Association between trauma exposure and mood trajectories in patients with mood disorders

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Research paper

Association between trauma exposure and mood trajectories in patients with mood disorders I. Ventimigliaa, A.S.J. Van der Wattb, , M. Kiddc, S. Seedatb ⁎

a

Psychiatry Unit, Department of Health Sciences, University of Florence, Florence, Italy Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa c Department of Statistics and Actuarial Sciences, University of Stellenbosch, Stellenbosch, South Africa b

ARTICLE INFO

ABSTRACT

Keywords: Childhood trauma Lifetime trauma Mood disorders Mood trajectories

Background: Trauma exposure is associated with the development of mood disorders and their phenotypic presentation. Cross-sectional associations between trauma exposure and mood disorders are well documented. Data on the association of trauma with longitudinal mood trajectories are lacking. We investigated the association between trauma exposure and weekly mood trajectories. Method: Mood disorder patients (N = 107; female = 81; mean age = 37.04 years), assessed for trauma exposure at baseline using the Childhood Trauma Questionnaire (CTQ) and Life Events Checklist (LEC), completed weekly telephonic mood assessments using the Quick Inventory of Depressive Symptomatology (QIDS) and Altman SelfRating Mania scale (ASRM) over a 16 week period commencing at one week post-discharge from hospital. Associations between trauma exposure, severity of mood symptoms and mood trajectories were analysed using Pearson's correlations, LS Mean scores, F-statistics, and RMANOVA. Results: Trauma exposure was persistently associated, albeit with some fluctuation in the strength of the association, with depressive symptomatology. Emotional abuse showed the most persistent association over time. Sexual abuse was minimally associated with depressive symptomatology. The severity of childhood trauma exposure was positively correlated with the severity of depressive symptoms. Lifetime traumatic events were significantly associated with mania scores, however there was no association between childhood trauma exposure and mania symptoms. Conclusion: Identification of both a history of childhood abuse and neglect and lifetime traumatic event exposure is important in the assessment and management of patients with mood disorders, as trauma can exert a persistent impact on depression trajectories and on symptom severity.

1. Introduction Mood disorders (including major depressive disorder and bipolar disorder) are among the most prevalent psychiatric disorders worldwide, with lifetime prevalence estimates ranging between 8.5% and 10.7% (Steel et al., 2014). Both major depressive disorder and bipolar disorder are highly recurrent disorders (Burcusa and Iacono, 2007; Zhang et al., 2006). These mood disorders are associated with functional impairment (Simon et al., 2007), decreased work productivity (Kessler, 2006), increased risk of premature death due to suicide and medical comorbidities (Baxter et al., 2011; Hayes et al., 2015), and increased use of health services (Miret et al., 2013). As such, mood disorders bear a heavy socio-economic burden, are deemed among the most disabling disorders, and constitute an important contributor to the total burden of disease worldwide. ⁎

Mood disorders are multifactorial, and their development and phenomenology are influenced by a complex interaction between genetic and environmental factors (Uher and Zwicker, 2017). Accordingly, mood disorders are often heterogeneous in their phenotypic presentation and course, with symptoms showing high interpatient variability as well as high intrapatient change over time (Nahum et al., 2017; Nandi et al., 2009). Given the personal, social, and economic costs of mood disorders, several studies have focused on identifying factors that may underlie this variability (Aldinger and Schulze, 2017; Gunn et al., 2013; Van Den Brink et al., 2018). One such underlying factor is the influence of trauma exposure, with associations described for a variety of childhood traumatic experiences (Copeland et al., 2018; Bruno Etain et al., 2013). Accordingly, childhood sexual abuse, physical abuse and neglect, and emotional abuse and neglect have consistently been associated with the development of mood disorders (Du Rocher

Corresponding author. E-mail addresses: [email protected] (A.S.J. Van der Watt), [email protected] (M. Kidd), [email protected] (S. Seedat).

https://doi.org/10.1016/j.jad.2019.10.057 Received 2 July 2019; Received in revised form 6 September 2019; Accepted 28 October 2019 Available online 01 November 2019 0165-0327/ © 2019 Elsevier B.V. All rights reserved.

Please cite this article as: I. Ventimiglia, et al., Journal of Affective Disorders, https://doi.org/10.1016/j.jad.2019.10.057

