- Email: [email protected]
Acute stress and substance use as predictors of suicidal behaviour in acute and transient psychotic disorders
Accepted Manuscript
Acute stress and substance use as predictors of suicidal behaviour in acute and transient psychotic disorders ´ Alvaro Lopez-D´ ıaz , Pablo Lorenzo-Herrero , Ignacio Lara , ´ Jose´ Luis Fernandez-Gonz alez , Miguel Ruiz-Veguilla ´ ´ PII: DOI: Reference:
S0165-1781(17)31334-3 https://doi.org/10.1016/j.psychres.2018.08.036 PSY 11630
To appear in:
Psychiatry Research
Received date: Revised date: Accepted date:
19 July 2017 23 June 2018 13 August 2018
´ Please cite this article as: Alvaro Lopez-D´ ıaz , Pablo Lorenzo-Herrero , Ignacio Lara , ´ Jose´ Luis Fernandez-Gonz alez , Miguel Ruiz-Veguilla , Acute stress and substance use as pre´ ´ dictors of suicidal behaviour in acute and transient psychotic disorders, Psychiatry Research (2018), doi: https://doi.org/10.1016/j.psychres.2018.08.036
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Highlights: There is a lack of research on suicide in patients with ATPD.
•
The study investigates whether there are predictors of suicidal behaviour in ATPD.
•
Acute stress and substance use are significantly associated with suicidal behaviour.
•
Screening both factors would aid assessment of suicide risk in ATPD patients.
AC
CE
PT
ED
M
AN US
CR IP T
•
1
ACCEPTED MANUSCRIPT Title: Acute stress and substance use as predictors of suicidal behaviour in acute and transient psychotic disorders
Álvaro López-Díaz a, Pablo Lorenzo-Herrero b, Ignacio Lara a, José Luis Fernández-González b, Miguel
CR IP T
Ruiz-Veguilla c
a
UGC Salud Mental. Hospital Universitario Virgen Macarena. Sevilla. Spain
b
UGC Salud Mental. Hospital San Juan de la Cruz. Úbeda. Spain
c
UGC Salud Mental. Hospital Universitario Virgen del Rocío. IBIS. Grupo Psicosis y Neurodesarrollo.
AN US
Sevilla. Spain
Corresponding autor:
Miguel Ruiz-Veguilla UGC Salud Mental. Hospital Universitario Virgen del Rocío. IBIS. Grupo Psicosis y Neurodesarrollo. Avda.Manuel Siurot sn. 41013 Seville. Spain Email: [email protected]
CE
PT
ED
M
AC
Abstract:
Several authors have reported high rates of suicidal behaviour in acute and transient psychotic disorders (ATPD). However, the literature in this area remains scarce. We wanted to find out whether there are predictors of suicidal behaviour in ATPD. Of 1,032 psychosis admissions examined over a five-year period, ATPD was confirmed in 39 patients according to the International Classification of Diseases (ICD-10) diagnostic criteria. These patients were classified as suicidal behaviour (20.5%) or non-risk (79.5%) using a structured interview to assess suicidal risk. The following variables were analysed:
2
ACCEPTED MANUSCRIPT previous history of suicide attempt or deliberate self-harm, history of depressive episodes, previous substance use history, education, ATPD subtype (polymorphic vs. non-polymorphic), type of onset (abrupt vs. acute), and presence of associated acute stress. Multivariate analysis revealed that acute stress and substance use are significantly associated with suicidal behaviour in ATPDs. To our knowledge, this is the first study identifying independent risk factors that could predict suicidal behaviour in individuals
CR IP T
with ATPD.
Keywords: acute and transient psychotic disorder; brief psychotic disorder; first-episode psychosis; suicide; International Classification of Diseases
Introduction
AN US
1.
Reports from the World Health Organization (WHO, 2015a) indicate that suicide is a global public health concern and represents one of the leading causes of preventable death. Suicide is a complex phenomenon involving a number of psychosocial variables and in which mental illness plays an undeniable central role (Haw and Hawton, 2015). A 45-fold increased risk of suicidality was found in a
M
recent meta-review comparing suicidal behaviour in individuals with psychiatric disorders versus the general population (Chesney et al., 2014). Even though there are no effective algorithms for suicide
ED
prediction in clinical practice, the search for predictors of suicide in mental disorders still constitutes a fundamental objective for prevention strategies (Hawgood and De Leo, 2016; Mann et al., 2005; Turecki
PT
and Brent, 2016).
Most studies addressing suicide in patients with psychosis have focused on schizophrenia
CE
(Cassidy et al., 2017; Hawton et al., 2005; Hor and Taylor, 2010; Popovic et al., 2014), with particular emphasis on the early stages (Nordentoft et al., 2015; Togay et al., 2015; Ventriglio et al., 2016). In fact,
AC
the highest rates of suicide attempts have been found before and after the first-episode of psychosis, specifically during the first year (Pompili et al., 2011; Dutta et al., 2013). Thus, in their meta-analysis on deliberate self-harm during the first-episode of psychosis, Challis et al. (2013) revealed that 9.8% of the patients presented with suicidal behaviour during the period of untreated psychosis and 11.4% developed it during the following 7 years. Factors associated with an increased risk of deliberate self-harm in patients with first-episode of psychosis are previous history of deliberate self-harm, expressed suicide
3
ACCEPTED MANUSCRIPT ideation, depressed mood, alcohol abuse, substance use, good insight and younger age of onset (Challis et al., 2013). However, there seems to be a lack of research in suicide prediction in patients with acute and transient psychotic disorders (ATPD), despite the fact that its annual incidence ranges from 4–10 per 100,000 people; further, it accounts for up to 19% of all first-episode psychosis. (Castagnini and Berrios, 2009; Castagnini and Fusar-Poli, 2017; Marneros and Pillman, 2004). The meta-analysis conducted by
CR IP T
Challis et al. (2013) mentioned above provides evidence of this lack of research. From the 23 studies included, only Nordentoft et al. (2002) mentions the frequency of suicidal behaviour in ATPD (10.7%, n = 3 at baseline and 0% during the first year of treatment). This may be due to the fact that ATPD, for a psychotic syndrome of brief duration and rapid remission, has been traditionally associated with a good
AN US
prognosis (Fusar-Poli et al., 2016a). Nevertheless, several authors have reported high rates of suicidal behaviour in patients with ATPD, both in the acute phase, during which psychotic symptomatology and the level of disturbance can become very severe, as well as during prospective long-term follow-up, during which suicide seems to be the major cause of premature death (Castagnini et al., 2013; Castagnini and Bertelsen, 2011; Pillmann et al., 2003). Although these findings are concerning, the literature remains
M
scarce in this area. The lack of research in this field can also be extended to brief psychotic disorder, the analogous, albeit not identical, category defined by the American Psychiatric Association's (APA)
ED
Diagnostic and Statistical Manual of Mental Disorders (DSM-V; APA, 2000; Castagnini and Fusar-Poli, 2017).
PT
The purpose of this study was to find out whether there are predictors of suicidal behaviour in ATPD patients. To our knowledge, this is the first time it has been attempted to determine whether the
CE
well-established risk factors for suicidality in schizophrenia are equally valid for ATPD patients, and also whether certain characteristic ATPD clinical features, such as acuteness of onset, shifting polymorphic
AC
symptomatology or associated acute stress could be of value in the prediction of suicidal behaviour in this disorder.
2.
Methods
2.1 Sample, measures and procedure
4
ACCEPTED MANUSCRIPT We studied all patients aged 18–65 years diagnosed with an episode of ATPD treated at the Mental Health Inpatient Unit at San Juan de La Cruz Hospital (Úbeda, Spain) between 2011 and 2015. This hospital covers a catchment area of 270,000 people in the north of Jaén (Andalusia). The Spanish version of the Mini International Neuropsychiatric Interview (MINI) was administered during hospital admission to assess the presence of psychotic disorders and extract the clinical features (Bobes, 1998). Other information provided by medical records and family members was
CR IP T
also used, when available, to complete the data collection. A provisional diagnosis of ATPD was coded based on a checklist incorporating the Tenth Revision of the International Classification of Diseases (ICD-10) research criteria (WHO, 1993). After hospital discharge, the subjects were referred to the outpatient mental health services, where they were followed up for as long as three months to confirm the ATPD diagnosis. Diagnostic validation followed ICD-10 temporal criteria, that is, the duration of ATPD
AN US
was restricted to ≤three months (or one month in patients with schizophrenic features). Only patients with a confirmed ATPD diagnosis were included in this study. All participants gave their informed consent and the study was approved by the local ethics committee.
The clinical variables and additional diagnostic features collected on ATPD patients included:
M
(1) First-degree family history of psychosis, (2) First episode or recurrent ATPD, (3) ATPD subtype (polymorphic vs. non-polymorphic), (4) Type of onset (abrupt if the psychotic state appeared within 48
ED
hours or acute if it developed over a period longer than 48 hours but shorter than two weeks), (5) Presence of associated acute stress (defined as stressful events occurring within two weeks before the
PT
onset of psychotic symptoms), (6) Presence of suicidal behaviour at baseline (comprising nonfatal suicidal thoughts and behaviours), (7) Previous history of suicide attempts or deliberate self-harm; (8)
CE
History of depressive disorder, and (9) Previous history of substance use (alcohol or any psychoactive drug). Among the demographic features were gender, age, education (high level of education vs. low and
AC
medium education), marital status (married/cohabiting or unmarried) and occupation (employed vs. unemployed/student). Acute stress associated with the psychotic episode was defined as stated in ICD-10 and referred
to the presence of recent adverse life events that would be regarded as stressful by most people in similar circumstances within the same cultural and social environment (WHO, 1993). These stressful events that must occur within 2 weeks before the onset of psychotic symptoms include bereavement, unexpected loss
5
ACCEPTED MANUSCRIPT of partner or job, marriage or the psychological trauma of combat, terrorism or torture (WHO, 1993). Chronic difficulties or problems would be classed outside this definition. Substance use was screened using the definition in the MINI structured interview (Sections J and K) as use of a moderate amount of alcohol or psychoactive drugs in the last year (Items J1 and K1), but not meeting the criteria for current abuse or dependence disorder (Bobes, 1998). This variable was dichotomised into substance use and non-substance use groups.
