RESEARCH ARTICLE Relatives’ attachment anxiety mediates the association between perceived loss and expressed emotion in early psychosis Lı́dia Hinojosa-Marqués1, Tecelli Domı́nguez-Martı́nez2, Tamara Sheinbaum3, Paula Cristóbal-Narváez4, Thomas R. Kwapil5, Neus Barrantes-Vidal ID1,6,7* 1 Departament de Psicologia Clı́nica i de la Salut, Universitat Autònoma de Barcelona, Barcelona, Spain, 2 Centro de Investigación en Salud Mental Global, Dirección de Investigaciones Epidemiológicas y a1111111111 Psicosociales, Instituto Nacional de Psiquiatrı́a “Ramón de la Fuente Muñiz”, Mexico City, Mexico, a1111111111 3 Department of Psychology, University of Southern California, Los Angeles, California, United States of America, 4 Unitat de Recerca, Docència i Innovació, Parc Sanitari Sant Joan de Déu, San Boi de Llobregat, a1111111111 Barcelona, Spain, 5 Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, a1111111111 Illinois, United States of America, 6 Sant Pere Claver- Fundació Sanitària, Barcelona, Spain, 7 Centre for a1111111111 Biomedical Research Network on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain * neus.barrantes@uab.cat OPEN ACCESS Abstract Citation: Hinojosa-Marqués L, Domı́nguez- Martı́nez T, Sheinbaum T, Cristóbal-Narváez P, A common reaction experienced by family members of patients with psychosis is grief for Kwapil TR, Barrantes-Vidal N (2019) Relatives’ the loss of their healthy relative. Importantly, high levels of perceived loss have been related attachment anxiety mediates the association to the manifestation of high expressed emotion (EE), which includes the negative attitudes between perceived loss and expressed emotion in early psychosis. PLoS ONE 14(10): e0223425. expressed by relatives toward an ill family member. However, the mechanisms underlying https://doi.org/10.1371/journal.pone.0223425 the relationship between relatives’ perceived loss and EE attitudes in the early stages of Editor: Sarah Hope Lincoln, Harvard University, psychosis are still not fully understood. In this regard, attachment theory has been sug- UNITED STATES gested as a useful framework for understanding this link. The current study aimed to exam- Received: February 5, 2019 ine: (1) whether relatives’ perceived loss was associated with relatives’ EE dimensions (i.e., criticism and emotional over-involvement (EOI)), and (2) whether such associations were Accepted: September 20, 2019 mediated by relatives’ attachment dimensions (i.e., anxiety and avoidance). Seventy-eight Published: October 7, 2019 relatives of patients with early psychosis completed the Mental Illness Version of the Texas Copyright: © 2019 Hinojosa-Marqués et al. This is Inventory of Grief for the assessment of loss reactions. Attachment dimensions and EE atti- an open access article distributed under the terms tudes were assessed by the Psychosis Attachment Measure and the Family Questionnaire, of the Creative Commons Attribution License, which permits unrestricted use, distribution, and respectively. Findings indicated that relatives’ perceived loss was associated with EE reproduction in any medium, provided the original dimensions. Relatives’ attachment anxiety, but not avoidance, mediated the relationship of author and source are credited. perceived loss with both criticism and EOI. Findings highlight the importance of examining Data Availability Statement: The authors of the the role of relatives’ attachment characteristics for understanding how perceptions of loss present study confirm that some access might impact the manifestation of EE attitudes in the early stages of psychosis. Family inter- restrictions apply to the data underlying the ventions aimed at assisting relatives to improve their management of negative emotional findings. The consent form that participants signed before participating in the study, approved by the reactions to loss are fundamental to prevent impairing loss reactions and the entrenchment Ethics Committee of the Unió Catalana d’Hospitals of high-EE attitudes. (Comitè d’Ètica d’Investigació Clı́nica (CEIC); number 09-40) and by the Ethics Committee of the Universitat Autònoma de Barcelona (Comissió d’Ètica en l’Experimentació Animal i Humana (CEEAH); number 2679) imposes restrictions for PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 1 / 13 Relatives’ perceived loss, attachment and expressed emotion making the data publicly available. Participants Introduction agreed for all the data collected to be available to the members of the research group Person- A prominent reaction described by family members of patients with psychosis is grief [1–3]. Environment Interaction in Psychopathology led by This grief results from a deep sense of loss: loss of the healthy relative, loss of specific hopes Prof. Neus Barrantes-Vidal (Address: Departament and aspirations for the relatives’ future, and loss of the pre-existing relationship between the de Psicologia Clı́nica i de la Salut, Facultat de relative and the patient [4–6]. Perceived loss has been found to have negative implications for Psicologia, Edifici B, Universitat Autònoma de relatives’ physical and psychological health, and also affects interactions with their ill family Barcelona, 08193 Cerdanyola del Vallès, Spain; telephone: +34 93 5813864; email: neus. member [7, 8]. However, grief is not necessarily a pathological phenomenon, but rather a nat- barrantes@uab.cat). Data available on request. ural process of adapting to or accommodating a changed reality [9]. Requests should be addressed to the contact Relatives’ perceived loss has been mostly examined in schizophrenia caregivers [10–12]. details provided above or to the Ethics Committee However, the few studies examining relatives’ loss reactions in the early stages of psychosis of the Universitat Autònoma de Barcelona indicated that high levels of perceived loss are already present in early phases of the illness [13– (Comissió d’Ètica en l’Experimentació Animal i Humana, Address: Plaça