Childhood adversity predicts persistence of suicidal thoughts differently in females and males at clinical high-risk patients of psychosis. Results of the EPOS project.

AIM: Depression and suicidal ideation (SUI) and behaviour are more prevalent in females than males, and common in clinical high-risk (CHR) patients. Childhood adversities and trauma (CAT) are associated with adult depression and SUI. The role of gender as a moderator and depression as a mediator for the effect of CAT on SUI has not been explored in CHR patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for SUI (thoughts of killing themselves) with the Beck Depression Inventory at baseline, 9-month and 18-month follow-ups. At baseline, clinical depression was assessed by the Structured Clinical Interview for DSM-IV (SCID-I), and CAT by the Trauma and Distress Scale (TADS) which includes the five domains of emotional, physical and sexual abuse, emotional and physical neglect. RESULTS: CAT total and all domains except physical neglect predicted SUI over the study period. The effect of CAT on SUI was mediated via clinical depression and concurrent depression symptoms differently for females and males. In females, the effect of emotional abuse and neglect on SUI was mediated via baseline depression. In males, emotional and physical abuse had a direct effect on SUI, and the effect of sexual abuse and emotional neglect was partly mediated via concurrent depression symptoms. CONCLUSIONS: For CHR females, the effect of CAT on adult SUI is mediated via depression, while for males, CAT and its domains have mainly direct effects in maintaining SUI. These gender differences should be taken into account when treating CHR patients with SUI.

Psychometric properties of the Trauma and Distress Scale, TADS, in an adult community sample in Finland.

BACKGROUND: There is increasing evidence that a history of childhood abuse and neglect is not uncommon among individuals who experience mental disorder and that childhood trauma experiences are associated with adult psychopathology. Although several interview and self-report instruments for retrospective trauma assessment have been developed, many focus on sexual abuse (SexAb) rather than on multiple types of trauma or adversity. METHODS: Within the European Prediction of Psychosis Study, the Trauma and Distress Scale (TADS) was developed as a new self-report assessment of multiple types of childhood trauma and distressing experiences. The TADS includes 43 items and, following previous measures including the Childhood Trauma Questionnaire, focuses on five core domains: emotional neglect (EmoNeg), emotional abuse (EmoAb), physical neglect (PhyNeg), physical abuse (PhyAb), and SexAb.This study explores the psychometric properties of the TADS (internal consistency and concurrent validity) in 692 participants drawn from the general population who completed a mailed questionnaire, including the TADS, a depression self-report and questions on help-seeking for mental health problems. Inter-method reliability was examined in a random sample of 100 responders who were reassessed in telephone interviews. RESULTS: After minor revisions of PhyNeg and PhyAb, internal consistencies were good for TADS totals and the domain raw score sums. Intra-class coefficients for TADS total score and the five revised core domains were all good to excellent when compared to the interviewed TADS as a gold standard. In the concurrent validity analyses, the total TADS and its all core domains were significantly associated with depression and help-seeking for mental problems as proxy measures for traumatisation. In addition, robust cutoffs for the total TADS and its domains were calculated. CONCLUSIONS: Our results suggest the TADS as a valid, reliable, and clinically useful instrument for assessing retrospectively reported childhood traumatisation.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND: The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS: At baseline, 54.3% of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4%. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION: Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

Pathways to care in subjects at high risk for psychotic disorders - a European perspective.

Evidence-based decisions on indicated prevention in early psychosis require large-scale studies on the pathways to care in high-risk subjects. EPOS (The European Prediction of Psychosis Study), a prospective multi-center, naturalistic field study in four European countries (Finland, Germany, The Netherlands and England), was designed to acquire accurate knowledge about pathways to care and delay in obtaining specialized high risk care. Our high risk sample (n=233) reported on average 2.9 help-seeking contacts, with an average delay between onset of relevant problems to initial help-seeking contact of 72.6 weeks, and between initial help-seeking contact and reaching specialized high risk care of 110.9 weeks. This resulted in a total estimated duration of an unrecognized risk for psychosis of 3 ½ years. Across EPOS EU regions, about 90% of care pathway contacts were within professional health care sectors. Between EPOS regions, differences in the pathways parameters including early detection and health-care systems were often very pronounced. High-risk participants who later made transition to a full psychotic disorder had significantly longer delays between initial help-seeking and receiving appropriate interventions. Our study underlines the need for regionally adapted implementation of early detection and intervention programs within respective mental health and health care networks, including enhancing public awareness of early psychosis.

