TYPE Original Research PUBLISHED 20 October 2022 DOI 10.3389/fpsyt.2022.931374 High incidence of PTSD OPEN ACCESS diagnosis and trauma-related symptoms in a trauma exposed EDITED BY Claudia Carmassi, University of Pisa, Italy REVIEWED BY Christoph Born, bipolar I and II sample Klinikum am Weissenhof, Germany Outi Linnaranta, National Institute for Health and Bridget Hogg1,2,3,4 , Alicia Valiente-Gómez1,2,4 , Welfare, Finland Rikinkumar S. Patel, Diego Redolar-Ripoll5,6 , Itxaso Gardoki-Souto1,3 , Duke University Medical Center, United States Marta Fontana-McNally1,2 , Walter Lupo1 , Esther Jiménez4,7 , *CORRESPONDENCE Mercè Madre8,9,10 , Laura Blanco-Presas9,10,11 , María Reinares4,7 , Ana Moreno-Alcázar Romina Cortizo12,13 , Anna Massó-Rodriguez14 , Juan Castaño13 , amoreno.centreforum@gmail.com Isabel Argila9,10 , José Ignacio Castro-Rodríguez13 , † These authors share senior authorship Mercè Comes4,7 , Marta Doñate13,15 , Elvira Herrería9 , SPECIALTY SECTION This article was submitted to Cristina Macias1,16 , Estanislao Mur2,13 , Patricia Novo14,17 , Mood Disorders, Adriane R. Rosa18,19,20 , Eduard Vieta4,7 , Joaquim Radua4,7,21,22 , a section of the journal Frontiers in Psychiatry Frank Padberg23 , Victor Pérez-Solà2,4,13,24 , RECEIVED 28 April 2022 Ana Moreno-Alcázar1,2,4*† and Benedikt L. Amann1,2,4,23,24† ACCEPTED 30 September 2022 1 PUBLISHED 20 October 2022 Centre Fòrum Research Unit, Institute of Neuropsychiatry and Addiction (INAD), Parc de Salut Mar, Barcelona, Spain, 2 Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain, 3 PhD CITATION Programme, Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Hogg B, Valiente-Gómez A, Barcelona, Spain, 4 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto Redolar-Ripoll D, Gardoki-Souto I, Carlos III, Madrid, Spain, 5 Neuromodulation Unit, Institut Brain, Barcelona, Spain, 6 Cognitive Fontana-McNally M, Lupo W, NeuroLab, Faculty of Psychology and Educational Sciences, Universitat Oberta de Catalunya (UOC), Jiménez E, Madre M, Blanco-Presas L, Barcelona, Spain, 7 Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Reinares M, Cortizo R, L’Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 8 Addictive Massó-Rodriguez A, Castaño J, Behaviours Unit, Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Argila I, Castro-Rodríguez JI, 9 Hospital Benito Menni-CASM, Sant Boi de Llobregat, Barcelona, Spain, 10 FIDMAG Germanes Comes M, Doñate M, Herrería E, Hospitalàries Research Foundation, Barcelona, Spain, 11 Programa TEPT-AGRESX, Instituto de Macias C, Mur E, Novo P, Rosa AR, Neurociencias (ICN), Hospital Clinic, Barcelona, Spain, 12 Centro Salud Mental Adultos Ciutat Vella, Vieta E, Radua J, Padberg F, Parc Sanitari Sant Joan de Déu, Barcelona, Spain, 13 Centro Salud Mental Adultos (CSMA), Institute of Pérez-Solà V, Moreno-Alcázar A and Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, Spain, 14 Centro de Salud Amann BL (2022) High incidence of Mental Infantil y Juvenil (CSMIJ), Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut PTSD diagnosis and trauma-related Mar, Barcelona, Spain, 15 Parc Sanitari Sant Joan de Deu, Sant Boi de Llobegrat, Spain, 16 Centre Emili symptoms in a trauma exposed bipolar Mira, Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, Spain, 17 Day I and II sample. Hospital, Centro de Psicoterapia de Barcelona (CPB), Barcelona, Spain, 18 Laboratory of Molecular Front. Psychiatry 13:931374. Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil, 19 Departamento de doi: 10.3389/fpsyt.2022.931374 Farmacologia, Instituto de Ciéncias Básicas de Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 20 Postgraduate Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande doSul (UFRGS), Porto Alegre, Brazil, 21 Department of Clinical Neuroscience, Karolinska Institutet (KI), Solna, Sweden, 22 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, 23 Clinic for Psychiatry and Psychotherapy, Klinikum der Universität München, Munich, Germany, 24 Departamento de Medicina y Ciencias de la Vida, Universitat Pompeu Fabra, Barcelona, Spain Background: Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. Objective: (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. Frontiers in Psychiatry 01 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 Methods: This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (https://clinicaltrials.gov; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. Results: The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Conclusion: Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients. KEYWORDS bipolar disorder, PTSD—post-traumatic stress disorder, psychological trauma, sexual abuse, physical abuse and neglect, dissociation Introduction Comorbidity of PTSD and BD leads to a higher symptom burden and lower quality of life (9), and psychological Bipolar disorder (BD) is a severe mental illness which trauma during childhood has been associated with a more negatively impacts life expectancy (1) and is characterized by severe form of the disease: it has been implicated in depressive and at least one manic or hypomanic episode in the an earlier onset of BD, increased suicidality, increased case of BD Type I (BD-I), and by depressive and at least one substance abuse, lower functioning, more hospitalizations, and hypomanic episode in the case of BD Type 2 (BD-II) (2). The faster cycling frequencies (6, 7, 12–14). It has also been aetiology of BD is understood to be complex, involving multiple associated with more psychosocial stressors occurring before genes (3) and gene x environment interactions (4), as well as the first and most recent affective episodes (6). Psychological environmental risk factors (5). trauma may partially mediate the relationship between a One factor which has received increasing attention in the family history of mood disorder and its expression (15), aetiology and prognosis of BD is psychological trauma, which and studies have shown that early life stress may interact predicts increased comorbidity with other mental and somatic with genes of several biological pathways to lead to a disorders (6), including, notably, post-traumatic stress disorder poorer prognosis in BD, including lower age at onset, or (PTSD) (7). The prevalence of PTSD in bipolar patients has increased suicide risk (4, 12). Even at the subsyndromal been estimated between 4 and 40% according to reviews (8, 9), level, post-traumatic stress symptoms are, like full PTSD, compared to an estimated lifetime prevalence of 6.2% in the associated with significant social and work impairment and a general population (10). Research suggests there may be a higher greater number of suicide attempts in the general population prevalence of PTSD in patients with BD-I compared to BD- (16), and were found to be associated with increased II (9, 11), but the symptom presentation appears to be similar symptoms of anxiety in BD patients during the COVID-19 across both subtypes (11). pandemic (17). Frontiers in Psychiatry 02 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 Evidence suggests that different forms of psychological 3. To investigate if the presentation of trauma symptoms, in trauma can increase the risk of psychiatric disorders in different terms of re-experiencing, avoidance, arousal, or dissociative ways (18). Physical, emotional, and sexual abuse in childhood symptoms, is the same across BD-I and BD-II. are all independently associated with a greater risk of BD (15), and have all been shown to predict an increased number of Our secondary research objectives were: suicide attempts and lower age of onset (6, 14, 19, 20), as well as cognitive impairment (21). However, childhood physical 1. To investigate if a lifetime PTSD diagnosis as compared abuse and sexual abuse have also both been