Acadèmica, Rectorat, 15]. Moreover, high levels of loss appraisals are related to the manifestation of high expressed Edifici A, Universitat Autònoma de Barcelona, emotion (EE) attitudes (i.e., criticism and emotional over-involvement (EOI); [13–16]). Patter- 08193 Cerdanyola del Vallès, Spain; telephone: +34 son et al. [14, 15] found that high levels of perceived loss were related to high EOI attitudes, 93 5813578; email: oh.ceea@uab.cat). whereas low levels of perceived loss were linked to high criticism. It seems that relatives’ per- Funding: Authors are supported by the Spanish ception of loss could motivate high EOI attitudes with the aim of reestablishing what has been Ministerio de Economı́a y Competitividad lost [14, 15]. However, coercive criticism has also been theoretically interpreted as a coping (PSI2017-87512-C2-01) and the Comissionat per a mechanism to deal with the pain of loss [17]. As argued by Patterson et al. [14, 15], this inter- Universitats i Recerca of Generalitat de Catalunya pretation is consistent with attachment theory, which states that coercive angry or critical atti- (2017SGR1612). NBV is supported by the tudes are a natural response to any perceived loss, with the goal to bring the person “back into Institució Catalana de Recerca i Estudis Avançats (ICREA) Academia Award and the Centro de line” through an activation of attachment responses [18–20]. Since the perception of loss may Investigación Biomédica en Red de Salud Mental be a major driver of high EE attitudes [21, 22], it would be relevant to identify the mediating (CIBERSAM), Instituto de Salud Carlos III, mechanisms by which perceived loss influences the manifestation of EE in early psychosis Barcelona, Spain. The funders had no role in study relatives. In this regard, attachment theory has been highlighted as a useful framework for design, data collection and analysis, decision to understanding how loss appraisals may contribute to the development of EE [14, 15, 23]. Spe- publish, or preparation of the manuscript. cifically, relatives’ attachment styles have received theoretical attention as potential underlying Competing interests: The authors have declared mechanisms in the association between perceived loss and EE attitudes [23]. that no competing interests exist. Attachment theory has become one of the foremost paradigms for understanding the griev- ing process after the loss of a significant person [24–26]. Insecure attachment has been pro- posed as a major risk factor for complications in adaptation to loss [27–28]. Regarding the dimensions underlying attachment style, attachment anxiety and avoidance [29–30], it seems that anxious attachment is more consistently associated with elevated grief symptoms than avoidant attachment after the loss of a loved one [31–32]. Moreover, anxious/ambivalent attachment has been related to increased parental grief in response to a family member’s men- tal illness [33]. Attachment theory indicates that threats and stressors to an attachment bond, such as ill- ness or loss, tend to activate the attachment system [30–34]. Indeed, persons with high levels of attachment anxiety or avoidance tend to rely on secondary attachment strategies [35–36], either hyperactivating or deactivating their attachment system for regulating threat-related dis- tress. Hyperactivating strategies observed in anxious individuals cause them to amplify nega- tive emotional responses to threats. In contrast, avoidant individuals attempt to inhibit emotional reactions with the goal of minimizing activation of the attachment system [30, 34, 37]. Thus, anxiously attached individuals’ tendency to intensify negative emotions would involve a heightened risk of distress after an actual or perceived loss, whereas avoidant individ- uals’ tendency to suppress negative emotions would promote an absence of conscious grieving [24, 37, 38]. According to Bowlby [20], parents develop their caregiving behaviors in consonance with their attachment systems and associated working models [39–42]. For instance, avoidant PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 2 / 13 Relatives’ perceived loss, attachment and expressed emotion individuals’ lack of interpersonal engagement and negative working models of others may also translate into a lack of caregiving behaviors, probably driven by deactivating strategies across both attachment and caregiving systems [43, 44]. Conversely, anxious individuals, who adopt a hyperactivating attachment strategy [43–45]. show a pattern of hyperactivated caregiving, which is intrusive or overinvolved, poorly timed, and burdensome [30, 34]. The parallelism between these caregiving behaviors and those exhibited by high EE individuals suggests that relatives’ insecure attachment styles may influence their caregiving behaviors, contributing to high EE levels under acute stress [46]. Therefore, insecure attachment has been hypothesized to contribute to the development of critical or EOI parenting styles [47, 48]. Specifically, attachment anxiety has been related to intrusive, overinvolved, and controlling forms of care- giving [42, 44, 49, 50], as well as with the use of authoritarian and dominant behaviors in high anxiety situations [51, 52]. Altogether, this emphasizes attachment theory as a potential frame- work for understanding how relatives’ attachment history influences the development of EE [53]. The relationship between relatives’ attachment styles and perceived loss in the early stages of psychosis has not yet been explored. Similarly, no studies have directly considered the possi- ble mediating role of insecure attachment styles in the association between relatives’ perceived loss and high EE attitudes. This study addressed these issues in a sample of relatives of early psychosis participants by: 1) examining whether relatives’ perceived loss is associated with EE dimensions (i.e., criticism and EOI); and 2) testing whether such associations are mediated by relatives’ dimensions of attachment (i.e., anxiety and avoidance). Despite the lack of previous studies, it was hypothesized based on the reviewed literature that relatives’ attachment anxiety would play a mediating role between perceived loss and EOI, as well as between perceived loss and criticism. Materials and methods Participants The study included 78 relatives of early psychosis participants, 48 of At-Risk Mental State (ARMS) and 30 of First-Episode (FEP) participants. They were recruited in the Sant Pere Cla- ver-Early Psychosis Program conducted in Barcelona, Spain [54]. Participating relatives were those who had the most regular contact and/or the most significant relationship with the patient. ARMS patients had to meet ARMS criteria as assessed by the Comprehensive Assess- ment of At-Risk Mental States [55] and/or the Schizophrenia Proneness Instrument Adult- Version [56]. FEP patients met DSM-IV-TR criteria [57] for any psychotic disorder or affective disorder with psychotic symptoms as established by the Structured Clinical Interview for DSM-IV [58]. All relatives provided written informed consent. The project was developed in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Ethical approval was granted by the Ethics Committee of the Unió Catalana d’Hospitals (Comitè d’Ètica d’Investigació Clı́nica (CEIC); number 09–40) and by the Ethics Committee of the Uni- versitat Autònoma de Barcelona (Comissió d’Ètica en l’Experimentació Animal i Humana (CEEAH); number 2679). Measures Relatives completed the Mental Illness Version of the Texas Inventory of Grief (MIV-TIG) [2] for the assessment of loss reactions. The MIV-TIG is a self-reported questionnaire that con- tains 24 items that measure relatives’ initial response to the loss of a family member’s mental health and the current feelings about their perceived loss. Responses were rated on a five-point PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 3 / 13 Relatives’ perceived loss, attachment and expressed emotion Likert scale from ‘completely true’ to ‘completely false’. The Cronbach’s alpha of the instru- ment was excellent in this sample (0.95). Attachment was assessed with the Psychosis Attachment Measure (PAM) [59], a self- reported adult attachment questionnaire referring to self-identified thoughts, feelings and behaviors in interpersonal relationships. The PAM contains 16 items that assess the two dimensions of adult attachment, anxiety and avoidance. Responses are made on a four-point Likert scale ranging from ‘not at all’ to ‘very much’. Reliability for these subscales was accept- able in this sample (Anxiety = 0.71; Avoidance = 0.68). Finally, relatives completed the Family Questionnaire (FQ) [60], a well-established instru- ment to measure EE. The FQ consists of 20 items equally distributed into two subscales (EOI and criticism) and scored on a four-point Likert scale ranging from ‘never/very rarely’ to ‘very often’. Reliability for the two subscales in this sample was 0.84 for EOI and 0.87 for criticism. Statistical analysis Pearson correlations were calculated to explore the association of relatives’ perceived loss with EOI and criticism, as well as association of these variables with the two attachment dimen- sions. The effect size of the correlations was interpreted following Cohen’s [61] guidelines (correlations of 0.10 indicate small effect sizes, 0.30 indicate medium effect sizes, and 0.50 indi- cate large effect sizes). Parallel multiple mediation analyses were performed using PROCESS [62]. These analyses examined the unique mediating effect of attachment anxiety and avoid- ance on the significant associations found between perceived loss and the EE dimensions. For each model, attachment anxiety and avoidance were entered simultaneously as mediators. The 95% bias-corrected confidence intervals were generated using bootstrapping with 10,000 resamples. Indirect effects were considered significant when the 95% bias-corrected confi- dence intervals did not include zero. Results Most relatives were parents who lived with the patient. Over half of them were females, specifi- cally patients’ mothers (see Table 1 for details about relatives’ socio-demographic characteris- tics). For the sake of completeness, descriptive data for all relatives’ measures are presented in Table 2. Firstly, we examined whether relatives of ARMS and FEP participants differed on levels of perceived loss. No significant differences emerged between them (t(76) = -1.17; p = 0.25; d = 0.27). Consequently, ARMS and FEP relatives were grouped together in the remaining analyses. Relatives’ perceived loss was significantly related to both EOI (r = 0.49, p <0.001) and criti- cism (r = 0.27, p<0.05). Following Cohen [61], effect sizes were of a medium and small magni- tude, respectively. As seen in Table 3, relatives’ attachment anxiety showed significant associations with rela- tives’ perceived loss and both EE dimensions. All effect sizes were of medium magnitude. In contrast, relatives’ attachment avoidance was significantly associated with relatives’ perceived loss but was not associated with the EE dimensions. Table 4 displays the results of the parallel multiple mediation analyses using relatives’ per- ceived loss as the independent variable. Two models were tested (one for EOI and one for criti- cism), with the two attachment dimensions entered simultaneously as mediators. The total, direct, and indirect effects are shown in Table 4. The specific indirect effect of attachment anx- iety was significant in the models for both EOI and criticism indicating that anxious attach- ment mediated the association of perceived loss with both EE factors. Note that the direct PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 4 / 13 Relatives’ perceived loss, attachment and expressed emotion Table 1. Descriptive data on socio-demographic characteristics of early psychosis relatives (n = 78). n (%) Age (mean, SD) 51.05 (9.7) Gender Males 25 (32.1) Females 53 (67.9) Ethnicity Caucasian-white 66 (84.6) Othera 12 (15.4)a Occupation Unemployed/unoccupied 34 (43.6) Employed 44 (56.4) Marital Status Single 4 (5.1) Married or analogous 50 (64.1) Separated/divorced/widowed 24 (30.8) Relationship to patient Father 19 (24.4) Mother 47 (60.2) Otherb 12 (15.4) Living with patient Yes 65 (83.3) No 13 (16.7) c Frequency of contact Between 1 and 14h a week 28 (35.9) Between 15 and 27h a week 14 (17.9) � 28h a week 28 (35.9) a Other ethnicity was comprised by Latin Americans = 5 (6.4), Asians = 2 (2.6), Eastern Europeans = 3 (3.8) and Arabs = 2 (2.6). b Other relationship was comprised by Siblings = 10 (12.8), Grandparent = 1 (1.3) and Stepfather = 1 (1.3). c Information about frequency of contact was available only for n = 72. https://doi.org/10.1371/journal.pone.0223425.t001 relationship of perceived loss and criticism no longer remained significant when the indirect pathway through anxious attachment was included. Avoidant attachment was not a significant mediator of the association between relatives’ perceived loss and EE dimensions. Table 2. Descriptive data on perceived loss, attachment and expressed emotion (N = 78). Mean SD Possible score range Observed score range Perceived loss (MIV-TIG) 63.44 20.95 24–120 24–116 Attachment (PAM) Anxious Attachment 0.90 0.43 0–3 0–2.38 Avoidant Attachment 1.22 0.45 0–3 0.38–2.25 Expressed Emotion (FQ) Emotional Over-Involvement 24.33 5.85 10–40 11–37 Criticism 20.63 6.02 10–40 11–37 MIV-TIG, Mental Illness Version of the Texas Inventory of Grief; PAM, Psychosis Attachment Measure; FQ, Family Questionnaire. https://doi.org/10.1371/journal.pone.0223425.t002 PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 5 / 13 Relatives’ perceived loss, attachment and expressed emotion Table 3. Pearson correlations of attachment dimensions with perceived loss and expressed emotion (N = 78). Attachment-Anxiety Attachment-Avoidance Perceived loss (MIV-TIG) 0.38��� 0.30�� Expressed Emotion (FQ) Emotional Over-Involvement 0.46��� 0.22 ��� Criticism 0.38 0.21 �� p�0.01 ��� p� 0.001. MIV-TIG, Mental Illness Version of the Texas Inventory of Grief; FQ: Family Questionnaire. Note: Medium effect sizes in bold. https://doi.org/10.1371/journal.pone.0223425.t003 Discussion To the best of our knowledge, this is the first study examining the relationship among relatives’ perceived loss, attachment styles, and EE, as well as the mediating role of relatives’ attachment dimensions in the association between perceived loss and EE, in the early stages of psychosis. Results demonstrated that relatives’ perceived loss was associated with EE attitudes as well as with relatives’ attachment anxiety and avoidance. These findings point out the importance of considering the role of relatives’ perceived loss along with other psychological mechanisms for understanding the ontogenesis of EE in the family environment. In addition, the current study indicated that relatives’ attachment anxiety, but not attachment avoidance, mediated the rela- tionship between perceived loss and EE, both for criticism and EOI attitudes. Altogether, these results emphasize the importance of considering the role of loss in the development of EE atti- tudes and that relatives’ attachment style is relevant to understand how appraisals of loss might impact the formation and/or expression of EOI and criticism in the critical period of the emer- gence of the disorder. Consistent with our predictions, relatives’ perceived loss was positively associated with both EOI and criticism. These results are in consonance with theoretical suggestions from the EE literature that relatives’ perception of loss may be a primary driver of high EE attitudes [21, Table 4. Mediation analyses examining the indirect effects of perceived loss on EOI and criticism via anxious and avoidant attachment. 95% Bias-corrected Confidence Interval Raw Parameter Estimate SE Lower Upper Emotional Over-Involvement (FQ) Total Effect 0.136� 0.028 0.080 0.191 Direct Effect 0.098� 0.030 0.039 0.157 � Total Indirect Effect 0.038 0.016 0.012 0.078 Indirect Effect via Anxiety 0.034� 0.014 0.013 0.071 Indirect Effect via Avoidance 0.003 0.009 -0.012 0.026 Criticism (FQ) Total Effect 0.077� 0.032 0.014 0.140 Direct Effect 0.035 0.034 -0.033 0.103 Total Indirect Effect 0.042� 0.019 0.012 0.091 Indirect Effect via Anxiety 0.033� 0.016 0.009 0.076 Indirect Effect via Avoidance 0.009 0.011 -0.007 0.037 � 95% Confidence Interval does not include zero. Note: Results are based on 10,000 bias-corrected bootstrap samples. https://doi.org/10.1371/journal.pone.0223425.t004 PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 6 / 13 Relatives’ perceived loss, attachment and expressed emotion 22]. The positive association between perceived loss and relatives’ EOI attitudes supports pre- vious findings by Patterson et al. [14, 15] in relatives of early psychosis patients. However, in contrast to Patterson et al. [14, 15], the present study also found a positive association between perceived loss and relatives’ criticism. This finding is consistent with attachment theory that indicates that coercive criticism is not an uncommon response to perceived loss as an attempt to restore what has been “lost” through the activation of attachment responses [18, 19, 20]. Anxious attachment in relatives, but not avoidant attachment, mediated the association of the perception of loss with both EOI and criticism. As hypothesized, this differential role of attachment styles might be explained by the specific distress regulation strategies characteriz- ing anxious and avoidant attachment. Anxious individuals respond to appraisals of loss with hyperactivating strategies of the attachment system, which impairs their capacity to regulate negative emotions and thus contributes to an intensification of distress [30, 34, 37]. Moreover, ineffective emotional regulation strategies may make relatives feel overwhelmed by personal distress, which may in turn interfere with the normative functioning of the caregiving