Psychosocial outcome in patients at clinical high risk of psychosis: a prospective follow-up.

PURPOSE: In patients at clinical high risk (CHR) of psychosis, transition to psychosis has been the focus of recent studies. Their broader outcome has received less attention. We studied psychosocial state and outcome in CHR patients. METHODS: In the European Prediction of Psychosis Study, 244 young help-seeking CHR patients were assessed with the Strauss and Carpenter Prognostic Scale (SCPS) at baseline, and 149 (61.1%) of them were assessed for the second time at the 18-month follow-up. The followed patients were classified into poor and good outcome groups. RESULTS: Female gender, ever-married/cohabitating relationship, and good working/studying situation were associated with good baseline SCPS scores. During follow-up, patients' SCPS scores improved significantly. Good follow-up SCPS scores were predicted by higher level of education, good working/studying status at baseline, and white ethnicity. One-third of the followed CHR patients had poor global outcome. Poor working/studying situation and lower level of education were associated with poor global outcome. Transition to psychosis was associated with baseline, but not with follow-up SCPS scores or with global outcome. CONCLUSION: The majority of CHR patients experience good short-term recovery, but one-third have poor psychosocial outcome. Good working situation is the major indicator of good outcome, while low level of education and non-white ethnicity seem to be associated with poor outcome. Transition to psychosis has little effect on psychosocial outcome in CHR patients. In treating CHR patients, clinicians should focus their attention on a broader outcome, and not only on preventing transition to psychosis.

Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries.

BACKGROUND: In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project, six European outpatient centres in four countries examined 245 young help-seeking patients, who fulfilled the inclusion criteria for clinical risk of psychosis according to the Structured Interview for Prodromal Syndromes (SIPS 3.0) or the Bonn Scale for the Assessment of Basic Symptoms - Prediction List basic symptoms (BASBS-P). Patients who had experienced a psychotic episode lasting more than one week were excluded. Baseline and life-time diagnoses were assessed by the Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by continuation of BLIPS for more than seven days and predicted in Cox-regression analysis. RESULTS: Altogether, 71% of the CHR patients had one or more life-time and 62% one or more current SCID-I diagnosis; about a half in each category received a diagnosis of life-time depressive and anxiety disorder. Currently, 34% suffered from depressive and 39% from anxiety disorder. Four percent received a current SCID diagnosis of bipolar, and 6.5% of somatoform disorder. During follow-up, 37 (15.1%) patients had developed full-blown psychosis. In bivariate analyses, current non-psychotic bipolar disorder associated significantly with TTP. In multivariate analyses, current bipolar disorder, somatoform and unipolar depressive disorders associated positively, and anxiety disorders negatively, with TTP. CONCLUSIONS: Both life-time and current mood and anxiety disorders are highly prevalent among clinical help-seeking CHR patients and need to be carefully evaluated. Among CHR patients, occurrence of bipolar, somatoform and depressive disorders seems to predict TTP, while occurrence of anxiety disorder may predict non-transition to psychosis.

Cognitive and affective empathy in depression linked to executive control.

Depression has been linked to executive dysfunction and emotion recognition impairments, associated with abnormalities in fronto-temporal and subcortical brain regions. Little is known about changes of different empathy subcomponents during depression, with potential impairments being related to the interpersonal difficulties of depressed patients. Twenty patients treated for an episode of unipolar depression and 20 matched healthy controls were assessed. Measures of dispositional and behavioural empathy components were administered along with tests of cognitive flexibility, response inhibition and working memory. Relative to controls, depressed patients showed higher self-reported dispositional empathy scores, mainly driven by increased personal distress scores. Patients and controls did not differ significantly in terms of behavioural cognitive empathy, empathic concern and personal affective involvement or in their executive function performance. In the patients, cognitive flexibility and response inhibition accuracy were associated with behavioural empathy. While an increased disposition towards feeling personal distress in response to other people's suffering seems to be in generally related to depressive symptoms, behavioural empathy might depend on the functional integrity of executive control during an episode of clinical depression. Impairments in this regard could contribute to the interpersonal difficulties depressed patients are frequently faced with which might have important implications for treatment.

