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Home , Psychosis, Schizoaffective disorder, Schizophrenia

Eur. J. Psychiat. Vol. 28, N.° 1, (27-38) 2014

Keywords: Trauma; Post-traumatic disorder; .

Trauma, posttraumatic stress disorder and psychosis: Etiopatho genic and nosological implications

Álvaro Frías Ibáñez*,** Carolina Palma Sevillano** Eloi Giné Serven* Elena Aluco Sánchez* * Unit. Hospital of Mataró ** FPCEE Blanquerna. Ramon Llull University SPAIN

ABSTRACT – Background and Objectives: The relationship between trauma, post-trau- matic stress disorder (PTSD), and psychosis has promoted heterogeneous research lines, in both etiopathogenic and nosological areas. The main aim of this review is to provide a systematic framework that encompasses this theoretical gap in the literature. Methods: A literature research was carried out through PubMed and PsycINFO be- tween 1980 and May 2013. One hundred and thirteen articles were recruited. A first part of this review describes the role of trauma in the development of psychosis. The second part focuses on research about PTSD and psychosis. Results: Longitudinal and cross-sectional studies with clinical and community samples confirm that (CT) is a vulnerability factor for and psy- chotic-like symptoms in adulthood. More empirical research is needed in order to assess the role of trauma as precipitant of acute psychosis. There is also preliminary evidence with cross-sectional samples that suggests that PTSD and psychosis are a for each other, with studies about post-psychotic PTSD (PP-PTSD) being outstanding. Final- ly, results from different comparative research studies postulate a subtype of PTSD with psychotic features (PTSD-SP). Conclusions: The role of trauma in psychosis is more conclusive as predispositional rather than as trigger factor. Nosological status of acute psychoses remains a focus of con- troversy unresolved. The association between PTSD and psychosis is complex, requiring more prospective research in order to determine causal relationships between these pathologies. Also, research in nosological status of PTSD-SP must encourage more com- parative studies not limited to neurobiological variables.

Received: 2 July 2013 Revised: 7 November 2013 Accepted: 12 November 2013 28 ÁLVARO FRÍAS IBÁÑEZ ET AL.