behav- ioral system [30, 34]. Theoretically, the caregiving system is activated by cues generated from care recipients in times of need [20], but it can also be activated by caregivers’ appraisals of danger or threat, which are directly influenced by caregivers’ own attachment system [40, 41]. Specifically, attachment anxiety has been associated with high levels of proximity and compul- sive caregiving that are inconsistent and lack sensitivity [42, 63]. Following Canterberry and Gillath [43], this type of caregiving behaviors could reflect the hyperactivation of the caregiving system. Therefore, anxious individuals, who rely on hyperactivating strategies in their attach- ment system, seem to adopt this strategy with their caregiving system [43–45]. Drawing on previous theoretical suggestions based on the interplay between the attachment and caregiving systems [45, 52], our findings suggest that relatives’ perceived loss might trigger the concurrent hyperactivation of the attachment and caregiving systems in anxiously attached relatives. The inability to regulate the negative emotions provoked by perceived loss may lead to excessive ruminations about the loss, amplifying the negative affective/cognitive reactions. This would contribute to the hyperactivation of the caregiving system and lead to EE-like intrusive, over- involved, or even critical patterns of caregiving, presumably driven by an attempt to restore the pre-illness situation and to mitigate the loss perceived (Fig 1). This explanation is partly consistent with previous suggestions (e.g., [14, 15]), even though the contribution of the care- giving behavioural system as the mechanism through which EE attitudes manifest had not been considered. Specifically, Patterson [23] proposed a theoretical model in which family ill- ness leads to an activation of carers’ and patients’ attachment behaviors. Therefore, relatives increased high EE attitudes should be conceived as an initial normative reaction. Previous work has linked attachment anxiety to caregiving behaviors that clearly resemble aspects of EOI behaviors (i.e., overinvolved, intrusive, controlling and/or compulsive forms of caregiving; [42, 44, 49, 50]). This has even led to the interpretation of EOI as a type of anxious attachment/caregiving behavior [64, 65]. In addition, attachment anxiety has also been related to the expression of critical attitudes through the use of authoritarian [52], aggressive [66, 67], dominant [51], and demanding behaviors in high anxiety situations [68]. Therefore, relatives’ insecure attachment could contribute to the development of either critical or EOI parenting styles [47, 48] and these two dimensions of EE could be considered as “special forms of attach- ment/caregiving” that are likely to lead to dysfunctional patterns of communication and prob- lem solving [65]. Interestingly, an unexpected positive correlation between perceived loss and attachment avoidance was observed. It is well recognized that the tendency to suppress negative emotions encourages an absence of conscious grieving [24, 38, 69]. Nevertheless, some studies have found an association between attachment avoidance and severe grief symptoms after the loss PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 7 / 13 Relatives’ perceived loss, attachment and expressed emotion Fig 1. Attachment anxiety as a mechanism linking relatives’ perceived loss and EE. Proposed mediational model of the relationship between relatives’ perceived loss and high EE attitudes (i.e., criticism and EOI) in anxiously attached relatives. Adapted from Patterson (2013). https://doi.org/10.1371/journal.pone.0223425.g001 of a loved one [70–72]. These findings have been interpreted as indicating that strategies of emotional deactivation might collapse under conditions of high cognitive load produced by highly stressful situations, thereby causing avoidant individuals to be less able to suppress sepa- ration thoughts. Therefore, the powerful threat of loss experienced by relatives of early psycho- sis individuals might weaken the suppression of the negative emotional experience of loss in relatives with avoidant attachment. Some limitations of the present study must be considered. First, the cross-sectional design limits drawing causal conclusions, which can only be determined by further longitudinal stud- ies. Second, it is important to note that attachment and EE-related constructs are dynamic pro- cesses influenced by bidirectional and interactional patterns within familiar relationships [73, 74]. Future studies should consider how the clinical features and attachment styles of care recipients contribute to the manifestation of high-EE attitudes within the family environment. Finally, it should be noted that although the FQ has been recognized as a reliable and valid measure to assess EE [60], it has not yet shown enough predictive validity for relapse in both chronic and early psychosis samples (e.g., [75, 76]). Therefore, further research is required to examine its predictive relevance in the course of the disorder. In conclusion, this study shows that relatives’ perception of loss is significantly associated with EE-criticism and EE-EOI attitudes in the early stages of coping with psychosis, and that relatives’ attachment anxiety is a mediator of the association between perceived loss and the manifestation of EE attitudes in early psychosis relatives. These results have important clinical applications. Considering the negative implications of perceived loss for relatives’ PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 8 / 13 Relatives’ perceived loss, attachment and expressed emotion psychological health and the potential etiological role of perceived loss on the development of high EE attitudes, family interventions should specifically take into consideration the psycho- logical aspects related to loss and the grief process experienced by relatives during the at-risk and onset stages of psychosis. This emphasizes