found to be to never having received a PTSD diagnosis is associated associated with faster cycling frequencies, more substance abuse with a history of psychotic symptoms, suicidal ideation and and comorbidity with other disorders, and more psychosocial suicide attempts, current rapid cycling, an earlier onset of stressors occurring before the first and most recent affective disease, a lower level of functioning, and a greater degree of episode (6, 19, 20). Specifically, sexual abuse has been shown cognitive impairment. to be the strongest predictor of rapid cycling (20), and also to 2. To investigate if reporting having experienced sexual be associated with an increased number of mood episodes and abuse, compared to not reporting having experienced with psychotic episodes (14). Meanwhile, physical abuse was sexual, is associated with a history of psychotic symptoms, associated with self-harm episodes, and both emotional abuse suicidal ideation and suicide attempts, current rapid and physical abuse were associated with lower functioning (14), cycling, an earlier onset of disease, and a greater number while more research is needed into the impact of emotional of hospital admissions. abuse in severe mental illness (22). 3. To investigate if reporting having experienced physical Despite strong evidence of the link between trauma and abuse, compared to not reporting having experienced BD, and high comorbidity with PTSD, there has been little physical abuse, is associated with a history of psychotic focus on how to treat this comorbidity (9). Additionally, symptoms, suicidal ideation and suicide attempts, current more research is needed into dissociative disorders in patients rapid cycling, an earlier onset of disease, and a greater with BD and other severe mental illnesses (22). To address number of hospital admissions. these gaps in current research, a multi-center study (23) was implemented to evaluate the effectiveness of a trauma- focused psychotherapy called Eye Movement Desensitization Materials and methods and Reprocessing (EMDR) (24) in a trauma-exposed sample of adult BD I and BD II patients. During the baseline Data visit for this trial, we collected data covering the detailed retrospective trauma history, symptoms related to reported The data in this paper is the baseline data from a study trauma and dissociation, and the clinical characteristics of evaluating the effectiveness of a trauma-focused therapy in a sample of 79 participants with BD and a history of traumatized bipolar patients (23). This was a multicenter project psychological trauma. comprising three hospitals from the Barcelona area of Spain In this paper, we present this data, the first to our knowledge (Hospital Benito Menni, Hospital Clínic of Barcelona and to review the sociodemographic and clinical characteristics of Hospital Parc de Salut Mar). The trial was registered prior to a trauma-exposed bipolar disorder sample, with or without the starting enrolment at Clinical Trials (https://clinicaltrials.gov) presence of a diagnosis of PTSD. Based on the aforementioned under reference NCT02634372. research, we hypothesized that there would be significantly greater comorbidity between BD-I and PTSD and BD-II and PTSD, but that there would not be significant differences in Participants the presentation of trauma symptoms according to BD subtype. Furthermore, we hypothesized that comorbidity with PTSD Participants who met criteria for BD-I or BD-II according in a sample of traumatized BD patients would be associated to DSM-IV criteria, based on clinical interview and a review with a worse disease course, and that reported sexual abuse of case notes, were referred to the study by their referent and physical abuse would each be associated with a worse psychiatrist. The inclusion criteria for participants was: (1) to disease course. Therefore, our primary research objectives were be aged between 18 and 65; (2) to have experienced two to the following: six affective episodes over the previous 12 months; (3) current clinical status of euthymia or subsyndromal symptoms at the 1. To present the sociodemographic, trauma, and clinical moment of the assessment, defined by a score representing the characteristics of a sample of trauma-exposed BD patients. past week on the Bipolar Depression Rating Scale (BDRS) of 2. To investigate if there is significantly greater comorbidity <14 and a score representing the previous 2 days on the Young between BD-I and PTSD than between BD-II and PTSD. Mania Rating Scale (YMRS) of <12; (4) Presence of a traumatic Frontiers in Psychiatry 03 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 event according to the Clinician Administered PTSD CAPS-DX 6. Current pharmacological treatment, based on their current scale 0; (5) Current trauma symptoms as indicated by a score >0 prescription, and current psychological treatment, based on on the Impact of Events Scale-Revised (IES-R). The inclusion patient report and medical records. criteria were designed to enable the testing of the primary 7. Family history of psychiatric disorder, based on patient hypothesis of the clinical trial comparing EMDR therapy with recall and review of medical records. Supportive Psychotherapy. The EMDR therapy protocol was 8. Use of substances, collected through patient self-report. designed for use with all patients excluding those with active acute symptoms in the present moment, and therefore we Clinical features, trauma history and symptomatology, screened for active acute symptoms. To be able to test the functioning and cognitive impairment were all assessed by impact on number of affective episodes, it was necessary to means of validated scales. Where available, we used scales include patients with multiple previous episodes, and the 12- specifically designed for use in a BD population, and where this month criteria ensures recent instability as well as permitting was not possible we used the gold standard or most widely used classification into rapid cycling (≥4 episodes in the previous scale. Clinical severity was measured using the following scales: year) or not. Exclusion criteria were: (1) current substance abuse/dependency, i.e., not meeting criteria for early remission 1. The Bipolar Depression Rating Scale (BDRS) (26), Spanish (three to 12 months without meeting criteria) or sustained validation (BDRS-S) (27). This clinician-administered scale remission (over 12 months without meeting criteria) (25), with is used to assess depressive and mixed symptoms in the exception of nicotine; (2) neurological disease or brain BD-I and BD-II patients. The BDRS includes 20 items, trauma history; (3) current suicidal ideation; (4) having received which sum to a total score between zero and 50. a trauma-focused therapy within the previous 2 years. Scores of <8 indicate euthymia and ≥8 and <14 the presence of subsyndromal symptoms. A score of ≥14 indicates the presence of an acute depressive episode. The Spanish validation was carried out with a relatively Variables of study small sample size but shows robust psychometric properties and captures depressive and mixed symptoms in Spanish Patient data was collected by trained evaluators who were bipolar patients. all qualified psychologists or psychiatrists working within the 2. The Young Mania Rating Scale (YMRS) (28), Spanish participating centers. Each patient was assigned a code, and this validation (29), is a clinician-administered scale composed was used throughout the data collection to ensure anonymity. A of 11 items aimed at quantifying the severity of manic and Case Report Form (CRF) was designed to capture baseline data hypomanic features. Of the 11 items, four items (irritability, such as sociodemographic variables and clinical variables related speech, thought