Introduction PTSD in subjects with psychosis. With this purpose, a literature research was carried out through PubMed and PsycINFO between The presence of trauma and post-traumatic 1980 and May 2013. The descriptors used stress disorder (PTSD) in subjects with psy- were “hysterical psychosis”, “psychogenic chotic symptoms has produced a consider- psychosis”, “post-traumatic psychosis”, “re- able amount of research, both heterogeneous active psychosis”, “trauma”, “childhood and unconnected in terms of approaches and trauma”, “psychosis”, “schizophrenia” and areas of development, mainly conditioned “post-traumatic stress disorder”. One hun- by the prevailing psychiatric paradigm in dred and thirteen articles were recruited, in- every historical period. In this , litera- cluding theoretical, quasi-experimental, and ture specialised in this topic has promoted di- descriptive studies. Studies that included ado- fferent etiopathogenic and nosological mo- lescent were excluded because of ex- dels in this issue. ceeding the scope and main goals of this re- Over the two first thirds of twentieth cen- view. Findings were grouped into two thematic tury, research in this issue was solely focused blocks. A first part describes the role of trauma in the role of trauma as a trigger factor for in the development of psychosis, whether as 1) acute psychoses, traditionally called hyster- predisposing factor for schizophrenia or pos- ical psychosis (HP) or psychogenic psychosis itive symptoms in adulthood, or as 2) trigger- (PP)1. However, in the last decade other re- ing variable for acute psychosis. On the other search lines have been promoted alien to tra- hand, the second part focuses on research ditional assumptions, with an inclusion of about PTSD and psychosis, with results being theoretical-clinical aspects not considered regrouped by considering 1) data, before. On the one hand, from an etiopatho- 2) theories explaining this relationship, and fi- genic perspective, many empirical studies nally 3) nosological status of PTSD-SP. have been carried out in relation to the role of childhood trauma (CT) as a predispositional factor for schizophrenia or psychotic-like symptoms in adulthood2. On the other hand, Role of trauma in the concerning the relationship between PTSD etiopathogenesis of psychoses and psychosis, the existence of a subgroup of subjects with PTSD with secondary psy- – CT as predisposing factor for schizophrenia chotic features (PTSD-SP) has been consid- or positive symptoms in adulthood ered3, as well as other patients with post- psychotic PTSD (PP-PTSD)4. With regard to the role of CT as a vulner- ability factor for psychosis, many cross-sec- tional and prospective studies agreed in con- sidering that the risk of having schizophrenia Objectives and method or positive symptoms (psychotic–like symp- toms) in adulthood is over two-fold to four- fold if the subject has been the victim of In this general framework, this theoretical some traumatic event in both childhood and review has the main aim of offering a system- periods5,6. These findings emerged atic analysis of the main research lines and in research studies with 1) clinical samples of empiric evidence available about trauma and chronic psychotic patients, “first episodes” TRAUMA, PTSD AND PSYCHOSIS 29 and ultra-high-risk (UHR) for psychosis7-12, ing that people with childhood trauma events 2) general adult population13,14, and 3) co- are at higher risk for psychosis in adulthood horts of women that had been sexually as- if they use in their early and/or mid saulted15. At a comparative level, no more adolescence6,35,36. history of CT was found in patients with psy- With regard to variables mediating the as- chosis when the control group were subjects sociation between CT and psychosis, differ- with another psychiatric pathology (e.g., ma- 2 ent explanatory factors have been proposed: jor ) . From a dimensional per- dysfunctional cognitive schemas, dissocia- spective, different community studies ob- tive mechanisms, high levels of , and tained a specific association between CT and 16-21 traumagenic neurodevelopment. From cog- presence of in adulthood , nitive-behavioural models, many studies with particularly if the traumatic events involved community samples found that the presence 22-24 sexual abuse . of a history of CT contributes to the devel- Additionally, different variables were pro- opment of negative cognitive schemas about posed as possible modifiers in the relation- the and the others, which predispose to ship between CT and psychosis: characteris- psychotic-like symptoms in adulthood, 15,26,28,37,38 tics of the trauma (frequency and nature), mainly paranoid . On the genetic predisposition, gender, and cannabis other hand, a series of research studies with abuse. As for the traumatic event, many re- samples of psychotic patients claimed that the search studies with clinical and community presence of processes following samples claimed that the relationship be- CT accounts for the emergence of psychotic- like symptoms in adulthood, particularly hal- tween these two variables is “dose-depen- 15,23,39-41 dent”, that is, the relative risk of having a psy- lucinations , Likewise, other studies chosis increases as the frequency of traumatic with clinical and community samples con- sidered that high anxiety partially results in events is higher in childhood25-31. Concerning