ANCOVA, analysis of covariance; PTSD, post-traumatic stress disorder; mTBI, mild traumatic brain injury; NSI, Neurobehavioral Symptom Inventory; Som-Sens, Somato-sensory; QOL, Traumatic Brain Injury Quality of Life; DEP, Depression; EBDYS, Emotional and Behavioral Dyscontrol; Cog-Gen, Cognitive Concerns-general; n ², partial eta squared (0.01 = small, 0.06 = medium, 0.14 = large).

Table 5.

Descriptive Statistics and Select Pairwise Comparisons (ANCOVA^b) for Neurobehavioral Measures by PTSD/Gender Subgroup: Injured Control Group

	1. PTSD-present men (n = 118)		2. PTSD-present women (n = 13)		3. PTSD-absent men (n = 167)		4. PTSD-absent women (n = 18)		Select pairwise comparisons: influence of gender within same PTSD classification
	1. PTSD-present men (n = 118)		2. PTSD-present women (n = 13)		3. PTSD-absent men (n = 167)		4. PTSD-absent women (n = 18)		1 v 2 PTSD present			3 v 4 PTSD absent
	Mean	Std. Err	Mean	Std. Err	Mean	Std. Err	Mean	Std. Err	p	n ²	Summary	p	n ²	Summary
NSI Total	44.0	1.2	46.4	3.7	22.8	0.4	23.5	1.3	0.541	0.003	-	0.542	0.002	-
NSI Vestibular	33.4	1.3	35.8	4.1	10.8	0.8	14.3	2.5	0.587	0.002	-	0.872	0.000	-
NSI Som-Sens	2.8	0.2	3.0	0.6	0.7	0.1	0.9	0.3	0.730	0.001	-	0.069	0.019	-
NSI Cognitive	8.7	0.5	8.7	1.4	3.0	0.3	3.2	0.8	0.999	0.000	-	0.032	0.026	-
NSI Affective	7.1	0.4	9.0	1.2	2.2	0.2	3.5	0.7	0.154	0.017	-	0.505	0.003	-
QOL Anger	12.1	0.5	13.3	1.4	4.0	0.3	6.0	0.9	0.418	0.005	-	0.562	0.002	-
QOL Anxiety	56.7	0.9	55.2	2.8	45.4	0.6	46.8	1.9	0.607	0.002	-	0.640	0.001	-
QOL DEP	58.7	0.8	60.3	2.3	47.3	0.6	48.5	2.0	0.496	0.004	-	0.822	0.000	-
QOL EBDYS	53.0	0.8	51.9	2.4	43.6	0.5	42.7	1.6	0.648	0.002	-	0.017	0.032	-
QOL Fatigue	50.2	0.8	51.6	2.6	41.4	0.6	41.8	1.8	0.619	0.002	-	0.674	0.001	-
QOL Headache	57.8	0.6	62.9	1.9	48.1	0.7	53.5	2.1	0.013	0.051		0.028	0.027	-
QOL Pain	53.3	0.7	54.4	2.3	45.9	0.6	46.8	1.9	0.629	0.002	-	0.182	0.010	-
QOL Cog-Gen^a	58.1	0.7	60.5	2.2	49.0	0.6	53.3	1.9	0.303	0.009	-	0.542	0.002	-

n = 316.

ANCOVA, analysis of covariance; PTSD, post-traumatic stress disorder; NSI, Neurobehavioral Symptom Inventory; Som-Sens, Somato-sensory; QOL, Traumatic Brain Injury Quality of Life; DEP, Depression; EBDYS, Emotional and Behavioral Dyscontrol; Cog-Gen, Cognitive Concerns-General; n ², partial eta squared (0.01 = small, 0.06 = medium, 0.14 = large).

Discussion

This study compared symptom reporting between men and women across three groups including mTBI, IC, and NIC, while controlling for combat exposure. MTBI and IC groups were also stratified by the presence or absence of PTSD. We identified differences between men and women with mTBI history, with women reporting more neurobehavioral, somatosensory, affective, anxiety, fatigue, and headache symptoms than men. When PTSD was present, gender differences for the TBI group were only significant for somatosensory symptoms, with women reporting more symptoms than men. A similar trend was noted for the IC group, in which women reported greater cognitive, fatigue, and pain symptoms than men. When the IC group was stratified by PTSD, there were no significant group differences between men and women. Although the NIC group was not stratified by PTSD, there were no significant gender differences in symptom reporting for the overall NIC group participants.

