Psychoneuroendocrinology 143 (2022) 105826

Contents lists available at ScienceDirect

Psychoneuroendocrinology
journal homepage: www.elsevier.com/locate/psyneuen

Psychobiological foundations of coping and emotion regulation: Links to

maltreatment and depression in a racially diverse, economically
disadvantaged sample of adolescent girls
Jason José Bendezú a, c, *, Elizabeth D. Handley b, Jody T. Manly b, Sheree L. Toth b,
Dante Cicchetti a
a
The Institute of Child Development, University of Minnesota, USA
b
Mt. Hope Family Center, University of Rochester, USA
c
Department of Psychology, University of Minnesota, USA

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

Keywords: Adolescent risk for depression and passive or active suicidal ideation (PASI) involves disturbance across multiple
Maltreatment systems (e.g., arousal regulatory, affective valence, neurocognitive). Exposure to maltreatment while growing up
Cortisol as a child or teenager may potentiate this risk by noxiously impacting these systems. However, research
C-reactive protein
exploring how coordinated disturbance across these systems (i.e., profiles) might be uniquely linked to
Adolescent
depressogenic function, and how past maltreatment contributes to such disturbance, is lacking. Utilizing a
Cognitive reappraisal
racially diverse, economically disadvantaged sample of adolescent girls, this person-centered study identified
psychobiological profiles and linked them to maltreatment histories, as well as current depressive symptoms and
PASI. Girls (N = 237, Mage=13.98, SD=0.85) who were non-depressed/non-maltreated (15.1%), depressed/non-
maltreated (40.5%), or depressed/maltreated (44.4%) provided morning saliva samples, completed question­
naires, a clinical interview, and a neurocognitive battery. Latent profile analysis of girls’ morning cortisol:C-
reactive protein ratio, positive and negative affect levels, and attentional set-shifting ability revealed four pro­
files. Relative to Normative (66.6%), girls exhibiting a Pro-inflammatory Affective Disturbance (13.1%), Severe
Affective Disturbance (10.1%), or Hypercortisol Affective Neurocognitive Disturbance (n = 24, 10.1%) profile re­
ported exposure to a greater number of maltreatment subtypes while growing up. Girls exhibiting these dysre­
gulated profiles were also more likely (relative to Normative) to report current depressive symptoms (all three
profiles) and PASI (only Pro-inflammatory Affective Disturbance and Hypercortisol Affective Neurocognitive Distur­
bance). Of note, girls’ cognitive reappraisal utilization moderated profile membership–depression linkages
(depressive symptoms, but not PASI). A synthesis of the findings is presented alongside implications for person-
centered tailoring of intervention efforts.

1. Introduction (Congressional Black Caucus, 2019; NIMH NOT-MH-21–1 202 020),

Adolescence is characterized by elevated rates of depressive symp­
toms and related symptomatology (e.g., passive of active suicidal idea­
tion, PASI; Nock et al., 2013). This may especially be the case for girls,
given their increased sensitivity to relational stressors (Hankin et al.,
2007) and developmental differences in arousal regulatory, affective,
and neurocognitive function (Beauchaine et al., 2019; Shields et al.,
2017; Slavich and Sacher, 2019). Recent reports have pointed to a
precipitous rise in depression among Black girls in particular
who are three times more likely to report depression-related sequela
than Black boys (Fitzpatrick et al., 2008). Utilizing a racially diverse,
economically disadvantaged sample of adolescent girls, the current
study aimed towards (a) a more nuanced understanding of the multi­
system etiology of girls’ risk for depressive symptoms and PASI, (b)
those relational stressors that contribute to such etiology, and (c) to
identify putative psychosocial buffers to be leveraged in the design of
more effective interventions.

* Correspondence to: Department of Psychology, S463 Elliott Hall, University of Minnesota, Minneapolis, MN 55455, USA.
E-mail address: bende369@umn.edu (J.J. Bendezú).

https://doi.org/10.1016/j.psyneuen.2022.105826
Received 10 February 2022; Received in revised form 2 June 2022; Accepted 3 June 2022
Available online 8 June 2022
0306-4530/© 2022 Elsevier Ltd. All rights reserved.

