Journal of Mood & Anxiety Disorders 6 (2024) 100045

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Journal of Mood & Anxiety Disorders

journal homepage: www.journals.elsevier.com/journal-of-mood-and-anxiety-disorders

Childhood unpredictability is associated with increased risk for long- and

short-term depression and anhedonia symptoms following
combat deployment☆
Christopher Hunt a, b, 1, Meghan Vinograd a, b, 1, Laura M. Glynn c, Elysia Poggi Davis d, e,
Tallie Z. Baram e, f, g, Hal Stern h, Caroline Nievergelt a, b, Bruna Cuccurazzu a, b, Cindy Napan a, b,
Dylan Delmar a, b, Dewleen G. Baker a, b, Victoria B. Risbrough a, b, *
a
Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, United States
b
Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
c
Department of Psychology, Chapman University, Orange, CA, United States
d
Psychology Department, University of Denver, Denver, CO, United States
e
Department of Pediatrics, University of California, Irvine, Irvine, CA, United States
f
Department of Neurology, University of California, Irvine, Irvine, CA, United States
g
Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, United States
h
Department of Statistics, University of California, Irvine, Irvine, CA, United States

A R T I C L E I N F O A B S T R A C T

Keywords: High unpredictability has emerged as a dimension of early-life adversity that may contribute to a host of dele­
Depression terious consequences later in life. Early-life unpredictability affects development of limbic and reward circuits in
Veterans both rodents and humans, with a potential to increase sensitivity to stressors and mood symptoms later in life.
Anhedonia
Here, we examined the extent to which unpredictability during childhood was associated with changes in mood
Early-life adversity
Deployment
symptoms (anhedonia and general depression) after two adult life stressors, combat deployment and civilian
Social support reintegration, which were assessed ten years apart. We also examined how perceived stress and social support
mediated and /or moderated links between childhood unpredictability and mood symptoms. To test these hy­
potheses, we leveraged the Marine Resiliency Study, a prospective longitudinal study of the effects of combat
deployment on mental health in Active-Duty Marines and Navy Corpsman. Participants (N = 273) were assessed
for depression and anhedonia before (pre-deployment) and 3–6 months after (acute post-deployment) a combat
deployment. Additional assessment of depression and childhood unpredictability were collected 10 years post-
deployment (chronic post-deployment). Higher childhood unpredictability was associated with higher anhe­
donia and general depression at both acute and chronic post-deployment timepoints (βs > 0.16, ps <.007). The
relationship between childhood unpredictability and subsequent depression at acute post-deployment was
partially mediated by lower social support (b = 0.07, 95% CI [0.03, 0.15]) while depression at chronic post-
deployment was fully mediated by a combination of lower social support (b = 0.14, 95% CI [0.07, 0.23]) and
higher perceived stress (b = 0.09, 95% CI [0.05, 0.15]). These findings implicate childhood unpredictability as a
potential risk factor for depression in adulthood and suggest that increasing the structure and predictability of
childhood routines and developing social support interventions after life stressors could be helpful for preventing
adult depression.

☆
A member of the Editorial Board is an author of this article. Editorial Board members are not involved in decisions about papers which they have written
themselves or have been written by family members or colleagues or which relate to products or services in which the editor has an interest. Any such submission is
subject to all of the journal’s usual procedures, with peer review handled independently of the relevant editor and their research groups.
* Correspondence to: Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr. La Jolla, San Diego, CA 92093-0804, United States.
E-mail address: [email protected] (V.B. Risbrough).
1
Authors contributed equally and share first authorship.

https://doi.org/10.1016/j.xjmad.2023.100045
Received 5 July 2023; Received in revised form 11 December 2023; Accepted 18 December 2023
Available online 23 December 2023
2950-0044/Published by Elsevier Inc. on behalf of Anxiety and Depression Association of America. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

