Depression is among the most common mental health problems in adolescence, as 17 % of adolescents in the United States ages 12–17 have experienced at least one major depressive episode in their lifetime (Substance Abuse and Mental Health Services Administration, 2021). In adulthood, adolescent-onset depression often is associated with a chronic or recurrent illness course, marked by difficulty with interpersonal relationships, increased physical problems, suicide risk (Thapar et al., 2012), and impairment in global functioning (Kertz et al., 2019). Because adolescent-emergent depression is associated with such poor outcomes and few individuals reach full symptomatic recovery (Conradi et al., 2011), researchers have sought to identify factors that influence disorder onset, maintenance, and reoccurrence in teenagers. One particular focus has been biological changes that occur during puberty. After puberty onset, the low prevalence of depression (<1 % in most childhood studies) rises substantially. Disorder prevalence changes to 2:1 for girls versus boys (Thapar et al., 2012) with a peak sex difference at age 16 across the lifespan (Salk et al., 2017). In older women, lower estradiol levels are linked to depression onset (Schmidt, 2005) and maintenance (Frey et al., 2008). However, the peri- and post-menopause phases examined in these studies are quite different from puberty, raising questions about whether a comparable relationship exists for teenage girls. Evidence is sparser about estradiol levels' relationship to depression onset, maintenance, and prevention in adolescents, despite evidence that adolescent depression is more closely linked to hormonal changes than to chronological age (Lewis et al., 2018). As such, it is important to understand the mechanisms through which estradiol levels might confer risk or resilience for mood disorder in this age group.

A common feature of depression found in clinical studies is the reliable presence of attentional biases, typically defined as a tendency for attention to be preferentially directed towards or away from different types of stimuli in the environment, such as a lack of attention towards positive information (Elgersma et al., 2018). Depressed persons also demonstrate better recall for depression-specific stimuli and recall more negative than positive stimuli (Fritzsche et al., 2010). Several experimental tasks have been used to measure attentional biases in depression, such as the Emotional Stroop task and the Emotional Dot Probe task. Studies using these paradigms in depressed individuals have produced equivocal results. Some studies have demonstrated attentional biases in depressed individuals (Winer and Salem, 2016; Scher et al., 2005); however, a larger number have failed to show this effect (Gotlib et al., 2004; Fritzsche et al., 2010). Only four studies have examined the association between estradiol and attentional biases. Most of these studies established links between higher estradiol and both greater early automatic visual processing (Lusk et al., 2015), and difficulty suppressing the processing of negative emotional stimuli (Lusk et al., 2017; Graham and Shin, 2018). In contrast, one found combined oral contraceptive use had no influence on attentional bias in healthy women (Scheuringer et al., 2020). We are unaware of any prior study that has examined the relationship of estradiol levels to attentional biases in adolescent females with and without depression.

An infrequently-used paradigm that can quantify attentional biases is the Emotional Interrupt Task (EIT). The EIT examines the interference of emotional stimuli on basic goal-directed behavior by measuring whether simple target identification reaction time is changed on trials where emotional information preceded and followed those trials. The EIT differs from the Emotional Stroop and Emotional Dot Probe tasks in the sense that the latter both assess the effects of emotional salience on response behavior when emotional information is presented contemporaneously with other information that competes for cognitive resources, while the EIT assesses the effects of emotional interference on subsequent responses to other stimuli. This provides researchers a measure that can be sensitive to influences on cognitive processing time from both bottom-up sensory processes like emotional salience, or top-down influences such as executive attentional mechanisms (Mitchell et al., 2008). The EIT has been used in only six studies since its conception in 2006. Healthy non-patient's responses are consistently slower when responding to a shape if that shape is temporally bracketed by an emotional stimulus, regardless of valence (Mitchell et al., 2006; Rich et al., 2010) – an attentional interference (AI) effect. In contrast, individuals theorized to have emotion processing deficits such as those with psychopathy or severe mood dysregulation have less AI to the emotional distractors (Mitchell et al., 2006, Rich et al., 2010). Although the EIT has not been used as often as the Emotional Stroop or the Emotional Dot Probe tasks, it has promise to add useful new information about attentional bias to researchers' efforts to understand attentional biases in depression.

In the present study, we compared EIT performance of female adolescents with either a current or a past diagnosis of MDD. This study design also offered the opportunity to determine whether there are any relationships between EIT performance and depression, as well as between attentional interference and absolute estradiol levels. Therefore, we also examined the relationship between estradiol levels and AI by EIT emotional distractors, because no prior study has examined if estradiol scores might differ between participant groups defined by the presence or absence of MDD in depressed female adolescents. Study goals were to determine: i) if EIT performance differed for either MDD study group relative to never depressed control adolescent females, ii) if estradiol levels differed between non-depressed, formerly-depressed, or currently-depressed study groups, iii) if estradiol levels predicted EIT performance, and iv) if the relationship between estradiol levels and AI might be different in the three participant groups. We predicted that higher estradiol levels would predict worse performance on the EIT in both the MDD current and the MDD remitted group on negative stimuli. This study is potentially informative because investigators do not yet have a full understanding of whether estradiol might modulate attentional biases in mood disorder in adolescent females. More information about any relationships between these factors is needed to further develop theories about the role of estradiol on this putative neurocognitive risk factor for depression.