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J.J. Bendezú et al.
1.1. Psychobiological Function and Depressive Symptomatology
Despite conceptualizations of adolescent risk for depression as
involving coordinated disturbance across arousal regulatory, affective,
and neurocognitive systems (Cha et al., 2019; Glenn et al., 2017),
empirical studies have yet to provide an integrative understanding of
how risk coalesces across these levels of analysis (Cicchetti and Dawson,
2002). Researchers have cited an over-reliance on single system ap­
proaches as a contributor to this empirical ambiguity (Hostinar et al.,
2021), examining systems in isolation or analyzing between-group dif­
ferences in the outcome of interest (e.g., MDD vs. No MDD) across sys­
tems. These studies have been useful in pointing to elevated negative
affect and emotionality (Enns et al., 2003; Fergusson et al., 2000), low
hedonic capacity (Auerbach et al., 2015), executive function deficits (e.
g., poor attentional control and set shifting ability; Wilkinson and
Goodyer, 2006), and dysregulated immuno-endocrine functioning (e.g.,
low cortisol:C-reactive protein (CRP) ratio reflective of pro-inflammatory
state, Suarez and Sundy, 2017; high cortisol:CRP ratio reflective of
hypercortisolemia, Landau et al., 2021) as potential etiological mecha­
nisms. Here, we propose that a person-centered approach (Cicchetti and
Rogosch, 1996; Warmingham et al., 2019) that spans these levels may
provide additional nuanced detail of how coordinated psychobiological
risk manifests within adolescent girls.
1.2. Psychobiological function and maltreatment history
The caregiver-youth relationship is one context in which some chil­
dren experience acute and chronic forms of relational stress. Child
maltreatment, specifically (i.e., severely adverse childhood experiences
such as emotional, sexual, and physical abuse, as well as physical and
emotional neglect; Cicchetti and Toth, 2016), is known to potentiate risk
for depressive symptoms (Humphreys et al., 2020) and PASI (Duprey
et al., 2021). Rates of child maltreatment are approximately twice as
high for Black relative to White youth (Sedlak et al., 2010), with studies
pointing to systemic biases in reporting systems as contributors (e.g.,
suspected maltreatment for Black youth is more likely to be reported,
proceed to investigation, and be substantiated; Detlaff & Boyd, 2020).
Also, Black youth with a history of maltreatment are more than five
times as likely to report suicidality relative to those without (Fitzpatrick
et al., 2008). Evidence suggests that one salient manner by which past
maltreatment confers the risk is via insults sustained to youth psycho­
biological function. A history of maltreatment is known to contribute to
dysregulated hypothalamic-pituitary-adrenal (HPA) axis and immune
system processes (Coelho et al., 2014; Doom et al., 2013), affect dys­
regulation (Courtney-Seidler et al., 2014; Crowell et al., 2009), and
impaired neurocognitive function (Cowell et al., 2015; Valentino et al.,
2009). However, similar to the depression etiology literature, much of
this work has examined these systems in isolation as well as by
comparing youth with and without a history of maltreatment. As such,
whether past maltreatment exposure contributes to heterogeneity in
coordinated psychobiological function is not yet known.
1.3. Psychobiological foundations of coping and emotion regulation
From a coping and emotion regulation perspective, the manner by
which past maltreatment contributes to emerging risk for psychopa­
thology may be through adolescents’ compromised ability to effica­
ciously mange stressors or their involuntary stress responses to them (e.
g., emotional reactivity, rumination). Indeed, evidence increasingly
suggests that maltreatment exposure may contribute to this risk by
noxiously affecting the psychobiological substrates that support coping
and emotion regulation and, thus, constrain efficacious strategy use
(Gruhn and Compas, 2020). As noted by Cicchetti and Bendezú (in
press) and others (Compas et al., 2017), a more nuanced understanding
of the psychobiological foundations of coping and emotion regulation is
needed. Attention to specific aspects of executive function (e.g.,
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Psychoneuroendocrinology 143 (2022) 105826
attentional control, set shifting) may highlight foundations that avail
adolescents the use of more sophisticated regulatory strategies (e.g.,
cognitive reappraisal, McRae et al., 2010). However, such a depiction is
likely to be incomplete without concomitantly considering affective and
arousal regulatory processes also requisite for efficacious coping and
emotion regulation.
In healthy individuals, affective experience such as moderate nega­
tive affect helps orient a person to a source of stress (e.g., stressor, in­
ternal response to a stressor) and prompts the need to take action (Selye,
1936). Arousal regulatory processes such as well-orchestrated immu­
no-endocrine function (e.g., healthy cortisol suppression of inflamma­
tion) mobilize physiological resources needed to take action without the
onset of sickness behaviors that might impede such action (Slavich and
Irwin, 2014). Executive functions such as attentional control and
cognitive flexibility support coping efforts insofar as they help a person
shift attention away from a negative affect-inducing stressor or think
differently about a stressor in a way that induces positive affect
(Eisenberg and Zhou, 2016). For maltreated individuals, dysregulation
across these multiple systems may increase risk for depression by
making it difficult to effectively cope with stress or regulate emotions.
For example, high negative affect and low positive affect may contribute
to attentional biases that interfere with accurate stressor detection
(Peckham et al., 2010). Excessive cortisol production that suppresses
immune system function (e.g., cellular immunity) may result in an
immunocompromised state that hampers ability to manage stressors
(Shields et al., 2017). Insufficient cortisol production relative to in­
flammatory activity may promote fatigue and withdrawal behavior in
place of active coping (Slavich and Irwin, 2014). Inability to shift one’s
attention or perspective may contribute to perseveration on a stressor
and limit cognitive access to alternate coping options (Uddin, 2021).
Whether profiles of psychobiological function may be more (e.g.,
healthy) or less (e.g., unhealthy, linked to maltreatment) amenable to
the use of specific strategies and, thereby, decrease or increase depres­
sogenic function (Bendezú et al., 2021a, 2021b) is not yet known.
Identification of such profiles may inform the tailoring of treatment
efforts to girls’ psychobiological strengths and weaknesses.
1.4. The current study: aims and hypotheses
The current study had the following aims and hypotheses. Aim 1.
Explore within-person patterns (i.e., profiles) of immuno-endocrine (i.e.,
cortisol:CRP ratio1), affective (i.e., self-reported positive (PA) and
negative (NA) affect), and neurocognitive (i.e., attentional set shifting)
function in a racially diverse, economically disadvantaged sample of
adolescent girls. Based on existing maltreatment, depression, and
emotion regulation research in the developmental psychobiology liter­
ature,2 we expected to identify two profiles: Normative (e.g., moderate
cortisol:CRP ratio, low NA, high PA, high attentional set shifting),
Multisystem Disturbance (e.g., high or low cortisol:CRP ratio, high NA,
1
Use of the cortisol:CRP ratio is relatively new and consensus on what a low
versus high ratio represents has not yet been reached (Landau et al., 2021).
However, we argue that including the cortisol:CRP ratio in a person-centered
framework such as ours has the potential to provide additional clarity insofar
as profiles of psychobiological function allow the cortisol:CRP ratio to connect
with affective and neurocognitive function within persons, perhaps in ways that
might compliment or extend current interpretation.
2
Our focus on these specific indices was also informed by evidence of their
association with all three of our focal study variables: maltreatment (e.g., affect,
Courtney-Seidler et al., 2014; attentional set-shifting, Gould et al., 2012;
cortisol and C-reactive protein, Doom et al., 2013; Ehrlich et al., 2021),
depressogenic function (e.g., affect, Enns et al., 2003; attentional set-shifting,
Wilkinson and Goodyer, 2006; cortisol and C-reactive protein, Landau et al.,
2021), cognitive reappraisal (e.g., affect, Andreotti et al., 2013; attentional
set-shifting, Eisenberg and Zhou, 2016; cortisol and C-reactive protein; Johnson
et al., 2019).
J.J. Bendezú et al.
low PA, low attentional set shifting). However, we also explored the
possibility of additional profiles that previous research may have over­
looked due to reliance on single-system approaches and predetermined
patterns. Aim 2. Examine maltreatment history as a correlate of profile
membership. We expected the likelihood of membership in Multisystem
Disturbance (relative to Normative) to increase with a history of expo­
sure to a greater number of maltreatment subtypes. Aim 3. Examine
profile membership to depression linkages and cognitive reappraisal as a
moderator of those linkages. We expected girls with Multisystem
Disturbance (relative to Normative) profiles to report greater current
depressive symptoms and PASI. We expected reappraisal to moderate
profile membership to depression linkages, such that reappraisal would
be associated with lower depressive symptoms and decreased likelihood
of PASI for girls with Normative profiles, and not associated (i.e., stably
elevated) or positively associated with depressive symptoms and PASI (i.
e., stably high likelihood) for girls with Multisystem Disturbance
profiles.
2. Method
2.1. Participants
Adolescent girls (N = 237, Mage=13.98, SD=0.85) were recruited
from an urban setting in upstate New York to participate in a random­
ized control trial of a depression intervention. We utilized data from the
larger study’s baseline assessment. Participants consisted of three
different groups: girls with subsyndromal symptoms of depression or
who met criteria for clinical depression with (MDD/MAL; 44.4%) and
without (MDD/NO MAL; 40.5%) a history of maltreatment, and controls
who were non-depressed and non-maltreated (NO MDD/NO MAL;
15.1%). Most girls were Black (62.4%), followed by White (23.2%),
multiracial (3.8%), Asian (0.4%), American Indian or Alaskan Native
(0.4%), and Other (6.8%). Also, 12.2% of girls were Latina. Average
annual household income was $28 353 (SD=$12 734).
2.2. Procedures
All study procedures were approved by the University’s Institutional
Review Board (IRB). As described in detail elsewhere (MASKED et al.,
2018), informed consent and assent were obtained from parents and
girls, respectively. By design, all families participating in the study were