This is the first study in this breadth of literature that includes two control groups as well as an mTBI group. Given that there were no gender differences observed in the NIC group and limited gender differences in the IC group, our results can be interpreted more conclusively. The fact that we found differences between men and women in the mTBI group, but not the control groups, can be more conclusively attributed to mTBI recovery than to differences in how men and women report symptoms. For example, somatosensory symptoms were unique to women recovering from mTBI, as this pattern was not seen in other forms of physical injury and remained a significant difference between men and women even in the absence of PTSD. In a prior study, increased somatosensory symptoms for women recovering from mTBI were found only in the PTSD group.¹⁷ Animal studies looking at differences between male and female animals following TBI have found objective evidence of sensory sensitivity in females compared with males, and have concluded that although sensory sensitivity is a primary symptom of TBI, females tend to be more impacted.³⁸ Sensitivity to light was among the most reported symptoms by women service members with mTBI.¹⁶ Orthopedically injured women reported greater level of pain than men, whereas women with mTBI reported more headache and anxiety-related symptoms than men. Fatigue symptoms were significantly greater for women than for men in both the mTBI and IC groups although not elevated in the NIC group, suggesting that symptoms associated with fatigue may be attributed to general injury. Further, there were no significant differences between men and women in self-reported cognitive symptoms in the mTBI group, although women reported greater cognitive symptoms than men in the IC group. This may reflect the non-specificity of cognitive complaints such as concentration difficulties, which are commonly observed in individuals with pain disorders. Studies investigating differences between men and women for cognitive symptoms following TBI have yielded mixed results in the past, with some studies reporting that women experience a greater number, severity, and/or duration of post-concussive symptoms including short-term memory impairment.³⁹

Several potential limitations and considerations with the current study are worth mentioning. First, as these participants were assessed 1 year post-mTBI, any possible differences in the acute recovery period are unknown. Future studies should look at differences between men and women in mTBI recovery across multiple time points to better understand the course of recovery. Additionally, by deferring to gender based on the pronouns used in medical records, we failed to take into account other ways in which service members can feel comfortable identifying themselves and as a result cannot make generalizations about gender as a non-binary construct. An important consideration is the clinical applicability or relevance of the current findings with small-to-medium effect size for gender differences in mTBI. Particularly when PTSD is present with MTBI, gender plays a smaller to possibly inconsequential role in symptom presentation. When men or women are impacted by PTSD, a wide range of symptoms are elevated, and neurobehavioral symptoms may not be specific to mTBI.

Study strengths include a sample of participants with well-characterized uncomplicated mTBI, the use of a symptom validity measure to exclude participants for exaggerated symptoms, the inclusion of two control groups, and a large sample size. Also, as women are typically under-represented in military research, this sample size of 115 women may bring greater awareness to an under-represented population. We hope this inspires future researchers to recruit representative samples of military women to expand our understanding of symptoms presentation and outcomes for women. Because of the inclusion of both IC and NIC groups, we were able to pinpoint the symptoms that are unique to women recovering from mTBI, while also controlling for important group differences including exposure to combat, as well as accounting for PTSD. These findings can assist in treatment planning and symptom management of mTBI. Given that there is a growing number of women who are at risk for injury as a result of expanded military opportunities, better monitoring and symptom management of a population who may be more vulnerable to specific symptoms is beneficial for guided treatment and long-term recovery. Finally, this study allows us to make stronger connections between the increased symptomatology experienced by women compared with men with mTBI.

Footnotes

Author Disclosure Statement

The views expressed in this manuscript are those of the authors and do not necessarily represent the official policy or position of the Defense Health Agency, Department of Defense, or any other U.S. government agency. This work was prepared under Contract HT0014-22-C-0016 with DHA Contracting Office (NM-CD) HT0014 and, therefore, is defined as U.S. Government work under Title 17 U.S.C.§101. Per Title 17 U.S.C.§105, copyright protection is not available for any work of the U.S. Government. For more information, please contact . Unclassified.

Funding Information

No funding was received.

Supplementary Material

Supplementary Table S1

Supplementary Table S2

Supplementary Table S3

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