CR IP T
The outcome measured in this study was suicidal behaviour in patients with ATPD. Suicidal symptoms were evaluated using the MINI-structured interview method (Section C; Bobes, 1998). As per this methodology, suicidality was assessed based on the response to a set of six questions related to the presence of death wishes, thoughts of non-suicidal self-injury, suicidal ideation, suicide plan, suicide
AN US
attempt within the past month and lifetime suicide attempts. Based on the number of items endorsed, the patients were classified into either the suicidal behaviour group (including patients who had suicidal ideations and plans/attempted suicide within the previous month) or the non-risk group. Only those individuals who showed a suicidal behaviour in clear continuity with the psychopathology of their ATPD episode were considered, similar to the method followed in the study conducted by Pillman et al. (2003).
M
It should be noted that under the term of ‘suicidal behaviour’ the presence of suicide ideation, plans or
2007a, 2007b).
PT
2.2 Data analysis
ED
attempts were included, as suggested by consensus papers on the study of suicide (Silverman et al.,
Multivariate logistic regression analysis using the enter method was performed to determine
CE
independent factors associated with suicidal behaviour in ATPD. In accordance with recommended practice (Steyerberg and Vergouwe, 2014), the variables included in the multivariate model were pre-
AC
specified a priori on the basis of previous knowledge of suicidal risk in schizophrenia. After review of the literature, the following potential predictors were selected: previous history of suicide attempt or deliberate self-harm, history of depressive episodes, substance use and high level of education (Hawton et al., 2005; Hettige et al., 2017; Hor and Taylor, 2010; Popovic et al. 2014). In addition, as mentioned in the study objectives, the presence of associated acute stress, type of onset (abrupt vs. acute) and ATPD subtype (polymorphic vs. non-polymorphic) were also included in the multivariate model to examine the role of these factors in suicidal behaviour.
6
ACCEPTED MANUSCRIPT Descriptive statistics were expressed using proportions, means or medians conforming to the measurement type and distribution. The type of distribution was verified using the Shapiro–Wilk test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the independent variables associated with suicidal behaviour in the regression analysis. The variance explained by the model was assessed using the Nagelkerke R2 (Nagelkerke, 1991). The model was calibrated by the HosmerLemeshow Test (Lemeshow and Hosmer, 1982). Model discrimination was evaluated using receiver–
CR IP T
operating characteristic (ROC) curves and the area under the curve (AUC). A classification table was used to summarize the overall predictive accuracy. Finally, to reduce overfit bias, internal validation of the model was addressed by bootstrapping the AUC (Skalská and Freylich, 2006). Significance was assumed at p < 0.05. All analyses were performed using MedCalc Statistical Software (version 15.8;
3.
AN US
MedCalc Software, Mariakerke, Belgium).
Results
3.1 Sample characteristics
From 2011 to 2015, there were a total of 1,032 hospital admissions with a diagnosis of psychosis
M
(ICD-10: F1x.4, F1x.5, F1x.7, F20–29, F30.2, F31.2, F31.5, F31.6, F32.3, F33.3) in our catchment area (pop. 270,000). Of these, 44 patients provisionally met the ATPD criteria at hospital discharge (29 first
ED
episode patients and 15 in relapse). The ATPD diagnosis was not retained by five of these patients at the end of the three-month follow-up period (diagnosed with other psychotic disorders according to the ICD-
PT
10 criteria). There were no missing patients or dropouts during the follow-up. Finally, 39 patients with a confirmed ATPD diagnosis met the inclusion criteria for this study (Fig 1).
CE
Of the total sample, 59% were women with a mean age of 33.28 years (SD = 10.94). The other
most frequent sociodemographic factors were: being unmarried (61.5%, n = 24), low and medium level of
AC
education (71.8%, n = 28) and unemployment status (56.4%, n = 22). A family history of psychosis was reported in 28.2% (n = 11) of the sample (Table 1). The majority of the patients (66.6%, n = 26) had experienced the first episode of ATPD. The distribution of the diagnosis was 41.1% (n = 16) for the polymorphous group and 58.9% (n = 23) for the non-polymorphic group. An abrupt onset was observed in 38.5% (n = 15) of cases. The frequency of substance use was 17.9% (n = 7) and associated acute stress was found in 35.8% (n = 14) of the patients. A history of depressive disorder was reported in 10.2% (n = 4) of the individuals. A history of deliberate self-harm was noted in 10.2% (n= 4) of the sample. Further,
7
ACCEPTED MANUSCRIPT the prevalence of suicidal behaviour was 20.5% (n = 8), of which 15.5% (n = 6) presented suicidal ideation and 5% (n = 2) had attempted suicide before admission (Table 1). None of the patients developed suicidal behaviour during the three months following discharge from the hospital.
3.2 Predictors of suicidal behaviour In the multivariate logistic regression model, suicidal behaviour was independently significantly
CR IP T
associated with acute stress (OR = 13.92, 95% CI = 1.09–176.75; p = 0.042) and substance use (OR = 12.61, 95% CI = 1.06–148.95; p = 0.044) (Table 2). The model was statistically significant (χ2 = 15.355 [7], p = 0.031) and the Hosmer and Lemeshow goodness-of-fit test was non-significant (χ2 = 8.74 [7], p = 0.271), indicating adequate fit. The Nagelkerke R2 statistic revealed that the model accounted for 51% of
AN US
the variance. The AUC for the final model was 0.837 (95% CI = 0.684–0.935), indicating excellent discriminatory ability. The overall percentage of correct predictions was 92.31%. After 1000 cycles of bootstrapping the AUC, model optimism was estimated at 0.002, indicating minimal overfitting (Table 2).
4.
Discussion
M
The aim of this study was to ascertain whether there are predictors of suicidal behaviour in ATPD. Our main findings were that acute stress and a history of substance use showed significant
ED
independent association with suicidal behaviour in ATPD patients. Other well-established predictors of suicidality in schizophrenia and characteristic ATPD manifestations, such as abrupt onset or shifting
PT
polymorphic symptomatology, were not statistically associated with suicide risk in our cohort. To the best of our knowledge, this is the first study identifying independent risk factors that could predict suicidal
CE
behaviour in individuals with ATPD. Our outcomes were in agreement with the previous literature, insofar as both acute stress and
AC
substance use have been previously related with suicide risk in psychosis (Hawton et al., 2005; Hettige et al., 2017; Pompili et al., 2011; Ventriglio et al., 2016). A systematic review on the predictors of suicidality in schizophrenia showed robust evidence of increased risk of suicide for substance use and stress associated with a recent loss (Hawton et al., 2005). In this review, Hawton et al. (2005) also found that these predictors of suicidal behaviour are the same as those for the general population. Furthermore, there is evidence of interdependence between acute stress reaction and substance use in the general population, with higher suicide rates when the two factors converge than separately (Gradus et al., 2010).
8
ACCEPTED MANUSCRIPT Although these two risk factors are already known, their identification in the specific context of ATPD is indeed novel, and accordingly adds to the limited existing knowledge on suicidal behaviour in ATPD. It is important to note that in our sample, a history of suicide attempt or deliberate self-injury was not found to be a significant independent variable in the logistic regression model. This finding contrasts with those of other studies that considered previous suicide attempts as one of the strongest predictors of suicidal behaviour both in general population (Bostwick et al., 2016) and patients with
CR IP T
schizophrenia (Cassidy et al., 2017; Hawton et al., 2005; Hor and Taylor, 2010; Popovic et al., 2014). This contrast can be attributed to the comparatively smaller sample size and limited number of events observed for this variable in our study. However, other authors have found no association between the history of suicide attempt or deliberate self-injury and a later suicidal behaviour in patients with psychosis
AN US
(Canal-Rivero et al., 2017).