1. Introduction A third possibility is that stress and reduced social support do not
interact with early-life unpredictability but are rather consequences of
There is clear evidence that early-life adversity impacts neuro­ unpredictability, which in turn increase risk for mood symptoms. In
development and subsequent risk for mood and anxiety disorders [31, other words, individuals with unpredictable childhoods may be at
47]. While research into the deleterious effects of early-life adversity has increased risk for experiencing subsequent stressors and more likely to
typically focused on the impact of objectively negative and traumatic withdraw from social support systems later in life, both of which may
life events (e.g., child abuse, parental divorce; e.g., [2,15]), a growing lead to greater symptoms of depression in adulthood. In this way,
body of evidence suggests that high levels early-life unpredictability perceived stress and social support may act as mediators that help
represents a distinct form of adversity that may negatively impact explain the relationships between unpredictable early-life experiences
emotion and cognition in adulthood [19,7]. In contrast to other forms of and later mood symptoms, rather than moderators that alter it. Indeed,
early-life adversity that pertain to the frequency/severity of stressors social support has been found to act as a mediator (rather than a
early in life, early-life unpredictability refers to the extent to which one’s moderator) of the relationship between early-life risk factors for
home, caregivers, and environment are predictable [25,42]. For depression (e.g., childhood maltreatment) and subsequent depression
instance, in both rats and humans, unpredictability can be quantified by symptoms ([36]; Struck et al., 2022), and similar mediational results
the rate at which mothers transition between different behavioral pat­ have been found for perceived stress levels [45]. However, lack of
terns and sensory signals (i.e., changes in visual, auditory, and tactile empirical data has left the roles of perceived stress and social support in
signals) regardless of whether those signals are positive or negative [19] the relationship between early-life unpredictability and mood symptoms
as well as predictability of household events and routines [23,37]. ambiguous. Such work is important for clarifying the mechanisms by
Unpredictability during development is associated with a number of which childhood unpredictability might contribute to increased levels of
poor functional outcomes in adulthood including increased anxiety and neuropsychiatric symptoms later in life.
depression [45], increased risk for intimate partner violence [52], Here, we examined the extent to which childhood unpredictability
cognitive dysfunction [19], and poorer physical health [39]. Hence, was associated with increases in both anhedonia and general depression
more research into the mechanisms underlying the negative impacts of symptoms before and after significant life stressors. We also investigated
early-life unpredictability is necessary to better understand how such social support and perceived stress as potential moderators and media­
impacts come about and can be prevented. tors of the relation between childhood unpredictability and increases in
In rodents, fragmented and unpredictable maternal care is linked these symptoms after significant life stressors. To test these questions,
specifically to disrupted reward-seeking [12,13,34,42] and aberrant we leveraged the Marine Resiliency Study, a prospective longitudinal
development of pleasure-reward circuitry [10,11,13]. In humans, there study of combat deployment effects on mental health at acute (within
are preliminary indications that unpredictability in early life is associ­ 3–6 months of deployment) and chronic (~10 yrs after deployment)
ated with alterations in neural circuits that subserve emotional salience, time points. Owing to the variety of stressful and life-threatening events
emotional regulation and memory and are also disrupted in major that can occur on military deployment, this event is frequently utilized
depressive disorder [31,20,37,67,4,14]. Indeed, exposure to childhood as a subsequent life stressor through which to test a stress-sensitization
unpredictability is linked to greater symptoms of depression and anhe­ model of mental illness stemming from earlier life adversity [19,6,53].
donia in both adolescents and adults [23]. There is also a preliminary Moreover, reintegrating into Civilian society following military service
link with maternal depression and negative affect: Greater variability in has its own set of occupational, social, and logistical challenges that
maternal mood during the prenatal period predicts the development of renders this period distinctly stressful as well [21].
negative affectivity in young children and depressive symptoms in ad­ Given extant cross-species evidence implicating early-life unpre­
olescents [22]. Taken together, these cross-species findings lead to the dictability as a contributor to mood symptoms, we hypothesized that
question of whether in humans early-life unpredictability and later Marine and accompanying Navy service members reporting greater
mental health problems may be linked specifically to anhedonia – unpredictability in childhood would experience greater increases in
defined as a deficit in the subjective ability to experience pleasure or anhedonia and depression between a) pre-deployment and acute post-
reward [30,46] – as well as to broader depression symptoms. deployment and b) between acute post-deployment and chronic post-
One factor that may play a critical role in how early-life unpredict­ deployment. We also explored the roles of perceived stress and social
ability leads to later reward disruption and mood symptoms is prior support in explaining the relationship between childhood unpredict­
stress exposure. Neurobiological models contend that exposure to early- ability and mood symptoms (anhedonia, general depression symptoms)
life unpredictability can disrupt the development of the stress-response by testing these factors as mediators and moderators across both time
system, as observed through improper maturation of the hippocampus periods. Together, these analyses should provide important verification
[17,19], disrupted reward circuits [10,11,27] and blunted release of of childhood unpredictability as a risk factor for adult mood symptoms
cortisol in response to stress [42]. For this reason, the consequences of and provide initial insight into mechanisms by which unpredictable
an aberrant stress-response system should emerge following stressful life childhood experiences might contribute to increases in anhedonia and
events, particularly through the development or worsening of mental depression in adulthood.
health problems – as summarized by the stress-sensitization hypothesis
[29,41,49]. As applied to the current investigation, this model would 2. Materials and method
suggest that childhood unpredictability might create a latent predispo­
sition that interacts with later stressors to produce mood symptoms like 2.1. Participants and Procedures
depression or anhedonia.
At the same time, there is also evidence that the negative conse­ Participants were prior enrollees of the Marine Resiliency Study [5],
quences of an aberrant stress-response system can partially be mitigated a longitudinal study of Marines and accompanying Navy Corpsmen.
through social support [20]. Indeed, social support remains one of the Study enrollees were assessed longitudinally: prior to deployment
strongest predictors of symptom severity across a range of mental health (pre-deployment timepoint), three to six months after deployment
disorders [28], including those in which depression symptoms and dis­ (acute post-deployment timepoint), and approximately eight to ten
ruptions of reward processes feature prominently [18,24,43]. Hence, in years after returning from the original index deployment (chronic
the same way that stress may interact with early-life unpredictability to post-deployment timepoint). Participants were invited to complete the
produce mood symptoms in adulthood, high social support might buffer chronic post-deployment assessment if they had consented to be
against increases in these symptoms among adults who experienced an re-contacted and had completed at least one acute post-deployment
unpredictable childhood. assessment. All study procedures were approved by the VA San Diego

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C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

Healthcare System and University of California, San Diego Institutional 0.11, t(365.97) = 2.15, p = .032. Completers and non-completers did not
Review Boards. differ in terms of race/ethnicity, depression or anhedonia symptoms at
Of the 3883 participants who were enrolled in the original Marine pre- or post-deployment, or in terms of perceived combat stress,
Resiliency Study, N = 323 met eligibility criteria, consented to the long- perceived unit support, or perceived social support at post-deployment
term follow-up interview and completed our measure of unpredictable (ps > .134). Full statistics for these comparisons can be found in
childhood experiences. Of these participants, N = 205 had the complete Table 1S of the Supplement.
data necessary for longitudinal analyses involving pre-deployment and
acute post-deployment while N = 221 had the complete data necessary
for analyses of acute post-deployment to chronic post-deployment. Full 2.2. Measures
information on participant recruitment flow can be found in Fig. 1 and
full demographic details of the final sample can be found in Table 1. 2.2.1. Questionnaire of Unpredictability in Childhood
Participants who completed the interview at chronic post-deployment The Questionnaire of Unpredictability in Childhood (QUIC; [23]) is a
were slightly older than those who did not, Mdiff = 0.61 years, t 38-item self-report measure of exposure to social, emotional and envi­
(353.033) = 2.43, p = .016, as well as slightly more educated, Mdiff = ronmental unpredictability in childhood. The QUIC asks respondents
specifically about their life prior to age 18 years, with a subset of

Fig. 1. Participant flow and recruitment diagram. The Marine Resiliency Study refers to the parent investigation that collected data at pre-deployment and acute
post-deployment. The long-term follow-up interview (chronic post-deployment) occurred approximately 8 – 10 years after participation in the original Marine
Resiliency Study had concluded.