required to be eligible for Temporary Assistance to Needy Families
(TANF). Efforts to recruit girls with a history of maltreatment included
collaborations with University Medical Center’s pediatric social
workers, local schools and mental health organizations, and a liaison in
the Department of Human Services (DHS) who examined Child Protec­
tive Services (CPS) reports for histories of maltreatment. Collaborators
at these various institutions contacted potentially eligible families.
Interested parents signed a release allowing their contact information to
be shared with study staff. Nonmaltreating families were also recruited
from a pool of participants similarly eligible for TANF. Restricting in­
come enabled examination of variability in maltreatment-related phe­
nomena without the potentially overriding contributions of
socioeconomic status (Sedlak et al., 2010). To ensure the integrity of the
data (e.g., variation due to reading ability and literacy), interviews and
questionnaires were read to participants, who read along and marked
their own answers. Interviewers were graduate students of clinical
psychology and post-bac research assistants. In addition to coursework
in cultural competency as part of their clinical training, graduate stu­
dents received training on cultural sensitivity via our standard research
protocol given our population, as did post-bac research assistants.
Questionnaires were checked by interviewers to ensure that items were
not skipped and that answers marked by participants were matched to
the appropriate item. Neuropsychological tests were nonverbal,
administered with touchscreen technology, with instructions read to
participants. Girls and their mothers were interviewed concurrently in
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Psychoneuroendocrinology 143 (2022) 105826
different rooms.
2.3. Primary measures
2.3.1. Immuno-endocrine regulation
Girls collected saliva samples on two consecutive weekdays via
Trident stimulated passive drool immediately upon waking
(Mwake_time=7:43 am, SD=2:12), circumventing morning cortisol waking
response (Susman et al., 2007) and morning routine (e.g., food or drink
consumption, tooth brushing, smoking) data contamination. The deci­
sion to utilize morning cortisol and CRP was motivated by a desire to
keep methodologically consistent with the only study to date that has
examined the cortisol:CRP ratio with saliva in relation to depression in
an adolescent sample (Landau et al., 2021). Girls stored samples in their
home refrigerators they could be collected by study staff and stored in a
medical grade ultra-low temperature freezer (− 40◦ C). Samples were
shipped on dry ice to Salimetrics Laboratories (State College, PA) for
assay. Salivary cortisol (µg/dl) and C-reactive protein (CRP) (pg/mL)
were assayed using an enzyme immunoassay kit (Salimetrics, State
College, PA). The average intra- and inter-assay coefficient of variation
for cortisol and CRP were < 5.0%, 10.0% and 10.0%, 15.0%, respec­
tively. Biomarker levels on each consecutive weekday were averaged to
create single cortisol (Cortave) and CRP (CRPave) indices.
2.3.2. Affect
Girls reported on the frequency of certain feelings and emotions in
the past two weeks using the Positive and Negative Affect Scale for
Children (PANAS-C; Laurent et al., 1999). Positive affect (PA) and
negative affect (NA) scores were computed by averaging across 12 PA
items (Interested, Excited, Happy, Strong, Energetic, Calm, Cheerful,
Active, Proud, Joyful, Delighted, Lively; α = 0.92) and 15 NA items (Sad,
Frightened, Ashamed, Upset, Nervous, Guilty, Scared, Miserable, Jittery,
Afraid, Lonely, Mad, Disgusted, Blue, Gloomy; α = 0.89). Higher scores
reflect greater frequency of experienced PA and NA.
2.3.3. Neurocognitive function
Girls were administered the Cambridge Neuropsychological Test
Automated Battery (CANTAB Eclipse, Cambridge Cognition, Cambridge,
UK). CANTAB tests several neurocognitive processes and executive
functions. We utilized the Intradimensional–Extradimensional (IDED)
Set Shifting module, which tests capacity for attentional set formation,
and the maintenance, shifting, and flexibility of attention. The module
consists of nine stages. Participants complete a stage after providing six
consecutive correct responses (i.e., establishing an attentional set).
Stage 1 consists of simple discrimination (SD), where participants must
correctly choose one of two stimuli of same dimension (e.g. “color-filled
shapes”). Stage 2 consists of simple reversal (SR), where contingencies
change and the previously correct stimuli is now incorrect. Stage 3
consists of compound discrimination (C_D), where the second dimension
is introduced (e.g., “white line”) as a distractor and the participant must
continue selecting the previously correct stimuli. At Stage 4, stimulus
complexity increases as stimuli from the second dimension become
superimposed on the stimuli from the first dimension. Stage 5 consists of
compound discrimination reversal (CDR), where the stimulus from the
first dimension with a superimposed stimulus from the second dimen­
sion that was previously incorrect now becomes the correct choice.
Stage 6 consists of an intra-dimensional shift (IDS), where participants
are presented with new versions of the stimuli from the two dimensions.
Participants must continue to correctly select the stimuli from the first
dimension. Stage 7 consists of an intra-dimensional shift reversal (IDR),
where participants must correctly select the previously incorrect stimuli
from the first dimension. Stage 8 consists of an extra-dimensional shift
(EDS), where participants are again presented with new versions of the
stimuli from the two dimensions. Here, participants must shift attention
from the first dimension to the second dimension, choosing the correct
stimuli from the second dimension rather than attempting to choose one
J.J. Bendezú et al.
of the two stimuli from the now incorrect first dimension. Stage 9 con­
sists of an extra-dimensional shift reversal (EDR), where participants
must shift the focus of their selection back to stimuli from the previously
incorrect first dimension. The module terminates when a participant
completes all nine stages or when the participant fails to establish an
attentional set on any given stage after 50 trials. We utilized number of
stages completed as an index of attentional set-shifting ability (M=8.21,
SD=1.21, Min=2.00, Max=9.00).
2.3.4. Maltreatment history
Girls completed the Childhood Trauma Questionnaire (CTQ; Bern­
stein et al., 2003), a 28-item measure assessing girls’ experiences of
maltreatment, abuse, and neglect as a child and teenager while growing
up. Girls rated a series of statements about specific maltreatment ex­
periences on a 5-point scale (1 =never true, 5 =very often true).
Maltreatment subtypes include emotional abuse (e.g., “People in my
family called me things like stupid, lazy, or ugly.”), physical abuse (e.g.,
“People in my family hit me so hard that it left me with bruises or
marks.”), sexual abuse (e.g., “Someone tried to touch me in a sexual way,
or tried to make me touch them.”), emotional neglect (e.g., “I thought
that my parents wished I had never been born.”), and physical neglect (e.
g., “I did not have enough to eat.”). Subscales demonstrated good in­
ternal consistency (α = 0.71–0.96). Following Walker et al. (1999),
severity ratings for each subtype were dichotomized to indicate whether
adolescents reported clinically significant maltreatment: emotional
abuse (nyes=63), physical abuse (nyes=55), sexual abuse (nyes=30),
emotional neglect (nyes=28), physical neglect (nyes=34). A count vari­
able was created by summing the number of maltreatment subtypes
experienced.
2.3.5. Cognitive reappraisal
Girls reported on their regulatory strategy use using the Emotion
Regulation Questionnaire (ERQ; Gross and John, 2003). The scale in­
cludes 10 Likert-type items (1 =Strongly Disagree, 4 =Strongly Agree).
Six items assess cognitive reappraisal (e.g., “I control my feelings about
things by changing the way I think about them.”, α = 0.74) and four
items assess expressive suppression (e.g., “I control my feelings by not
showing them.”, α = 0.67). Researchers have observed that certain
children (e.g., stress-affected, emotional and behavioral difficulties,
girls) tend toward greater overall endorsement of strategy utilization
items and have, thus, recommended the use of ratio scores to account for
such potential differences in item endorsement base rates (Connor-­
Smith et al., 2000; Hilt et al., 2010). As such, we divided the cognitive
reappraisal score (i.e., average of cognitive reappraisal items) by the
sum of all scale item ratings. The resulting ratio score reflects the pre­
dominance of cognitive reappraisal utilized as a strategy for managing
stressors and difficult emotions.
2.3.6. Depressive symptoms
Girls reported on current depressive symptoms using the Beck
Depression Inventory for Youth (BDI-Y; Beck et al., 2005). The scale
includes 20 items (0 =Never, 3 =Always). Raw total scores (α = 0.93)
were converted to T-scores to ensure scale rating integrity.
2.3.7. Passive or active suicidal ideation (PASI)
Girls and a parent reported on the frequency of girls’ current
thoughts of death (e.g., “Sometime children who get upset or feel bad,
wish they were dead or feel they’d be better off dead.”) and suicide (e.g.,
“Sometimes children who get upset or feel bad think about dying or even
killing themselves.”) via the Kiddie Schedule for Affective Disorders and
Schizophrenia-Present and Lifetime Version (K-SADS–PL; Kaufman
et al., 1997). Consensus was established across interviews and the
summary score was used. PASI (nyes=55) was indicated by a threshold (i.
e., “recurrent”) summary score of the frequency of thoughts of death or
suicide.
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Psychoneuroendocrinology 143 (2022) 105826
2.4. Covariates
Covariates include chronological age, pubertal status, income to
needs ratio (INR), body mass index (BMI), medication use, and morning
saliva sample time. Though chronological age is confounded with pu­
bertal status, it also affects HPA and immune system function in ways
not directly accounted for by reproductive hormones (e.g., regulatory
gland size and structure; Linton and Dorshkind, 2004). Chronological
age was, thus, controlled for in Aims 2 and 3 analyses. Girls completed
the Pubertal Development Scale (Petersen et al., 1988), which consists of
five Likert type items (1 =no development, 4 =development seems
complete) about physical development, including body hair, skin
changes, growth spurt, breast development and menarche (dichoto­
mous). A mean score (M=3.35, SD=0.48) was computed across items (α
= 0.62). Given that poverty has been linked to immuno-endocrine
dysregulation (for review, see Jensen et al., 2017) and executive func­
tion deficits (for review, see Blair and Raver, 2016), we controlled for
INR in Aims 2 and 3 analyses. INR is an index of household income