psychotic-like symptoms in subjects with the nature of the traumatic event, there is no traumatic events in their childhood or ado- consistent data to confirm a higher risk of lescence phases22,42-44. Finally, from a bio- having psychosis among people that have logical perspective, a “traumagenic neurode- been victims of a specific type of CT6. In this velopmental model” was proposed, which sense, many research studies with community states that the stress created by CT would or UHR for psychosis population observed cause early impairments in the hypothalamic- that the relative risk increases in those subjects pituitary-adrenal (HPA) axis and that had been victims of either sexual abuse7,11 regulation, increasing the possibility of hav- or physical abuse29,32,33. With regard to bio- ing a psychosis45-47. Additionally, a cross- logical predisposition, a study with a sample sectional research with high- of observed that the probability of hav- lighted a positive relationship between CT ing psychotic-like symptoms connected to and hippocampal and amygdalar volumes in CT is modulated by a genetic predisposition a sample of first psychotic episodes48. for depression34. As for the subjects’ gender, a research study with a community sample In sum, childhood traumatic events are an with control group found higher CT fre- unspecific risk factor for psychosis in adult- quency in women (versus men) with first hood, particularly hallucinations. Cannabis psychotic episodes33. Finally, concerning abuse and accumulation of traumas increase , there is agreement in point- this probability. At a dimensional level, the 30 ÁLVARO FRÍAS IBÁÑEZ ET AL. development of negative cognitive schemas other acute psychoses of a more endogenous and dissociative processes has been associ- nature (e.g., cycloid psychosis), focusing on ated to the presence of paranoid delusions time or evolutionary criteria for their group- and hallucinations, respectively. ing. This explains that research studies car- ried out in the last two decades have been – Trauma as a triggering factor for acute mainly aimed at distinguishing this hetero- psychosis geneous group of acute psychoses from schizophrenia54-56. With regard to the role of trauma as trig- gering acute psychosis, there are scarce em- In contrast to this current nosological pirical studies that have assessed this issue in framework, there is some historical back- the last fifteen years. Over this period, most ground that illustrates and delimits these psy- of these studies have focused in elucidating chotic disorders triggered by trauma. On the the general role of life events rather than trau - one hand, French psychiatry coined the term matic ones as a trigger factor for psychosis. HP57 in the second half of the nineteenth cen- Concerning to this topic, there are prelimi- tury, with this pathology being conceptualized nary evidences suggesting that psychotic pa- as a dissociative phenomenon58. On the other tients have a 3-fold greater risk of life events hand, the Scandinavian school developed, in prior to their onset compared with control the first third of the twentieth century, a sim- groups49. Likewise, amongst the few studies ilar concept called PP1. Both approaches con- aimed to establish the specific role of trauma verged when observing that this kind of psy- in the outset of acute psychosis not classified chotic disorder has 1) an abrupt onset after a as schizophrenia, one study found that the traumatizing event, 2) a self-limited duration presence of a intrusive event (e.g., physical of a few weeks, 3) positive symptomatology, assault) was more likely to be associated with 4) mood lability, and 5) recovery ad inte- an increased risk of psychosis, most com- grum59-61. Despite this remarkable clinical monly in the 3 months pre-onset (34% cases agreement, both nosological constructs fell vs 3% controls)50. into disuse in the decades following their for- Overall, this current deficit of studies is mulation. With regard to HP, many patients due to a lack of agreement in relation to the were diagnosed with schizophrenia once this nosological status of acute psychoses trig- term had been introduced in psychiatric nosol- gered by serious stressors, a fact that is re- ogy. Concerning PP, its dissemination was flected in the relevance given to these clini- limited from the very beginning due to the use cal entities in current psychiatric . of a minority language62,63. In the case of HP, On the one hand, the ICD-1051 describes a se- some authors tried to apply this construct ries of “acute and transient psychotic disor- later64, with no conclusive data about its noso- ders”, which can be or not secondary to logical , particularly concerning its stressful situations. As for the DSM-IV-TR52, brief or transient nature65-68. it recognises the existence of the “brief psy- chotic disorder”, which may be preceded or In summary, current psychiatric nosology not by a severe triggering factor, with its recognises post-traumatic psychoses in a presence being equivalent to the “brief reac- residual manner. Despite having relative clin- tive psychosis” already defined in the DSM- ical validity69, there is no agreement when III-TR53. Both manuals classify this kind of defining their distinctive characteristics from psychotic conditions in the same cluster that an empirical perspective. TRAUMA, PTSD AND PSYCHOSIS 31