the importance to go beyond educating rela- tives about psychosis (e.g., [77]) by implementing treatments in which the provision of infor- mation is adapted to caregivers’ needs and allows emotional processing [78]. Consequently, this would help relatives to gain a better understanding of their own psychological situation. In addition, these findings highlight the need of tailoring interventions to relatives’ attachment needs. This would include assessing relatives’ attachment patterns, since the specific subtypes of insecure attachment style will provide guidance to moving forward in the therapeutic pro- cess, for example in building the working alliance or setting relevant treatment goals [79]. Early psychosis is a critical period in which relatives’ appraisals and attitudes are forming and might be more malleable; therefore, it is fundamental to support relatives in adjusting to the grief process with the aim of preventing unresolved loss reactions and the entrenchment of high-EE attitudes over time. Acknowledgments The authors appreciate the support offered by the Fundació Sanitària Sant Pere Claver and thank the families who participated in the study. We acknowledge Cristina Medina-Pradas and Nieves Guardia for their contribution in the data collection. Author Contributions Conceptualization: Lı́dia Hinojosa-Marqués, Thomas R. Kwapil, Neus Barrantes-Vidal. Data curation: Lı́dia Hinojosa-Marqués, Tecelli Domı́nguez-Martı́nez, Tamara Sheinbaum, Paula Cristóbal-Narváez, Thomas R. Kwapil. Formal analysis: Lı́dia Hinojosa-Marqués, Tamara Sheinbaum, Paula Cristóbal-Narváez, Thomas R. Kwapil, Neus Barrantes-Vidal. Funding acquisition: Neus Barrantes-Vidal. Investigation: Lı́dia Hinojosa-Marqués, Tecelli Domı́nguez-Martı́nez, Paula Cristóbal-Nar- váez, Neus Barrantes-Vidal. Methodology: Thomas R. Kwapil, Neus Barrantes-Vidal. Project administration: Neus Barrantes-Vidal. Supervision: Thomas R. Kwapil, Neus Barrantes-Vidal. Writing – original draft: Lı́dia Hinojosa-Marqués. Writing – review & editing: Lı́dia Hinojosa-Marqués, Tecelli Domı́nguez-Martı́nez, Tamara Sheinbaum, Paula Cristóbal-Narváez, Thomas R. Kwapil, Neus Barrantes-Vidal. References 1. Davis DJ, Schultz CL. Grief, parenting, and schizophrenia. Soc Sci Med. 1998; 46: 369–379. https://doi. org/10.1016/s0277-9536(97)00167-6 PMID: 9460818 2. Miller F, Dworkin J, Ward M, Barone D. A preliminary study of unresolved grief in families of seriously mentally ill patients. Hosp Community Psychiatry. 1990; 41: 1321–1325. https://doi.org/10.1176/ps.41. 12.1321 PMID: 2276725 3. Osborne J, Coyle A. Can parental responses to adult children with schizophrenia be conceptualized in terms of loss and grief? A case study analysis. Couns Psychol Q. 2002; 15: 307–323. PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 9 / 13 Relatives’ perceived loss, attachment and expressed emotion 4. Miller F. Grief therapy for relatives of persons with serious mental illness. Psychiatr Serv. 1996; 47: 633–637. https://doi.org/10.1176/ps.47.6.633 PMID: 8726492 5. Parker BA. Living with mental illness: the family as caregiver. J Psychosoc Nurs Ment Heal Serv. 1993; 31: 19–21. 6. Young J, Bailey G, Rycroft P. Family grief and mental health: a systemic, contextual and compassionate analysis. Aust N Z J Fam Ther. 2004; 24: 188–197. 7. Geraghty K, McCann K, King R, Eichmann K. Sharing the load: parents and carers talk to consumer consultants at a child and youth mental health inpatient unit. Int J Ment Health Nurs. 2011; 20: 253–262. https://doi.org/10.1111/j.1447-0349.2011.00730.x PMID: 21362120 8. Richardson M, Cobham V, McDermott B, Murray J. Youth mental illness and the family: parents’ loss and grief. J Child Fam Stud. 2013; 22: 719–736. 9. MacGregor P. Grief: The unrecognized parental response to mental illness in a child. Soc Work. 1994; 39: 160–166. PMID: 8153758 10. Jones DW. Families and serious mental illness: working with loss and ambivalence. Br J Soc Work. 2004; 34: 961–979. 11. Ozgul S. Parental grief and serious mental illness: a narrative. Aust. N. Z. J. Fam. Ther. 2004; 25: 183– 187. 12. Richardson M, Cobham V, Murray J, McDermott B. Parents’ grief in the context of adult child mental ill- ness: a qualitative review. Clin Child Fam Psychol Rev. 2011; 14: 28–43. https://doi.org/10.1007/ s10567-010-0075-y PMID: 20645000 13. Mulligan J, Sellwood W, Reid GS, Riddell S, Andy N. Informal caregivers in early psychosis: evaluation of need for psychosocial intervention and unresolved grief. Early Interv Psychiatry. 2013; 7: 291–299. https://doi.org/10.1111/j.1751-7893.2012.00369.x PMID: 22741743 14. Patterson PJ, Birchwood M, Cochrane R. Preventing the entrenchment of high expressed emotion in first episode psychosis: early developmental attachment pathways. Aust N Z J Psychiatry. 2000; 34 Suppl: S191–S197. 15. Patterson P, Birchwood M, Cochrane R. Expressed emotion as an adaptation to loss: prospective study in first-episode psychosis. Br J Psychiatry. 2005; 187 Suppl: S59–S64. 16. Raune D, Kuipers E, Bebbington PE. Expressed emotion at first-episode psychosis: investigating a carer appraisal model. Br J Psychiatry. 2004; 184: 321–326. https://doi.org/10.1192/bjp.184.4.321 PMID: 15056576 17. Stirling J, Tantam D, Thomas P, Newby D, Montague L, Ring N, et al. Expressed emotion and schizo- phrenia: the ontogeny of EE during an 18-month follow-up. Psychol Med. 1993; 23: 771–778. https:// doi.org/10.1017/s003329170002554x PMID: 8234583 18. Bowlby J. Attachment and loss: Vol. 2. Separation: Anxiety and anger. New York: Basic Books; 1973. 19. Bowlby J. Attachment and loss: Vol. 3. Sadness and depression. New York: Basic Books; 1980. 20. Bowlby J. Attachment and loss: Vol. 1. Attachment. 2nd ed. New York: Basic Books; 1982. 21. Birchwood M. Familial factors in psychiatry. Curr. Opin. Psychiatry. 1992; 5: 295–299. 22. Birchwood M, Spencer E. Psychotherapies for schizophrenia: a review. In: Maj M, Sartorius N, editors. Schizophrenia. Chichester: Wiley; 1999. pp. 139–241. 