relative to national poverty line norms (adjusted for number of family
members residing in the household). Middle-income family INR ranges
between 2.0 and 4.0 while an INR of 1.0 is indicative of poverty (Duncan
et al., 1993; Evans and Marcynyszyn, 2004). Though the sample was low
income, an examination of INR descriptive statistics suggested that there
was variability with respect economic disadvantage to be considered
(M=1.13, SD=0.49). Though 45.4% of the sample lived at or below the
poverty line, 44.0% of families lived above the poverty line, with 10.6%
of families approaching or meeting middle income status cutoffs. As
obesity is also associated with a number of our study variables (e.g.,
inflammation, executive function; Spyridaki et al., 2016; Yang et al.,
2018), we controlled for BMI in Aims 2 and 3 analyses. Girls’ height and
weight were obtained during their study visit. Age-specific BMI per­
centiles calculated following Center for Disease Control (CDC) guide­
lines (M=81.93, SD=20.27). Medications known to influence
immune-endocrine function or saliva collection were noted (e.g., corti­
costeroids, anxiolytics, mood stabilizers, selective serotonin reuptake
inhibitors, birth control; Granger et al., 2009). A dichotomous variable
was created for girls who were (yes=1) and were not (no=0) taking such
medications (nyes=47). Because wake time can impact morning cortisol
levels (Kudielka and Kirschbaum, 2003), we controlled for girls’ waking
saliva sample time in Aims 2 and 3 analyses.
2.5. Data preparation
2.5.1. Cortisol:CRP ratio
As per Suarez and Sundy (2017), we divided Cortave by CRPave and
the resulting ratio was log10 transformed for latent profile analysis. No
outliers (+/- 3 SDs from the grand mean) were noted in the transformed
cortisol:CRP ratio variable.
2.5.2. IDED set-shifting
A ceiling effect emerged for IDED Set Shifting – stages completed,
which has been observed in other studies of adolescent mood disorders
(e.g., Dickstein et al., 2007; Dickstein et al., 2016). In all, 61.2% of girls
completed Stage 9, 7.5% completed only up to Stage 8 (i.e., did not
complete Stage 9), 29.3% completed only up to Stage 7 (i.e., did not
complete Stage 8 or 9), 0.7% completed only up to Stage 4, and 1.4%
completed only up to Stage 2. Following Leeson et al. (2009) as well as
others (Barnett et al., 2005; Jazbec et al., 2007), a “pass/fail” variable
was created (0 = module not completed, 1 = module completed). Given
that the majority of participants who did not complete the IDED module
had difficulty completing Stages 7 and 8 which consists of the
extra-dimensional (ED) shift, our dichotomized IDED variable can be
thought to reflect attentional set-shifting proficiency and inefficiency
with respect to ED set-shifting ability in particular. This dichotomous
variable was modeled as a categorical indicator in our latent profile
analyses.
J.J. Bendezú et al.
2.6. Overview of analyses
2.6.1. Aim 1
To identify subgroups of girls with unique psychobiological profiles,
latent profile analysis (LPA) via MPLUS (Version 8; Muthén & Muthén,
1998–2017) was used and classified girls based on the extent to which
they exhibited similar within-person patterns of psychobiological func­
tion across our four indicators of interest: cortisol:CRP ratio, negative
affect, positive affect, IDED set shifting. Model specification began with
a one-class solution and additional, more complex solutions (e.g.,
two-class, three-class) were evaluated across a series of model fit sta­
tistics: Akaike information criterion (AIC; Akaike, 1973), Bayesian in­
formation criterion (BIC; Schwarz, 1978), adjusted Bayesian
information criterion (adjusted BIC; Sclove, 1987). Simulations studies
have demonstrated BIC and Adjusted BIC to be conservative fit statistics
for determining superior class specification (Magidson and Vermunt,
2004; Yang, 2006), with lower values indicating the most optimal so­
lution. The entropy statistic was also utilized during model specification
(Celeux and Soromenho, 1996), with values approaching 1 indicative of
a superior solution. Though we expected to identify at least two profiles,
we allowed both theory and model fit indices to guide us to the most
informative solution (e.g., 3-profile, 4-profile; Masyn, 2013; Tein et al.,
2013). At present, there are no firm guidelines on determining the
appropriateness of subgroup size in LPA. However, LPA methodologists
have previously suggested that subgroup sizes should not be smaller
than 5% of the overall sample size (Weller et al., 2020). Once specified,
girls were categorized into subgroups based on the highest posterior
probability of class membership. After categorization, distinction ana­
lyses comparing mean indicator levels across systems and subgroups
helped to characterize the profiles and informed our labeling
conventions.
2.6.2. Aim 2
Multinomial logistic regression was used to examine number of
maltreatment subtypes as a correlate of profile membership. Simulation
studies have shown that examining correlates of categorical profile
membership (i.e., assigning participants to subgroups based on the
highest posterior probability of class membership) is suitable for latent
profile analysis solutions with an entropy greater than .80 (Clark and
Muth´en, 2009). Study covariates (e.g., age, pubertal status, INR, BMI,
medication use, and morning saliva sample time) and number of
maltreatment subtypes were examined in a single model.
2.6.3. Aim 3
Three regression models were used to examine a) profile member­
ship to depressive symptoms (multiple linear regression) and PASI (lo­
gistic regression) linkages, and b) cognitive reappraisal as a moderator
of those linkages. As a more stringent test of the predictive capacity of
our identified profiles, the number of maltreatment subtypes girls
experienced was also included as a covariate in addition to our estab­
lished set of study covariates.3 In two initial models, profile membership
and cognitive reappraisal were examined independently as predictors.
3
Aim 3 analyses included a small group of non-depressed, non-maltreated
girls (15.1%). These girls were included in our Aim 1 and 2 analyses given our
interest in identifying potentially well-regulated and dysregulated psychobio­
logical profiles and linking those profiles to maltreatment history. While
including number of maltreatment subtypes as covariate in models predicting
depression poses certain methodological issues when including this small group
of girls (i.e., conflation by design as they were both non-depressed and non-
maltreated), our aim was less focused on predicting depression via maltreat­
ment and more focused on examining the contribution of our identified profiles
to depression beyond that accounted for by maltreatment. Also, Aim 3 analyses
conducted with this group removed returned similar results and did not alter
conclusions. Thus, this group was retained in our Aim 3 analyses.
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Psychoneuroendocrinology 143 (2022) 105826
In our final model, profile membership by cognitive reappraisal (grand
mean centered) interactive effects were examined.
2.6.4. Post-hoc analyses
To shed light on ways that a multisystem, person-centered approach
provided unique information relative to conventional methods, we
compared girls with and without maltreatment histories on our study
variables of interest. Specifically, we conducted t-tests comparing these
two groups on our psychobiological indicators, cognitive reappraisal,
and depressive functioning.
3. Results
Results are organized by study aim. Descriptive statistics and
bivariate correlations for key study variables are presented in Table 1.
Cortisol levels across days were positively correlated, as were CRP
levels. With the exception of positive and negative affect, which were
inversely correlated, no significant between-person correlations across
our psychobiological indicators of interest emerged, further supporting
our aim of examining within-person profiles of psychobiological func­
tioning. Negative affect was positively correlated with number of
maltreatment subtypes, depressive symptoms, and PASI. Positive affect
was not associated with number of maltreatment subtypes, but nega­
tively correlated with depressive symptoms and PASI. Cortisol, CRP, and
IDED set shifting were not correlated with number of maltreatment
subtypes, depressive symptoms, or PASI. Cognitive reappraisal was
positively correlated with positive affect and negatively correlated with
negative affect, number of maltreatment subtypes and depressive
symptoms. Depressive symptoms were positively correlated with PASI.
3.1. Aim 1: psychobiological foundation profiles
LPA model specification supported a four-profile solution (Table S1,
see supplementary materials). Model fit indices did not uniformly settle
on a single solution. As recommended (Masyn, 2013; Tein et al., 2013),
we utilized both theory and model fit indices as conceptual and statis­
tical guide posts and determined that the four profile solution was most
informative. Profile specific means and standard deviations for each
continuous indicator in each profile are presented in Table S2 (see
supplementary materials). Proportions are reported for binary in­
dicators in each profile (e.g., proportion of participants completing the
IDED set-shifting module). To aid interpretation of the cortisol:CRP
ratio, raw and standardized cortisol and CRP levels for each profile are
presented in Table S3 (see supplementary materials). Profile specific
deviations from the sample mean or probability for continuous and bi­
nary indicators, respectively, in each profile are graphically depicted in
Fig. 1. The Normative profile was consistent with expectation, the largest
of all groups (n = 15 866.6%), and characterized by moderate cortisol:
CRP ratio levels, low negative affect levels, high positive affect levels,
and moderate probability of completing the IDED set-shifting module.
Three smaller subgroups emerged whose profiles reflected various
within-person patterns of psychobiological dysregulation. The Pro-in­
flammatory Affective Disturbance profile (n = 31, 13.1%) was character­
ized by the lowest cortisol:CRP ratio levels in the sample, high negative
affect levels, low positive affect levels, but also the highest probability of
completing the IDED set-shifting module in the sample. The Severe Af­
fective Disturbance subgroup (n = 24, 10.1%) was characterized by
moderate cortisol:CRP ratio levels, the highest negative affect and
lowest positive affect levels in the sample, and moderate probability of
completing the IDED set-shifting module. The Hypercortisol Affective
Neurocognitive Disturbance (n = 24, 10.1%) subgroup was characterized
by the highest cortisol:CRP ratio levels in the sample, high negative
affect levels, moderate positive affect levels, and the lowest probability
of completing the IDED set-shifting module in the sample.
J.J. Bendezú et al. Psychoneuroendocrinology 143 (2022) 105826