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C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

Table 1 measure of depressive symptoms in the past two weeks, with a higher
Demographic and clinical characteristics of the sample. score indicating greater severity of depressive symptoms. In addition to
Variable % Mean (SD) the total BDI-2 score, two subscales were calculated from BDI-2: The
BDI-2 anhedonia items (BDI-A) and the BDI-2 depression items (BDI-D).
Sex
% Men 100 – These subscales were computed by summing items relevant to anhe­
% Women 0 – donia and general depression, respectively, as guided by results of a
Ethnicity – principal components analysis conducted in the full data set of the
% Black/African American 3.2 – Marine Resiliency Study (see [1]). Participants completed the BDI-II at
% Native American 2.3 –
% Asian 4.0 –
the pre-deployment, acute post-deployment and chronic
% Pacifier Islander 1.2 – post-deployment timepoints. Reliability of the BDI-2 and its subscales
% Hispanic/Latino 18.4 – ranged from good to very good across the three timepoints (Cronbach’s
% White/Caucasian 66.9 – alpha =.739 − .838).
Education
% Some High School 1.5 –
% GED 1.5 – 2.2.3. Deployment Risk and Resiliency Inventory (DRRI; [35])
% High School Diploma 61.5 – The DRRI is a self-report scale that assesses key psychosocial risk and
% Some College 24.4 – resilience factors for military personnel deployed to war zones or other
% Associate degree 1.5 – hazardous environments. The full DRRI yields 14 distinct constructs
% 4-Year College Degree 4.2 –
% Masters Degree 0.4 –
related to pre-deployment, deployment, and post-deployment factors.
% Doctoral Degree 0.4 – The DRRI and its subscales have demonstrated strong evidence of val­
Parental Education Level* idity and reliability [35] including in samples of soldiers deployed to
% Parent with 4-Year College Degree 39.6 – Iraq and Afghanistan like those examined in the present study [51].
% Parent without 4-Year College Degree 60.4 –
Of the available DRRI subscales, the following were analyzed in the
Mean Age (SD) – 23.13 (4.38)
Mean QUIC (SD) – 10.48 (8.70) present investigation. First, the Deployment Concerns subscale (DRRI
Mean DRRI DCON (SD) – 35.25 (10.58) DCON) was used as a measure of perceived stress during deployment (e.
Mean DRRI PDS (SD) – 3.92 (2.86) g., “I thought I would never survive”), and was administered during the
BDI-A acute post-deployment timepoint. Second, the General Post-deployment
Mean Pre-deployment (SD) – 0.80 (1.27)
Support subscale (DRRI GPDS) was used as a measure of general social
Mean Acute post-deployment (SD) – 1.06 (1.54)
Mean Chronic post-deployment (SD) – 2.42 (2.33) support following deployment (e.g., “The American people made me feel at
BDI-D home when I returned”), and was administered during both the acute and
Mean Pre-deployment (SD) – 2.27 (3.14) chronic post-deployment timepoints. Third, the Unit Support subscale
Mean Acute post-deployment (SD) – 2.54 (3.90)
(DRRI US) was used as a measure of support from the respondent’s
Mean Chronic post-deployment (SD) – 5.65 (6.23)
BDI-2 military comrades within their unit both during deployment and after
Mean Pre-deployment (SD) – 6.25 (6.79) returning from deployment (e.g., “My unit is like a family to me.”), and
Mean Acute post-deployment (SD) – 7.46 (8.12) was administered during both the acute and chronic post-deployment
Mean Chronic post-deployment (SD) – 13.41 (11.97) timepoints. Finally, the post-deployment stressors (DRRI PDS) subscale
DRRI US
was used to assess the perceived stress during the reintegration period
Mean Acute post-deployment (SD) – 33.60 (11.48)
Mean Chronic post-deployment (SD) – 47.97 (10.31) following deployment (e.g., “Since returning home I have experienced
DRRI GPDS serious financial problems.”), and was administered at the chronic post-
Mean Acute post-deployment (SD) – 54.70 (10.16) deployment timepoint.
Mean Chronic post-deployment (SD) 38.28 (8.04)
For perceived stress during deployment (DRRI DCON), participants
Note. All demographic variables were assessed at pre-deployment except for were directed to respond according to their experiences on deployment.
parental education level, which as assessed at the chronic post-deployment For DRRI PDS, GPDS, and US, participants were directed to respond to
timepoint. DRRI DCON was assessed at acute post-deployment, DRRI PDS was the time period since their last deployment. Thus, when administered at
assessed at chronic post-deployment, and QUIC was assessed at chronic post- acute post-deployment, DRRI GPDS and US measures reflected
deployment. Acute post-deployment refers to the interval from 3-6 months perceived levels of support in the 3 – 6 months since returning from
after returning from deployment; chronic post-deployment refers to the interval
deployment. When DRRI GPDS, US, and PDS were administered at
between 8 – 10 years following return from deployment. GED = General edu­
chronic post-deployment, they reflected perceived levels of stress/sup­
cation degree; QUIC = Questionnaire of Unpredictability in Childhood; BDI-A =
Beck Depression Inventory Anhedonia Items; BDI-D = Beck Depression In­ port in the 8–10 years since returning from deployment.
ventory Depression items; BDI-2 = Beck Depression Inventory Two; DRRI =
Deployment Risk and Resilience Inventory; DCON = Deployment Concerns 2.2.4. Childhood socioeconomic status
subscale; PDS = Post-deployment stressors subscale; US = Unit support subscale; In addition to our main outcomes, we also assessed participants’
GPDS = General post-deployment support subscale. N = 221 for chronic post- parental education levels during childhood as a proxy for childhood
deployment; N = 205 for acute post-deployment. socioeconomic status, which was used to gauge general levels of
adversity during childhood. Specifically, participants reported the edu­
questions focused on events more likely to occur prior to age 12 years. A cation level and occupation of both their parents when the participant
higher QUIC score indicates greater exposure to childhood unpredict­ was 8 years old and 16 years old. Participants reported parental edu­
ability. Internal consistency for the QUIC in the current study was cation during visits from the chronic post-deployment timepoint.
excellent (Cronbach’s alpha =.91). The QUIC was administered during Parental education was coded as a dichotomized variable related to the
the chronic post-deployment period (8–10 years following deployment). highest parental education level at age 16 years wherein participants
A subset of participants (n = 53) completed the QUIC multiple times with a parent who earned a bachelor’s degree or higher were coded as
during this period (n = 34 two completions, n = 19 three completions). ‘1’ and all others were coded as ‘0’.
The intraclass correlation coefficient for these multiple completions was
.91, indicating excellent test-retest reliability. 2.3. Analytical plan