content and disruptive/aggressive to the onset and course of BD. The following data was collected behavior) are graded on a scale of 0 to 8, while the through clinical interview contrasted with a review of medical remaining seven items are graded on a 0 to 4 scale. Total case notes: scores range between 0 and 60: scores of <6 indicate euthymia, between ≥7 and <12 indicate the presence of 1. Age of onset, defined as the first manic, hypomanic, mixed subsyndromal symptoms, while scores of ≥12 indicate the or depressive episode as per DSM-IV criteria. This data presence of moderate to severe manic symptomatology. was based on patient recall during the clinical interview, The Spanish validation shows this is a reliable tool for the contrasted with notes from medical records. assessment of manic symptoms in patient with manic or 2. History of psychotic symptoms, defined as having ever hypomanic symptoms in Spain. experienced psychotic symptoms in line with DSM-IV criteria, based on clinical interview and a review of Reported trauma history and symptomatology were medical records. evaluated using the below scales: 3. Number of relapses over the last year, with a relapse defined as a manic, hypomanic, mixed, or depressive affective 1. The Clinician-Administered PTSD Scale (CAPS-DX) (30), episode as per DSM-IV criteria, with data gathered through Spanish validation (31). The CAPS is the gold standard for clinical interview and a review of medical records. determining a diagnosis of PTSD according to DSM-IV 4. Current rapid cycling, defined as four or more affective criteria. It provides a diagnosis of both current and lifetime episodes over the previous 12 month period, with data PTSD. The Spanish validation showed good reliability, gathered through clinical interview and a review of internal consistency and rest-retest values, similar to the medical records. original version. 5. History of suicide attempts, based on patient recall and 2. The Impact of Event Scale-Revised (IES-R) (32), Spanish review of medical records. validation (33). The IES-R is a 22-item self-report scale. Frontiers in Psychiatry 04 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 It measures the presence of subjective distress related to a verbal learning, working memory, verbal language, and specific traumatic event, yielding an overall score and one processing speed. The scale provides a score for each for each of its three subscales, intrusion, avoidance, and subdomain and then a global score obtained by summing hyperarousal, which correspond to the DSM-IV diagnostic all scores. Lower scores indicate a greater level of cognitive criteria for PTSD. Higher scores indicate greater distress impairment. The Spanish validation was carried out in a and a score of >32 has been suggested as the cut off for the psychiatric population of patients with schizophrenia, and presence of PTSD symptoms (34). The Spanish validation showed good validity and reliability. in a large sample showed adequate internal consistency and convergent validity with other scales of psychopathology, but some difficulties with the test-retest validity. Data analysis 3. The Holmes-Rahe Life Stress Inventory (35), Spanish validation (36). This scale measures the number of stressful Since the data in this paper come from a study where the events that have occurred over the previous 12 months. sample size was determined to understand the effectiveness of Each potential stressful event is accorded a weighted score EMDR therapy compared to Supportive Therapy, in which the depending on how stressful it is estimated to be, and these sample size calculation was based on a survival analysis using the are summed to provide a total score. A score of under statistical package “powerSurvEpi” for R (http://www.r-project. 150 reflects low levels of stress and a low risk of stress- org/) (40), we performed a second sample size calculation to related illness, scores from 150–299 reflect a moderate level ensure the sample size is sufficient to meet the objectives of of stress which can imply a 50% risk of developing a stress- the current paper. In this case, the sample size was based on a related illness, and scores of 300 and over reflect a high level correlation test, given the difficulty of exact data regarding the of stress which can imply an 80% risk of developing a stress- prevalence of BD patients with a history of psychological trauma related illness. The Spanish validation includes a cultural in the population. A sample of 79 patients, with a statistical adaptation of the items. power of 80% and a type I error rate of 0.05, is sufficient to detect 4. Dissociative Experiences Scale (DES) (37), Spanish low correlations (R = 0.31) (43, 44). validation (38). This scale assesses the presence of All statistical analyses were carried out using STATA dissociation, by asking participants the percentage of time Statistics/Data analysis, version 16.1 (StataCorp LLC, Texas, they experience a range of dissociative symptoms. The USA). Fitness to parametric assumptions was checked for results yield an average total score and an average score all variables, and the Shapiro–Wilk test was used to assess for each of the three subscales: amnesia, absorption, and the normality of data distribution. With regards to the depersonalization. Total scores of 30 or higher indicate descriptive analysis of the sociodemographic and clinical data, a potential Dissociative Identity Disorder. The DES is the arithmetic mean was used for quantitative variables and the scale most often employed to measure dissociative the proportion for categorical variables. In the case of the symptoms in bipolar patients (39). The Spanish validation impossibility of reconciling patient recall data with medical was carried out in healthy adults and in inpatients with history, or failure to log a valid response to an item, listwise schizophrenia. The scale was shown to be valid in both deletion was applied and analyses are based on the total populations, with improved validity in a psychiatric number of valid responses for each question. The standard population when the scale was administered by a clinician. area and the confidence interval, set at 95%, were calculated for both quantitative and categorical variables. Pearson Chi The level of functioning and cognitive impairment was squared test was used to analyze the relationship between evaluated using the following scales: two binomial categorical variables, and a two-sample t-test was used for analysing the relationship with the quantitative 1. Functioning Assessment Short Test (FAST) (40). This scale dependent variables. evaluates level of functioning through 24 items assessing six Firstly, the relationship between BD-I or BD-II and a lifetime domains: autonomy, work, cognitive functioning, finances, diagnosis of PTSD was analyzed. The lifetime PTSD group interpersonal relationships, and leisure. Each item is scored comprised both those with a current and lifetime diagnosis from 0–3, and overall scores range from 0-72. Higher of PTSD; while those who had never met criteria for PTSD scores indicate a lower level of functioning. This scale was comprised the non-PTSD group. The current and lifetime PTSD originally developed in Spanish for a Spanish population. diagnoses were included together as most of the variables against 2. Screen for Cognitive Impairment in Psychiatry (SCIP) which it was planned to be analyzed were not current (e.g., (41), Spanish validation (42). The SCIP is a clinician- lifetime number of hospital admissions, lifetime number of administered scale which assesses cognitive impairment in suicide attempts, ever having experienced psychotic symptoms, psychiatric patients. This scale briefly assesses five different ever having