Table 1
Descriptives and Correlations for Key Study Variables.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

1. Cortisol (µg/dl) – day 1 —

2. Cortisol (µg/dl) – day 2 0.43 * —
3. CRP (pg/mL) – day 1 -0.11 -0.07 —
4. CRP (pg/mL) – day 2 -0.11 -0.07 0.60 * —
5. Negative affect -0.01 0.04 -0.04 -0.08 —
6. Positive affect 0.01 0.04 -0.06 -0.04 -0.28 * —
7. IDED set-shiftinga -.11 -0.06 0.08 0.05 -0.04 -0.08 —
8. Maltreatment subtypes -0.03 0.08 -0.05 -0.07 0.36 * -0.17 0.02 —
9. Cognitive reappraisal 0.04 0.03 -0.07 -0.11 -0.19 * 0.35 * -0.04 -0.28 * —
10. Depressive symptoms 0.06 0.02 -0.05 -0.02 0.67 * -0.37 * -0.08 0.37 * -0.35 * —
11. PASIa .11 0.02 0.01 -0.03 0.39 * -0.21 * -0.14 0.19 * -0.17 0.45 * —
Means (Proportions) 0.33 0.30 6419.07 6613.28 1.90 3.11 (0.61) 0.91 0.55 48.94 (0.23)
SD 0.24 0.23 15,104.7 17,629.2 0.68 0.68 0.49 1.28 0.08 12.06 0.42
Min 0.01 0.02 102.60 135.11 1.00 1.08 0.00 0.00 0.25 34.00 0.00
Max 1.49 1.29 115,322.7 181,512.4 4.00 5.00 1.00 5.00 0.78 100.00 1.00

Note. CRP = C-reactive protein; IDED = Intra Dimensional-Extra Dimensional, PASI = Passive or active suicidal ideation. IDED set-shifting coded 0 for “module not
completed” and 1 for “module completed.” PASI coded 0 for “not indicated” and 1 for “indicated.”
a
= Spearman’s Rho
*p < .05.

Fig. 1. Profile specific deviations from the sample mean for psychobiological indices.

3.2. Aim 2: maltreatment history correlates of psychobiological

Table 2
foundation profiles
Odds Ratios (95% Lower CI, 95% Upper CI) for Multinomial Logistic Regressions
Predicting Profile Membership.
Parameter estimates for our multinomial logistic regression models
Comparison Pro-inflammatory Severe Hypercortisol
are shown in Table 2. Medication use and saliva sample time were not
Profile Affective Affective Affective
associated with our dependent variables in Aim 2 or 3 analyses and Disturbance Disturbance Neurocognitive
were, thus, removed in the interest of model parsimony.4 The Normative Disturbance
profile (i.e., largest, healthy) was used as the reference profile. Our co­ Age 1.08 (0.65, 1.78) 0.91 (0.49, 1.23 (0.70, 2.16)
variate model was not significant. Neither age, pubertal status, INR, or 1.69)
BMI were associated with profile membership. Our maltreatment model Pubertal status 0.77 (0.33, 1.76) 1.10 (0.37, 0.86 (0.33, 2.27)
was significant. As hypothesized, relative to Normative, girls exhibiting 3.25)
Income-to-needs 0.99 (0.43, 2.31) 1.98 (0.75, 1.15 (0.46, 2.89)
any of the three dysregulated profiles were more likely to have experi­
ratio 5.22)
enced a greater number of maltreatment subtypes while growing up. Body mass index 1.00 (0.98, 1.02) 1.01 (0.98, 1.00 (0.97, 1.02)
1.04)
3.3. Aim 3: psychobiological foundation profile to depressive function Number of 1.44 * (1.04, 2.00) 2.06 * (1.47, 1.66 * (1.18, 2.34)
linkages maltreatment 2.89)
subtypes
Х2 (df) 27.80 (15)
3.3.1. Depressive symptoms Nagelkerke’s R2 .14
Parameter estimates for our linear regression models predicting
Note. CI = confidence interval. The Normative profile served as the reference
group.
* p < .05.
4
Similar to the findings controlling for medication use more generally,
neither corticosteroid (nyes=31) or birth control (nyes=10) use were associated
with our dependent variables in Aim 2 or 3 analyses. They were, thus, omitted
from Aim 2 and 3 analyses in the interest of model parsimony.

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J.J. Bendezú et al. Psychoneuroendocrinology 143 (2022) 105826

Table 3 depressive symptoms. Cognitive reappraisal was negatively associated

Parameter Estimates for a Nested Taxonomy of Multiple Linear Regression with depressive symptoms. A significant interaction between subgroup
Models Predicting Depressive Symptoms. membership and cognitive reappraisal emerged (Fig. 2). For Normative
Profile Cognitive Profile × and Pro-inflammatory Affective Disturbance girls, cognitive reappraisal
Reappraisal Cognitive was not associated with depressive symptoms (i.e., stably low). How­
Reappraisal ever, for girls exhibiting the Severe Affective Disturbance or Hypercortisol
Independent B SE B SE B SE Affective Neurocognitive Disturbance profiles, cognitive reappraisal was
Variables negatively associated with depressive symptoms.
Intercept 32.33 * 11.06 43.08 * 11.27 30.48 * 10.73
Age 0.62 0.78 0.76 0.76 0.62 0.75 3.3.2. PASI
Pubertal status -0.67 1.34 -0.41 1.31 0.30 1.30 Parameter estimates for logistic regression models predicting PASI
Income-to-needs 1.03 1.29 1.62 1.28 1.23 1.26
ratio
are shown in Table 4. Age, pubertal status, and INR were not associated
Body mass index 0.03 0.03 0.03 0.03 0.02 0.03 with PASI. However, BMI and number of maltreatment subtypes were
Number of 2.52 * 0.54 2.29 * 0.53 2.10 * 0.53 associated with increased likelihood of PASI. Relative to Normative, girls
maltreatment exhibiting the Pro-inflammatory Affective Disturbance or Hypercortisol
subtypes
Affective Neurocognitive Disturbance profiles (but not Severe Affective
Profilea
Pro-inflammatory 8.55 * 1.89 8.04 * 1.85 8.59 * 1.84 Disturbance) were more likely to report PASI.
Affective Reappraisal was not associated with PASI. No significant profile
Disturbance membership by cognitive reappraisal interaction emerged.
Severe Affective 16.47 * 2.27 16.30 * 2.22 16.42 * 2.17
Disturbance
Hypercortisol 13.74 * 2.11 13.51 * 2.06 13.39 * 2.02 3.4. Post-hoc analyses
Affective
Neurocognitive
A comparison of girls with and without maltreatment histories on
Disturbance
Cognitive -25.17 * 7.56 our psychobiological indicators of interest, cognitive reappraisal,
reappraisal depressive symptoms, and PASI is shown in Table S4 (see supplementary
Normative -9.90 9.65 materials). Differences between girls with and without maltreatment
× cognitive
histories emerged on negative affect, positive affect, depressive symp­
reappraisal
Pro-inflammatory 2.54 21.97 toms, and PASI. No other significant differences emerged.
Affective
Disturbance 4. Discussion
× cognitive
reappraisal
Severe Affective -50.54 * 20.94 Utilizing a racially diverse, economically disadvantaged sample of
Disturbance adolescent girls, the current study identified distinct profiles of psy­
× cognitive chobiological function that were meaningfully associated with girls’
reappraisal past maltreatment exposure and current depressogenic functioning. Our
Hypercortisol -63.59 * 23.59
Affective
Neurocognitive Table 4
Disturbance Parameter estimates for a nested taxonomy of logistic regression models pre­
× cognitive dicting passive or active suicidal ideation.
reappraisal
Profile Cognitive Profile ×
a
= Normative served as the reference profile. Reappraisal Cognitive
* p < .05. Reappraisal