2.2.2. Beck Depression Inventory-II 2.3.1. Data processing

The Beck Depression Inventory-II (BDI-II; [9]) is a 21-item self-report Scores for all questionnaires (QUIC, BDI-A, DRRI subscales) were

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computed by taking an average of all completed items and multiplying PDS were tested as potential moderators/mediators.
by the total number of items on the scale, which allowed us to derive To reduce redundancy in these analyses, we utilized an analytic
inferred total scores for participants in the case of missing items. If framework guided by the MacArthur approach, which helps unambig­
multiple assessments of depression (BDI-2) or stress (DRRI DCON, DRRI uously categorize variables as potential moderators or mediators [16].
PDS) had been completed within a given post-deployment timeframe (i. In this framework, zero-order associations are tested between the X
e., acute or chronic), the highest score was used to capture the most variable (i.e., QUIC), and the Y variable (i.e., the BDI measure), and the
severe clinical state or highest perceived stress level of the participant potential moderators/mediators of interest. Variables that are not
during the time period. If multiple assessments of the DRRI support associated with X (i.e., independent of X) are considered candidate
measures (i.e., DRRI US, DRRI GPDS) had been completed within a given moderators, variables that associated with both X and Y are considered
post-deployment timeframe, the lowest score was used to capture the candidate mediators, and variables that are only associated with X are
lowest perceived support during the interval. If multiple assessments of not considered further.
the QUIC or parental education were completed during the chronic post- Potential moderators were then tested by examining whether the
deployment timeframe, the earlier score was used to minimize the interaction between the X (i.e., QUIC) and the moderator predicted
temporal gap between childhood and the current assessment. additional, significant variance in the outcome variable (i.e., BDI mea­
sure at the later timepoint) in a regression model that included the BDI
2.3.2. Testing longitudinal relations between childhood unpredictability and measure from the earlier timepoint (step 1), the main effect of QUIC
depression change (step 2), the main effect of the potential moderator (step 3), and finally
To investigate the relationship between childhood unpredictability the QUIC x Moderator interaction (step 4). Potential mediators were
and changes in mood symptoms (anhedonia and general depression), we tested using the model 1 of the PROCESS Macro for SPSS (Preacher &
first conducted hierarchical regression analyses for each interval (i.e., Hayes, 2004), which yields an indirect effect of the mediator on the
pre-deployment to acute post-deployment, acute post-deployment to outcome variable by testing it across k samples of the data’s sample size
chronic post-deployment). For the acute post-deployment interval, each with replacement (k = 10000 for the study study) and computing a 95%
BDI-2 measure (BDI-A, BDI-D, BDI-2 total) was tested as an outcome in bootstrapped confidence interval (CI). The indirect effect of the medi­
separate regression models. For predictors, the corresponding depres­ ator is considered significant if the 95% bootstrapped CI does not
sion measure from pre-deployment was entered first, followed by total contain zero. Here, the outcome variable again was the BDI measure of
scores from the QUIC, which tested whether higher childhood unpre­ interest at the later timepoint, QUIC was X variable, and the corre­
dictability would predict higher depression symptomology after con­ sponding BDI measure from the earlier timepoint was entered as a
trolling for the same measure of depression symptomology from pre- control variable. Thus, these models tested whether a significant pro­
deployment (i.e., change in depression symptomology from pre- portion of the effect of QUIC on the BDI measure at the later timepoint
deployment to acute post-deployment). An identical set of models was could be accounted for by the candidate mediator. In cases where
tested for the interval from acute post-deployment to chronic post- multiple mediators were found, they were tested simultaneously in a
deployment, with the depression measure from chronic post- parallel mediation model to determine whether their mediating effects
deployment serving as the outcome variable and the same measure were unique or redundant.
from the acute post-deployment being entered in the first step, followed All predictors were z-scored to aid interpretability. All reported
by QUIC in the second step. regression coefficients are taken from the regression model in which
Next, we further examined the specificity of childhood unpredict­ they were first entered. Alpha was set at.05 (two-tailed) for all tests.
ability as a predictor of anhedonia or depression change by testing Analyses were conducted in SPSS Version 28.
whether any effect of QUIC remained significant after accounting for
parental education, which served as a proxy for childhood socioeco­ 3. Results
nomic status (CSES). Children from low SES backgrounds are at
heightened risk for a variety of environmental stressors during child­ 3.1. Associations between childhood unpredictability and post-
hood (Merrick et al., 2018; Domornay et al., 2023), so controlling for deployment depression symptoms
CSES can help establish whether the effect of childhood unpredictability
on mood symptoms is distinct from other forms of early-life adversity. In As hypothesized, levels of QUIC significantly predicted higher BDI-A
these models, the BDI measure at the earlier timepoint were entered first scores at both acute post-deployment, β = 0.16, 95% CI[0.05, 0.29],
(i.e., pre-deployment BDI for acute post-deployment models; acute post- p = .007, and chronic post-deployment, β = 0.25, 95% CI[13, 0.39],
deployment BDI for chronic post-deployment models), followed by p < .001, after controlling for levels of BDI-A at the earlier timepoint.
parental education, and finally the QUIC total score, which tested Thus, participants who reported greater unpredictability during child­
whether the relationship between childhood unpredictability and hood tended to experience greater increases in anhedonia from both pre-
depression symptom change was independent of childhood SES. Of note, deployment to acute post-deployment and from acute post-deployment
these analyses were conducted with a reduced sample as only a subset of to chronic post-deployment. QUIC was also a significant predictor of
participants completed the parental education measure (N = 189). general depression symptoms as measured by the BDI-D subscale and
total BDI-2 at both times timepoints. Specifically, higher QUIC signifi­
2.3.3. Testing potential moderators and mediators of the relationship cantly predicted greater acute post-deployment scores on the BDI-D,
between childhood unpredictability and depression change β = 0.22, 95% CI[0.10, 0.34], p < .001, and total BDI-2, β = 0.21,
Finally, to help better understood the mechanisms by which child­ 95% CI[0.09, 0.32], p < .001 as well as greater chronic post-deployment
hood unpredictability might lead to increases in mood symptoms, we scores on the BDI-D, β = 0.17, 95% CI[0.05, 0.31], p = .009, and total
tested perceived levels of stress and social support as potential moder­ BDI-2, β = 0.20, 95% CI[0.08, 0.33], p = .002. Thus, participants
ators and mediators of the longitudinal QUIC-BDI relationship. Exami­ reporting greater unpredictability in childhood appeared to experience
nation of potential moderators and mediators was conducted separately larger increases in more general symptoms of depression, not specif­
for each interval (i.e., pre-deployment to acute post-deployment; acute ically anhedonia. Accordingly, only models involving the total BDI-2
post-deployment to chronic post-deployment). For analyses predicting scale were considered in subsequent analyses for the purposes of
acute post-deployment mood symptoms, the DRRI US, DRRI GPDS, and parsimony.
DRRI DCON from the acute post-deployment timepoint were tested as
potential moderators/mediators. For analyses predicting chronic post-
deployment mood symptoms, the DRRI US, DRRI GPDS, and DRRI