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2. Materials and method

Schudlich et al., 2015; Klumparendt et al., 2019; Maniglio, 2013; Martins et al., 2014; Negele et al., 2015). Additionally, a history of childhood trauma may impact on the clinical expression of mood disorders leading to an earlier age of onset, more recurrent episodes, and increased severity of symptoms (Aas et al., 2016; Maes et al., 2018), with significant associations being reported between the severity of trauma and worse clinical outcomes. Such associations have been investigated in terms of both the characteristics of the individual and the features of the traumatic event that are more likely to predispose to the development of affective psychopathology. There is evidence of an increased vulnerability of females to the consequences of trauma (Carmassi et al., 2018). Additionally, several studies have focused on individual traits which might act as mediating factors in the relationship between trauma and mood symptoms, including maladaptive cognition and negative cognitive styles (Gibb et al., 2001); dysfunctional emotional regulation (Hopfinger et al., 2016) and ruminative thinking (Dell'Osso et al., 2019). Moreover, in terms of traumatic events, there is evidence for the differential effect of childhood trauma subtype on the development and clinical expression of mood disorders (Norman et al., 2012). For example, in their summary of 184 studies, Nelson and colleagues (2017) found emotional neglect to be the most commonly reported form of childhood trauma in individuals with depression, while emotional abuse was most strongly associated with depression severity (Nelson et al., 2017). In addition to childhood trauma, trauma exposure later in life has been shown to impact on the phenomenology of mood disorders (Blakey et al., 2019; Shannon et al., 2011). However, the majority of studies have focused on childhood trauma. As such, there is a lack of research on the influence of lifetime trauma on mood disorders in contrast to posttraumatic stress disorder (PTSD). Moreover, there is a lack of information on the specific influence of trauma exposure on weekly mood trajectories. Since assessing temporal change is key to targeting time-varying associations in clinical outcomes that may otherwise be missed (Umemura et al., 2017), longitudinal designs can help shed further light on the impact of trauma exposure on the course of mood disorders. Up to now, longitudinal studies have investigated the relationship between trauma exposure and mood symptoms through yearly assessments (Spatz et al., 2007; Tanskanen et al., 2004). However, patient care in clinical settings is typically provided through weekly/two weekly/monthly follow-up. Accordingly, a better understanding of the influence of trauma exposure on the manifestations of, and fluctuation in, mood symptoms using more frequent monitoring may facilitate more timely and holistic interventions, improving the effectiveness of care. This is especially needed in South Africa, where the present study was conducted, as trauma in the country is ubiquitous, posing a burden on the already strained health care system.

We conducted secondary analysis of data derived from the Mood Monitoring Study (MMS). The aforementioned study comprised telephonic inter-episodal mood monitoring in participants with mood and/ or anxiety disorders. The primary aim was to longitudinally track mood fluctuations in psychiatric patients, post-discharge. A detailed description of the MMS is published elsewhere van der Watt et al., 2018a,b. 2.1. Sample For the present analysis, we included MMS participants who met the following criteria: (i) diagnosis of a mood disorder as confirmed by the post-discharge record,1 (ii) age of 18 years or older, (iii) the ability to provide informed consent, and (iv) access to reliable telephonic communication. As such, 107 participants were included in the analysis set. 2.2. Procedure The MMS protocol was approved by the Human Research Ethics Committee at Stellenbosch University (S15/03/048). To recruit participants, purposive sampling was used. Potentially eligible participants were referred to the research team by psychiatry residents and consultants at three government hospitals (one general tertiary academic and two psychiatric hospitals) in the Western Cape. Patients were recruited prior to discharge and provided informed consent. At the baseline assessment, they were informed that they would be telephoned weekly, starting with the first week post-discharge. Clinical discharge summaries (hospital records) of participants were accessed post-discharge. 2.3. Measures At baseline, in addition to recording basic demographic information (including age, ethnicity, sex, marital status, employment status, religious orientation, education, and basic income), participants completed the Childhood Trauma Questionnaire (CTQ) and Life Events Checklist (LEC). Mood trajectories were telephonically assessed on a weekly basis over 16 weeks using the Quick Inventory of Depressive Symptomatology (QIDS) and the Altman Self-Rating Mania scale (ASRM). 2.3.1. Childhood trauma questionnaire – short form The short form of the CTQ was used to measure exposure to adverse childhood events (Bernstein et al., 2003). The CTQ is a validated 28item self-report questionnaire that investigates histories of abuse and neglect in childhood. Items are rated on a Likert-type scale, ranging from 1 = never, to 5 = very often; based on the frequency of the events. The questionnaire assesses five types of maltreatment: emotional abuse (items 3, 8, 14, 18, and 25), emotional neglect (items 5, 7, 13, 19, and 28), physical abuse (items 9, 11, 12, 15, and 17), physical neglect (items 1, 2, 4, 6, and 26), and sexual abuse (items 20, 21, 23, 24, and 27). For each type of trauma, scores range from 5 to 25. The total or summary score ranges from 25 to 125, with higher scores indicating higher levels of childhood trauma exposure (score of 25–31 = no trauma, 41–51 = low-to-moderate, 56–68 = moderate-to-severe, and 73–125 = severe-to-extreme). Additionally, the CTQ utilises a minimization/denial (MD) scale to detect potential under-reporters of trauma. However, as MD scores are infrequently reported and validation studies of the MD sub-scale are lacking, we decided not to include this scale in our analysis (Church et al., 2017).