Independent Variables B SE B SE B SE
current depressive symptoms are shown in Table 3. Neither age, pu­ Intercept -4.87 3.36 -3.81 3.48 -5.69 3.52
bertal status, INR, or BMI were associated with depressive symptoms. Age 0.03 0.23 0.05 0.23 0.05 0.26
Number of maltreatment subtypes was positively associated with Pubertal status 0.08 0.39 0.11 0.39 0.12 0.41
depressive symptoms. Relative to Normative, girls exhibiting any of the Income-to-needs ratio -0.20 0.40 -0.14 0.40 -0.22 0.41
Body mass index 0.03 * 0.01 0.03 * 0.01 0.03 * 0.01
three dysregulated profiles were more likely to report elevated
Number of maltreatment 0.50 * 0.14 0.48 * 0.14 0.45 * 0.15
subtypes
Profilea
Pro-inflammatory Affective 1.40 * 0.49 1.36 * 0.49 1.32 * 0.52
Disturbance
Severe Affective Disturbance 0.98 0.57 0.95 0.58 0.88 0.66
Hypercortisol Affective 1.19 * 0.56 1.14 * 0.56 1.12 0.60
Neurocognitive Disturbance
Cognitive reappraisal -2.78 2.31
Normative × cognitive 3.39 3.42
reappraisal
Pro-inflammatory Affective -10.70 6.49
Disturbance × cognitive
reappraisal
Severe Affective Disturbance -15.16 7.94
× cognitive reappraisal
Hypercortisol Affective -9.38 7.80
Neurocognitive Disturbance
× cognitive reappraisal
Fig. 2. Moderation effects of cognitive reappraisal on profile membership to
a
girls’ depressive symptoms. Effects plotted at - 1 SD and + 1 SD for illustra­ = Normative served as the reference profile.
tive purposes. * p < .05.