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3.2. Testing the specificity of childhood unpredictability relative to Table 3

childhood SES Associations between childhood unpredictability, depression symptoms, and
potential moderator and mediator variables at acute post-deployment time
Results of regression models used to predict post-deployment BDI-2 point.
scores at acute and chronic post-deployment from QUIC after controlling 1 2 3 4 5
for childhood socioeconomic status (i.e., parental education) can be 1. QUIC Total 1 .28* * .07 -.20** -.33**
found in Table 2. Parental education did not significantly predict BDI-2 2. BDI-2 Total 1 .31** -.31** -.46**
scores at either acute post-deployment (p = .122) or chronic post- 3. DRRI DCON 1 -.08 -.07
deployment (p = .095). Moreover, the effect of QUIC remained signifi­ 4. DRRI US 1 .55**
5. DRRI GPDS 1
cant at both post-deployment timepoints even after controlling for
parental education and BDI-2 at the earlier timepoint (ps < .003). Thus, Note. QUIC was assessed at chronic post-deployment; all other variables were
the effect of childhood unpredictability on post-deployment depression assessed at acute post-deployment. Acute post-deployment refers to the interval
symptoms appeared to be independent of parental education. from 3-6 months after returning from deployment; chronic post-deployment
refers to the interval between 8 – 10 years following return from deployment.
QUIC = Questionnaire of Unpredictability in Childhood; BDI-2 = Beck Depres­
3.3. Testing mediators and moderators of relationship between childhood
sion Inventory-II;. DRRI = Deployment Risk and Resilience Inventory; DCON
unpredictability and depression change = Deployment concerns subscale; US = Unit support subscale; GPDS = General
post-deployment support subscale.* * p < .01. N = 205.
3.3.1. Acute post-deployment
Associations between QUIC, acute post-deployment BDI-2, and the
perceived stress during deployment was predictive of higher depression
three candidate moderators/mediators at acute-post-deployment (i.e.,
symptoms following deployment, it did not moderate the relationship
DRRI DCON, DRRI US, DRRI GPDS) can be found in Table 3. While
between childhood unpredictability and depression symptoms following
perceived stress during deployment (DRRI DCON) was positively asso­
deployment.
ciated with acute post-deployment BDI-2 (p < .001), it was unrelated to
To test whether general social support (DRRI GPDS) and unit support
QUIC (p = .278). Therefore, perceived deployment stress was tested as a
(DRRI US) mediated the relationship between QUIC and BDI-2 at acute
potential moderator of the relationship between QUIC and acute post-
post-deployment, we input these variables as mediators in model 1 of
deployment depression symptoms. In contrast, DRRI US and DRRI
the SPSS PROCESS macro, with QUIC serving as the X variable, acute
GPDS were negatively associated with both QUIC and total BDI-2 scores
post-deployment BDI-2 as the Y variable, and pre-deployment BDI-2 as a
(ps < .001), suggesting that general social support (DRRI GPDS) and
control variable. These tests revealed that while the indirect effect of
unit support (DRRI US) at acute post-deployment were potential medi­
DRRI US was not significant, b = 0.01, 95% CI [− 0.002, 0.05], the in­
ators of the relationship between childhood unpredictability and acute
direct effect of DRRI GPDS was significant, b = 0.07, 95% CI [0.03,
post-deployment depression symptoms.
0.15], and explained approximately 34% of the effect of QUIC on acute
To test perceived stress during deployment (DRRI DCON) as a
post-deployment BDI-2 scores. Notably, the direct effect of QUIC on
moderator, we ran an additional regression in which the QUIC x DRRI
post-deployment BDI-2 remained significant after accounting for DRRI
DCON interaction was tested as a predictor of acute post-deployment
GPDS, b = 0.14, 95% CI [0.02, 0.26], p = .023, suggesting that DRRI
BDI-2 scores. Although the main effect of DRRI DCON was significant,
GPDS is only a partial mediator of this relationship (see Fig. 2 for a full
β = 0.25, 95% CI [.15,.37], p < .001, the DRRI DCON x QUIC interac­
illustration of the mediating model). Thus, the relationship between
tion was not, β = 0.08, 95% CI [− 0.03,.19], p = .146. Thus, while
childhood unpredictability and increased depression symptoms at acute
post-deployment is partially attributable to lower levels of general social
Table 2 support at acute post-deployment, and unrelated to support from one’s
Hierarchical regression analyses predicting depression symptoms from child­ military unit.
hood unpredictability adjusting for parental education level.
Outcome variable Step Predictor ΔR2 β t p 3.3.2. Chronic post-deployment
(95% CI)
Associations between QUIC, chronic post-deployment BDI-2, and the
BDI-2 at acute 1 BDI-2 at pre- .296 0.54 8.29 < .001 three candidate moderators/mediators at chronic post-deployment (i.e.,
post- deployment (0.43 – DRRI PDS, DRRI US, DRRI GPDS) can be found in Table 4. In contrast to
deployment 0.70)
2 Parent Edu .010 -0.10 -1.56 .122
results from acute post-deployment, all three candidate variables were
(− 0.23 –
0.03)
3 QUIC Total .057 0.25 3.81 < .001
(0.12 –
0.39)
BDI-2 at 1 BDI-2 at acute .086 0.29 4.20 < .001
chronic post- post- (0.18 –
deployment deployment 0.49)
2 Parent Edu .014 -0.12 -1.68 .095
(− 0.25 –
0.02)
3 QUIC Total .042 0.22 3.00 .003
(0.07 –
Fig. 2. Effect of childhood unpredictability on depression symptoms 3–6
0.37)
months post deployment as mediated by general social support at acute post-
Note. Coefficients displayed for each variable are taken from the regression deployment. Acute post-deployment refers to the interval from 3–6 months
model in which they were first entered. Parent Edu was coded such that after returning from deployment. Childhood unpredictability was measured by
0 = neither parent achieved a 4-year college degree and 1 = at least one parent the QUIC, post-deployment social support by the DRRI GPDS, and depression
achieved a 4-year college degree. Acute post-deployment refers to the interval with the BDI-2. Pre-deployment BDI-2 was entered as a covariate to control for
between 3-6 months after returning from deployment; chronic post-deployment depression symptoms at pre-deployment. QUIC = Questionnaire of unpredict­
refers to the interval between 8 – 10 years following return from deployment. ability in childhood; DRRI GPDS = Deployment risk and resilience inventory
QUIC = Questionnaire of Unpredictability in Childhood; BDI-2 = Beck Depres­ general post-deployment support subscale; BDI-2 = Beck Depression Inventory
sion Inventory-II; Parent Edu = Parental education level. N = 189. II. * p < .05; * * p < .001.