Comparing our results with others focused on ATPD, the study by Pillman et al. (2003) is the only one that we are aware of that has specifically examined factors that might be predictive of suicidal symptoms in patients with ATPD. In their research, which included 42 subjects with first episode ATPD, no sociodemographic variables or personality traits were found to be independently associated with
M
suicidal behaviour (Pillman et al., 2003). The prevalence of suicidal symptoms at baseline in our study (20.5%, n = 8) was slightly lower than that reported by Pillman et al. (2003; 26.1%, n = 11), and the
ED
frequency of suicide attempts before admission was substantially different in that study (5.12%, n = 2 in our sample vs. 19%, n = 8 in Pillman et al., 2003). These variations could be partly explained by the high
PT
proportion of women in their sample (78.6%, n = 33), since the rate of suicide attempts in females is about three to four times that in men (Callanan and Davis, 2012). They could also be explained by the
CE
variability in suicide rates between the two countries (according to WHO statistics, the rates in Germany are higher than those in Spain) (WHO, 2015b). Lastly, none of our ATPD patients presented suicidal
AC
behaviour in the three months following hospital discharge, whereas Pillman et al. (2003) found a high prevalence of subsequent suicidal behaviours (35.7%, n = 15) in the follow-up of their sample. These suicidal symptoms mainly occurred during psychotic relapse of their patients, who however, had low rates of suicidal behaviour during the remission stages. In light of these observations, they concluded that suicidal risk in ATPD is linked to acute symptomatology (Pillman et al., 2003). Castagnini and Bertelsen (2011) reviewed the suicide rates of ATPD patients listed in the Danish Psychiatric Central Register. They determined the long-term mortality causes associated with this
9
ACCEPTED MANUSCRIPT disorder and identified a high risk of suicide in ATPD patients (standardised mortality ratio of 30.9), especially in the first 2 years following the initial admission (Castagnini and Bertelsen, 2011). In a later study, Castagnini et al. (2013) compared the suicide mortality of ATPDs with that of schizophrenia and bipolar disorder. They reported that suicide in ATPD accounted for 25% of mortality and was the major cause of death in such patients. Moreover, compared with the patients with schizophrenia, those with ATPD were more likely to die by suicide during the early course of the illness (Castagnini et al., 2013). In
CR IP T
this study, the authors also found a higher risk of premature death in ATPD patients who experienced acute stressful events. Such findings are in line with earlier reports on mortality in reactive or psychogenic psychoses, a traditional diagnosis in Scandinavian countries before the introduction of the ICD-10, which encompassed psychotic episodes triggered by acute stress or psychological trauma in
AN US
prone individuals (Jørgensen and Mortensen, 1992). These reports revealed that patients with reactive psychoses had higher mortality rates than the general population and that suicide was the most frequent cause of death (Jørgensen and Mortensen, 1992). Nevertheless, in comparison to the concept of reactive psychoses, it should be noted that acute stress is only an additional diagnostic feature in the current ICD10 definition of ATPD, as it may or may not be associated with stressful life events which occurred
M
within the previous two weeks and is coded using a 5-digit combination (i.e. F23.x0/1). Finally, within the framework of short-lived psychotic experiences, two further issues must be
ED
considered. First, our findings should be interpreted with caution in DSM-V brief psychotic disorder (BPD). Although ATPD and BPD address related diagnostic concepts, the concordance among these two
PT
categories is only partly due to the differences in terms of their onset, duration and symptomatology (Castagnini and Fusar-Poli, 2017; Fusar-Poli et al., 2016a; Pillman et al., 2002). Hence, while ATPD
CE
comprises six subtypes in which psychotic symptoms should have an acute onset shorter than two weeks and complete remission within one to three months, in the BPD diagnostic criteria, the time of onset is
AC
not specified and the duration of the syndrome should be at least one day but less than one month. Second, ATPD features also substantially overlap with the concept of brief limited intermittent psychotic symptoms (BLIPS) (Fusar-Poli et al., 2017a, 2017b). Patients with BLIPS are defined as a group of ‘young people with brief self-limited episodes of psychotic experiences that spontaneously resolve in less than a week’ (Fusar-Poli et al., 2016b). In these young populations, transient psychotic symptoms are present in the previous 12 months with a frequency of at least three to four times per week and have a maximum duration of one week without the use of antipsychotics (Fusar-Poli et al., 2016a). From the
10
ACCEPTED MANUSCRIPT clinical perspective of the ultra-high risk (UHR) paradigm, patients with BLIPS may not receive a diagnosis of established psychosis (Fusar-Poli et al., 2017a). However, Fusar-Poli et al. (2017a) demonstrated that two-thirds of patients with BLIPS meet the ICD-10 criteria for ATPD. We therefore suggest that the findings of our study be considered in the preventive approaches adopted for UHR patients with BLIPS. The findings of this study should be interpreted in the light of the following potential limitations.
CR IP T
First, our sample size was quite limited, even for ATPD cohorts, resulting in very large confidence intervals. Second, selection bias may have been possible, because only hospitalised subjects were included, and this may have conditioned the prevalence of suicidal behaviour in our sample. Third, there is also a possibility of temporal bias in the retrospective ascertainment of the sequence of events.
AN US
However, we attempted to minimise such bias through an exhaustive compilation of information that allowed us to discern the logical sequence of events (i.e. 1st: acute stress and/or substance use; 2nd: ATPD and 3rd: suicidal behaviour). Finally, some limitations may be derived from a disorder for which longitudinal studies have demonstrated wide diagnostic instability (Fusar-Poli et al., 2016c) and partial overlapping with other brief psychotic conditions (Fusar-Poli et al., 2016a).
M
In summary, we conclude that suicidal behaviour in ATPD is a common clinical feature that occurs at the climax of the psychotic syndrome and disappears after remission of the episode. The
ED
presence of acute stress and a history of substance use seem to be predictors of suicidal behaviour in these patients. Our findings could have implications in the therapeutic management and short-term prognosis of
PT
these disorders, especially for psychiatric emergencies, during which the abrupt changes in psychopathology experienced by patients may result in clinicians underestimating the high suicide risk
CE
associated with ATPD. Therefore, when evaluating a patient with ATPD, the history of substance use and/or presence of recent acute stress should be considered as a warning sign for increased risk of suicide.
AC
Future research in this area should aim to determine whether screening for one or both of these risk factors could yield value for the clinical prediction of subsequent suicidal symptoms during long-term follow-up, either in the remission or relapse phases.
Conflict of interest The authors declare that they have no conflict of interest.
11
ACCEPTED MANUSCRIPT References
American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Pub.
Bobes, J., 1998. A Spanish validation study of the mini international neuropsychiatric interview. Eur. Psychiatry 13, 198s-199s.
Bostwick, J.M., Pabbati, C., Geske, J.R., McKean, A.J., 2016. Suicide attempt as a risk factor for completed suicide: even more lethal than we knew. Am. J. Psychiatry 173, 1094-1100. Callanan, V.J., Davis, M.S., 2012. Gender differences in suicide methods. Soc. Psychiatry Psychiatr. Epidemiol.
CR IP T
47, 857-869.
Canal-Rivero, M., Lopez-Moriñigo, J.D., Barrigón, M.L., Perona-Garcelán, S., Jimenez-Casado, C., David, A.S., Obiols-Llandrich, J., Ruiz-Veguilla, M., 2017. The role of premorbid personality and social cognition in suicidal behaviour in first-episode psychosis: a one-year follow-up study. Psychiatry Res. 256, 13–20.
Cassidy, R.M., Yang, F., Kapczinski, F., Passos, I.C., 2017 (in press). Risk factors for suicidality in patients with
AN US
schizophrenia: a systematic review, meta-analysis, and meta-regression of 96 studies. Schizophr. Bull.
Castagnini, A., Berrios, G.E., 2009. Acute and transient psychotic disorders (ICD-10 F23): A review from a european perspective. Eur. Arch. Psychiatry Clin. Neurosci. 259, 433-443
Castagnini, A.C., Bertelsen, A., 2011. Mortality and causes of death of acute and transient psychotic disorders. Soc. Psychiatry Psychiatr. Epidemiol. 46, 1013–1017.
Castagnini, A., Foldager, L., Bertelsen, A., 2013. Excess mortality of acute and transient psychotic disorders:
M
comparison with bipolar affective disorder and schizophrenia. Acta Psychiatr. Scand. 128, 370–375. Castagnini, A., Fusar-Poli, P., 2017. Diagnostic validity of ICD-10 acute and transient psychotic disorders and
ED
DSM-5 brief psychotic disorder. Eur. Psychiatry. 45, 104–113.
Castagnini, A. C., Munk-Jørgensen, P., Bertelsen, A., 2016. Short-term course and outcome of acute and transient
PT
psychotic disorders: differences from other types of psychosis with acute onset. Int J Soc Psychiatry 62, 51–56. Challis, S., Nielssen, O., Harris, A., Large, M., 2013. Systematic meta‐analysis of the risk factors for deliberate
CE
self‐harm before and after treatment for first‐episode psychosis. Acta Psychiatr. Scand. 127, 442-454.
Chesney, E., Goodwin, G.M., Fazel, S., 2014. Risks of all‐cause and suicide mortality in mental disorders: a meta‐ review. World Psychiatry 13, 153-160.
AC
Dutta, R., Murray, R.M., Hotopf, M., Allardyce, J., Jones, P.B., Boydell, J., 2013. Reassessing long-term risk of suicide after a first episode of psychosis. Lancet 381, S37. Fusar-Poli, P., Cappucciati, M., Bonoldi, I., Hui, L.C., Rutigliano, G., Stahl, D.R., Borgwardt, S., Politi, P., Mishara, A.L., Lawrie, S.M., Carpenter, W.T., McGuire, P.K., 2016a. Prognosis of brief psychotic episodes: a meta-analysis. JAMA Psychiatry 73, 211–220.
Fusar-Poli, P., Cappucciati, M., Borgwardt, S., Woods, S.W., Addington, J., Nelson, B., Nieman, D.H., Stahl, D.R., Rutigliano, G., Riecher-Rossler, A., Simon, A.E., Mizuno, M., Lee, T.Y., Kwon, J.S., Lam, M.L., Perez, J., Keri, S., Amminger, P., Metzler, S., Kawohl, W., Rossler, W., Lee, J., Labad, J., Ziermans, T., An, S.K., Liu, C., Woodberry, K.A., Braham, A., Corcoran, C., McGorry, P., Yung, A.R., McGuire, P.K., 2016b. Heterogeneity of
12
ACCEPTED MANUSCRIPT psychosis risk within individuals at clinical high risk: a meta-analytical stratification. JAMA Psychiatry 73, 113120.