experienced suicidal ideation). Secondly, analyses cognitive domains: immediate verbal learning, delayed were carried out for the relationship between BD-I and BD-II Frontiers in Psychiatry 05 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 and the impact of the traumatic event (IES-R) and dissociative sample, 40.5% (n = 32) were single, 38.0% (n = 30) married or symptoms (DES). Thirdly, the relationship between a lifetime in a civil partnership, 1.3% (n = 1) widowed and 20.3% (n = 16) diagnosis of PTSD and a range of clinical symptoms: having separated. The majority (61.8%, n = 47) were on temporary or experienced suicidal ideation, attempted suicide, experienced permanent sick leave, while 22.3% (n = 17) were employed and psychotic symptoms, rapid cycling, number of suicide attempts, working either full- or part-time. These results can be seen in full age of BD onset, number of hospital admissions, stressful in Table 1. events over the previous 12 months (Holmes & Rahe scale), The average age of onset of BD in our sample was 29.53 (SD level of functioning (FAST), and level of cognitive impairment ± 10.840) years old. Age of onset was significantly higher in BD- (S-SCIP) was analyzed. Fourthly, analyses were carried out II patients than BD-I (33.10 years compared to 28.39 years, p = to determine the relationship between sexual abuse and four 0.044), and in women compared to men (30.89 years compared categorical variables (whether the participant had experienced to 24.65 years, p = 0.017). suicidal ideation, had a history of suicide attempts, had Patients had experienced on average 3.27 hospital admission experienced psychotic symptoms, and rapid cycling), and two during their lifetime, and 2.48 affective episodes in the previous quantitative variables (age of onset of BD, and number of 12 months. In our sample, 73.4% (n = 58) had a diagnosis of BD- hospital admissions). Finally, this analysis was repeated with I compared to 26.6% (n = 21) with a diagnosis of BD-II, 13.9% physical abuse instead of sexual abuse as the independent (n = 11) experienced rapid cycling, and 46.2% (n = 36) had variable. In all analyses, p-value significance was set at <0.05. experienced psychotic symptoms. Regarding suicidality, 79.7% We also present adjusted p-values based on applying the (n = 63) had experienced suicidal ideation and 39.7% (n = 31) Holm-Bonferroni correction for multiple comparisons (45). had attempted suicide. Data regarding severity was available for Although only two independent groups are compared in the 29 patients, and in over half of those cases (51.7%; n = 15) study, several dependent variables are evaluated. Performing the attempt had resulted in severe injury. The most common multiple comparisons of the two independent groups for the medications taken by our sample were mood stabilizers (94.6%; independent variables may increase the type I error (alpha n = 70) and anti-psychotics (75.7%; n = 56). α1 type error), increasing the risk of falsely rejecting the null Comparison of the sociodemographic and clinical variables hypothesis, being true in the population. To account for this in the current study, as compared to large BD samples from possible effect, we performed the Holm-Bonferroni procedure. four other studies which are not specifically in a traumatized However, applying the adjustment for multiple comparisons population (45–48), as well as sociodemographic data for the increases the risk of a type II error, of falsely accepting the null Barcelona area can be seen in Supplementary Table S1. Our hypothesis, and this risk is arguably greater where the analyses sample had a higher proportion of females and higher age of are pre-planned and based on prior evidence (46–49). Therefore, onset than other studies. The proportion of BD-II patients was, we present both adjusted and unadjusted p-values. while a minority, greater than in the majority of other studies. Educational level was lower than in other studies and reflected the norms for the Barcelona area. Suicidality was similar to other Ethical approval studies, while a history of psychotic symptoms and current rapid cycling were lower than in most other studies. The study received ethical approval from the Ethics Committee of the Germanes Hospitalàries del Sagrat Cor de Jesús (reference number: PR-2014-15), the Hospital Clínic Reported trauma symptoms and profile of Barcelona (reference number: HCB/2015/1005) and the Hospital Parc de Salut Mar (reference number: 2015/6502/l). All The majority (79.7%; n = 59) had experienced a relevant participants signed informed consent prior to enrolment. stressful life event prior to onset of BD. Over half of our sample (51.9%; n = 40) had a lifetime diagnosis of PTSD according to the CAPS. In more than half of these cases, the lifetime diagnosis Results of PTSD was current, meaning 27.3% of the total sample (n = 21) had a current PTSD diagnosis. To carry out the clinical Sociodemographic and clinical variables interview for PTSD, using the CAPS scale, participants are asked for the reported traumatic event which most affects them. In In total, 82 subjects agreed to participate in the study, but nearly half of cases (45.3%; n = 34), this was not related to three did not complete the baseline assessment, leaving a total a specific reported traumatic event category. Following this, sample of 79. Most of our sample were females (77.2%, n = physical abuse, sexual abuse, and the sudden death of a loved 61) and Caucasian (94.6%, n = 70). The mean age was 46.56 one were all chosen by 12.0% of participants (n = 9), followed by [SD (standard deviation) ± 8.408] and participants had spent violent death (9.3%; n = 7), followed by a life-threatening illness an average of 13.74 (SD ± 3.834) years in education. Of the (5.3%; n = 4) and transport accident (4.0%; n = 3). The average Frontiers in Psychiatry 06 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 TABLE 1 Sociodemographic characteristics of the sample. Variable Obs/Freq Mean /Percentage* Std. Err. [95% Conf. Interval] Age 79 46.56 1 45 48 Education (years of studies) 57 13.74 1 13 15 Sex Male 18 22.8% 0.050 0.142 0.34 Female 61 77.2% 0.050 0.661 0.858 Race Caucasian 70 94.6% 0.027 0.857 0.979 Latin American 3 4.1% 0.024 0.013 0.125 Asian 1 1.4% 0.014 0.002 0.096 Relationship status Single 32 40.5% 0.058 0.299 0.528 Married/civil partnership 30 38.0% 0.057 0.261 0.486 Widowed 1 1.3% 0.014 0.002 0.096 Separated/divorced 16 20.3% 0.048 0.130 0.324 Employment status Student 4 5.3% 0.027 0.021 0.143 Homemaker 1 1.3% 0.014 0.002 0.096 Employed full-time 14 18.4% 0.047 0.119 0.308 Employed part-time 3 3.9% 0.020 0.007 0.108 Temporary sick leave 32 42.1% 0.059 0.325 0.555 Permanent disability payments due to mental illness 14 18.4% 0.044 0.098 0.277 Permanent disability payments for other reasons 1 1.3% 0.014 0.002 0.096 Unemployed 5 6.8% 0.030 0.029 0.160 Other 2 2.6% 0.014 0.002 0.096 Data are presented as mean or number (%). Obs/Freq: Number of cases observed/Frequency; Std. Error: Standard Error; Conf.: Confidence. *Age and education data are presented as means. The rest of the variables are presented as percentages. age of the participant at the time of the event was 24.18 (SD ± presence or not of a lifetime diagnosis of PTSD [χ2 (1) = 0.702, 16.327). However, approximately half of our sample (50.0%; n p = 0.402]. = 38) reported having experienced sexual abuse, while a lower percentage reported having experienced physical abuse (42.1%, n = 32). In our sample, over the previous 12 months, participants Trauma symptom profile per BD subtype reported on the Holmes and Rahe scale having experienced an average of 6.72 stressful events each, with an average total score Our results showed no significant differences in the of 214, indicating a