6
C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

Table 4 34,42], we tested the hypothesis that greater unpredictability during

Associations between childhood unpredictability, depression symptoms, and childhood increases risk for symptoms of depression across distinct pe­
potential moderator and mediator variables at chronic post-deployment. riods of stress. We examined the longitudinal association between
1 2 3 4 5 childhood unpredictability as measured by the QUIC and the increases
1. QUIC Total 1 .33** .37** -.22** -.44**
in mood symptoms (anhedonia and general depression symptoms) in the
2. BDI-2 Total 1 .46** -.29** -.46** aftermath of both combat deployment (~3–6 months post-deployment;
3. DRRI PDS 1 -.23** -.25** referred to as ’acute post-deployment’) and the period of reintegration
4. DRRI US 1 .44** into Civilian society (~8–10 yrs later; referred to as ’chronic post-­
5. DRRI GPDS 1
deployment’). Participants reporting higher childhood unpredictability
Note. All variables were assessed at chronic post-deployment. Chronic post- experienced larger increases in depression symptoms across both pe­
deployment refers to the interval between 8 – 10 years following return from riods. This association remained significant after controlling for an in­
deployment. QUIC = Questionnaire of Unpredictability in Childhood; BDI- dicator of childhood socioeconomic status (CSES), suggesting that the
2 = Beck Depression Inventory-II; DRRI = Deployment Risk and Resilience In­ effect of unpredictable childhood experiences was not merely a proxy for
ventory; PDS = Post-deployment stressors subscale; US = Unit support subscale;
greater childhood adversity. The relationship between higher childhood
GPDS = General post-deployment support subscale. **p < .001. N = 221.
unpredictability and increased depression symptoms at acute
post-deployment was partially mediated by lower levels of general social
significantly associated with both QUIC scores and BDI-2 total scores support during the acute post-deployment period. The association be­
(ps < .001). Thus, levels of perceived stress (DRRI PDS), unit support tween unpredictability and increased depression at chronic
(DRRI US), and general social support (DRRI GPDS) were all tested as post-deployment was fully mediated by the combination of lower levels
mediators of the relationship between childhood unpredictability and of general social support and higher perceived stress during the chronic
depression symptoms at chronic post-deployment. post-deployment period – as indexed by disruptions in psychosocial
Next, all three variables were tested in separate models as mediator functioning and adjustment. Overall, these findings support the notion
variables using the SPSS PROCESS macro, with QUIC serving as the X that childhood unpredictability might play a role in increasing depres­
variable, chronic post-deployment BDI-2 as the Y variable, and acute sion symptoms following stressful transitionary periods and suggest that
post-deployment BDI-2 as a control variable. These tests revealed sig­ disruptions in psychosocial adjustment and social support in early
nificant indirect effects for all three variables: DRRI PDS, b = 0.10, 95% adulthood my serve as critical links in the relationship between child­
CI [0.05, 0.17], DRRI US, b = 0.03, 95% CI [0.0003, 0.08], and DRRI hood unpredictability and depression later in life.
GPDS, b = 0.15, 95% CI [0.07, 0.24]. Since indirect effects for all three Our study complements existing cross-sectional studies demon­
variables were significant, we next entered them all into a parallel strating an association between early-life unpredictability and adult
mediation model to determine whether they reflected unique or psychopathology by demonstrating that childhood unpredictability also
redundant mediating pathways. In this overall model, the indirect effect predicts longitudinal increases in mental health symptoms – namely
of DRRI PDS remained significant, b = 0.09, 95% CI [0.05, 0.15], as did depression – over time [22]. Importantly, the longitudinal relationship
the indirect effect of DRRI GPDS, b = 0.14, 95% CI [0.07, 0.23]. In between childhood unpredictability and depression was demonstrated
contrast, the indirect effect of DRRI US was no longer significant, b across two distinct timespans (i.e., pre-deployment to acute
= − 0.003, 95% CI [− 0.03, 0.02]. In the overall mediation model, in­ post-deployment, acute post-deployment to chronic post-deployment),
direct effects accounted for 90% of the total effect of QUIC on chronic each with their own distinct challenges (i.e., combat deployment and
post-deployment BDI-2, and the direct effect of QUIC on chronic post- civilian reintegration). The prospective, longitudinal nature of our
deployment BDI-2 was no longer significant, b = − 0.03, 95% CI design not only helps further implicate childhood unpredictability as a
[− 0.16, 0.10], p = .691. An illustration of the complete mediation risk factor for adult psychopathology but suggests that childhood
model for chronic post-deployment can be found in Fig. 3. unpredictability continues to confer risk for increasing mental health
symptoms across different phases of the lifespan after exposure to
4. Discussion certain kinds of stressors.
Foundational rodent studies indicate that early-life unpredictability
Consistent with past work linking early-life unpredictability to the disrupts circuits associated with both reward (e.g. striatal circuit con­
development of diminished reward response across species [12,13,22, nectivity) as well as emotional regulation and stress responding (e.g.
hippocampal circuit function and hypothalamic-pituitary-axis re­
sponses), suggesting unpredictability modulates multiple neural circuits
implicated in anhedonia and depression ([19,42]; Birne et al., 2020; [13,
42]). Consistent with these animal data, our study is the first to link
unpredictability earlier in life to increased levels of depression symp­
toms in adulthood. Contrary to expectations however, childhood
unpredictability did not interact with levels of perceived stress to predict
depression, as would be hypothesized based on a stress-sensitization
model (Stroud et al., 2011). In the case of depression symptoms expe­
rienced in the acute post-deployment period, childhood unpredictability
Fig. 3. Effect of childhood unpredictability on chronic post-deployment and deployment stress appeared to exert independent effects: Higher
depression symptoms as mediated by general social support and post- levels of both were predictive of depression symptoms following return
deployment stressors chronic post-deployment. Chronic post-deployment mea­ from deployment and were not related to each other. In the case of
sures were assessed between 8 – 10 years following return from deployment. chronic post-deployment, higher perceived stress during the reintegra­
Childhood unpredictability was measured by the QUIC, post-deployment social tion period mediated the effect of childhood unpredictability on
support by the DRRI GPDS, post-deployment stress with the DRRI PDS, and
depression symptoms at chronic post-deployment. This finding suggests
depression with the BDI-2. Pre-deployment BDI-2 was entered as a covariate to
that higher childhood unpredictability could increase risk for experi­
control for depression symptoms at pre-deployment. QUIC = Questionnaire of
childhood unpredictability; DRRI = Deployment risk and resilience inventory; encing stressors during the Civilian reintegration period, which would in
GPDS = General post-deployment support subscale; PDS = Post-deployment turn increase risk for depression symptoms. The discrepancy in the effect
stressors subscale; BDI-2 = Beck Depression Inventory II. of perceived stress at the acute versus chronic post-deployment periods
* * p < .05; * * p < .001. may be due to differences in the controllability of these stressors:

7
C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

Whereas deployment stress may be heavily dictated by experiences retrospectively and could be subject to self-report biases that skewed the
outside the individual’s control (e.g., combat events), stressors in the accuracy of reported experiences. Test-retest reliability of the QUIC was
civilian reintegration represent psychosocial disruptions that are rela­ high across a two-year period (albeit in a small sample), suggesting that
tively more controllable (e.g., financial problems), perhaps allowing participants’ perceptions of their childhood unpredictability were stable
individual differences in previous developmental experiences (e.g., and thus unlikely to have been dictated by factors that shift across time
childhood unpredictability) to exert greater influence. How an unpre­ (e.g., life circumstances, mood states at the time of administration). The
dictable childhood might increase risk for psychosocial disruption dur­ QUIC was also associated with anhedonia and depression over three
ing civilian reintegration is unclear, though previous studies have found timepoints spanning more than a decade, suggesting its relationship to
links between childhood unpredictability and impairments related to anhedonia is not state specific. Moreover, the QUIC has been shown to
the same reintegration stressors that mediated the association between prospectively predict longitudinal changes in unpredictability within
childhood unpredictability and adult depression in our investigation. the family and home environment in developmental samples, offering
For example, greater unpredictability during childhood has been linked further evidence that the instrument validly assesses unpredictability
to greater impairment in social and romantic relationships in adulthood despite its retrospective assessment method [23]. Nonetheless, greater
[38,8,52] and to greater difficulty making career decisions in adulthood validity would undoubtedly be achieved by assessing childhood unpre­
[66] – similar to the relationship- and employment-related reintegration dictability during or closer to childhood, which should be a priority for
stressors that composed our measure of perceived stress in this study. future studies looking to verify the relationship between this construct
This study also demonstrates that social support is a potential and mental health symptoms later in life.
mediating variable in the relationship between childhood unpredict­ Second, our study did not examine the relationship between child­
ability and adult psychopathology. Lower social support in both the hood unpredictability and depression change in individuals who did not
months following return from deployment and approximately a decade experience a stressful life event (i.e., participants who did not go on
later explained a large proportion of the effect of childhood unpredict­ military deployment). For this reason, it is difficult to determine the
ability on increased depression symptoms over both intervals. One extent to which stressful life experiences contribute to increased
possible interpretation of this finding is that unpredictable childhood depression among those who had unpredictable childhoods, as we do
environments negatively influence interpersonal functioning in a way not know the ‘normative’ trajectories of depression symptoms among
that makes individuals more likely to withdraw from or underutilize individuals of similar backgrounds who did not experience such stressful
support networks as adults. Conversely, predictable childhood care may periods. Notably, there was no interaction between childhood unpre­
strengthen support expectations in later relationships [40], thereby dictability and perceived stress levels during either time interval in
enhancing engagement with social support networks that buffer against predicting later depression. Thus, it appears that at minimum, greater
the development of mood symptoms after significant life stressors. In stress exposure does not amplify the effect of childhood unpredictability
support, predictability during childhood has been linked to prosocial on later mental health symptoms.
behavior in adulthood [40,48] and social support has been found to Finally, our sample was all men, which necessarily limits our ability
mediate broad range of evidence-based treatment effects on symptom to generalize these findings to women. Early-life adversity has different
change in depression, suggesting that factors that influence social sup­ effects on reward circuits and behaviors in male versus female rodents
port may consequently influence depression symptoms [20]. Alterna­ and humans [3,29,36], which may contribute to higher rates of
tively, social support following deployment may have partially included depression observed among women [44]. Thus, future research is
the same support network that existed in childhood, with unpredictable needed to compare longitudinal associations between childhood
networks and predictable networks mediating increased and decreased unpredictability and depression across men versus women.
risk of depression respectively. These explanations are not mutually
exclusive: predictable caregiver support in childhood could render in­ 5. Conclusions
dividuals more likely to seek support in adulthood and continue to be
part of a robust adult support network itself. Future research may clarify The purpose of this study was to examine the association between