1.1. Goal of the study Taking the above into account, this study explored the impact of trauma on mood disorder trajectories in a clinical sample. Trauma exposure was assessed in terms of childhood abuse and neglect (Childhood Trauma Questionnaire) and common lifetime PTSD-producing traumatic events (Life Events Checklist). The Childhood Trauma Questionnaire assesses total childhood trauma exposure and exposure to different subtypes (physical abuse/neglect, sexual abuse, and emotional abuse/neglect). The specific aims were to investigate: (i) The association between trauma exposure (childhood and lifetime) and mood trajectories over 16 weeks; (ii) The association between trauma exposure severity (childhood and lifetime) and mood symptom severity across time; and (iii) The influence of trauma on the fluctuation in mood symptom severity over 16 weeks.

1 Participants with co-morbid anxiety and mood disorder were included. However, if no mood disorder (either as working diagnosis or as differential diagnosis) was present, the participant was excluded.

2

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The CTQ has a high degree of reliability (Bernstein et al., 1994) and was recently used to assess patients with mood disorders in both highincome and low- and middle-income countries (Janiri et al., 2015; Marx et al., 2017). In the present study, the Cronbach's alphas for the CTQ ranged from 0.66 for physical neglect to 0.93 for sexual abuse. As such, the physical neglect subscale's reliability fell below acceptable parameters. This is in accordance with previous research indicating the necessity of modifying the CTQ for South African samples (Spies et al., 2019)

Table 1 Low and high trauma exposure groups. CTQ Emotional Abuse Physical Abuse Sexual Abuse Emotional Neglect Physical Neglect CTQ total score

2.3.2. Life events checklist Lifetime trauma exposure was screened for using the LEC (Gray et al., 2004a). The LEC- is a self-report measure which was designed to screen for a wide range of potentially traumatic events that qualify for a diagnosis of PTSD (Gray et al., 2004b) in accordance with the Diagnostic and Statistical Manual of Mental Disorders, 5th edition’s (DSM-5) definition of trauma. The LEC has been used cross-culturally and validated in multiple populations (Gray et al., 2016). One of the unique features of the LEC is that it enquires about modes of exposure to potentially traumatic events that a participant may have personally experienced, witnessed, learned about them happening to someone close to them, or as part of their job (Spies and Seedat, 2014). A total score is derived from the total exposure to different types of events (whether experienced, witnessed etc.), with higher scores indicative of greater exposure to different lifetime traumatic events.

Minimum trauma exposure Score n

Maximum trauma exposure Score n

≤ ≤ ≤ ≤ ≤ ≤

≥ ≥ ≥ ≥ ≥ ≥

LEC Total Trauma Exposure

8 7 5 9 7 36

31 38 44 41 54 26

16 13 13 18 13 73

47 31 32 27 21 26

Score

n

Score

n

≤6

24

≥ 12

32

Note: CTQ = Childhood Trauma Questionnaire; LEC = Life Events Checklist.

we stratified participants on the basis of CTQ and LEC total scores. For the CTQ, stratification was based on guidelines by Bernstein and colleagues (1994). For the LEC, we used the 25th and 75th percentiles. This yielded low score and high score groups for the CTQ subscales, the CTQ-Total, and the LEC-Total (see Table 1). Additionally, in order to explore the influence, if any, of childhood and lifetime trauma exposure severity on fluctuation in mood symptom severity over time, we analysed mood trajectories over time using mixed model ANOVA with time and, where applicable, group as a fixed effect. Participants were included in the model as a random effect. Least squares means (LS means) were plotted over time to indicate trends. In some cases, linear regression curves were fitted through the means over time for different groups and group slopes compared using the “drc” package in R.

2.3.3. Quick inventory of depressive symptomatology Depression symptomatology was assessed using the QIDS (Rush et al., 2003). The QIDS is a 16-item self-report questionnaire that assesses the nine DSM-5 major depressive disorder symptoms, as experienced over the past seven days. The scores on the QIDS can be grouped into five severity levels (a score of 0–5 = no depression, 6–10 = mild depression, 11–15 = moderate depression, 16–20 = severe depression, and 21–27 = very severe depression). This reliable and valid instrument has recently been used in mood monitoring studies conducted in both high-income and low- and middle-income country settings (Miklowitz et al., 2012).

3. Results 3.1. Participant demographic data, trauma exposure, and mood trajectories Of the 107 participants included in the study, 71 completed at least 16 weeks of mood monitoring, while 36 dropped out prior to completing 16 weeks. Participants had, on average, 11 years of education (i.e. Gr 11, Mean = 11.70 years). More detailed demographic information is presented in Table 2. Childhood trauma exposure ranged from minimal exposure to extreme exposure (Bernstein et al., 2003) (see Table 3), while the mean number of lifetime traumatic events was 9.9 (SD = 5.459, range 0–36). Mood trajectories (N = 107) over the 16 weeks of monitoring postdischarge are indicated in Figs. 1 and 2. In terms of depression, participants’ scores decreased significantly over time F(15, 1 057) = 2.1271, p = 0.007. Similarly, mania scores decreased across time, however this decrease was not significant F(15, 1 058) = 1.627, p = 0.060.