Fusar-Poli, P., Cappucciati, M., Rutigliano, G., Heslin, M., Stahl, D., Brittenden, Z., Caverzasi, E., McGuire, P., Carpenter, W.T., 2016c. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: Meta-analysis. Schizophr. Bull.42, 1395-1406.
Fusar-Poli, P., Cappucciati, M., De Micheli, A., Rutigliano, G., Bonoldi, I., Tognin, S., Ramella-Cravaro, V., Castagnini, A., McGuire, P., 2017a. Diagnostic and prognostic significance of brief limited intermittent psychotic symptoms (BLIPS) in individuals at ultra high risk. Schizophr. Bull. 43, 48–56. Fusar-Poli, P., Rutigliano, G., Stahl, D., Davies, C., De Micheli, A., Ramella-Cravaro, V., Bonoldi, I., McGuire, P.,
CR IP T
2017b. Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders. Eur. Psychiatry. 42, 49–54.
Gradus, J.L., Qin, P., Lincoln, A.K., Miller, M., Lawler, E., Sørensen, H.T., Lash, T.L., 2010. Acute stress reaction and completed suicide. Int. J. Epidemiol. 39, 1478-1484
Haw, C., Hawton, K., 2015. Suicide is a complex behaviour in which mental disorder usually plays a central role. Aust. N. Z. J. Psychiatry 49, 13-15.
AN US
Hawgood, J., De Leo, D., 2016. Suicide Prediction – A Shift in Paradigm Is Needed. Crisis 37, 251-255
Hawton, K., Sutton, L., Haw, C., Sinclair, J., Deeks, J.J., 2005. Schizophrenia and suicide: Systematic review of risk factors. Br. J. Psychiatry 187, 9-20.
Hettige, N.C., Bani-Fatemi, A., Sakinofsky, I., De Luca, V., 2017. A biopsychosocial evaluation of the risk for
M
suicide in schizophrenia. CNS Spectr. 24, 1–11.
Hor, K., Taylor, M., 2010. Review: Suicide and schizophrenia: A systematic review of rates and risk factors. J.
ED
Psychopharmacol. 24, 81-90.
Jørgensen P., Mortensen P.B., 1992. Causes of death in reactive psychosis. Acta Psychiatr. Scand. 85, 351–353.
Lemeshow, S., Hosmer Jr, D.W., 1982. A review of goodness of fit statistics for use in the development of logistic
PT
regression models. Am. J. Epidemiol. 115, 92–106.
Mann, J.J., Apter, A., Bertolote, J., Beautrais, A., Currier, D., Mehlum, L., Malone, K., Marusic, A., Lonnqvist, J.,
CE
Rutz, W., Varnik, A., Hegerl, U., Rihmer, Z., Takahashi, Y., Schmidtke, A., Shaffer, D., SIlverman, M., Haas, A., Patton, G., Yip, P., Hendin, H., Phillips, M., Wasserman, D., 2005. Suicide Prevention Strategies: A Systematic
AC
Review. JAMA 294, 2064-2074.
Marneros, A., Pillmann, F., 2004. Acute and transient psychoses. Cambridge: Cambridge University Press
Nagelkerke, N. J., 1991. A note on a general definition of the coefficient of determination. Biometrika. 78, 691–
692. Nordentoft, M., Jeppesen, P., Abel, M., Kassow, P., Petersen, L., Thorup, A., Krarup, G., Hemmingsen, R., Jørgensen, P., 2002. OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with firstepisode psychosis. Br. J. Psychiatry 43, s98-s106
Nordentoft, M., Madsen, T., Fedyszyn, I., 2015. Suicidal behavior and mortality in first-episode psychosis. J. Nerv. Ment. Dis. 203, 387-392.
13
ACCEPTED MANUSCRIPT
Pillmann, F., Balzuweit, S., Haring, A., Blöink, R., Marneros, A., 2003. Suicidal behavior in acute and transient psychotic disorders. Psychiatry Res. 117, 199-209
Pillmann, F., Haring, A., Balzuweit, S., Blöink, R., Marneros, A., 2002. The concordance of ICD-10 acute and transient psychosis and DSM-IV brief psychotic disorder. Psychol. Med. 32, 525–533.
Pompili, M., Serafini, G., Innamorati, M., Lester, D., Shrivastava, A., Girardi, P., Nordentoft, M., 2011. Suicide risk in first episode psychosis: A selective review of the current literature. Schizophr. Res. 129, 1–11.
Popovic, D., Benabarre, A., Crespo, J.M., Goikolea, J.M., González-Pinto, A., Gutiérrez-Rojas, L., Montes, J.M.,
Psychiatr. Scand. 130, 418–426.
CR IP T
Vieta, E., 2014. Risk factors for suicide in schizophrenia: systematic review and clinical recommendations. Acta
Silverman, M.M., Berman, A.L., Sanddal, N.D., O'carroll, P.W., Joiner, T.E., 2007a. Rebuilding the tower of babel: A revised nomenclature for the study of suicide and suicidal behaviors part 1: background, rationale, and methodology. Suicide Life Threat. Behav. 37, 248–263.
Silverman, M.M., Berman, A.L., Sanddal, N.D., O'carroll, P.W., Joiner, T.E., 2007b. Rebuilding the tower of
AN US
babel: a revised nomenclature for the study of suicide and suicidal behaviors. Part 2: suicide-related ideations, communications, and behaviors. Suicide Life Threat. Behav. 37, 264–277.
Skalská, H., Freylich, V., 2006. Web-bootstrap estimate of area under ROC curve. Austrian J. Stat. 35, 325–330.
Steyerberg, E.W., Vergouwe, Y., 2014. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur. Heart J. 35, 1925–1931.
Turecki, G., Brent, D.A., 2016. Suicide and suicidal behaviour. Lancet 387(10024), 1227-1239.
Ventriglio, A., Gentile, A., Bonfitto, I., Stella, E., Mari, M., Steardo, L., Bellomo, A., 2016. Suicide in the early
M
stage of schizophrenia. Front. Psychiatry 7, 1–9.
World Health Organization, 1993. The ICD-10 classification of mental and behavioural disorders: diagnostic
ED
criteria for research.
World Health Organization, 2015a. Preventing suicide: a global imperative. Geneva, Switzerland: World Health
PT
Organization; 2014.
World Health Organization, 2015b. Suicide rates data by country. Global Health Observatory Data Repository.
AC
CE
Available at: http://apps.who.int/gho/data/node.main.MHSUICIDE/ (accessed 30.12.15).
14
ACCEPTED MANUSCRIPT Table 1. Sociodemographic and clinical characteristics Total sample (n = 39) Age (years), mean ± SD
33.28 ± 10.94
Gender, n (%) Male
16 (41.1%)
Female
23 (58.9%)
Marital status, n (%) 15 (30.5%)
Unmarried
24 (61.5%)
Educational level, n (%) Low and medium level of education High level of education
17 (43.6%)
Unemployed/student
AN US
Employed
22 (56.4%)
Family history of psychosis, n (%) ATPD subtype, n (%) PM
11 (28.2%)
16 (41.1%)
Type of episode, n (%) First episode
ED
Recurrence
23 (58.9%)
M
NPM
Abrupt
PT
Acute
Acute stress, n (%)
CE
Substance use, n (%)
AC
28 (71.8%) 11 (28.2%)
Occupation, n (%)
Onset
CR IP T
Married/cohabiting
26 (66.6%) 13 (33.3%)
15 (38.5%) 24 (61.5) 14 (35.8%) 7 (17.9%)
History of depressive disorder, n (%)
4 (10.2%)
History of suicide attempt or deliberate self-harm, n (%)
4 (10.2%)
Suicidal symptoms, n (%)
8 (20.5%)
Suicidal ideation
6 (15.3%)
Suicide attempts
2 (5.1%)
Abbreviations: ATPD = acute and transient psychotic disorders; NPM = nonpolymorphic subtype; PM = polymorphic subtype; SD = standard deviation.
15
ACCEPTED MANUSCRIPT
Table 2. Predictors of suicidal behaviour in ATPD: Results of multivariate logistic regression analysis (n = 39) Coefficient
SE
Wald
p-value
OR
95% CI
1.91
1.86
1.053
0.305
6.75
0.17—259.39
History of depressive episodes
0.98
2.81
0.124
0.725
2.68
0.01—659.41
History of substance use
2.53
1.26
4.051
0.044
12.61
1.06–148.95
High level of education
-0.18
1.32
0.020
0.886
0.82
0.06—11.13
Abrupt onset
-0.06
1.52
0.002
0.965
0.93
0.04—18.49
Polymorphic subtype of ATPD
-1.65
1.68
0.962
0.326
0.19
0.01—5.19
Acute stress
2.63
1.29
4.128
0.042
13.92
Constant
-2.91
Previous history of suicide
Model Summary χ2 [df] (p-value)
8.74 [7] (p = 0.271)
2
AN US
0.51
Overall percentage of correct predictions (%)
92.31%
AUC (95% CI)
0.837 (95% CI = 0.684–0.935)
Bootstrap AUC (95% CI) a a
1.09–176.75
15.355 [7] (p = 0.031)
Hosmer and Lemeshow χ2 [df] (p-value) Nagelkerke R
CR IP T
attempt or deliberate self-harm
0.835 (95% CI = 0.60–1)
Bootstrap (1.000 replicates; random seed). Web program developed by Skalská and Freylich (2006)
AC
CE
PT
ED
M
Abbreviations: ATPD = acute and transient psychotic disorder; AUC = area under the curve; df = degree of freedom; OR = odds ratio; SE = standard error; 95% CI = 95% confidence interval
16
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
AN US
CR IP T
Figure 1. Flowchart of inclusion of patients.