An fMRI study of "theory of mind" in at-risk states of psychosis: comparison with manifest schizophrenia and healthy controls.

OBJECTIVE: Poor social functioning is a hallmark of schizophrenia and may precede the onset of illness. One of the most robust predictors of social impairment is a deficit in the ability to appreciate the mental states of others ("theory of mind"; ToM). We therefore examined ToM in subjects at risk of developing psychosis using an fMRI paradigm and compared brain activations with those of patients with manifest schizophrenia and healthy controls. METHOD: Ten subjects with at-risk ("prodromal") states of psychosis, 22 schizophrenia patients and 26 healthy controls were recruited. During fMRI scanning, participants were shown a series of cartoons. The task was to infer the mental states of the cartoon characters in terms of beliefs, states of knowledge and intentions. RESULTS: Subjects at risk of psychosis activated the ToM neural network comprising the prefrontal cortex, the posterior cingulate cortex, and the temporoparietal cortex more strongly than patients with manifest schizophrenia, and, in part, also more strongly than healthy controls. Manifest schizophrenia patients and controls activated the ToM neural network differently with little overlap of activated regions, where overall, controls showed stronger activations than schizophrenia patients. CONCLUSIONS: Individuals with at-risk states of schizophrenia activate the ToM neural network differently, and in part, more strongly compared to patients with schizophrenia and controls. This could suggest a compensatory overactivation of brain regions critical for empathic responses during mental state attribution in at-risk subjects for schizophrenia.

Disability in people clinically at high risk of psychosis.

BACKGROUND: Decline in social functioning occurs in individuals who later develop psychosis. AIMS: To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD: Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS: At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (ß = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS: Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study.

CONTEXT: Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. OBJECTIVE: To develop a differential predictive clinical model of transition to first-episode psychosis. DESIGN: Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. SETTING: Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. PARTICIPANTS: Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom-based criterion cognitive disturbances (COGDIS). MAIN OUTCOME MEASURE: Incidence of transition to psychosis. RESULTS: At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. CONCLUSIONS: The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Basic symptoms in early psychotic and depressive disorders.

BACKGROUND: Depression is a frequent condition in early psychosis. Therefore, early detection instruments should distinguish depression from beginning psychosis. AIMS: To examine whether basic symptoms, i.e. subtle subjective deficits, differ between participants suffering from a potential prodrome (n=146), first-episode schizophrenia (n=153) and non-psychotic depression (n=115). METHOD: Basic symptoms were assessed with the Schizophrenia Proneness Instrument. RESULTS: The prodrome and schizophrenia groups did not differ in level of basic symptoms but both had higher levels than the depression group. DSM-IV depression was frequent in those suffering from a potential prodrome (38%) and first-episode schizophrenia (21%). In both groups, participants with and without depression did not differ in basic symptoms. In multivariate analyses, consideration of current depression generally facilitated correct group classification, except for participants suffering from both a potential prodrome and depression. CONCLUSIONS: Cognitive basic symptoms distinguished well between all three groups. However, identification of persons suffering from a potential prodrome might be enhanced by considering current affective status.

Relationship between subjective and objective cognitive function in the early and late prodrome.

BACKGROUND: Cognitive disturbances have been demonstrated in individuals with potentially prodromal symptoms in objective-neuropsychological as well as subjective-symptomatic studies. Yet, the relation between subjective and objective deficits and to different prodromal states is unclear. AIMS: To explore interactions between subjective and objective cognitive measures in different prodromal states. METHOD: In participants with an early (n=33) or late (n=69) initial prodromal state, cognitive subjective and objective deficits were assessed with the Schizophrenia Proneness Instrument and a comprehensive neuropsychological test battery. RESULTS: Participants with an early initial prodromal state were less impaired than those with a late initial state. Subjective and objective cognitive deficits were unrelated, except time-limited neurocognitive speed measures and subjectively reduced stress tolerance, especially in participants with an early initial prodromal state. CONCLUSIONS: Subjective and objective cognitive deficits are generally unrelated in the psychosis prodrome and as such they can add complementary information valuable for prediction. However, possible associations between the two levels might be better detectable in the less impaired early initial prodromal state.