moderate level of stress. These results can be expression of trauma symptoms between BD subtypes in terms seen in Table 2. of intrusion, avoidance, hyperarousal, or dissociative symptoms. Across our sample, the mean score on the IES-R was 38.95, These results can be seen in Supplementary Table S2. indicating PTSD symptoms. In this scale, participants with a lifetime diagnosis of PTSD had a significantly higher average score of 47.19 compared to 29.72 in the non PTSD group [t(72) = −2.783, p = 0.007]. Regarding dissociative symptoms, the Impact of PTSD on disease course and average score on the DES was 13.24, and was significantly higher cognition in the PTSD group (an average score of 15.53 compared to 10.75), [t(70) = −2.224, p = 0.029]. A lifetime PTSD diagnosis was significantly associated with having experienced psychotic symptoms [χ2 (1) = 5.404, p = 0.02]. Our results showed that PTSD did not have a significant impact on disease course in terms of suicidal ideation or BD subtype and presence of lifetime behavior, or rapid cycling (please see Table 3). No significant diagnosis of PTSD difference was found between lifetime PTSD diagnosis and age of onset, number of hospital admissions, level of functioning The Chi squared analysis found no significant between- according to the FAST, or cognition according to the SCIP, when group differences between Bipolar Type (BD-I or BD-II) and the compared to the sample without a PTSD diagnosis. These results Frontiers in Psychiatry 07 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 TABLE 2 Clinical characteristics of the sample. Variable Obs/Freq Mean/Percentage* Std. Err. (95% Conf. Interval) Age of onset of bipolar disorder 78 29.53 1 28 33 Number of hospital admissions 77 3.27 1 2 5 Number of affective episodes in the last year 79 2.48 0 2 3 Number of suicide attempts 78 0.85 0 0 1 BDRS (total score) 79 9.29 1 8 11 YMRS (total score) 79 2.23 0 2 3 Holmes and Rahe Scale (number of events) 74 6.72 1 6 8 Holmes and Rahe Scale (total score) 74 214 18 177 251 Age of CAPS event 57 24.18 2 20 29 IES-R (total score) 75 38.95 2.973 33.1 44.8 DES (total score) 74 13.24 1.105 11.1 15.4 BD subtype BD-I 58 73.4% 0.093 0.447 0.815 BD-II 21 26.6% 0.093 0.185 0.553 Presence of rapid cycling No 68 86.1% 0.071 0.6424 0.944 Yes 11 13.9% 0.071 0.056 0.358 Ever experienced psychotic symptoms No 42 53.8% 0.093 0.447 0.815 Yes 36 46.2% 0.093 0.185 0.553 Stressful event at time on onset No 15 20.3% 0.077 0.079 0.399 Yes 59 79.7% 0.077 0.601 0.921 Ever experienced suicidal ideation No 16 20.3% 0.052 0.018 0.275 Yes 63 79.7% 0.052 0.725 0.982 Suicide attempt No 47 60.3% 0.056 0.494 0.712 Yes 31 39.7% 0.056 0.288 0.506 Severity of Suicide attempt No 14 48.3% 0.098 0.276 0.658 Yes 15 51.7% 0.098 0.342 0.724 Adherence to treatment Good 73 94.8% 0.063 0.684 0.964 Partial 4 5.2% 0.063 0.036 0.316 Mood stabilizers No 4 5.4% 0.052 0.018 0.275 Yes 70 94.6% 0.052 0.725 0.982 Antipsychotic No 18 24.3% 0.071 0.056 0.358 Yes 56 75.7% 0.071 0.642 0.944 Anxiolytic No 41 55.4% 0.095 0.214 0.589 Yes 33 44.6% 0.095 0.411 0.786 Antidepressant No 42 57.5% 0.097 0.376 0.755 Yes 31 42.5% 0.095 0.214 0.589 Other Meds No 59 79.7% 0.077 0.601 0.921 Yes 15 20.3% 0.077 0.079 0.399 CAPS selected event Accident (transport) 3 4.0% 0.052 0.018 0.275 Physical abuse 9 12.0% 0.071 0.056 0.358 Sexual abuse 9 12.0% 0.063 0.036 0.316 Life-threatening illness 4 5.3% 0.038 0.005 0.246 Violent death 7 9.3% 0.052 0.018 0.275 Sudden death 9 12.0% 0.071 0.056 0.358 Other 34 45.3% 0.095 0.214 0.589 Data are presented as mean or number (%). Obs/Freq: Number of cases observed/Frequency; Std. Error: Standard Error; Conf.: Confidence; BDRS: Bipolar Depression Rating Scale; YMRS: Young Mania Rating Scale; IES-R: Impact of Event Scale-Revised; DES: Dissociative Experiences Scale. * Variables up to and including “DES Score” are presented as means. The rest of the variables are presented as percentages. Frontiers in Psychiatry 08 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 can be seen in Table 4. The p-values were no longer significant the average age at which the most important traumatic event following application of the Holm-Bonferroni to adjust for occurred was 24.18. multiple comparisons. The level of education of our participants was representative We conducted sensitivity analyses to understand whether for the Barcelona area (see Supplementary Table S2), and lower there was a significantly different impact from a current PTSD than in other studies, where the samples were found to be diagnosis as compared to a historical (but not current) PTSD more highly educated than the general population (45, 46, diagnosis. We found no significant differences between the 48). Most patients in our sample were unable to work either current and historical PTSD group, or the current and never temporarily or permanently due to BD. Most of our sample PTSD groups, on any of the variables tested (total FAST score, of traumatized BD patients (79.7%) had suffered from suicidal total SCIP score, rapid cycling, history of psychotic symptoms, ideation at some point in their lives, and 39.7% had carried out age of onset, history of suicide attempts or suicidal ideation). The a suicide attempt, comparable to data from other BD samples only significant difference on these variables when comparing (see Supplementary Table S2). Of note, current suicidal ideation the lifetime PTSD group with the never PTSD group was in the was a criterion for exclusion in our study. In our sample, history of psychotic symptoms [χ2 (1) = 6.175, p = 0.013; please 13.9% currently experienced rapid cycling, lower than in other see Supplementary Table S3], in line with the findings from our samples but participants were excluded from our study if they main analysis. had experienced >6 mood episodes in the previous 12 months. A history of psychotic symptoms was present in 46.2% of our overall sample, lower than in some other samples but this may Impact of sexual and physical abuse on partially be due to the higher proportion of BD-II patients, where disease course psychotic symptoms are not a feature of the disease course. The average age of participants in our sample was 46.56 years Sexual abuse was shown to be significantly associated and the average age of BD onset was 29.53 years. The age of with rapid cycling [χ2 (1) = 4.15, p = 0.042]; results were onset in our study is much higher than the late teens and early not significant following application of the Holm-Bonferroni twenties reported in other studies (see Supplementary Table S1). to adjust for multiple comparisons. There was no significant This may partially be explained by the fact that, as compared association between sexual abuse and suicidal ideation, to other studies, the mean age of our sample was higher, there psychotic symptoms, or history of ever having attempted was a higher percentage of females, and BD-II patients formed suicide, or physical abuse and any of the aforementioned a larger proportion of the total sample than in other studies: variables (see Table 3). Similarly, there was no significant females were shown in our study to have a significantly later association between sexual or physical abuse and number age of onset than males, and the same pattern was found for of suicide attempts, age of onset of BD, or number of BD-II patients as compared to BD-I, both patterns reflected hospital admissions. These results can be seen in full in in other research (52). However, a surprising finding was that Supplementary Table S4. there was no significant association between age of onset and physical abuse, sexual abuse, or a lifetime PTSD diagnosis, although our data showed a non-significant trend towards a Discussion higher age of onset than participants who had never had a