2.3.4. Altman self-rating mania scale Mania-related symptoms were measured using the ASRM (Altman et al., 1997). The ASRM is a five-item self-report questionnaire that measures the frequency and the severity of mania-related symptoms over the course of the previous week. Total ASRM scores range from 0 to 20; a score of six (or more) indicates significant manic or hypomanic symptoms. The ASRM does not differentiate between a manic or hypomanic episode (Bopp et al., 2010). The ASRM has established psychometric properties for detecting mania symptoms among bipolar patients (Altman et al., 2001), and has previously been used in studies in South African samples (Savitz et al., 2008). 2.4. Analysis plan

3.2. Association between childhood and lifetime trauma exposure and mood trajectories

Data were analysed using the software packages SSPS version 25 (IBM Corp., 2017) and Statistica (Dell, 2014). Continuous variables (e.g., level of education) were expressed as means and standard deviations (SDs) while categorical variables (e.g., religious denomination, psychiatric history) were reported as frequency distributions. Variables indicating trauma exposure at baseline were reported for CTQ total scores, CTQ subtypes scores, and LEC scores. First, to investigate the association between trauma exposure and mood trajectories over 16 weeks, Pearson correlations were run for weekly QIDS/ASRM scores and childhood (CTQ total score and CTQ subscale scores) and lifetime (LEC total scores) trauma exposure scores, respectively. Second, to investigate the association, if any, between trauma exposure severity and the severity of depression/mania scores over time,

3.2.1. Depression As indicated in Table 4, there was a significant correlation between CTQ total scores and depression scores which was maintained weekly up to 14 weeks. However, this correlation was not statistically significant after week 14 (no significant correlation between CTQ total score and mood trajectory between weeks 14 and 16). In terms of childhood trauma subtypes, a significant, albeit weekly fluctuating association, was found between all childhood trauma subtype scores and depression scores. Childhood emotional abuse scores showed the most persistent association with depression scores over time. In turn, childhood sexual abuse scores were the least persistently associated with depression scores, with correlations found at only four time points (Week 2, 3, 7, and 10). With the exception of a significant association at week 1, there were no significant associations between LEC total scores 3

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the high and low childhood trauma exposure groups (total and subgroups) in terms of total mean depression score across the 16 weeks of monitoring, with greater depression severity in the high childhood trauma group. The exception to this was the childhood sexual abuse subgroup, with F(0.32), p = 0.57, where the degree of childhood sexual abuse was not associated with depression severity over time. Interestingly, there was no significant difference between high and low lifetime trauma exposure groups, on the LEC, in terms of total mean depression score across 16 weeks of monitoring.

Table 2 Participant Characteristics. Descriptive statistic

n (%)

Age (years) Sex Male Female Ethnicity African/Black Caucasian/White Mixed race (Coloured) Other Missinga Specific Religion Catholic/Protestant Pentecostal African/Other Atheist/Agnostic Length of recent stay (days) Relationship status Single/No relationship In a relationship Employment Employed Unemployed Actively religious No Yes Inclusion diagnosis Bipolar Unipolar Comorbid Mood & Anxiety Otherb Medication on discharge Mood stabiliser Anti-depressant Anti-psychotic Sedatives Other

Mean = 37.04 SD = 10.862 Range = 18–58 26 (24.3) 81 (75.8) 6 (5.6) 48 (44.9) 51 (47.7) 1 (0.9) 1 (0.9)

3.3.2. Mania group effect In contrast to depression, we found no statistically significant difference between high and low childhood trauma exposure groups (total and subgroups) and high and low lifetime trauma groups in terms of total mean mania score across the 16 weeks of monitoring (see Table 5). As such, childhood and lifetime trauma severity exposure did not appear to influence mania severity over time.

44 (41.1) 14 (13.1) 25 (23.4) 21 (19.6) Mean = 33.67 SD = 14.527 Range = 2–78 58 (54.2) 49 (45.8)

3.4. Trauma and fluctuation in mood symptom severity over 16 weeks 3.4.1. Depression and time interaction effect As indicated in Table 6, there was no significant difference between the high and low childhood trauma exposure groups (total and subgroups) in terms of the fluctuations in depression severity over 16 weeks. This was with the exception of emotional neglect, with F (15,697) = 2.10, p < 0.01. By itself, severity of trauma exposure – albeit childhood or lifetime exposure – did not appear to influence the fluctuations in depression symptom severity over 16 weeks. As indicated in Fig. 3, there was a greater reduction over time in depression scores for the high childhood emotional neglect exposure group (difference = 3.287), as compared to the low childhood emotional neglect exposure group (difference = 1.632), with p < 0.01. However, there was no significant difference in the slopes (p = 0.69) (see Fig. 4). This may be attributed to the large fluctuations in depression symptom severity over time.

