Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

EPA guidance on the early detection of clinical high risk states of psychoses.

The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion 'cognitive disturbances' (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The 'genetic risk and functional decline' UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.

EPA guidance on the early intervention in clinical high risk states of psychoses.

This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project.

PURPOSE: In patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment. METHODS: In all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed. RESULTS: During the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model. CONCLUSION: A great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.

Prediction of psychosis in clinical high-risk patients by the Schizotypal Personality Questionnaire. Results of the EPOS project.

OBJECTIVE: Schizotypal features indicate proneness to psychosis in the general population. It is also possible that they increase transition to psychosis (TTP) among clinical high-risk patients (CHR). Our aim was to investigate whether schizotypal features predict TTP in CHR patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project, 245 young help-seeking CHR patients were prospectively followed for 18 months and their TTP was identified. At baseline, subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). Associations between SPQ items and its subscales with the TTP were analysed in Cox regression analysis. RESULTS: The SPQ subscales and items describing ideas of reference and lack of close interpersonal relationships were found to correlate significantly with TTP. The co-occurrence of these features doubled the risk of TTP. CONCLUSIONS: Presence of ideas of reference and lack of close interpersonal relations increase the risk of full-blown psychosis among CHR patients. This co-occurrence makes the risk of psychosis very high.

Childhood trauma and distress experiences associate with psychotic symptoms in patients attending primary and psychiatric outpatient care. Results of the RADEP study.

GOAL: We studied the prevalence of and association between psychotic symptoms and childhood trauma experiences in primary care patients compared with psychiatric care patients. PATIENTS AND METHODS: We note 911 primary care and psychiatric care patients over 16 years of age filled in a questionnaire including a list of lifetime psychotic symptoms of the Composite International Diagnostic Interview (CIDI) and the childhood Trauma and Distress Scale (TADS). Prevalence of and correlations between psychotic symptoms and childhood trauma and stressful experiences were calculated. Association between the sum of CIDI symptoms and the TADS sum score was analysed by Anova. RESULTS: In primary care, more than half of the patients had had at least one psychotic symptom during their lifetime, and nearly 70% of patients had experienced a childhood trauma at some time or more often. In psychiatric care patients, CIDI symptoms were more prevalent and TADS scores were higher than in primary care patients. In the whole sample, CIDI symptoms correlated with TADS scores. The association remained even when the effects of age, service, and patient's functioning were taken into account. There was a dose-response between TADS scores and CIDI symptoms. CONCLUSION: Childhood trauma experiences associate with psychotic symptoms. In clinical work, it is important to acknowledge that psychotic symptoms and childhood trauma experiences are common not only in psychiatric care but also in primary care patients, and thus require adequate attention.

The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis.

OBJECTIVE: To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. METHOD: Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. RESULTS: At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). CONCLUSION: The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes.

Physical illnesses, developmental risk factors and psychiatric diagnoses among subjects at risk of psychosis.

BACKGROUND: Subjects with psychoses have significantly increased rates of physical illnesses, but the nature of the relationship remains largely unknown. MATERIAL AND METHODS: The present study is part of the European Prediction of Psychosis Study (EPOS). Data were collected from 245 help-seeking individuals from six European centers (age 16-35) who met criteria for ultra-high risk of psychosis criteria. This paper seeks to investigate self-reported physical ill health and its associations with psychiatric symptoms and disorders, risk factors, and onset of psychosis during 48 months of follow-up. RESULTS: In multivariate analysis, lifetime panic disorder (OR=2.43, 95%CI: 1.03-5.73), known complications during pregnancy and delivery (OR=2.81, 95%CI: 1.10-7.15), female gender (OR=2.88, 95%CI: 1.16-7.17), family history of psychosis (OR=3.08, 95%CI: 1.18-8.07), and having a relationship (OR=3.44, 95%CI: 1.33-8.94) were significantly associated with self-reported physician-diagnosed illness. In the Cox proportional hazard model we found no significant differences between those who had undergone a transition to psychosis and those who had not. CONCLUSIONS: The physical health of patients defined to be at ultra-high risk of psychosis seems to be commonly impaired and associated with female gender, marital status, complications during pregnancy and birth, lifetime panic disorder, and genetic risk of psychosis.

Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis.

OBJECTIVE: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high-risk symptoms in subjects at clinical high risk for psychosis. METHOD: Prospective multicenter, naturalistic field study with an 18-month follow-up period in 245 help-seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia. RESULTS: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < r(s) < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants. CONCLUSION: Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals. Cannabis use in early adolescence should be discouraged.

Perceived negative attitude of others predicts transition to psychosis in patients at risk of psychosis.

AIM: Our previous study (Salokangas et al., 2009) suggested that the subjective experience of negative attitude of others (NAO) towards oneself is an early indicator of psychotic development. The aim of this prospective follow-up study was to test this hypothesis. METHODS: A total of 55 young psychiatric outpatients assessed as being at current risk of psychosis (CROP) were followed for up to 60 months and rates of transition to psychosis (TTP) identified. CROP was assessed employing the Bonn Scale for assessment of basic symptoms (Schultze-Lutter and Klosterkötter, 2002) and the Structured Interview for prodromal symptoms (Miller et al., 2002). TTP was defined by a psychotic episode lasting for more than one week. Associations between NAO at baseline and TTP were analyzed by a Cox regression survival analysis. RESULTS: Eight (14.5%) TTP were identified: four (57.1%) within seven NAO patients and four (8.7%) within forty-six non-NAO patients. In the multivariate Cox regression analysis, NAO at baseline significantly (P=0.007) predicted TTP. CONCLUSION: The prospective follow-up results support our hypothesis that subjective experience of NAO is an early indicator of psychotic in development.