PTSD and psychosis – Theories explaining the association in traumatized subjects between PTSD and psychosis From these results on prevalence, different – Prevalence hypotheses have been proposed as possible With regard to prevalence data between etiopathogenic mechanisms of the relation- PTSD and psychosis, two types of studies ship between PTSD and psychosis (schizo- have been carried out. On the one hand, re- phrenia or psychotic-like symptoms). On the search studies with psychotic patients aimed one hand, one of the two disorders would at determining with PTSD. On emerge as predisposing for the other (unidi- the other hand, studies in subjects with PTSD, rectional theory). On the other hand, third va - which assessed the presence of psychotic- riables would justify this co-occurrence (the- like symptoms associated with this condition, ory of common risk factors). a clinical phenotype called PTSD-SP70. With regard to the first approach, there is As for the comorbidity between PTSD and empirical evidence to claim that both patholo- schizophrenia, prevalence data are in a range gies are a vulnerability variable for the other between 11% and 53%71-74. These findings in disorder. In the case of subjects with PTSD, samples of psychotic patients are signifi- different cross-sectional research studies with cantly higher to the percentage of subjects community samples showed that the risk of with PTSD in general adult population, with having psychotic-like symptoms is at least an estimated range from 3% to 5%75. With re- twice as higher as the one observed in general gard to the prevalence of PTSD-SP, avail- population ( = 1.8-3.5), with a able data in samples of former combatants higher predisposition to delusional sympto- show that 17-20% of these subjects with matology being outstanding28,38,76,79,80. Con- PTSD have secondary positive symptoms as- cerning this hypothesis, a model of continu- sociated with trauma (e.g., paranoid delu- ity between PTSD and psychosis has been sions)76-78. Two factors have been pointed as proposed, in such a way that the psychotic responsible for possibly overestimating this condition would indeed be an exacerbation of association. On the one hand, comorbid men- the former condition79,81. tal disorders that would really account for the presence of psychotic-like symptoms in On the other hand, within this unidirec- PTSD samples (e.g., psychotic depression). tional theory, a series of mainly cross-sec- On the other hand, potential biases when dis- tional studies have aimed at determining the risk of having PTSD as a result of psychosis tinguishing re-experiencing symptoms (e.g., 4 intrusive images) from psychotic ones (e.g., onset, a fact called PP-PTSD . On this issue, visual hallucinations). As for the first issue, many studies with clinical samples of sub- a study that excluded those patients with ma- jects with first psychotic episodes showed jor depression reduced PTSD-SP prevalence that the prevalence of PTSD ranges from in 2.5% in samples of traumatized patients76. 11% to 67%, being diagnosed in a third of patients assessed on average4,82-88. Two vari- In sum, there are epidemiological findings ables have been identified as potential pre- in clinical samples suggesting that the asso- cursors of this post-traumatic condition: pos- ciation between PTSD and psychosis hap- itive symptoms and the type of psychiatric pens with higher probability than in general admission (e.g., voluntary vs. involuntary). population. Concerning the first factor, there are partially 32 ÁLVARO FRÍAS IBÁÑEZ ET AL. consistent findings to establish a positive re- At a methodological level, most of these lationship between presence or severity of research studies have been conducted with positive symptoms and PTSD82,85,87,88. As war veteran samples diagnosed with PTSD for the kind of admission and/or treatment, “with” versus “without” psychotic-like symp- the association is less conclusive82,84,85,87. toms, with different neurobiological markers Together, these data have posed the question being used as dependent variables. The main of what variables could be modulating the re- results of these studies show that subjects lationship between these variables and PTSD. with PTSD-SP have 1) a higher concentration In this sense, current findings suggest that the of platelet , 2) higher levels of cor- presence of PTSD in subjects with first psy- ticotropin-releasing factor in the cerebros pi - chotic episodes is higher if 1) they have a pre- nal fluid, 3) a higher concentration of plasma vious history of trauma, 2) use dysfunctional dopamine beta-hydroxylase, 4) specific de - assessment and coping strategies in front of ficits in smooth pursuit eye movement, and 5) stress (e.g., experience of uncontrollability), a higher presence of Met in the BDNF and 3) show comorbid depressive symp- Val66Met polymorphism94-98. Likewise, dif- toms4,82-84,88-90. ferent open clinical trials found that the ad- ministration of neuroleptics as a monotherapy Finally, regarding the existence of com- for 6-8 weeks reduces symptoms in those mon factors in PTSD and psychosis, only subjects with PTSD-SP resistant to conven- two proposals have been carried out from di- tional treatment99-101. On the vergent approaches. On the one hand, a “mo- other hand, at a psychopathological level, del of cognitive integration” has been pro- subjects with PTSD-SP have a more severe posed, which considers that both disorders 80 would be pathologies in the post-traumatic posttraumatic condition . Finally, from sta- spectrum with similar explanatory mecha- tistical techniques such as latent class analy- nisms at the level of cognitive schemas, at- sis, evidence has been found in favour of this 102 tributional styles and dissociative processes91. nosological approach . On the other hand, from a neurobiological In summary, there is preliminary evidence, perspective, it is considered that both disor- particularly at a neurobiological level, to ad- ders imply a dysfunction in the HPA axis, vocate a subtype of PTSD-SP103,104. thus causing a dysregulation in the release of cortisol in response to stress45. In summary, there is empirical evidence to suggest a possible reciprocal influence be- Discussion and conclusions tween both types of . As for the presence of third variables, there is scarce – Summary research comparing PTSD and schizophrenia In this theoretical review, we have pre- to determine this approach. sented the main findings and research studies about trauma and PTSD in subjects with psy- – Nosological status of PTSD-SP chosis. With regard to the role of CT, there is The high prevalence of subjects with PTSD conclusive evidence about its influence as and co-occurring positive symptoms has en- an unspecific risk factor, both for schizo- couraged a last line of research aimed at de- phrenia and positive symptoms (psychotic- termining the nosological status of those pa- like symptoms) in adulthood. Concerning the tients with PTSD-SP3,92,93. relevance of trauma as a triggering factor of TRAUMA, PTSD AND PSYCHOSIS 33 acute psychotic conditions, there is scarce of psychosocial dysfunctionality, neurocog- empirical research that assesses this etiopath- nitive profile). Likewise, controlled clinical ogenic approach, with these psychoses being trials have to be conducted with long-term residually integrated into current psychiatric follow-up in order to assess the efficiency of nosology. On the other hand, concerning the neuroleptics in this subgroup of patients. Fi- theories explaining the relationship between nally, there are not comparative studies re- PTSD and psychosis (schizophrenia or pos- garding clinical and functional differences itive symptoms), there is preliminary evi- between PP-PTSD and PTSD-SP. Thus, fur- dence to establish a two-directional causality ther research is warranted in this last issue. between both pathologies. Finally, consis- tent results have been obtained that would – Clinical implications confirm a subtype of PTSD-SP. • In the field of primary prevention, it is required to develop in – Methodological limitations those subjects with CT and UHR for With regard to the limitations of studies on psychosis, thus focusing the intervention trauma and psychosis, there is a lack of em- on negative cog nitive schemas and dis- pirical research aimed at clarifying the noso- sociative mechanisms involved. logical status and clinical characteristics of • At a nosological level, false positive di- acute psychoses triggered by a trauma or se- agnosis of chronic psychosis has to be rious stressor, particularly in view of distin- avoided in those subjects that develop guishing them from other more endogenous psychotic experiences after a serious acute psychoses. In this sense, studies that de- stressful event. It is necessary to assess termine the role of trauma in the pathoplasty the evolutionary course in order to carry of psychosis have to be encouraged, particu- out the appropriate . larly in relation to the content of delusions or hallucinations. In this issue, there are some • In subjects with a primary diagnosis of research studies that show a relationship be- schizophrenia, the possible occurrence tween history of sexual abuse and nature of of PTSD has to be assessed and treated psychotic symptoms24,105,106. As for the the- with conventional psychotherapy107-111, ories explaining the association between especially considering that co-morbidity PTSD and psychosis, prospective research is an indicator of higher suicidal risk71,74. has to be promoted to reliably determine the Specifically, the potential post-traumatic relationships of causality between both types symptoms in subjects with first psy- of psychopathology. Likewise, there are chotic episodes (PP-PTSD) has to be as- scarce studies comparing PTSD versus psy- sessed, with the optimization of coping chosis with the aim of assessing potential strategies in front of stress and the inte- common factors at the neurobiological, neu- gration of the psychotic experience be- ropsychological and/or cognitive level. With ing a priority in these cases85,86,112,113. regard to the nosological status of PTSD-SP, • In subjects with a primary diagnosis of more comparative research studies have to be PTSD, it is necessary to assess associated encouraged to determine this question, with psychotic-like symptoms (PTSD-SP), in the inclusion of other external criteria apart which case treatment with neuroleptics from neurobiological variables (e.g., degree should be implemented. 34 ÁLVARO FRÍAS IBÁÑEZ ET AL.