38 (35.5) 69 (64.5) 23 (21.5) 84 (78.5) 34 (31.8) 62 (57.9) 7 (6.5) 4 (3.7) 42 75 37 45 51

(39.3) (70.1) (34.6) (42.1) (47.7)

a

Participant did not want ethnicity to be recorded. This included participants with substance use disorder with major depressive disorder as differential diagnosis, conversion disorder with major depressive disorder as differential diagnosis, and schizoaffective disorder. b

3.4.2. Mania and time interaction effect We found no significant influence of childhood trauma exposure on fluctuations in mania severity over 16 weeks (see Table 6). Similarly, we found no significant influence of lifetime trauma exposure on the fluctuation in mania severity over 16 weeks. It was only at week 16 that participants who reported high lifetime trauma exposure (as indicated by the LEC-Tot score) showed a greater decrease in mania severity in comparison to the low lifetime trauma exposure group, with F (15.591) = 1.89, p = 0.02. However, since no clear trends over time were identified in either of the LEC groups, this may represent a chance finding.

Table 3 Childhood Trauma Questionnaire. Childhood trauma questionnaire

Mean

SD

Range

Emotional Abuse Physical Abuse Sexual Abuse Emotional Neglect Physical Neglect Total Childhood Trauma

14.46 10.81 10.36 12.82 8.73 57.18

6.902 5.964 6.912 6.393 4.315 22.740

5–25 5–25 5–25 5–25 5–25 25–117

4. Discussion

Note: SD = Standard deviation.

We investigated the association between childhood abuse and neglect and lifetime PTSD-qualifying trauma exposures and mood trajectories in a clinical sample. Trauma exposure was assessed in terms of total childhood abuse and neglect, specific childhood trauma subtypes, and lifetime traumatic events. Further, we aimed to evaluate whether the severity of trauma exposure was associated with the severity of mood symptoms, as reported by patients over 16 weeks. Lastly, we set out to explore the influence of trauma severity on weekly fluctuation in mood symptom severity across time.

(lifetime trauma exposure) and depression scores over time. 3.2.2. Mania Over the 16 weeks of monitoring there were no significant continuous correlations between either CTQ scores or LEC total scores, and mania scores, (see Table 4). For week 13 only significant negative correlations between mania and total childhood trauma (−0.26), childhood physical assault (−0.30), and lifetime trauma exposure (−0.25) scores were observed.

4.1. Association between childhood and lifetime trauma exposure, and mood trajectories

3.3. Association between childhood and lifetime trauma exposure severity and mood symptom severity across time

4.1.1. Depression Our results show a significant association between total childhood trauma exposure and depression trajectories across 16 weeks of mood

3.3.1. Depression group effect As indicated in Table 5, there was a significant difference between 4

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Fig.1. Participants' Depression Trajectories across 16 Weeks. Note: QIDS = Quick Inventory of Depressive Symptomatology; W = week.

monitoring. This is in keeping with previous research on the impact of childhood trauma on mood disorder development (Hovens et al., 2009; Negele et al., 2015; Ross et al., 2019). Unique to this study, however, is the evaluation of baseline trauma in relation to repeated weekly assessments of these associations across 16 weeks. As such, the findings indicate that a history of childhood trauma may have an ongoing impact on the manifestation of depressive symptomatology in patients with mood disorders. Additionally, our results indicate that some subtypes of childhood trauma exposure have a more persistent weekly association with depression over time, as compared to others. Specifically, childhood emotional abuse and neglect, and childhood physical abuse and neglect showed the most persistent weekly association with depressive symptomatology. Surprisingly, childhood sexual abuse showed the weakest weekly association over time. These findings add depth to the existing literature on childhood trauma and mood disorders, as they point not only to the strength of the association between childhood trauma exposure and depression, but also to its persistency over time. While childhood sexual abuse has received much attention as a major early life experience (Cong et al., 2012; Cutajar et al., 2010; Musliner and Singer, 2014), its association with depression is neither continuous, nor as persistent as other forms of maltreatment which have received less attention. This finding might suggests that other factors played a role in modulating the strength of the association over time. Furthermore, despite emotional maltreatment not classifies as an index trauma for

PTSD in the DSM-5 (American Psychiatric Association, 2013), our results show a robust association with depressive symptoms. Further research is warranted to examine inconsistency in findings of childhood trauma exposure and depression over time, and why some subtypes of childhood trauma show a more persistent associations than others. Interestingly, we found no significant association between lifetime trauma exposure and depression trajectories across the 16 weeks of mood monitoring. Since lifetime trauma refers to traumatic events across the lifespan, and as such, includes childhood trauma exposure (although does not explicitly enquire about abuse and neglect), the lack of concordance between the LEC and CTQ may be linked to the fact that these assessment tools measure exposures that are not directly overlapping. Specifically, while the LEC assesses life-threatening, PTSDqualifying events, the CTQ includes non PTSD-qualifying events, such as emotional maltreatment. This highlights the need to screen for a wider range of traumatic experiences. 4.1.2. Mania No significant association between childhood trauma or lifetime trauma exposure and mania symptoms across time were found. As for the lack of association between childhood trauma and mania, the current findings are in contrast to previous epidemiological studies (Palmier-Claus et al., 2016; van Nierop et al., 2015; Zavaschi et al., 2006) which have pointed to a history of childhood trauma as a significant environmental factor in the development of bipolar disorder.