PTSD diagnosis. This tendency was against expectations, given Our study is one of the first to analyze a range of the prior research showing that childhood trauma is associated clinical and trauma variables in a sample of BD patients with a significantly lower age of onset (12). In our study, in the exclusively with a history of psychological trauma. Our sample majority of cases (79.7%), BD onset happened in the context was mostly Caucasian and 77.2% were female, which was of a stressful life event, which supports previous findings that higher than the proportion of females in previous studies adverse life events can precede mood symptoms (53, 54), and with large bipolar samples (see Supplementary Table S1) and that traumatic stress disorders can significantly increase the despite evidence showing BD is estimated to affect both genders probability of subsequent onset of BD (55). However, our data almost equally (49). The large proportion of females in our points to a bidirectional relationship between BD and trauma. specific sample of BD patients with a history of trauma may Firstly, our results showed that the sample had on average reflect evidence showing women are more likely to experience experienced levels of stressful life events in the 12 months prior high-impact trauma, experience trauma at an earlier age, and to evaluation which put them at a 50% risk of developing are approximately two to three times more likely to suffer a stress-related illness, which supports previous findings that from PTSD (50). In BD patients, PTSD is a more common BD patients suffer more adverse life events in general than comorbidity in female BD patients than in male (49, 51). Just healthy controls (56). Furthermore, the average age for the most over half of our sample (54.1%) had a lifetime diagnosis of traumatic event experienced by our sample was 24.18 (although PTSD, with this being current in 30.4% of the total sample, and this figure is subject to bias as this variable was the only one Frontiers in Psychiatry 09 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 TABLE 3 The impact of a lifetime PTSD diagnosis, sexual and physical abuse on categorical variables of disease course. No Yes Mean Std. Err. 95% CI χ2 (1) P-value Lifetime PTSD diagnosis History of psychotic symptoms No 24 16 0.333 0.079 0.179 0.487 5.404 0.020 Yes 12 24 0.6 0.077 0.448 0.752 History of suicidal ideation No 8 7 0.784 0.068 0.651 0.916 0.208 0.648 Yes 29 33 0.825 0.060 0.707 0.943 History of suicide attempts No 24 22 0.333 0.079 0.179 0.487 1.079 0.299 Yes 12 18 0.45 0.079 0.296 0.604 Rapid Cycling No 34 32 0.081 0.045 −0.007 0.169 2.220 0.136 Yes 3 8 0.2 0.063 0.076 0.324 Sexual abuse History of psychotic symptoms No 24 17 0.351 0.078 0.198 0.505 3.065 0.080 Yes 13 21 0.553 0.081 0.395 0.711 History of suicidal ideation No 10 6 0.737 0.071 0.597 0.877 1.267 0.260 Yes 28 32 0.842 0.059 0.726 0.958 History of suicide attempts No 22 24 0.405 0.081 0.247 0.564 0.108 0.742 Yes 15 14 0.368 0.078 0.215 0.522 Rapid Cycling No 36 30 0.053 0.036 −0.018 0.124 4.146 0.042 Yes 2 8 0.211 0.066 0.081 0.340 Physical abuse History of psychotic symptoms No 25 16 0.432 0.075 0.285 0.578 0.199 0.656 Yes 19 15 0.484 0.090 0.308 0.660 History of suicidal ideation No 10 6 0.773 0.063 0.649 0.897 0.176 0.675 Yes 34 26 0.813 0.069 0.677 0.948 History of suicide attempts No 30 16 0.318 0.070 0.181 0.456 2.105 0.147 Yes 14 15 0.484 0.090 0.308 0.660 Rapid Cycling No 36 30 0.182 0.058 0.068 0.296 2.308 0.129 Yes 8 2 0.063 0.043 −0.021 0.146 Std. Error: Standard Error; CI: Confidence Interval. with a substantial amount of missing data [n = 57], due to of the BD disease course, in addition to screening for not being systematically collected in the CAPS). In nearly a childhood trauma. third of the sample where age of trauma event was available The data from our study showed participants experienced (32.14%, n = 18), the traumatic event selected for the CAPS on average high levels of current trauma symptoms. The impact occurred after the onset of bipolar disorder, and in 14.29% (n caused by the traumatic event, measured by the IES-R, was = 8) of cases, the traumatic event stemmed from a BD affective on average well above the cut off for clinical post-traumatic episode, While there is a body of research showing that the stress symptoms in the group with lifetime PTSD diagnosis, experience of psychosis can cause PTSD (57), there has been with an average score of 47.19 compared to a cut off score no similar research to the authors’ knowledge into PTSD related of >32 (34), indicating high levels of distress caused by the to BD mood episodes, despite these clearly having the potential traumatic event. Yet it is of note that the group with no lifetime to be traumatic based on our data. Our data points to the diagnosis of PTSD also had on average symptoms nearing this importance of research focusing not just on childhood trauma cut off point (29.72), suggesting a high level of subsyndromal but also on adult traumatic experiences, including experiences post-traumatic stress symptoms even in those in our sample related to severe mood episodes and hospitalization experiences, without a lifetime PTSD diagnosis. In terms of dissociation, to further elucidate the complex relationship between trauma there was a significantly higher level of dissociative symptoms and clinical disease course. Additionally, clinicians may need in the lifetime PTSD group than in the non-lifetime PTSD to include ongoing assessment of the occurrence and impact group. However, the scores in both groups were well below of adult trauma experiences, experienced in the context the >25 score correlated with PTSD, and in line with the Frontiers in Psychiatry 10 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 TABLE 4 Impact of lifetime diagnosis of PTSD on quantitative variables of disease course. Obs Mean Std. Err. Std. Dev. 95% Conf. Interval t Deg. Freedom P-value Age of onset No lifetime PTSD Dx 37 27.892 1.809 11.002 23.851 36.788 0.748 74 0.162 Lifetime PTSD Dx 39 31.410 1.716 10.718 27.400 40.275 Number of hospital admissions No lifetime PTSD Dx 36 2.778 1.105 6.629 0.535 5.021 −0.747 73 0.458 Lifetime PTSD Dx 39 3.744 0.710 4.435 2.306 5.181 FAST total No lifetime PTSD Dx 37 30.703 2.187 13.304 26.267 35.138 0.748 75 0.457 Lifetime PTSD Dx 40 28.275 2.379 15.045 23.463 33.087 SCIP total No lifetime PTSD Dx 36 65.667 2.833 16.996 59.916 71.417 −0.237 73 0.813 Lifetime PTSD Dx 39 66.641 2.955 18.455 60.658 72.624 Obs: Number of cases observed; Std. Error: Standard Error; Conf.: Confidence; Deg.: Degrees of; Dx: Diagnosis; FAST: Functioning Assessment Short Test for Bipolar Disorder; SCIP: The Screen for Cognitive Impairment in Psychiatr. mean score of 14.8 on this scale for BD patients, according to of the relationship between patient recall of trauma and clinical a recent meta-analysis which found bipolar disorder patients BD course. to be the psychiatric group with lowest levels of dissociation Regarding our first hypothesis, an association was found (58). Our results also support dissociative symptoms not being between BD comorbidity with PTSD and psychotic symptoms. at a clinical level, even in a sample of traumatized BD This no longer reached statistical significance once adjustments patients, and our results indicate that the sample was not for multiple comparisons, to decrease possibility of a type I error characterized by complex PTSD, where it has been argued (i.e., a false positive) were applied. However, adjustments for that dissociation is a major feature (59). Our data is useful multiple comparisons increase the risk of a type II error (i.e., given the previous lack of information focusing on dissociative a false negative), and arguably are not indicated in