23. Patterson P. Attachment, loss and expressed emotion: developmental processes in psychosis. In: Gumley A, Gillham A, Taylor K, Schwannauer M, editors. Psychosis and emotion: the role of emotions in understanding psychosis, therapy and recovery. London: Routledge; 2013. pp. 136–148. 24. Shaver PR, Fraley RC. Attachment, loss, and grief: Bowlby’s views and current controversies. In: Cas- sidy J, Shaver PR, editors. Handbook of attachment: theory, research, and clinical applications. New York: Guilford Press; 2008. pp. 48–77. 25. Shear K, Shair H. Attachment, loss, and complicated grief. Dev Psychobiol. 2005; 47: 253–267. https:// doi.org/10.1002/dev.20091 PMID: 16252293 26. Stroebe M, Schut H, Stroebe W. Attachment in coping with bereavement: a theoretical integration. Rev Gen Psychol. 2005; 9: 48–66. 27. Fraley RC, Bonanno GA. Attachment and loss: a test of three competing models on the association between attachment-related avoidance and adaptation to bereavement. Personal Soc Psychol Bull. 2004; 30: 878–90. 28. Neimeyer RA, Prigerson HG, Davies B. Mourning and meaning. Am Behav Sci. 2002; 46: 235–251. 29. Bartholomew D, Horowitz LM. Attachment styles among young adults: A test of a four-category model. J Pers Soc Psychol. 1991; 61: 226–244. https://doi.org/10.1037//0022-3514.61.2.226 PMID: 1920064 PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 10 / 13 Relatives’ perceived loss, attachment and expressed emotion 30. Mikulincer M, Shaver PR. Attachment in adulthood: Structure, dynamics, and change. New York: Guil- ford Press; 2007. 31. Burke LA, Neimeyer RA. Prospective risk factors for complicated grief: a review of the empirical litera- ture. In: Stroebe MS, Schut H, van der Bout J, Boelen P, editors. Complicated grief. New York: Rout- ledge; 2012. pp. 145–161. 32. Meier AM, Carr DR, Currier JM, Neimeyer RA. Attachment anxiety and avoidance in coping with bereavement: two studies. J Soc Clin Psychol. 2013; 32: 315–34. 33. Godress J, Ozgul S, Owen C, Foley-Evans L. Grief experiences of parents whose children suffer from mental illness. Aust N Z J Psychiatry. 2005; 39: 88–94. https://doi.org/10.1111/j.1440-1614.2005. 01518.x PMID: 15660710 34. Mikulincer M, Shaver PR. Attachment in adulthood: Structure, dynamics, and change. 2nd ed. New York: Guilford Press; 2016. 35. Cassidy J, Kobak RR. Avoidance and its relationship with other defensive processes. In: Belsky J, Nez- worski T, editors. Clinical implications of attachment. Hillsdale: Erlbaum; 1988. pp. 300–323. 36. Main M. Cross-cultural studies of attachment organization: recent studies, changing methodologies, and the concept of conditional strategies. Hum Dev. 1990; 33: 48–61. 37. Mikulincer M, Shaver PR. Adult attachment and affect regulation. In: Cassidy J, Shaver PR, editors. Handbook of attachment: theory, research, and clinical applications, 2nd ed. New York: Guilford Press; 2008. pp. 503–531. 38. Mikulincer M, Shaver PR. Attachment insecurities and disordered patterns of grief. In: Stroebe M, Schut H, Boelen P, van den Bout J, editors. Complicated grief: scientific foundations for health care profes- sionals. New York: Routledge; 2012. pp. 190–203. 39. Collins NL, Ford MB. Responding to the needs of others: the caregiving behavioral system in intimate relationships. J Soc Pers Relat. 2010; 27: 235–244. 40. George C, Solomon J. The caregiving system: a behavioral systems approach to parenting. In: Cassidy J, Shaver PR, editors. Handbook of attachment: theory, research, and clinical applications. New York: Guilford Press; 2008. pp. 833–857. 41. Jones JD, Cassidy J, Shaver PR. Parents’ self-reported attachment styles: a review of links with parent- ing behaviors, emotions, and cognitions. Personal Soc Psychol Rev. 2015; 19: 44–76. 42. Kunce LJ, Shaver PR. An attachment theoretical approach to caregiving. In: Bartholomew K, Perlman D, editors. Attachment processes in adulthood. Advances in personal relationships. London: Jessica Kingsley; 1994. pp. 205–237. 43. Canterberry M, Gillath O. Attachment and caregiving functions, interactions, and implications. In: Noller P, Karantzas GC, editors. The Wiley-Blackwell handbook of couples and family relationships. Chiches- ter: Wiley-Blackwell; 2012. pp. 207–219. 44. Feeney BC, Collins NL. Predictors of caregiving in adult intimate relationships: an attachment theoreti- cal perspective. J Pers Soc Psychol. 2001; 80: 972–994. PMID: 11414378 45. Karantzas GC, Simpson JA. Attachment and aged care. In: Simpson JA, Rholes WS, editors. Attach- ment theory and research: new directions and emerging themes. New York: Guilford; 2012. pp. 319– 345. 46. Chen CK. The relationship between attachment quality and expressed emotion among adult children caring for parents with dementia. Thesis, The University of North Carolina at Chapel Hill. 2006. Avail- able from: https://cdr.lib.unc.edu/indexablecontent/uuid:ef702a96-6796-4067-9960-06057adb5292 47. Diamond D, Doane JA. Disturbed attachment and negative affective style: an intergenerational spiral. Br J Psychiatry. 1994; 164: 770–781. https://doi.org/10.1192/bjp.164.6.770 PMID: 7952983 48. Paley G, Shapiro DA, Worrall-Davies A. Familial origins of expressed emotion in relatives of people with schizophrenia. J Ment Health. 2000; 9: 655–663. 49. Adam EK, Gunnar MR, Tanaka A. Adult attachment, parent Emotion, and observed parenting behavior: mediator and moderator models. Child Dev. 2004; 75: 110–122. https://doi.org/10.1111/j.1467-8624. 2004.00657.x PMID: 15015678 50. Bosquet M, Egeland B. Associations among maternal depressive symptomatology, state of mind and parent and child behaviors: implications for attachment-based interventions. Attach Hum Dev. 2001; 3: 173–199. https://doi.org/10.1080/14616730010058007 PMID: 11708736 51. Garcı́a-Ruiz M, Rodrigo MJ, Hernández-Cabrera JA, Máiquez ML. Contribution of parents’ adult attach- ment and separation attitudes to parent-adolescent conflict resolution. Scand J Psychol. 