Fig. 2. Participants' Mania Trajectories across 16 Weeks Note: ASRM = Altman Self-Rating Mania Scale; W = week. 5

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Table 4 Pearson's correlations of CTQ/ LEC scores and weekly ASRM/QIDS scores over 16 weeks (N = 107).

CTQ_Tot: QIDS ASRM PN: QIDS ASRM EA: QIDS ASRM EN: QIDS ASRM PA: QIDS ASRM SA: QIDS ASRM LEC_Tot: QIDS ASRM

W1

W2

W3

W4

W5

W6

W7

W8

W9

W10

W11

W12

W13

W14

W15

W16

0.31** −0.01

0.39** −0.04

0.42** −0.16

0.46** −0.10

0.43** −0.12

0.39** 0.01

028* 0.11

0.30** 0.06

0.28* −0.14

0.46** 0.02

0.40** 0.08

0.28* 0.09

0.28* −0.26*

0.19 −0.07

0.19 0.08

0.18 0.19

0.30** 0.12

0.34** 0.03

0.46** −0.09

0.35** −0.01

0.41** −0.09

0.34** 0.05

0.21 0.16

0.33** 0.09

0.20 −0.03

0.40** 0.02

0.30** 0.07

0.29** 0.04

0.29** −0.17

0.17 −0.09

0.19 −0.01

0.22 0.12

0.25** −0.10

0.29** 0.01

0.30** −0.13

0.46** −0.19

0.43** −0.09

0.34** −0.01

0.23* 0.10

0.29** 0.05

0.28** −0.03

0.41** 0.13

0.35** 0.08

0.26* 0.09

0.23 −0.12

0.09 −0.04

0.18 0.09

0.17 0.20

0.28** −0.07

0.37** −0.07

0.37** −0.08

0.38** −0.06

0.41** −0.17

0.31** −0.05

0.16 0.13

0.20 0.01

0.22 −0.18

0.40** −0.00

0.40** 0.06

0.25* −0.01

0.12 −0.22

0.00 −0.14

0.01 −0.03

0.03 0.15

0.24** −0.01

0.25* 0.06

0.31** −0.14

0.35** −0.09

0.31** −0.06

0.36** −0.09

0.22 −0.05

0.27* −0.02

0.22 −0.13

0.31** −0.01

0.25* 0.20

0.18 0.07

0.32** −0.30*

0.22 −0.05

0.20 0.10

0.13 0.16

0.11 0.06

0.22* −0.14

0.22* −0.15

0.20 −0.02

0.17 −0.06

0.13 0.16

0.24* 0.08

0.08 0.09

0.15 −0.14

0.25* −0.06

0.22 −0.08

0.11 0.15

0.13 −0.19

0.24 0.03

0.16 0.13

0.16 0.09

−0.224* 0.187

−0.12 −0.07

−0.03 −0.18

−0.03 −0.05

0.09 0.04

−0.01 −0.11

−0.08 −0.17

0.00 0.10

−0.14 0.09

0.06 −0.12

−0.05 0.03

−0.04 0.01

0.09 −0.25*

−0.03 0.06

−0.03 0.08

−0.03 −0.04

Note: *p ≤ 0.05, **p ≤ 0.01; PN = Physical Neglect, EA = Emotional Abuse, EN = Emotional Neglect, PA = Physical Abuse, SA = Sexual Abuse, CTQ_Tot = Total Childhood Trauma Questionnaire score; ASRM = Altman Self-Rating Mania Scale; QIDS = Quick Inventory of Depressive Symptomatology.

Additionally, studies addressing the psychopathological sequelae of trauma exposure, have found that a history of childhood trauma may lead to alterations in significant functional dimensions; including emotional regulation, impulse regulation, and cognitive functioning. In turn, such alterations can drive several different clinical outcomes, including bipolar disorders, and as such manic episodes (Marwaha et al., 2016; Thompson et al., 2011). Research in terms of the association between lifetime trauma exposure and mania is less clear with mixed findings for severe negative life events in relation to mania (Johnson et al., 2008). As such, the present findings neither confirm nor refute existing literature. Therefore, further research on the psychopathological sequelae of lifetime trauma on mood disorders, including depressive and manic symptoms, is warranted.