situations symptoms in severe mental illness (22), but contrasts with some where hypotheses are planned a priori based on prior evidence, prior studies which have found higher levels of dissociation rather than testing for multiple random associations (67–70). in BD patients (39, 60). One possible explanation for this Therefore, we present both adjusted and unadjusted p-values is that these studies appear to have applied the DES as a and note that the interpretation of results must be made self-administered scale, whereas to improve validity and avoid with caution. inflated scores in psychiatric patients, we applied the DES as The tendency in our results to a link with psychosis is a clinician-administered scale (38). Additionally, in our study, unsurprising given the large body of literature which supports a no participants were in an acute affective phase, and further link between trauma and psychosis generally (71). Psychological research can clarify the effect of an acute mood episode on trauma may increase risk of psychotic symptoms in people dissociative symptoms. vulnerable to psychosis (72), and previous research has shown Of note, in our study, we use retrospective reports of a link between comorbid PTSD in BD and psychotic symptoms trauma. Retrospective and prospective reports show a poor (73). Within our sample, 46.2% had experienced psychotic level of agreement (61), and while retrospective reports symptoms, lower than in some studies which have estimated of adverse childhood experiences can predict negative life that over half of BD patients experience psychotic symptoms outcomes and psychopathology (62, 63), retrospective reports (74, 75), although our study included BD-II patients. It has of childhood maltreatment are more strongly associated with been argued that psychotic symptoms do not necessarily reflect early adult life psychopathology than prospective reports, a worse disease course as they do not have a significant impact suggesting that the recollection of having been maltreated is on functioning (75) yet psychotic symptoms can be traumatizing more closely associated with psychopathology than prospective for those experiencing them (76). The association between measures (64), although other studies have found both psychotic symptoms in BD and PTSD and its implications for retrospective and prospective reports of childhood trauma treatment warrant further research. predict psychopathology (65, 66). There is a dearth of studies No significant association was found between PTSD and analyzing the association between BD and prospective measures an earlier onset of BD or suicidality, which was somewhat of trauma, and our data should be interpreted in the context unexpected given previous research (6, 7, 51). There was also no Frontiers in Psychiatry 11 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 significant difference found in level of functioning or cognitive Our fourth hypothesis, that the presence of reported sexual impairment. Our results are striking compared to the wide body abuse would be correlated with a worse disease course, was of literature showing that a PTSD diagnosis in non-BD patients proven only in the case of rapid cycling, when p-values were is associated with increased suicidality (77) and can negatively unadjusted. This is in line with previous studies that found affect functioning and cognition (78, 79). Furthermore, previous childhood trauma is related to rapid cycling (12) and sexual research in BD patients has shown that comorbid PTSD has abuse is the strongest predictor of it (20). Rapid cycling can a significant further negative impact (20) over and above the indicate poor prognosis and be associated with a greater number negative impact that BD itself has on functioning and cognition of suicide attempts (87). The impact of sexual abuse can be (80, 81). Our sample only included BD patients with a history treated with psychological treatments such as Trauma Focused of trauma, which is not representative of all BD patients. In Cognitive Behavioral Therapy (TF-CBT) and EMDR (88), and fact, a trauma history may be present in as few as 50% of BD these therapeutic approaches can be adapted specifically for patients (82), although other studies suggest higher estimates PTSD within the context of bipolar disorder (89, 90). Further (73). One possible explanation for our results is the high level of research can investigate whether including trauma-focused subsyndromal psychological trauma symptoms even in the non- treatment for BD patients with a history of sexual abuse can PTSD diagnosis group. Indeed, subsyndromal PTSD has been improve symptoms of rapid cycling. shown in other populations to be associated with significant Our fifth hypothesis, that reported physical abuse would psychosocial impairment (83, 84) and with increased suicidality be correlated with a worse disease course as compared to not (85). One study which compared three groups of BD patients reporting having experienced physical abuse, was not proven (patients with comorbid PTSD, patients with trauma but no with any variables. Our findings for sexual and physical abuse PTSD diagnosis, and patients with no trauma history), found do not support previous findings regarding their negative impact that BD patients with PTSD were significantly more likely than on disease course (6, 14, 20). Our results are the first, to the BD patients with no trauma to have a worse disease course, in authors’ knowledge, to review the impact of physical and sexual terms of significantly more rapid cycling and manic symptoms, abuse only in a sample of BD patients with a psychological but there was no significant difference when comparing the trauma history. Therefore, while sexual and physical abuse have comorbid PTSD group with the trauma group, or the trauma been shown in previous research to have a significant impact on group with the no trauma group (86). The impact of comorbidity disease course, this effect seems to be muted when compared between BD and psychological trauma, without a diagnosis of against people who have suffered trauma but not specifically PTSD, warrants further investigation. If psychological trauma sexual or physical abuse. Another explanation is that our study without a PTSD diagnosis has a similar impact on disease course, did not specify physical and sexual abuse in childhood, and this would have important ramifications for screening for and there is a strong body of evidence showing that the impact of treating psychological trauma in BD patients. trauma is greater in childhood (18). Further research can clarify Our second hypothesis, that there would be significantly the specific effects of sexual, physical, and emotional abuse at more cases of PTSD in BD-I patients than BD-II, was not different life stages within a traumatized sample, and whether proven, which contrasted with prior evidence from Hernandez these warrant specific treatment approaches. et al. (11). In the study by Hernandez and colleagues, the Regarding the clinical implications of our research, the lifetime PTSD diagnosis was 21.3% in BD-I and 15.6% in BD- high rates of PTSD within our traumatized sample reflect an II. Unsurprisingly, in our sample of BD patients with a history important comorbidity which not only can impact prognosis of trauma, the proportion was higher: 49.1% of BD-I and 57.1% (13) and treatment outcomes (91) but also warrants treatment of BD-II patients had a lifetime PTSD diagnosis. It is possible as a clinical disorder with its own impact on functioning and that BD-I patients may suffer more rates of psychological trauma suffering. Our research supports not only general screening for but, within BD subtypes with a trauma history, there is not comorbid psychological trauma and