2013; 54: 459– 67. https://doi.org/10.1111/sjop.12077 PMID: 24117437 52. Millings A, Walsh J, Hepper E, O’Brien M. Good partner, good parent. Personal Soc Psychol Bull. 2013; 39: 170–180. PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 11 / 13 Relatives’ perceived loss, attachment and expressed emotion 53. Berry K, Barrowclough C, Wearden A. A review of the role of adult attachment style in psychosis: unex- plored issues and questions for further research. Clin Psychol Rev. 2007; 27: 458–475. https://doi.org/ 10.1016/j.cpr.2006.09.006 PMID: 17258365 54. Domı́nguez-Martı́nez T, Vainer E, Antonia Massanet M, Torices I, Jané M, Barrantes-Vidal N. The need-adapted integrated treatment in Sant Pere Claver-Early Psychosis Program (SPC-EPP) in Barce- lona, Spain. Salud Ment. 2011; 34: 517–24. 55. Yung AR, Yuen HP, McGorry PD, Phillips LJ, Kelly D, Dell’Olio M, et al. Mapping the onset of psychosis: the comprehensive assessment of at-risk mental states. Aust N Z J Psychiatry. 2005; 39: 964–971. https://doi.org/10.1080/j.1440-1614.2005.01714.x PMID: 16343296 56. Schultze-Lutter F, Addington J, Ruhrmann S, Klosterkötter J. Schizophrenia proneness instrument– adult version (SPI-A). Rome: Giovanni Fioriti; 2007. 57. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders: DSM- IV-TR. Washington, DC: American Psychiatric Association; 2000. 58. First MB, Spitzer RL, Gibbon M, Williams JB. Structured clinical interview for DSM-IV Axis I Disorders- Patient ed. (SCID-I/P, Version 2.0). New York: Biometrics Research Department; 1995. 59. Berry K, Wearden A, Barrowclough C, Liversidge T. Attachment styles, interpersonal relationships and psychotic phenomena in a non-clinical student sample. Pers Individ Dif. 2006; 41: 707–718. 60. Wiedemann G, Rayki O, Feinstein E, Hahlweg K. The Family Questionnaire: Development and valida- tion of a new self-report scale for assessing expressed emotion. 2002; 109: 265–279. 61. Cohen J. A power primer. Psychol Bull. 1992; 112: 155–159. https://doi.org/10.1037//0033-2909.112. 1.155 PMID: 19565683 62. Hayes AF. Introduction to mediation, moderation, and conditional process analysis: A regression-based approach. New York: Guilford Press; 2013. 63. Collins NL, Feeney BC. A safe haven: An attachment theory perspective on support seeking and care- giving in intimate relationships. J Pers Soc Psychol. 2000; 78: 1053–1073. https://doi.org/10.1037// 0022-3514.78.6.1053 PMID: 10870908 64. Álvarez-Jiménez M, Gleeson JF, Cotton SM, Wade D, Crisp K, Yap MBH, et al. Differential predictors of critical comments and emotional over-involvement in first-episode psychosis. Psychol Med. 2010; 40: 63–72. https://doi.org/10.1017/S0033291708004765 PMID: 19079825 65. Wynne LC. Current concepts about schizophrenics and family relationships. J Nerv Ment Dis. 1981; 169: 82–89. https://doi.org/10.1097/00005053-198102000-00003 PMID: 7009785 66. O’Connell Corcoran K, Mallinckrodt B. Adult attachment, self-efficacy, perspective talking, and conflict resolution. J Couns Dev. 2000; 78: 474–483. 67. Simpson JA, Rholes WS, Phillips D. Conflict in close relationships: an attachment perspective. J Pers Soc Psychol. 1996; 71: 899–914. https://doi.org/10.1037//0022-3514.71.5.899 PMID: 8939040 68. Feeney AJ. Parental attachment and conflict behavior: Implications for offspring’s attachment, loneli- ness, and relationship satisfaction. Pers Relatsh. 2006; 13: 19–36. 69. Mikulincer M, Shaver PR. An attachment perspective on bereavement. In: Stroebe M, Hansson RO, Stroebe W, editors. Handbook of bereavement research and practice: 21st century perspectives. Washington, DC: American Psychological Association; 2008. pp. 87–110. 70. Currier JM, Irish JEF, Neimeyer RA, Foster JD. Attachment, continuing bonds, and complicated grief following violent loss: testing a moderated model. Death Stud. 2015; 39: 201–10. https://doi.org/10. 1080/07481187.2014.975869 PMID: 25551174 71. Jerga AM, Shaver PR, Wilkinson RB. Attachment insecurities and identification of at-risk individuals fol- lowing the death of a loved one. J Soc Pers Relat. 2011; 28: 891–914. 72. Wijngaards-De Meij L, Stroebe M, Schut H, Stroebe W, Van Den Bout J, Van Der Heijden PGM, et al. Patterns of attachment and parents’ adjustment to the death of their child. Personal Soc Psychol Bull. 2007; 33: 537–548. 73. Bowlby J. A secure base: parent-child attachment and healthy human development. New York: Basic Books; 1988. 74. Miklowitz DJ. The role of family systems in severe and recurrent psychiatric disorders: A developmental psychopathology view. 2004; 16: 667–688. PMID: 15605631 75. Koutra K, Triliva S, Roumeliotaki T, Basta M, Simos P, Lionis C, et al. Impaired family functioning in psy- chosis and its relevance to relapse: a two-year follow-up study. Compr Psychiatry 2015; 62: 1–12. https://doi.org/10.1016/j.comppsych.2015.06.006 PMID: 26343461 76. Zanetti ACG, Ciol MA, Wiedemann G, de Azevedo-Marques JM, Dantas RAS, da Silva Gherardi- Donato EC, et al. Predictive Validity of the Brazilian Portuguese Version of the Family Questionnaire for PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 12 / 13 Relatives’ perceived loss, attachment and expressed emotion Relapse in Patients With Schizophrenia. J Nurs Meas. 2017; 25: 559–572. https://doi.org/10.1891/ 1061-3749.25.3.559 PMID: 29268835 77. Crisp K, Gleeson J. Working with families to prevent relapse in first episode psychosis. In: Lobban F, Barrowclough C, editors. A casebook of family interventions for psychosis. Chichester: John Wiley & Sons; 2009. pp. 67–90. 78. Lobban F, Postlethwaite A, Glentworth D, Pinfold V, Wainwright L, Dunn G, et al. A systematic review of randomised controlled trials of interventions reporting outcomes for relatives of people with psychosis. Clin Psychol Rev. 2013; 33: 372–382. https://doi.org/10.1016/j.cpr.2012.12.004 PMID: 23410719 79. Harris T. Implications of attachment theory for working in psychoanalytic psychotherapy. Int Forum Psy- choanal. 2004; 13: 147–56. PLOS ONE | https://doi.org/10.1371/journal.pone.0223425 October 7, 2019 13 / 13