4.2. Association between childhood and lifetime trauma exposure severity and mood symptom severity across time 4.2.1. Depression and mania group effects The analysis indicated a significant correlation between the severity of childhood trauma exposure and the severity of depressive symptomatology across 16 weeks. Specifically, the severity of depressive symptomatology was consistently greater in the high trauma exposure group as compared to the low trauma exposure group. These findings are in line with recent research. While there is consistent evidence that childhood trauma exposure has a negative impact on the clinical expression of mood disorders (Maes et al., 2018), recent studies indicate that it is not only the presence of exposure but also the degree of exposure that plays a role in modulating clinical features (Rehan et al., 2017). In terms of depression symptomatology, for example,

Table 5 Comparison between minimum and maximum trauma exposure in terms of QIDS and ASRM scores. Depression Group Effect QIDS LS Mean (SE) Emotional abuse: Low exposure High exposure Physical abuse: Low exposure High exposure Sexual abuse: Low exposure High exposure Emotional neglect: Low exposure High exposure Physical neglect: Low exposure High exposure CTQ_Total: Low exposure High exposure LEC_Total: Low exposure High exposure

F

p

9.570 (1.002) 13.107 (0.786)

7.72

<0.01

10.592 (0.943) 13.742 (1.027)

5.10

11.403 (0.905) 12.187 (1.041)

Mania Group Effect ASRM LS Mean (SE)

F

p

2.614 (0.392) 2.845 (0.301)

0.22

0.64

0.03

2.519 (0.326) 2.452 (0.352)

0.02

0.89

0.32

0.57

2.798 (0.321) 2.682 (0.361)

0.06

0.81

10.046 (0.824) 14.699 (1.005)

12.82

<0.01

2.754 (0.328) 2.285 (0.400)

0.82

0.37

9.955 (0.779) 14.372 (1.242)

9.08

<0.01

2.404 (0.293) 2.441 (0.469)

0.00

0.95

9.019 (1.073) 13.463 (1.040)

8.84

<0.01

2.715 (0.419) 2.542 (0.397)

0.09

0.77

10.631 (1.208) 10.524 (1.021)

0.00

0.95

2.950 (0.484) 2.506 (0.401)

0.50

0.48

Note: QIDS = Quick Inventory of Depressive Symptomatology; W = week; ASRM = Altman Self-Rating Mania Scale; CTQ = Childhood Trauma Questionnaire; LEC = Life Events Checklist; LS = Least Square; SE = Standard Error. 6

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Table 6 Comparison between minimum and maximum trauma exposure in terms of QIDS and ASRM scores and time interaction effecta. QIDS and Time Interaction Effect LS Mean (SE) W1 W16 Emotional Abuse: Low exposure High exposure Physical Abuse: Low exposure High exposure Sexual Abuse: Low exposure High exposure Emotional Neglect: Low exposure High exposure Physical Neglect: Low exposure High exposure CTQ_Total: Low exposure High exposure LEC_Total: Low exposure High exposure

F

P

ASRM and Time Interaction Effect LS Mean (SE) W1 W16

F

p

11.413 (1.198) 14.202 (0.970)

8.260 (1.360) 11.498 (1.126)

0.92

0.54

3.676 (0.607) 3.088 (0.485)

1.704 (0.731) 2.915 (0.621)

0.79

0.69

11.719 (1.120) 14.452 (1.220)

10.010 (1.216) 12.354 (1.372)

0.70

0.79

3.298 (0.535) 3.290 (0.581)

1.448 (0.626) 2.446 (0.724)

0.70

0.78

12.732 (1.065) 13.625 (1.232)

10.951 (1.192) 11.092 (1.381)

0.69

0.79

2.876 (0.510) 3.469 (0.582)

1.914 (0.618) 2.500 (0.718)

0.99

0.47

11.263 (0.998) 16.074 (1.210)

9.631 (1.097) 12.787 (1.458)

2.10

<0.01

3.518 (0.489) 2.815 (0.592)

1.696 (0.273) 2.188 (0.786)

0.91

0.55

11.114 (0.925) 15.143 (1.416)

9.090 (1.019) 13.211 (1.701)

1.23

0.25

2.852 (0.419) 3.714 (0.660)

1.494 (0.488) 2.257 (0.836)

0.98

0.47

10.877 (1.283) 15.192 (1.263)

7.971 (1.410) 10.951 (1.407)

0.69

0.80

3.178 (0.650) 3.077 (0.631)

1.486 (0.751) 3.112 (0.760)

1.41

0.14

13.100 (1.410) 10.969 (1.200)

9.850 (1.528) 10.100 (1.338)

1.21

0.26

2.279 (0.671) 4.093 (0.573)

2.179 (0.773) 1.607 (0.688)

1.89

0.02

Note: QIDS = Quick Inventory of Depressive Symptomatology; W = week; ASRM = Altman Self-Rating Mania Scale; CTQ = Childhood Trauma Questionnaire; LEC = Life Events Checklist; LS = Least Square; SE = Standard Error. a For practical purposes, only the mean scores of Week 1 and Week 16 are presented here. However, various non-significant random fluctuations occurred across the 16 weeks.

Klumparendt and colleagues (2019), found that higher levels of childhood maltreatment were related to more severe symptoms in a sample of individuals with depression (Klumparendt et al., 2019). A correlation between higher childhood trauma exposure severity and more severe depressive symptoms was evident in our sample for all the assessed childhood trauma variables, with the exception of sexual abuse. As such, participants who reported higher exposure to childhood

sexual abuse did not report more severe symptomatology over time. In contrast to childhood trauma exposure, we found no significant difference between low and high lifetime trauma exposure groups in terms of depression severity across 16 weeks. Further research is needed on other factors that may mitigate the impact of sexual abuse and other lifetime traumatic events on depressive symptoms, in terms of both symptom development and severity.