17
Acute stress and substance use as predictors of suicidal behaviour in acute and transient psychotic disorders ´ Alvaro Lopez-D´ ıaz , Pablo Lorenzo-Herrero , Ignacio Lara , ´ Jose´ Luis Fernandez-Gonz alez , Miguel Ruiz-Veguilla ´ ´ PII: DOI: Reference:
S0165-1781(17)31334-3 https://doi.org/10.1016/j.psychres.2018.08.036 PSY 11630
To appear in:
Psychiatry Research
Received date: Revised date: Accepted date:
19 July 2017 23 June 2018 13 August 2018
´ Please cite this article as: Alvaro Lopez-D´ ıaz , Pablo Lorenzo-Herrero , Ignacio Lara , ´ Jose´ Luis Fernandez-Gonz alez , Miguel Ruiz-Veguilla , Acute stress and substance use as pre´ ´ dictors of suicidal behaviour in acute and transient psychotic disorders, Psychiatry Research (2018), doi: https://doi.org/10.1016/j.psychres.2018.08.036
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Highlights: There is a lack of research on suicide in patients with ATPD.
•
The study investigates whether there are predictors of suicidal behaviour in ATPD.
•
Acute stress and substance use are significantly associated with suicidal behaviour.
•
Screening both factors would aid assessment of suicide risk in ATPD patients.
AC
CE
PT
ED
M
AN US
CR IP T
•
1
ACCEPTED MANUSCRIPT Title: Acute stress and substance use as predictors of suicidal behaviour in acute and transient psychotic disorders
Álvaro López-Díaz a, Pablo Lorenzo-Herrero b, Ignacio Lara a, José Luis Fernández-González b, Miguel
CR IP T
Ruiz-Veguilla c
a
UGC Salud Mental. Hospital Universitario Virgen Macarena. Sevilla. Spain
b
UGC Salud Mental. Hospital San Juan de la Cruz. Úbeda. Spain
c
UGC Salud Mental. Hospital Universitario Virgen del Rocío. IBIS. Grupo Psicosis y Neurodesarrollo.
AN US
Sevilla. Spain
Corresponding autor:
Miguel Ruiz-Veguilla UGC Salud Mental. Hospital Universitario Virgen del Rocío. IBIS. Grupo Psicosis y Neurodesarrollo. Avda.Manuel Siurot sn. 41013 Seville. Spain Email: [email protected]
CE
PT
ED
M
AC
Abstract:
Several authors have reported high rates of suicidal behaviour in acute and transient psychotic disorders (ATPD). However, the literature in this area remains scarce. We wanted to find out whether there are predictors of suicidal behaviour in ATPD. Of 1,032 psychosis admissions examined over a five-year period, ATPD was confirmed in 39 patients according to the International Classification of Diseases (ICD-10) diagnostic criteria. These patients were classified as suicidal behaviour (20.5%) or non-risk (79.5%) using a structured interview to assess suicidal risk. The following variables were analysed:
2
ACCEPTED MANUSCRIPT previous history of suicide attempt or deliberate self-harm, history of depressive episodes, previous substance use history, education, ATPD subtype (polymorphic vs. non-polymorphic), type of onset (abrupt vs. acute), and presence of associated acute stress. Multivariate analysis revealed that acute stress and substance use are significantly associated with suicidal behaviour in ATPDs. To our knowledge, this is the first study identifying independent risk factors that could predict suicidal behaviour in individuals
CR IP T
with ATPD.
Keywords: acute and transient psychotic disorder; brief psychotic disorder; first-episode psychosis; suicide; International Classification of Diseases
Introduction
AN US
1.
Reports from the World Health Organization (WHO, 2015a) indicate that suicide is a global public health concern and represents one of the leading causes of preventable death. Suicide is a complex phenomenon involving a number of psychosocial variables and in which mental illness plays an undeniable central role (Haw and Hawton, 2015). A 45-fold increased risk of suicidality was found in a
M
recent meta-review comparing suicidal behaviour in individuals with psychiatric disorders versus the general population (Chesney et al., 2014). Even though there are no effective algorithms for suicide
ED
prediction in clinical practice, the search for predictors of suicide in mental disorders still constitutes a fundamental objective for prevention strategies (Hawgood and De Leo, 2016; Mann et al., 2005; Turecki
PT
and Brent, 2016).
Most studies addressing suicide in patients with psychosis have focused on schizophrenia
CE
(Cassidy et al., 2017; Hawton et al., 2005; Hor and Taylor, 2010; Popovic et al., 2014), with particular emphasis on the early stages (Nordentoft et al., 2015; Togay et al., 2015; Ventriglio et al., 2016). In fact,
AC
the highest rates of suicide attempts have been found before and after the first-episode of psychosis, specifically during the first year (Pompili et al., 2011; Dutta et al., 2013). Thus, in their meta-analysis on deliberate self-harm during the first-episode of psychosis, Challis et al. (2013) revealed that 9.8% of the patients presented with suicidal behaviour during the period of untreated psychosis and 11.4% developed it during the following 7 years. Factors associated with an increased risk of deliberate self-harm in patients with first-episode of psychosis are previous history of deliberate self-harm, expressed suicide
3
ACCEPTED MANUSCRIPT ideation, depressed mood, alcohol abuse, substance use, good insight and younger age of onset (Challis et al., 2013). However, there seems to be a lack of research in suicide prediction in patients with acute and transient psychotic disorders (ATPD), despite the fact that its annual incidence ranges from 4–10 per 100,000 people; further, it accounts for up to 19% of all first-episode psychosis. (Castagnini and Berrios, 2009; Castagnini and Fusar-Poli, 2017; Marneros and Pillman, 2004). The meta-analysis conducted by
CR IP T
Challis et al. (2013) mentioned above provides evidence of this lack of research. From the 23 studies included, only Nordentoft et al. (2002) mentions the frequency of suicidal behaviour in ATPD (10.7%, n = 3 at baseline and 0% during the first year of treatment). This may be due to the fact that ATPD, for a psychotic syndrome of brief duration and rapid remission, has been traditionally associated with a good
AN US
prognosis (Fusar-Poli et al., 2016a). Nevertheless, several authors have reported high rates of suicidal behaviour in patients with ATPD, both in the acute phase, during which psychotic symptomatology and the level of disturbance can become very severe, as well as during prospective long-term follow-up, during which suicide seems to be the major cause of premature death (Castagnini et al., 2013; Castagnini and Bertelsen, 2011; Pillmann et al., 2003). Although these findings are concerning, the literature remains
M
scarce in this area. The lack of research in this field can also be extended to brief psychotic disorder, the analogous, albeit not identical, category defined by the American Psychiatric Association's (APA)
ED
Diagnostic and Statistical Manual of Mental Disorders (DSM-V; APA, 2000; Castagnini and Fusar-Poli, 2017).
PT
The purpose of this study was to find out whether there are predictors of suicidal behaviour in ATPD patients. To our knowledge, this is the first time it has been attempted to determine whether the
CE
well-established risk factors for suicidality in schizophrenia are equally valid for ATPD patients, and also whether certain characteristic ATPD clinical features, such as acuteness of onset, shifting polymorphic
AC
symptomatology or associated acute stress could be of value in the prediction of suicidal behaviour in this disorder.
2.
Methods
2.1 Sample, measures and procedure
4
ACCEPTED MANUSCRIPT We studied all patients aged 18–65 years diagnosed with an episode of ATPD treated at the Mental Health Inpatient Unit at San Juan de La Cruz Hospital (Úbeda, Spain) between 2011 and 2015. This hospital covers a catchment area of 270,000 people in the north of Jaén (Andalusia). The Spanish version of the Mini International Neuropsychiatric Interview (MINI) was administered during hospital admission to assess the presence of psychotic disorders and extract the clinical features (Bobes, 1998). Other information provided by medical records and family members was
CR IP T
also used, when available, to complete the data collection. A provisional diagnosis of ATPD was coded based on a checklist incorporating the Tenth Revision of the International Classification of Diseases (ICD-10) research criteria (WHO, 1993). After hospital discharge, the subjects were referred to the outpatient mental health services, where they were followed up for as long as three months to confirm the ATPD diagnosis. Diagnostic validation followed ICD-10 temporal criteria, that is, the duration of ATPD
AN US
was restricted to ≤three months (or one month in patients with schizophrenic features). Only patients with a confirmed ATPD diagnosis were included in this study. All participants gave their informed consent and the study was approved by the local ethics committee.
The clinical variables and additional diagnostic features collected on ATPD patients included:
M
(1) First-degree family history of psychosis, (2) First episode or recurrent ATPD, (3) ATPD subtype (polymorphic vs. non-polymorphic), (4) Type of onset (abrupt if the psychotic state appeared within 48
ED
hours or acute if it developed over a period longer than 48 hours but shorter than two weeks), (5) Presence of associated acute stress (defined as stressful events occurring within two weeks before the
PT
onset of psychotic symptoms), (6) Presence of suicidal behaviour at baseline (comprising nonfatal suicidal thoughts and behaviours), (7) Previous history of suicide attempts or deliberate self-harm; (8)
CE
History of depressive disorder, and (9) Previous history of substance use (alcohol or any psychoactive drug). Among the demographic features were gender, age, education (high level of education vs. low and
AC
medium education), marital status (married/cohabiting or unmarried) and occupation (employed vs. unemployed/student). Acute stress associated with the psychotic episode was defined as stated in ICD-10 and referred
to the presence of recent adverse life events that would be regarded as stressful by most people in similar circumstances within the same cultural and social environment (WHO, 1993). These stressful events that must occur within 2 weeks before the onset of psychotic symptoms include bereavement, unexpected loss
5
ACCEPTED MANUSCRIPT of partner or job, marriage or the psychological trauma of combat, terrorism or torture (WHO, 1993). Chronic difficulties or problems would be classed outside this definition. Substance use was screened using the definition in the MINI structured interview (Sections J and K) as use of a moderate amount of alcohol or psychoactive drugs in the last year (Items J1 and K1), but not meeting the criteria for current abuse or dependence disorder (Bobes, 1998). This variable was dichotomised into substance use and non-substance use groups.