comorbid PTSD in BD a significantly greater chance of developing PTSD. Indeed, patients, which is already implemented in some countries and our third hypothesis, that there would be no difference in settings but is not universal, but also ongoing evaluating of trauma symptom profile between BD-I and BD-II was shown whether there has been a traumatic impact due to a BD mood to be correct: there was no significant difference in levels of episode or hospitalization. post-traumatic stress symptoms or levels of dissociation. This Clinicians can use information about comorbid trauma adds to previous evidence (9, 11) which suggests that the symptoms to tailor the BD treatment plan, paying particular different BD subtypes do not influence the expression of trauma attention to possible indicators of worse prognosis such symptoms. This data suggests also that addressing PTSD as as rapid cycling or psychotic symptoms. Additionally, the a comorbidity in BD does not need to differentiate by BD inclusion of pharmacological and psychological treatment for subtype, which could be a useful insight for planning therapeutic clinical trauma symptoms can help clinicians in alleviating the approaches for addressing the presentation of trauma symptoms overall symptomatology in patients, and future research should in BD. elucidate if this can improve the prognosis of BD course itself. Frontiers in Psychiatry 12 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 Strengths of this multicentric study include the exhaustive Data availability statement trauma evaluation, including dissociative symptoms which have received little attention to date (22), and which were The data that support the findings of this study are openly assessed through a clinician-administered scale to reduce bias available in Figshare at https://figshare.com/articles/dataset/ (38), and the PTSD diagnosis which was determined through Bipolar_Disorder_and_psychological_trauma/19601359. clinical interview using the gold-standard CAPS. A further strength is that we included “real world” bipolar patients within a pragmatic randomized controlled trial (RCT) with Ethics statement few exclusion criteria. However, some limitations have to be considered as well. We did not evaluate further psychiatric The study received Ethical Approval from the comorbidities using a (semi) structured diagnostic interview, Ethics Committee of the Germanes Hospitalàries del although comorbidities were checked through a review of Sagrat Cor de Jesús (Reference Number: PR-2014-15), case notes. Our patients clinically had further psychiatric and the Hospital Clínic of Barcelona (Reference Number: somatic comorbidities and it would have been interesting HCB/2015/1005) and the Hospital Parc de Salut Mar including this variable in our analysis, as prior results indicate (Reference Number: 2015/6502/l). The patients/participants negative effects on the course of the illness (92). Furthermore, provided their written informed consent to participate in our study did not include a control group of BD patients this study. without psychological trauma, as the data was taken from a RCT comparing EMDR vs. ST in trauma-exposed bipolar patients. The lack of a non-traumatized control group makes Author contributions interpretation of the impact of subsyndromic trauma symptoms BA conceived the idea for the study and led the study. AM- more challenging. In our study, we collected data regarding A coordinated the study. BH, AV-G, IG-S, WL, EJ, MM, LB-P, the total lifetime number of BD episodes for each participant MR, RC, AM-R, and JC were involved in the recruitment and but many subjects struggled to identify hypomanic episodes evaluation of patients and data collection. BH, IG-S, MF-M, or quantify episodes, so this data was not reliable enough to and AM-A prepared the data for analysis. DR carried out the be used. Additionally, emotional abuse was not evaluated, and statistical analysis. BH worked on the first draft of the paper the timepoint for reported sexual abuse and physical abuse with BA, AM-A, DR-R, and AV-G. All authors contributed to was not assessed. Due to the cross-sectional design of this the interpretation of results and the final draft and approved the study, conclusions about causality cannot be drawn. Trauma final draft. history was based on subjective recall, which can result in recall bias (93). However, it has been shown that psychopathology is associated more with subjective than objective recall of Funding traumatic events (94). Additionally, trauma history was gathered through use of the gold standard CAPS interview, and we This work was supported by a grant for BA from the have clarified throughout the paper that this is reported Plan Nacional de I + D + i and co-funded by the Instituto trauma history. de Salud Carlos III-Subdirección General de Evaluación y In summary, our paper provides further evidence of the Fomento de la Investigación, Plan Nacional 2008-2011 with the lack of difference in how trauma symptoms are presented following Research Project (PI/15/02242). Furthermore, across BD subtypes, and provides important data regarding BA has been supported by a NARSARD Independent the high levels of trauma symptoms in BD subjects, even Investigator Grant from the Brain and Behavior Research when criteria for a PTSD diagnosis are not met. The Foundation (Number: 24397). evidence shows there are few differences in clinical BD severity between the PTSD and subsyndromic PTSD group, although we also found a possible tendency for there to be Acknowledgments a correlation between PTSD and psychotic symptoms, as well as between sexual abuse and rapid cycling, which can be BA is very grateful to the Instituto de Salud Carlos clinically helpful in the identification and treatment of both. III-Subdirección General de Evaluación y Fomento de la It prompts further investigation to understand the impact Investigación, Plan Nacional 2008-2011 and 2013-2016 for a of comorbidity with a history of psychological trauma in specific Grant (PI/15/02242) for this project, and to the Brain BD patients, including subsyndromal PTSD symptoms, and & Behavior Research Foundation, NARSAD for an Independent highlights the importance of screening for psychological trauma Investigator Grant (24397) related to this project. AM-A wants in the BD population. to thank also to the Secretaria d’Universitats i Recerca del Frontiers in Psychiatry 13 frontiersin.org Hogg et al. 10.3389/fpsyt.2022.931374 Departament d’Economia i Coneixement (2017 SGR 46 to Publisher’s note Unitat de Recerca del Centre Fòrum), Generalitat de Catalunya (Government of Catalonia) for the recognition as an Emerging All claims expressed in this article are solely those of the Research Group. BH thanks the support and funding of the authors and do not necessarily represent those of their affiliated Instituto de Salud Carlos III with a PFIS Grant (FI10/00017). organizations, or those of the publisher, the editors and the We acknowledge also the continuous support by the CIBERSAM reviewers. Any product that may be evaluated in this article, or (Centro de Investigación Biomédica en Red de Salud Mental, claim that may be made by its manufacturer, is not guaranteed Instituto Carlos III). or endorsed by the publisher. Conflict of interest Supplementary material The authors declare that the research was conducted in the The Supplementary Material for this article can be absence of any commercial or financial relationships that could found online at: https://www.frontiersin.org/articles/10.3389/ be construed as a potential conflict of interest. fpsyt.2022.931374/full#supplementary-material References 1. Kessing LV, Vradi E, Andersen PK. Life expectancy in bipolar disorder. 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