Fig. 3. Trajectories of low emotional neglect and high emotional neglect groups on the QIDS Note: QIDS = Quick Inventory of Depressive Symptomatology; W = week; EN = Emotional Neglect. 7

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Fig. 4. Low and high emotional neglect QIDS slopes Note: QIDS = Quick Inventory of Depressive Symptomatology; W = week; EN = Emotional Neglect.

Our results indicated no association between the severity of trauma exposure, including both childhood and lifetime trauma, and the severity of manic symptoms reported by participants within the 16 weeks.

5. Conclusions This study extends previous findings by highlighting weekly timevarying associations between trauma exposure and mood symptoms through tracking clinical outcomes in relation to a history of trauma. The findings underline the persistent role of childhood trauma exposure in influencing depression symptomatology at multiple points in time, and highlight the importance of assessing childhood trauma exposure, in particular emotional maltreatment, in depressed populations. Moreover, careful enquiry about past trauma exposure in inpatient settings is key and should be factored into clinical monitoring, as past trauma has a persistent correlation with symptoms across time. Additionally, our study identified a pattern in clinical outcomes that was sustained over time; as such, the severity of childhood trauma exposure was linked to the severity of depressive symptomatology on a weekly, albeit fluctuating, basis. However, it is encouraging that high compared to low trauma exposure did not result in more compromised outcomes in terms of depression improvement across 16 weeks.

4.3. Trauma and fluctuation in mood symptom severity over 16 weeks 4.3.1. Depression and time interaction effect Analysis of weekly fluctuations across the 16 weeks indicated numerous random weekly spikes in depression severity, as expected. Participants in both high and low trauma exposure groups (including childhood and lifetime trauma exposure) reported an overall decrease in symptom severity from weeks 1 to 16. At 16 weeks of monitoring there was no difference between the groups in overall rate of improvement from week 1 to week 16. As such, this suggests that, although individuals with an increased level of childhood trauma exposure (high group) may develop clinically severe depression, clinical improvement over time may not be impacted by trauma severity. This is in contrast with previous research linking the severity of trauma to unfavourable outcomes over time (Wiersma et al., 2009). For example, Negele and colleagues (2015) reported that major exposure to childhood adversities not only led to more depressive symptomatology but also affected recovery and was associated to poorer outcomes, such as chronicity of symptoms (Negele et al., 2015). However, this contradictory finding should be considered keeping the context in mind. Specifically, the inherent therapeutic effect of weekly telephonic mood monitoring (van der Watt et al., 2018c,d) should be considered in terms of its potential role as a mitigating factor contributing to beneficial outcomes.

5.1. Strengths, limitations, and recommendations There is an abundance of research exploring the impact of trauma on the aetiology, clinical expression, and symptom progression of mood disorders. However, to our knowledge, this is the first study to investigate the effects of trauma exposure on mood through longitudinal weekly assessments. As such, the present study adds further insights, highlighting time-varying associations which occur weekly and that might otherwise be missed. Nevertheless, the present findings should be interpreted keeping some limitations in mind. First, retrospective assessments of traumatic exposure during childhood may be influenced by uncontrolled recall bias (Hardt and Rutter, 2004). Second, patients may under- or overreport histories of childhood trauma according to their current mood symptoms (Etain et al., 2015). Further, the generalizability of our results is limited as they are based on small sample comprising a lowincome, low-educated population. Future research should include larger, more diverse samples. The possibility of response bias in terms of weekly mood symptoms, for example bipolar participants downplaying their mania symptoms, should be considered. Additionally, a

4.3.2. Mania and time interaction effect There were random weekly spikes in mania severity over time. Despite these spikes, participants in both high and low childhood trauma exposure groups reported an overall clinical improvement from week 1 to week 16. Similar to the improvement in depression scores, we found that the overall rate of improvement was the same for high and low childhood trauma exposure groups from week 1 to week 16. As such, the severity of childhood trauma exposure did not appear to have a negative impact on manic episode outcomes at 16 weeks. 8

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lack of data on treatment adherence limits the interpretation of the present findings. As such, we recommend future research to include weekly assessment of treatment adherence. Furthermore, whilst major depressive disorder and bipolar disorder are delineated as distinct disorders in the DMS-5 (American Psychiatric Association, 2013), in our analysis we pooled these patients together and adopted a transdiagnostic, dimensional approach in analysing temporal trends in depressive symptoms. Larger sample studies that allow for stratification by mood disorder category are needed. Lastly, the small sample of male participants is a limitation. Consequently we were not able to assess gender differences in trauma exposure (Olff, 2017) which may in turn influence the psychopathological effects of abuse. This is an important consideration in assessing mood fluctuations over time in future studies.

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