CR IP T
The outcome measured in this study was suicidal behaviour in patients with ATPD. Suicidal symptoms were evaluated using the MINI-structured interview method (Section C; Bobes, 1998). As per this methodology, suicidality was assessed based on the response to a set of six questions related to the presence of death wishes, thoughts of non-suicidal self-injury, suicidal ideation, suicide plan, suicide
AN US
attempt within the past month and lifetime suicide attempts. Based on the number of items endorsed, the patients were classified into either the suicidal behaviour group (including patients who had suicidal ideations and plans/attempted suicide within the previous month) or the non-risk group. Only those individuals who showed a suicidal behaviour in clear continuity with the psychopathology of their ATPD episode were considered, similar to the method followed in the study conducted by Pillman et al. (2003).
M
It should be noted that under the term of ‘suicidal behaviour’ the presence of suicide ideation, plans or
2007a, 2007b).
PT
2.2 Data analysis
ED
attempts were included, as suggested by consensus papers on the study of suicide (Silverman et al.,
Multivariate logistic regression analysis using the enter method was performed to determine
CE
independent factors associated with suicidal behaviour in ATPD. In accordance with recommended practice (Steyerberg and Vergouwe, 2014), the variables included in the multivariate model were pre-
AC
specified a priori on the basis of previous knowledge of suicidal risk in schizophrenia. After review of the literature, the following potential predictors were selected: previous history of suicide attempt or deliberate self-harm, history of depressive episodes, substance use and high level of education (Hawton et al., 2005; Hettige et al., 2017; Hor and Taylor, 2010; Popovic et al. 2014). In addition, as mentioned in the study objectives, the presence of associated acute stress, type of onset (abrupt vs. acute) and ATPD subtype (polymorphic vs. non-polymorphic) were also included in the multivariate model to examine the role of these factors in suicidal behaviour.
6
ACCEPTED MANUSCRIPT Descriptive statistics were expressed using proportions, means or medians conforming to the measurement type and distribution. The type of distribution was verified using the Shapiro–Wilk test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the independent variables associated with suicidal behaviour in the regression analysis. The variance explained by the model was assessed using the Nagelkerke R2 (Nagelkerke, 1991). The model was calibrated by the HosmerLemeshow Test (Lemeshow and Hosmer, 1982). Model discrimination was evaluated using receiver–
CR IP T
operating characteristic (ROC) curves and the area under the curve (AUC). A classification table was used to summarize the overall predictive accuracy. Finally, to reduce overfit bias, internal validation of the model was addressed by bootstrapping the AUC (Skalská and Freylich, 2006). Significance was assumed at p < 0.05. All analyses were performed using MedCalc Statistical Software (version 15.8;
3.
AN US
MedCalc Software, Mariakerke, Belgium).
Results
3.1 Sample characteristics
From 2011 to 2015, there were a total of 1,032 hospital admissions with a diagnosis of psychosis
M
(ICD-10: F1x.4, F1x.5, F1x.7, F20–29, F30.2, F31.2, F31.5, F31.6, F32.3, F33.3) in our catchment area (pop. 270,000). Of these, 44 patients provisionally met the ATPD criteria at hospital discharge (29 first
ED
episode patients and 15 in relapse). The ATPD diagnosis was not retained by five of these patients at the end of the three-month follow-up period (diagnosed with other psychotic disorders according to the ICD-
PT
10 criteria). There were no missing patients or dropouts during the follow-up. Finally, 39 patients with a confirmed ATPD diagnosis met the inclusion criteria for this study (Fig 1).
CE
Of the total sample, 59% were women with a mean age of 33.28 years (SD = 10.94). The other
most frequent sociodemographic factors were: being unmarried (61.5%, n = 24), low and medium level of
AC
education (71.8%, n = 28) and unemployment status (56.4%, n = 22). A family history of psychosis was reported in 28.2% (n = 11) of the sample (Table 1). The majority of the patients (66.6%, n = 26) had experienced the first episode of ATPD. The distribution of the diagnosis was 41.1% (n = 16) for the polymorphous group and 58.9% (n = 23) for the non-polymorphic group. An abrupt onset was observed in 38.5% (n = 15) of cases. The frequency of substance use was 17.9% (n = 7) and associated acute stress was found in 35.8% (n = 14) of the patients. A history of depressive disorder was reported in 10.2% (n = 4) of the individuals. A history of deliberate self-harm was noted in 10.2% (n= 4) of the sample. Further,
7
ACCEPTED MANUSCRIPT the prevalence of suicidal behaviour was 20.5% (n = 8), of which 15.5% (n = 6) presented suicidal ideation and 5% (n = 2) had attempted suicide before admission (Table 1). None of the patients developed suicidal behaviour during the three months following discharge from the hospital.
3.2 Predictors of suicidal behaviour In the multivariate logistic regression model, suicidal behaviour was independently significantly
CR IP T
associated with acute stress (OR = 13.92, 95% CI = 1.09–176.75; p = 0.042) and substance use (OR = 12.61, 95% CI = 1.06–148.95; p = 0.044) (Table 2). The model was statistically significant (χ2 = 15.355 [7], p = 0.031) and the Hosmer and Lemeshow goodness-of-fit test was non-significant (χ2 = 8.74 [7], p = 0.271), indicating adequate fit. The Nagelkerke R2 statistic revealed that the model accounted for 51% of
AN US
the variance. The AUC for the final model was 0.837 (95% CI = 0.684–0.935), indicating excellent discriminatory ability. The overall percentage of correct predictions was 92.31%. After 1000 cycles of bootstrapping the AUC, model optimism was estimated at 0.002, indicating minimal overfitting (Table 2).
4.
Discussion
M
The aim of this study was to ascertain whether there are predictors of suicidal behaviour in ATPD. Our main findings were that acute stress and a history of substance use showed significant
ED
independent association with suicidal behaviour in ATPD patients. Other well-established predictors of suicidality in schizophrenia and characteristic ATPD manifestations, such as abrupt onset or shifting
PT
polymorphic symptomatology, were not statistically associated with suicide risk in our cohort. To the best of our knowledge, this is the first study identifying independent risk factors that could predict suicidal
CE
behaviour in individuals with ATPD. Our outcomes were in agreement with the previous literature, insofar as both acute stress and
AC
substance use have been previously related with suicide risk in psychosis (Hawton et al., 2005; Hettige et al., 2017; Pompili et al., 2011; Ventriglio et al., 2016). A systematic review on the predictors of suicidality in schizophrenia showed robust evidence of increased risk of suicide for substance use and stress associated with a recent loss (Hawton et al., 2005). In this review, Hawton et al. (2005) also found that these predictors of suicidal behaviour are the same as those for the general population. Furthermore, there is evidence of interdependence between acute stress reaction and substance use in the general population, with higher suicide rates when the two factors converge than separately (Gradus et al., 2010).
8
ACCEPTED MANUSCRIPT Although these two risk factors are already known, their identification in the specific context of ATPD is indeed novel, and accordingly adds to the limited existing knowledge on suicidal behaviour in ATPD. It is important to note that in our sample, a history of suicide attempt or deliberate self-injury was not found to be a significant independent variable in the logistic regression model. This finding contrasts with those of other studies that considered previous suicide attempts as one of the strongest predictors of suicidal behaviour both in general population (Bostwick et al., 2016) and patients with
CR IP T
schizophrenia (Cassidy et al., 2017; Hawton et al., 2005; Hor and Taylor, 2010; Popovic et al., 2014). This contrast can be attributed to the comparatively smaller sample size and limited number of events observed for this variable in our study. However, other authors have found no association between the history of suicide attempt or deliberate self-injury and a later suicidal behaviour in patients with psychosis
AN US
(Canal-Rivero et al., 2017).