the relevance of these two explanations by conducting a more granular childhood unpredictability and the development of depression symp­
examination of the specific aspects of a support network mediating the toms following military deployment and civilian reintegration, as well
relationship between childhood unpredictability and later depression. as evaluate the roles of perceived stress and social support in these as­
In terms of what circuits might mediate the associations reported sociations. Participants who reported greater unpredictability during
here, early-life unpredictability disrupts maturation of striatal [12,13, childhood experienced a greater increase in both general depression
34,42] and hippocampal circuits [19]. Disruption of both circuits are symptoms and anhedonia, from before to after military deployment and
linked to anhedonia and depression symptoms [14], and these circuits from immediately after military deployment to approximately a decade
are sensitive to early-life adversity effects across species [50,32]. These later. The effect of childhood unpredictability on depression symptoms
circuits are also important for social behavior and reward [65], sug­ was mediated by lower perceived social support in both the short-term
gesting they could contribute to the observed relationship between and long-term following return from deployment, as well as by greater
childhood adversity, social support and risk for depression and anhe­ disruptions in psychosocial functioning during the civilian reintegration
donia. Hippocampal volume is also inversely related to social support in period. Overall, this study offers further evidence that childhood
adults who had experienced other forms of childhood adversity [21], unpredictability contributes to the development of depression symp­
and hippocampal abnormalities have been linked to disruptions in a toms and builds upon the results of previous investigations by shedding
range of social processes (e.g., tracking dynamic social behavior, light on the possible psychosocial factors through which childhood
remembering social rules) that could lead to diminished engagement in unpredictability confers risk for later depression. Future research should
support networks [41]. Further research is needed to understand if these aim to replicate this work with prospective measures of childhood
(or other) circuits or others mediate the observed links between child­ unpredictability, examine mediating brain circuitry, and compare the
hood unpredictability and subsequent increases in depression effect of childhood unpredictability on depression development between
symptoms. men and women. Clinically, these results could ultimately inform novel
strategies for preventing depressive disorders that involve increasing the
4.1. Limitations structure and predictability of childhood routines as well as developing
social support interventions after life stressors.
Results of the present study must be considered in light of several
important limitations. First, childhood unpredictability was assessed

8
C. Hunt et al. Journal of Mood and Anxiety Disorders 6 (2024) 100045

Declaration of Competing Interest [18] Davis EP, Korja R, Karlsson L, Glynn LM, Sandman CA, Vegetabile B, et al. Across
continents and demographics, unpredictable maternal signals are associated with
children’s cognitive function. EBioMedicine 2019;46:256–63. https://doi.org/
VBR has received consulting fees from Engrail and Fallon Capital in 10.1016/j.ebiom.2019.07.025.
the last 36 months. All other authors report no disclosures or conflicts of [19] Davis EP, McCormack K, Arora H, Sharpe D, Short AK, Bachevalier J, et al. Early
interest. life exposure to unpredictable parental sensory signals shapes cognitive
development across three species. Front Behav Neurosci 2022;16:960262.
[20] Dour HJ, Wiley JF, Roy-Byrne P, Stein MB, Sullivan G, Sherbourne CD, et al.
Acknowledgements Perceived social support mediates anxiety and depressive symptom changes
following primary care intervention. Depress Anxiety 2014;31(5):436–42.
[21] Förster K, Danzer L, Redlich R, Opel N, Grotegerd D, Leehr EJ, et al. Social support
Support for this work includes NIMH P50MH096889 (DGB, VBR), and hippocampal volume are negatively associated in adults with previous
the Office of Academic Affiliations, Advanced Fellowship Program in experience of childhood maltreatment. J Psychiatry Neurosci 2021;46(3):328–36.
Mental Illness Research and Treatment, Department of Veterans Affairs [22] Glynn LM, Baram TZ. The influence of unpredictable, fragmented parental signals
on the developing brain. Front Neuroendocrinol 2019;53:100736.
(MV, CH), BLR&D VA Research Career Scientist Award (VBR), and the [23] Glynn LM, Davis EP, Luby JL, Baram TZ, Sandman CA. A predictable home
Center of Excellence for Stress and Mental Health (MV, CH, BC, DGB, environment may protect child mental health during the COVID-19 pandemic.
VBR). Neurobiol Stress 2021;14.
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10.1016/j.jad.2017.11.065.
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Supplementary data associated with this article can be found in the
Measuring novel antecedents of mental illness: the Questionnaire of
online version at doi:10.1016/j.xjmad.2023.100045. Unpredictability in Childhood. Neuropsychopharmacology 2019;44(5):876–82.
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