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J.J. Bendezú et al.
adoption of a person-centered (Cicchetti and Rogosch, 1996), multiple
levels of analysis (Cicchetti and Dawson, 2002) approach helped illus­
trate varied ways in which coordinated disturbance across the
immuno-endocrine, affective valence, neurocognitive systems manifest
within adolescents (Cha et al., 2019; Glenn et al., 2017). Specifically,
latent profile analysis (LPA) of girls’ morning cortisol:CRP ratios, posi­
tive affect levels, negative affect levels, and attentional set shifting ca­
pacities revealed four profiles. These profiles connected with
maltreatment and maladjustment in ways that potentially point to
person-specific psychobiological mechanisms the may underlie mal­
treated girls’ risk for depression during adolescence. Interestingly,
cognitive reappraisal to depression linkages varied across profiles,
highlighting various sources of psychobiological resilience that might
mitigate such risk by differentially supporting the use of this potentially
efficacious strategy. Our findings provide nuanced detail of the psy­
chobiological foundations of coping and emotion regulation (Compas
et al., 2017), with implications for tailoring of prevention and inter­
vention efforts targeting the emergence of depression in maltreated
adolescent girls.
Our study identified four profiles, one reflecting healthy psychobi­
ological function and three reflecting varied forms of psychobiological
dysregulation. Negative affect disruptions were common across all three
dysregulated profiles, whereas disturbance across other systems studied
were not. Negative affect may, therefore, fail to differentiate among
profiles of psychobiological dysregulation, consistent with the argument
that negative affectivity is a non-specific feature of internalizing diffi­
culties more broadly (Kotov et al., 2017). Person-centered, multilevel
studies of adolescent psychobiological function have also shown
elevated negative affect to be a common feature across identified dys­
regulated profiles (Bendezú et al., 2021a, Bendezú et al., 2021b; Koss
et al., 2017). Our study suggests that concurrent attention to positive
affect, immuno-endocrine, and neurocognitive function may provide a
more nuanced and comprehensive understanding of the heterogeneity
involved in adolescent girls’ psychobiological risk for depression.
To our knowledge, Landau and colleagues (2021) is the only study to
date that has examined the morning cortisol:CRP ratio using saliva in
relation depression in adolescents. No studies have examined the ratio in
a racially diverse, economically disadvantaged sample of adolescent
girls. Our multi-system, person-centered study helped to address this gap
in the literature. In so doing, our results also help to clarify inconsistent
findings from studies using variable-centered methods (e.g., linear
regression) to examine the cortisol:CRP ratio as it pertains to internal­
izing symptomatology. Specifically, both high and low cortisol:CRP ra­
tios were observed in our dysregulated profiles. Lower ratios have been
associated with depression in females and stress-induced negative affect
in depressed adults (Suarez et al., 2015; Suarez and Sundy, 2017).
Higher ratios have been associated with anxiety in females and
first-onset depression in at-risk adolescents (Landau et al., 2021; Suarez
et al., 2015). In agreement with Landau and colleagues, our
person-centered findings suggest the possibility that both lower and
higher ratios within the same study and sample may reflect qualitatively
distinct forms of immuno-endocrine dysregulation and, thus, index risk.
If so, conclusions drawn from variable-centered methods (e.g., linear
regression) that average across potential subgroups at both ends of the
cortisol:CRP ratio distribution may be erroneous (e.g., concluding that
higher cortisol:CRP ratios weakly confer risk for internalizing problems
when in actuality both higher and lower cortisol:CRP ratios moderately
or strongly confer risk).
4.1. Psychobiological foundation profiles
Relative to Normative, girls exhibiting the Pro-inflammatory Affective
Disturbance profile presented with lower cortisol:CRP ratios. For these
girls, lower cortisol:CRP ratios may reflect the inadequate release of
cortisol relative to CRP, a pattern often attributed to chronic stress-
related glucocorticoid resistance whereby immune cells (e.g.,
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Psychoneuroendocrinology 143 (2022) 105826
monocytes, macrophages) become less sensitive to cortisol’s anti-
inflammatory signaling properties (Slavich and Irwin, 2014).
Pro-inflammatory states can also contribute to depressive states
(Anacker et al., 2011; Dantzer, 2001), which is consistent with the
observation that these girls also exhibited high negative affect and low
positive affect levels. Notably, our simultaneous attention to neuro­
cognitive systems revealed a potential psychobiological protective fac­
tor: better than average attentional set shifting skills. The capacity to
effortfully focus attention on task-related demands and intentionally
shift this focus in service of goal-directed behavior is thought to be a core
component for the modulation of emotion (e.g., felt sadness; Eisenberg
and Zhou, 2016), perhaps reflected in these girls relatively mild eleva­
tions in negative affect. That Pro-inflammatory Affective Disturbance girls
exhibited better than average attentional set-shifting capacity is also
consonant with claims about the adaptive function of chronic
stress-related attenuated cortisol release patterns, which are thought to
protect adolescents’ developing brains (e.g., hippocampus, prefrontal
cortex) against the potential neurotoxic effects of cortisol overexposure
(Fries et al., 2005; Gunnar and Vazquez, 2001).
Girls exhibiting the Severe Affective Disturbance profile displayed
psychobiological function characterized by disruptions primarily of the
affective valence system. Both low positive affect and high negative
affect have conceptual and empirical links to risk for depression
(Chorpita and Daleiden, 2002; Olino et al., 2011). However, our
concomitant consideration of both neurocognitive and
immuno-endocrine functioning uncovered a set of psychobiological
protective factors parallel to these girls’ affective disruptions. In addi­
tion to exhibiting attentional set-shifting abilities similar to that
observed in Normative, girls exhibiting the Severe Affective Disturbance
profile displayed a moderate ratio of morning cortisol to CRP levels.
Such close correspondence between morning cortisol and CRP levels is
believed to index homeostatic equilibrium between the HPA and im­
mune system (Landau et al., 2021). Such countervailing effects are
believed to support healthy stressor management, where by cortisol
mobilizes metabolic resources needed to efficaciously respond to a
stressor while corresponding inflammatory processes facilitate recovery
(i.e., physical healing, limit infection) from stress exposure (Slavich and
Irwin, 2014). Indeed, homeostatic immuno-endocrine equilibrium has
been implicated as a biological buffer of girls’ risk for depression during
the adolescent transition (for review, see Slavich and Sacher, 2019).
Relative to Normative, Hypercortisol Affective Neurocognitive Distur­
bance girls exhibited disrupted functioning across multiple (but not all)
systems. First, these girls exhibited relatively higher morning cortisol:
CRP ratios. Elevated cortisol:CRP ratios are thought to indicate the
overproduction of cortisol to CRP (Guilliams and Edwards, 2010), a
pattern often attributed to chronic stress-related glucocorticoid immuno­
suppression whereby excessive cortisol via its anti-inflammatory
signaling properties unduly suppresses immune system function (e.g.,
cellular immunity). The resulting immunocompromised state can in­
crease risk for psychopathology (e.g., depression, Slavich and Irwin,
2014). That Hypercortisol Affective Neurocognitive Disturbance girls also
displayed the lowest attentional set-shifting abilities is further consistent
with this claim, as excessive HPA activation and cortisol overexposure
noxiously impact neurobiological circuits that support healthy executive
function (Shansky and Lipps, 2013). These girls, however, also displayed
normative levels of positive affect, consistent with a prior
person-centered, multisystem study of depressed adolescent girls’ stress
responsivity and its identified Hyperresponsive profile (J.J. Bendezú,
Calhoun et al., 2021; J. J. Bendezú, Calhoun et al., 2021). Positive
emotionality can be a source of resilient function (Curtis and Cicchetti,
2007) and buffer of negative emotions and related sequelae (Fre­
drickson, 2004), which may explain these girls’ relatively mild eleva­
tions of negative affect.
J.J. Bendezú et al.
4.2. Links to maltreatment history
The validity of our profiles was supported through their connections
with maltreatment. Relative to Normative, girls exhibiting profiles
thought to reflect psychobiological dysregulation reported having been
exposed to a greater number of maltreatment subtypes while growing up
as a child and teenager. Exposure to maltreatment has been indepen­
dently linked to youth affective valence disturbance (e.g., elevated
negative affect, emotional lability; Courtney-Seidler et al., 2014; Cro­
well et al., 2009), which findings from our post-hoc conventional ana­
lyses are consistent with. However, by spanning multiple levels of
analysis to identify qualitatively unique within-person profiles of coor­
dinated psychobiological function, our person-centered approach
strengthens inference about how immuno-endocrine and neurocognitive
disruptions that have been previously independently linked to
maltreatment (e.g., elevated and blunted cortisol levels; Cicchetti et al.,
2010; Doom et al., 2013; elevated CRP and pro-inflammatory cytokine
levels; Coelho et al., 2014; Ehrlich et al., 2021; compromised memory
and executive functioning; Cowell et al., 2015; Valentino et al., 2009)
may interact with one another within maltreated girls.
In so doing, our person-centered, multisystem approach illustrated
profile-specific immuno-endocrine (e.g., Severe Affective Disturbance)
and neurocognitive (e.g., Pro-inflammatory Affective Disturbance)
strengths that may potentially offset the contributions of past
maltreatment exposure to profile-specific weaknesses (e.g., affective
difficulties common across dysregulated profiles). This finding is note­
worthy, insofar as it would be reasonable to hypothesize from the
summarized maltreatment research focusing on systems in isolation that
maltreatment would be associated with profiles characterized by
disturbance across all systems (e.g., Multisystem Disturbance). Our study,
however, suggests that psychobiological dysregulation as it relates to
maltreatment exposure is far more nuanced and complex. For example,
while neurocognitive impairment and maltreatment history linkages are
well-documented (Cowell et al., 2015; Gould et al., 2012), our
concomitant consideration of affective valence in the Hypercortisol Af­
fective Neurocognitive Disturbance profile pointed to positive affect as
potential undocumented strength. These findings highlight the utility of
our multisystem approach. As we discuss later, identification of these
profiles has the potential to inform tailored care approaches to inter­
vention that might better capitalize on and circumvent maltreated girls’
profile-specific strengths and weaknesses.
4.3. Links to depressive symptoms
Our identified profiles were also linked to depressogenic function in
expected ways. Relative to Normative, girls exhibiting profiles reflecting