Comparing our results with others focused on ATPD, the study by Pillman et al. (2003) is the only one that we are aware of that has specifically examined factors that might be predictive of suicidal symptoms in patients with ATPD. In their research, which included 42 subjects with first episode ATPD, no sociodemographic variables or personality traits were found to be independently associated with
M
suicidal behaviour (Pillman et al., 2003). The prevalence of suicidal symptoms at baseline in our study (20.5%, n = 8) was slightly lower than that reported by Pillman et al. (2003; 26.1%, n = 11), and the
ED
frequency of suicide attempts before admission was substantially different in that study (5.12%, n = 2 in our sample vs. 19%, n = 8 in Pillman et al., 2003). These variations could be partly explained by the high
PT
proportion of women in their sample (78.6%, n = 33), since the rate of suicide attempts in females is about three to four times that in men (Callanan and Davis, 2012). They could also be explained by the
CE
variability in suicide rates between the two countries (according to WHO statistics, the rates in Germany are higher than those in Spain) (WHO, 2015b). Lastly, none of our ATPD patients presented suicidal
AC
behaviour in the three months following hospital discharge, whereas Pillman et al. (2003) found a high prevalence of subsequent suicidal behaviours (35.7%, n = 15) in the follow-up of their sample. These suicidal symptoms mainly occurred during psychotic relapse of their patients, who however, had low rates of suicidal behaviour during the remission stages. In light of these observations, they concluded that suicidal risk in ATPD is linked to acute symptomatology (Pillman et al., 2003). Castagnini and Bertelsen (2011) reviewed the suicide rates of ATPD patients listed in the Danish Psychiatric Central Register. They determined the long-term mortality causes associated with this
9
ACCEPTED MANUSCRIPT disorder and identified a high risk of suicide in ATPD patients (standardised mortality ratio of 30.9), especially in the first 2 years following the initial admission (Castagnini and Bertelsen, 2011). In a later study, Castagnini et al. (2013) compared the suicide mortality of ATPDs with that of schizophrenia and bipolar disorder. They reported that suicide in ATPD accounted for 25% of mortality and was the major cause of death in such patients. Moreover, compared with the patients with schizophrenia, those with ATPD were more likely to die by suicide during the early course of the illness (Castagnini et al., 2013). In
CR IP T
this study, the authors also found a higher risk of premature death in ATPD patients who experienced acute stressful events. Such findings are in line with earlier reports on mortality in reactive or psychogenic psychoses, a traditional diagnosis in Scandinavian countries before the introduction of the ICD-10, which encompassed psychotic episodes triggered by acute stress or psychological trauma in
AN US
prone individuals (Jørgensen and Mortensen, 1992). These reports revealed that patients with reactive psychoses had higher mortality rates than the general population and that suicide was the most frequent cause of death (Jørgensen and Mortensen, 1992). Nevertheless, in comparison to the concept of reactive psychoses, it should be noted that acute stress is only an additional diagnostic feature in the current ICD10 definition of ATPD, as it may or may not be associated with stressful life events which occurred
M
within the previous two weeks and is coded using a 5-digit combination (i.e. F23.x0/1). Finally, within the framework of short-lived psychotic experiences, two further issues must be
ED
considered. First, our findings should be interpreted with caution in DSM-V brief psychotic disorder (BPD). Although ATPD and BPD address related diagnostic concepts, the concordance among these two
PT
categories is only partly due to the differences in terms of their onset, duration and symptomatology (Castagnini and Fusar-Poli, 2017; Fusar-Poli et al., 2016a; Pillman et al., 2002). Hence, while ATPD
CE
comprises six subtypes in which psychotic symptoms should have an acute onset shorter than two weeks and complete remission within one to three months, in the BPD diagnostic criteria, the time of onset is
AC
not specified and the duration of the syndrome should be at least one day but less than one month. Second, ATPD features also substantially overlap with the concept of brief limited intermittent psychotic symptoms (BLIPS) (Fusar-Poli et al., 2017a, 2017b). Patients with BLIPS are defined as a group of ‘young people with brief self-limited episodes of psychotic experiences that spontaneously resolve in less than a week’ (Fusar-Poli et al., 2016b). In these young populations, transient psychotic symptoms are present in the previous 12 months with a frequency of at least three to four times per week and have a maximum duration of one week without the use of antipsychotics (Fusar-Poli et al., 2016a). From the
10
ACCEPTED MANUSCRIPT clinical perspective of the ultra-high risk (UHR) paradigm, patients with BLIPS may not receive a diagnosis of established psychosis (Fusar-Poli et al., 2017a). However, Fusar-Poli et al. (2017a) demonstrated that two-thirds of patients with BLIPS meet the ICD-10 criteria for ATPD. We therefore suggest that the findings of our study be considered in the preventive approaches adopted for UHR patients with BLIPS. The findings of this study should be interpreted in the light of the following potential limitations.
CR IP T
First, our sample size was quite limited, even for ATPD cohorts, resulting in very large confidence intervals. Second, selection bias may have been possible, because only hospitalised subjects were included, and this may have conditioned the prevalence of suicidal behaviour in our sample. Third, there is also a possibility of temporal bias in the retrospective ascertainment of the sequence of events.
AN US
However, we attempted to minimise such bias through an exhaustive compilation of information that allowed us to discern the logical sequence of events (i.e. 1st: acute stress and/or substance use; 2nd: ATPD and 3rd: suicidal behaviour). Finally, some limitations may be derived from a disorder for which longitudinal studies have demonstrated wide diagnostic instability (Fusar-Poli et al., 2016c) and partial overlapping with other brief psychotic conditions (Fusar-Poli et al., 2016a).
M
In summary, we conclude that suicidal behaviour in ATPD is a common clinical feature that occurs at the climax of the psychotic syndrome and disappears after remission of the episode. The
ED
presence of acute stress and a history of substance use seem to be predictors of suicidal behaviour in these patients. Our findings could have implications in the therapeutic management and short-term prognosis of
PT
these disorders, especially for psychiatric emergencies, during which the abrupt changes in psychopathology experienced by patients may result in clinicians underestimating the high suicide risk
CE
associated with ATPD. Therefore, when evaluating a patient with ATPD, the history of substance use and/or presence of recent acute stress should be considered as a warning sign for increased risk of suicide.
AC
Future research in this area should aim to determine whether screening for one or both of these risk factors could yield value for the clinical prediction of subsequent suicidal symptoms during long-term follow-up, either in the remission or relapse phases.
Conflict of interest The authors declare that they have no conflict of interest.
11
ACCEPTED MANUSCRIPT References
American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Pub.
Bobes, J., 1998. A Spanish validation study of the mini international neuropsychiatric interview. Eur. Psychiatry 13, 198s-199s.
Bostwick, J.M., Pabbati, C., Geske, J.R., McKean, A.J., 2016. Suicide attempt as a risk factor for completed suicide: even more lethal than we knew. Am. J. Psychiatry 173, 1094-1100. Callanan, V.J., Davis, M.S., 2012. Gender differences in suicide methods. Soc. Psychiatry Psychiatr. Epidemiol.
CR IP T
47, 857-869.
Canal-Rivero, M., Lopez-Moriñigo, J.D., Barrigón, M.L., Perona-Garcelán, S., Jimenez-Casado, C., David, A.S., Obiols-Llandrich, J., Ruiz-Veguilla, M., 2017. The role of premorbid personality and social cognition in suicidal behaviour in first-episode psychosis: a one-year follow-up study. Psychiatry Res. 256, 13–20.
Cassidy, R.M., Yang, F., Kapczinski, F., Passos, I.C., 2017 (in press). Risk factors for suicidality in patients with
AN US
schizophrenia: a systematic review, meta-analysis, and meta-regression of 96 studies. Schizophr. Bull.
Castagnini, A., Berrios, G.E., 2009. Acute and transient psychotic disorders (ICD-10 F23): A review from a european perspective. Eur. Arch. Psychiatry Clin. Neurosci. 259, 433-443
Castagnini, A.C., Bertelsen, A., 2011. Mortality and causes of death of acute and transient psychotic disorders. Soc. Psychiatry Psychiatr. Epidemiol. 46, 1013–1017.
Castagnini, A., Foldager, L., Bertelsen, A., 2013. Excess mortality of acute and transient psychotic disorders:
M
comparison with bipolar affective disorder and schizophrenia. Acta Psychiatr. Scand. 128, 370–375. Castagnini, A., Fusar-Poli, P., 2017. Diagnostic validity of ICD-10 acute and transient psychotic disorders and
ED
DSM-5 brief psychotic disorder. Eur. Psychiatry. 45, 104–113.
Castagnini, A. C., Munk-Jørgensen, P., Bertelsen, A., 2016. Short-term course and outcome of acute and transient
PT
psychotic disorders: differences from other types of psychosis with acute onset. Int J Soc Psychiatry 62, 51–56. Challis, S., Nielssen, O., Harris, A., Large, M., 2013. Systematic meta‐analysis of the risk factors for deliberate
CE
self‐harm before and after treatment for first‐episode psychosis. Acta Psychiatr. Scand. 127, 442-454.
Chesney, E., Goodwin, G.M., Fazel, S., 2014. Risks of all‐cause and suicide mortality in mental disorders: a meta‐ review. World Psychiatry 13, 153-160.
AC
Dutta, R., Murray, R.M., Hotopf, M., Allardyce, J., Jones, P.B., Boydell, J., 2013. Reassessing long-term risk of suicide after a first episode of psychosis. Lancet 381, S37. Fusar-Poli, P., Cappucciati, M., Bonoldi, I., Hui, L.C., Rutigliano, G., Stahl, D.R., Borgwardt, S., Politi, P., Mishara, A.L., Lawrie, S.M., Carpenter, W.T., McGuire, P.K., 2016a. Prognosis of brief psychotic episodes: a meta-analysis. JAMA Psychiatry 73, 211–220.
Fusar-Poli, P., Cappucciati, M., Borgwardt, S., Woods, S.W., Addington, J., Nelson, B., Nieman, D.H., Stahl, D.R., Rutigliano, G., Riecher-Rossler, A., Simon, A.E., Mizuno, M., Lee, T.Y., Kwon, J.S., Lam, M.L., Perez, J., Keri, S., Amminger, P., Metzler, S., Kawohl, W., Rossler, W., Lee, J., Labad, J., Ziermans, T., An, S.K., Liu, C., Woodberry, K.A., Braham, A., Corcoran, C., McGorry, P., Yung, A.R., McGuire, P.K., 2016b. Heterogeneity of
12
ACCEPTED MANUSCRIPT psychosis risk within individuals at clinical high risk: a meta-analytical stratification. JAMA Psychiatry 73, 113120.