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109. van den Berg M, Hendriks GJ, van Minnen A. Imag- of to reduce post psychotic trauma symp- inal exposure treatment for a post-traumatic stress disorder toms. Behav Res Ther 2009; 47: 454-462. in a patient with a comorbid psychotic disorder. Tijdschr 113. Jackson C, Bernard M, Birchwood M. The Psychiatr 2010; 52: 191-195. of psychotherapy in reducing post-psychotic trauma. Epi- 110. van den Berg DP, van der Gaag M. Treating trauma demiol Psychiatr Sci 2011; 20: 127-131. in psychosis with EMDR: a pilot study. J Behav Ther Exp Psychiatry 2012; 43: 664-671. 111. van der Vleugel BM, van den Berg DP, Staring AB. Corresponding author: Trauma, psychosis, post-traumatic stress disorder and the ap- Álvaro Frías Ibáñez plication of EMDR. Riv Psichiatr 2012; 47: 33-38. Servicio de Psiquiatría. Hospital de Mataró 112. Jackson C, Trower P, Reid I, Smith J, Hall M, Tow- Ctra. Cirera s/n CP: 08304 Mataró (Barcelona) nend M, et al. Improving psychological adjustment follow- Phone number: +34 93 7417700 (ext. 4701) ing a first episode of psychosis: a randomised controlled trial E-mail address: [email protected]