psychobiological dysregulation were more likely to report current
depressive symptoms, even after adjusting for past maltreatment expo­
sure. When examined in isolation, depression has been independently
linked high negative affect (Enns et al., 2003; Fergusson et al., 2000),
low positive affect (Auerbach et al., 2015), executive function diffi­
culties (Wilkinson and Goodyer, 2006), and dysregulated
immuno-endocrine function (e.g., Landau et al., 2021; Suarez and
Sundy, 2017). Our investigation is one the first to provide a more
nuanced, comprehensive depiction of the varied ways these systems
might interact in an etiological sense to confer risk for depression in
adolescent girls.
Depressive symptom levels also varied across profiles by girls’ use of
cognitive reappraisal, a finding that extends the psychobiological
foundations of coping and emotion regulation literature (Compas et al.,
2017). While Normative and Pro-inflammatory Affective Disturbance girls
displayed mild depressive symptom levels irrespective of their cognitive
reappraisal utilization, cognitive reappraisal was negatively related to
depressive symptoms for Severe Affective Disturbance and Hypercortisol
Affective Neurocognitive Disturbance girls. Regarding the Severe Affective
Disturbance profile, these girls’ high negative affect and low positive
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Psychoneuroendocrinology 143 (2022) 105826
affect levels may constrain the efficacious use of certain coping skills
(Compas, 2009). However, if their moderate cortisol:CRP ratios and
normative attentional set shifting skills indicate the healthy suppression
of inflammatory processes by the HPA, which together support adaptive
functional changes in brain regions and circuitry (e.g., amygdala, pre­
frontal cortex) implicated in executive function and self-regulation
(Shields et al., 2017), then it is possible that these girls’
immuno-endocrine and neurocognitive strengths support the use of
cognitive reappraisal for managing depressive symptoms in a way that
circumvents their affective predispositions. Similarly, Hypercortisol Af­
fective Neurocognitive Disturbance girls may rely on normative positive
affect levels to support their use of cognitive reappraisal. Indeed, posi­
tive emotionality promotes flexible thinking and adaptive coping with
negative emotions (Folkman and Moskowitz, 2000; Fredrickson and
Branigan, 2005). This strength might circumvent a possible neuro­
cognitive proclivity towards perseveration (i.e., being “stuck” on stimuli
from previously established dimension the ED stages of the IDED
set-shifting module; Henry and Bettenay, 2010; Yerys and Munakata,
2006) that would otherwise interfere with reappraisal utilization. In
each case, knowledge about girls’ psychobiological profiles may help
clinicians leverage clients’ strengths in service of teaching this
multi-faceted strategy (e.g., harnessing positive affect to identify the
“silver lining,” harnessing executive function to brainstorm numerous
reinterpretations, select the most optimal solution, and shift to a
different solution in case the first fails) in ways that may circumvent
these girls’ weaknesses.
4.4. Links to passive or active suicidal ideation (PASI)
Findings obtained when PASI was the outcome of interest com­
plemented but also diverged from our depressive symptoms findings.
Relative to Normative, girls exhibiting the Pro-inflammatory Affective
Disturbance or Hypercortisol Affective Neurocognitive Disturbance profiles
(but not Severe Affective Disturbance) were more likely to report PASI.
This finding is consistent with recent conceptualizations of adolescent
girls’ risk for suicidality as failure of the arousal regulatory, affective
valence, and neurocognitive systems (Beauchaine et al., 2019; Crowell
et al., 2009). However, our study extends the literature by empirically
illustrating how coordinated disturbance across such systems may
manifest within adolescent girls to confer such risk. Given that only
Pro-inflammatory Affective Disturbance or Hypercortisol Affective Neuro­
cognitive Disturbance girls were more likely to report PASI, it is possible
that these profiles reflect more pathological states of psychobiological
dysregulation, perhaps due to disruptions across multiple as opposed to
a single (e.g., affect) system (e.g., Severe Affective Disturbance).
Contrary to expectation, cognitive reappraisal was not significantly
associated with PASI and this association did not vary by girls’ psy­
chobiological functioning. This finding runs counter to evidence sug­
gesting that the tendency to use cognitive reappraisal in response to
difficult emotions helps reduce risk for suicidal ideation (Forkmann
et al., 2014; Ong and Thompson, 2019), and that girls’ ability to do so
may depend on their psychobiological foundations (Compas et al.,
2017). It is possible that unexamined individual differences in exposure
to recent stressful life events may have contributed to our nonsignificant
findings (e.g., Boyes et al., 2016; Duprey et al., 2021; Franz et al., 2021).
From a stress sensitization perspective (Hammen et al., 2000), girls with
maltreatment histories and resulting dysregulated psychobiological
function may be most prone to suicidal ideation when they are also
unduly exposed to recent life stressors (Heim and Nemeroff, 2001). For
Black youth, experiences with racial/ethnic discrimination may be one
specific form of contextualized life stress that has been understudied in
this respect. Black preadolescent youth are unduly exposed to racial
discrimination (Argabright et al., 2021), with experience sampling
studies suggesting that these youth encounter on average five experi­
ences per day (English et al., 2020). If so, their maltreatment-related
heightened sensitivity to ongoing racial discrimination may also have
J.J. Bendezú et al.
implications for how efficacious their use of coping and emotion regu­
lation strategies might be in managing their depressogenic mood and
thought patterns (Gruhn and Compas, 2020). Some studies have sug­
gested that cognitive reappraisal and related strategies (e.g., positive
thinking) may “backfire” for minoritized youth when attempting to
manage depressotypic thoughts and feelings in the face of racial/ethnic
discrimination, due to (a) limited positive reinterpretations about
experienced racial transgressions and threats in offensive contexts, as
well as (b) inadvertent internalization of the message that depressotypic
thoughts about discrimination are the problem to be resolved rather
than discrimination itself (Perez and Soto, 2011; Perzow et al., 2021;
Wadsworth et al., 2020). Research is needed to understand whether girls
with maltreatment-linked dysregulated psychobiological profiles ability
to utilize such strategies for effectively managing PASI depends on
minoritized stress exposure.
4.5. Limitations and future directions
The lack of evidence with respect to one of our focal anticipated
outcomes is also noteworthy. Though our findings provided support for
our anticipated Normative profile, we did not find any evidence of a
Multisystem Disturbance profile. Future studies utilizing larger sample
sizes and recruitment strategies that target more severe clinical pre­
sentations (e.g., inpatient) may be needed in order to identify this pro­
file. Nevertheless, our identified profiles, those which provided close but
incomplete approximations of Multisystem Disturbance, illustrated
unique patterns of psychobiological strengths and weaknesses that
pointed to person-specific sources of clinically informative resilience.
Our study also had several limitations that point to directions for
future research. Our findings are limited to a racially diverse, econom­
ically disadvantaged sample of adolescent girls, some of whom were
depressed and/or maltreated, who were not treatment-seeking. Future
research is needed to determine whether our findings generalize to other
genders, non-maltreated, and non-clinical populations of adolescents.
Indeed, given that our sample was economically disadvantaged and
poverty has been linked pro-inflammatory profiles (for review, see
Jensen et al., 2017), our Pro-inflammatory Affective Disturbance profile
may be unique to this demographic aspect. Though our sample size was
similar to other notable person-centered studies of psychobiological
function (Del Giudice et al., 2012; Koss et al., 2017; Turpyn et al., 2015),
it was small for our approach. Though common in LPA, unequal sub­
group sizes emerged and may have reduced power to detect effects in
our maltreatment and depression analyses and precluded examination
of moderation effects by race. Thus, cautious interpretation and repli­
cation in studies with larger sample sizes is warranted, moderation
findings from which may strengthen inference about whether effects are
most pronounced for Black, economically disadvantaged adolescent
girls in particular. Though we controlled for girls’ waking saliva sample
time and use of pain medications (e.g., Aspirin), morning
immuno-endocrine levels can be impacted by variables which were
unmeasured in our study (e.g., sleep quality, sunlight, chronic stress).
Thus, replication in studies that account for these factors is warranted.
Cortisol levels are increased when chewing gum compared to unstimu­
lated passive drool, whereas salivary CRP levels are not. Although
confounds related to collection method were constant across partici­
pants, this pattern of effects from gum chewing may have led to slightly
higher cortisol levels. Studies using passive drool methods may find
different cortisol:CRP ratio distributions among identified profiles. Our
study relied on retrospective self-reports of child maltreatment, which
can be potentially impacted by several biases (e.g., forgetting, subse­
quent life-events; Hardt and Rutter, 2004; Tajima et al., 2004). We also
focused on the specific number of subtypes girls experienced over the
course of their childhood and early adolescence. Child maltreatment,
however, is multidimensional (Manly et al., 2001), and maltreatment to
psychobiological dysregulation linkages in our study may have been
better explained were differences in timing (i.e., developmental period
10
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Psychoneuroendocrinology 143 (2022) 105826
during which maltreatment initially occurred) and chronicity (i.e.,
number of developmental periods during which maltreatment occurred)
examined. Future studies focusing on these temporal aspects may find
that profiles reflecting greater degrees of psychobiological dysregulation
may not only be linked to greater number of subtypes experienced, but
also earlier timing and more chronic exposure over the course of youths’
development. Our cross-sectional design precludes causal inference
about linkages among child maltreatment, psychobiological func­
tioning, and depressogenic outcomes (Kraemer et al., 1997). Future
research incorporating longitudinal designs may be better situated to
test whether identified profiles function as psychobiological mecha­
nisms of risk involved in past maltreatment exposure (i.e., antecedent)
to future depressogenic function (i.e., outcome) linkages.
Funding sources
Manuscript preparation was supported by NIMH Grant T32
MH015755 awarded to Dr. Dante Cicchetti, NIDA Grant T32 DA050560
awarded to Drs. Monica Luciana and Scott Vrieze, NICHD Grant P50-
HD096698 awarded to Drs. Dante Cicchetti and Sheree Toth, and NIMH
Grant R01-MH091070 awarded to Drs. Sheree L. Toth, Dante Cicchetti,
and Jody Manly.
Declarations of interest
None.
Appendix A. Supporting information
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.psyneuen.2022.105826.
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