Fusar-Poli, P., Cappucciati, M., Rutigliano, G., Heslin, M., Stahl, D., Brittenden, Z., Caverzasi, E., McGuire, P., Carpenter, W.T., 2016c. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: Meta-analysis. Schizophr. Bull.42, 1395-1406.
Fusar-Poli, P., Cappucciati, M., De Micheli, A., Rutigliano, G., Bonoldi, I., Tognin, S., Ramella-Cravaro, V., Castagnini, A., McGuire, P., 2017a. Diagnostic and prognostic significance of brief limited intermittent psychotic symptoms (BLIPS) in individuals at ultra high risk. Schizophr. Bull. 43, 48–56. Fusar-Poli, P., Rutigliano, G., Stahl, D., Davies, C., De Micheli, A., Ramella-Cravaro, V., Bonoldi, I., McGuire, P.,
CR IP T
2017b. Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders. Eur. Psychiatry. 42, 49–54.
Gradus, J.L., Qin, P., Lincoln, A.K., Miller, M., Lawler, E., Sørensen, H.T., Lash, T.L., 2010. Acute stress reaction and completed suicide. Int. J. Epidemiol. 39, 1478-1484
Haw, C., Hawton, K., 2015. Suicide is a complex behaviour in which mental disorder usually plays a central role. Aust. N. Z. J. Psychiatry 49, 13-15.
AN US
Hawgood, J., De Leo, D., 2016. Suicide Prediction – A Shift in Paradigm Is Needed. Crisis 37, 251-255
Hawton, K., Sutton, L., Haw, C., Sinclair, J., Deeks, J.J., 2005. Schizophrenia and suicide: Systematic review of risk factors. Br. J. Psychiatry 187, 9-20.
Hettige, N.C., Bani-Fatemi, A., Sakinofsky, I., De Luca, V., 2017. A biopsychosocial evaluation of the risk for
M
suicide in schizophrenia. CNS Spectr. 24, 1–11.
Hor, K., Taylor, M., 2010. Review: Suicide and schizophrenia: A systematic review of rates and risk factors. J.
ED
Psychopharmacol. 24, 81-90.
Jørgensen P., Mortensen P.B., 1992. Causes of death in reactive psychosis. Acta Psychiatr. Scand. 85, 351–353.
Lemeshow, S., Hosmer Jr, D.W., 1982. A review of goodness of fit statistics for use in the development of logistic
PT
regression models. Am. J. Epidemiol. 115, 92–106.
Mann, J.J., Apter, A., Bertolote, J., Beautrais, A., Currier, D., Mehlum, L., Malone, K., Marusic, A., Lonnqvist, J.,
CE
Rutz, W., Varnik, A., Hegerl, U., Rihmer, Z., Takahashi, Y., Schmidtke, A., Shaffer, D., SIlverman, M., Haas, A., Patton, G., Yip, P., Hendin, H., Phillips, M., Wasserman, D., 2005. Suicide Prevention Strategies: A Systematic
AC
Review. JAMA 294, 2064-2074.
Marneros, A., Pillmann, F., 2004. Acute and transient psychoses. Cambridge: Cambridge University Press
Nagelkerke, N. J., 1991. A note on a general definition of the coefficient of determination. Biometrika. 78, 691–
692. Nordentoft, M., Jeppesen, P., Abel, M., Kassow, P., Petersen, L., Thorup, A., Krarup, G., Hemmingsen, R., Jørgensen, P., 2002. OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with firstepisode psychosis. Br. J. Psychiatry 43, s98-s106
Nordentoft, M., Madsen, T., Fedyszyn, I., 2015. Suicidal behavior and mortality in first-episode psychosis. J. Nerv. Ment. Dis. 203, 387-392.
13
ACCEPTED MANUSCRIPT
Pillmann, F., Balzuweit, S., Haring, A., Blöink, R., Marneros, A., 2003. Suicidal behavior in acute and transient psychotic disorders. Psychiatry Res. 117, 199-209
Pillmann, F., Haring, A., Balzuweit, S., Blöink, R., Marneros, A., 2002. The concordance of ICD-10 acute and transient psychosis and DSM-IV brief psychotic disorder. Psychol. Med. 32, 525–533.
Pompili, M., Serafini, G., Innamorati, M., Lester, D., Shrivastava, A., Girardi, P., Nordentoft, M., 2011. Suicide risk in first episode psychosis: A selective review of the current literature. Schizophr. Res. 129, 1–11.
Popovic, D., Benabarre, A., Crespo, J.M., Goikolea, J.M., González-Pinto, A., Gutiérrez-Rojas, L., Montes, J.M.,
Psychiatr. Scand. 130, 418–426.
CR IP T
Vieta, E., 2014. Risk factors for suicide in schizophrenia: systematic review and clinical recommendations. Acta
Silverman, M.M., Berman, A.L., Sanddal, N.D., O'carroll, P.W., Joiner, T.E., 2007a. Rebuilding the tower of babel: A revised nomenclature for the study of suicide and suicidal behaviors part 1: background, rationale, and methodology. Suicide Life Threat. Behav. 37, 248–263.
Silverman, M.M., Berman, A.L., Sanddal, N.D., O'carroll, P.W., Joiner, T.E., 2007b. Rebuilding the tower of
AN US
babel: a revised nomenclature for the study of suicide and suicidal behaviors. Part 2: suicide-related ideations, communications, and behaviors. Suicide Life Threat. Behav. 37, 264–277.
Skalská, H., Freylich, V., 2006. Web-bootstrap estimate of area under ROC curve. Austrian J. Stat. 35, 325–330.
Steyerberg, E.W., Vergouwe, Y., 2014. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur. Heart J. 35, 1925–1931.
Turecki, G., Brent, D.A., 2016. Suicide and suicidal behaviour. Lancet 387(10024), 1227-1239.
Ventriglio, A., Gentile, A., Bonfitto, I., Stella, E., Mari, M., Steardo, L., Bellomo, A., 2016. Suicide in the early
M
stage of schizophrenia. Front. Psychiatry 7, 1–9.
World Health Organization, 1993. The ICD-10 classification of mental and behavioural disorders: diagnostic
ED
criteria for research.
World Health Organization, 2015a. Preventing suicide: a global imperative. Geneva, Switzerland: World Health
PT
Organization; 2014.
World Health Organization, 2015b. Suicide rates data by country. Global Health Observatory Data Repository.
AC
CE
Available at: http://apps.who.int/gho/data/node.main.MHSUICIDE/ (accessed 30.12.15).
14
ACCEPTED MANUSCRIPT Table 1. Sociodemographic and clinical characteristics Total sample (n = 39) Age (years), mean ± SD
33.28 ± 10.94
Gender, n (%) Male
16 (41.1%)
Female
23 (58.9%)
Marital status, n (%) 15 (30.5%)
Unmarried
24 (61.5%)
Educational level, n (%) Low and medium level of education High level of education
17 (43.6%)
Unemployed/student
AN US
Employed
22 (56.4%)
Family history of psychosis, n (%) ATPD subtype, n (%) PM
11 (28.2%)
16 (41.1%)
Type of episode, n (%) First episode
ED
Recurrence
23 (58.9%)
M
NPM
Abrupt
PT
Acute
Acute stress, n (%)
CE
Substance use, n (%)
AC
28 (71.8%) 11 (28.2%)
Occupation, n (%)
Onset
CR IP T
Married/cohabiting
26 (66.6%) 13 (33.3%)
15 (38.5%) 24 (61.5) 14 (35.8%) 7 (17.9%)
History of depressive disorder, n (%)
4 (10.2%)
History of suicide attempt or deliberate self-harm, n (%)
4 (10.2%)
Suicidal symptoms, n (%)
8 (20.5%)
Suicidal ideation
6 (15.3%)
Suicide attempts
2 (5.1%)
Abbreviations: ATPD = acute and transient psychotic disorders; NPM = nonpolymorphic subtype; PM = polymorphic subtype; SD = standard deviation.
15
ACCEPTED MANUSCRIPT
Table 2. Predictors of suicidal behaviour in ATPD: Results of multivariate logistic regression analysis (n = 39) Coefficient
SE
Wald
p-value
OR
95% CI
1.91
1.86
1.053
0.305
6.75
0.17—259.39
History of depressive episodes
0.98
2.81
0.124
0.725
2.68
0.01—659.41
History of substance use
2.53
1.26
4.051
0.044
12.61
1.06–148.95
High level of education
-0.18
1.32
0.020
0.886
0.82
0.06—11.13
Abrupt onset
-0.06
1.52
0.002
0.965
0.93
0.04—18.49
Polymorphic subtype of ATPD
-1.65
1.68
0.962
0.326
0.19
0.01—5.19
Acute stress
2.63
1.29
4.128
0.042
13.92
Constant
-2.91
Previous history of suicide
Model Summary χ2 [df] (p-value)
8.74 [7] (p = 0.271)
2
AN US
0.51
Overall percentage of correct predictions (%)
92.31%
AUC (95% CI)
0.837 (95% CI = 0.684–0.935)
Bootstrap AUC (95% CI) a a
1.09–176.75
15.355 [7] (p = 0.031)
Hosmer and Lemeshow χ2 [df] (p-value) Nagelkerke R
CR IP T
attempt or deliberate self-harm
0.835 (95% CI = 0.60–1)
Bootstrap (1.000 replicates; random seed). Web program developed by Skalská and Freylich (2006)
AC
CE
PT
ED
M
Abbreviations: ATPD = acute and transient psychotic disorder; AUC = area under the curve; df = degree of freedom; OR = odds ratio; SE = standard error; 95% CI = 95% confidence interval
16
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
AN US
CR IP T
Figure 1. Flowchart of inclusion of patients.
17