Seven-year outcome of depression in primary and psychiatric outpatient care: results of the TADEP (Tampere Depression) II Study.

The objective of this article was to determine a 7-year naturalistic progression of depression as well as a number of potential prognostic factors among Finnish primary care and psychiatric care patients. Depression-screened patients from primary care and psychiatric care, aged 18-64, were interviewed in 1991-92 with the Present State Examination (PSE) as the diagnostic instrument. The patients were re-contacted in 1998-99, and their depression at final assessment (FinalA) and during the follow-up period (F-up) was assessed by telephone interview using the Composite International Diagnostic Interview--Short Form (CIDI-SF). 250 primary care (58.1%) and 170 (40.2%) psychiatric care patients were successfully followed. Of the primary care patients with severe depression at baseline, 42.4% had had depression during F-up and 21.2% had depression at FinalA. For the patients with mild depression at baseline, the corresponding figures were nearly the same, but for the patients with depressive symptoms clearly lower. Of the psychiatric care patients with severe depression at baseline, 61.0% had had depression during F-up and 26.2% had depression at FinalA. As with primary care patients, the corresponding figures were nearly the same for mild depression at baseline but clearly lower for depressive symptoms. Experienced lifetime mood elevation was associated with having depression during F-up in both primary care and psychiatric care patients. High Depression Scale (DEPS) score at baseline was associated with having depression at FinalA in primary care patients, but in psychiatric care patients, it was the high Hamilton Rating Scale for depression (HAM-D) and drinking problems. Severe depression and mild depression are predictive for subsequent depression at both levels of care. The long-term prognosis for depression is better in primary care. DEPS and HAM-D are useful, prognostic instruments.

Cigarette smoking in long-term schizophrenia.

PURPOSE: Cigarette smoking is a great health problem and prevalent among subjects with schizophrenia. Our aim was to investigate the prevalence and associations of cigarette smoking in patients with long-term schizophrenia. METHODS: Seven hundred and sixty schizophrenia patients were interviewed and their cigarette smoking was recorded. RESULTS: Smoking was more prevalent men than in women patients. In logistic regression analysis, male gender, duration of illness (DUI) from 10 to 19 years, being divorced or separated, lower education and high daily doses of neuroleptics (DDN) associated significantly with regular smoking. Heavy smoking associated, in men, with hospital treatment. CONCLUSIONS: In schizophrenia patients, smoking is associated with long DUI, high DDN and institutional care. Interventions for cessation and/or reduction of cigarette smoking should be a part of the treatment for patients with schizophrenia.

Psychodynamic personality profile in first-episode severe mental disorders.

OBJECTIVE: The aim of this study was to relate measures of psychoanalytically derived personality traits to descriptive diagnosis and psychopathology in severe mental disorders. METHOD: Sixty-one consecutive first-episode patients with schizophrenia, bipolar disorder and severe major depression were interviewed. Personality traits were assessed with the Karolinska Psychodynamic Profile (KAPP) and compared with the DSM-IV diagnosis and symptom clusters derived from the BPRS. RESULTS: There were no marked differences in personality traits between the three diagnostic groups, between schizophrenia and affective disorders or between psychotic and non-psychotic illness. However, personality traits had significant associations with symptoms, especially with the emotional retardation cluster. CONCLUSION: Our findings do not support the hypothesis that severe mental disorders would differ from each other in terms of long-standing psychodynamic personality profiles. Certain dysfunctional personality traits may predict especially negative emotional symptoms and possibly also predispose a person to them.

PROD-screen--a screen for prodromal symptoms of psychosis.

The aim of this study was to describe the PROD-screen, an instrument for screening prodromal symptoms indicating risk for psychotic conversion in the near future. PROD-screen consists of 29 questions assessing performance and symptoms. Clinical construct validity was tested by comparing scores from the unselected general population (GP, n = 64) with those of general psychiatric patients from a community mental health centre (CMHC, n = 107). The concordant validity of PROD-screen for prodromal symptoms of psychosis was assessed in a large epidemiologically mixed sample of research subjects (n = 132) by comparing PROD-screen scores with the prodromal diagnosis made by Structured Interview for Prodromal Symptoms as a gold standard. Using the cut-off point of 2/12 specific symptoms, PROD-screen gave correct classification of prodromal status in 77% of cases, distinguishing prodromal from non-prodromal subjects with reasonable sensitivity (80%) and specificity (75%) in the epidemiologically mixed sample. According to subsample analysis PROD-screen functions well with first-degree relatives of schizophrenic patients and probably also with general population samples, but not with psychiatric outpatients. In conclusion, PROD-screen is a useful tool for screening prodromal symptoms of psychosis and selecting subjects for more extensive research interviews.

Inadequate treatment of depression after myocardial infarction.

OBJECTIVE: The objective of the study was to investigate the prevalence of depressive symptoms and the self-reported psychiatric treatment after myocardial infarction. METHOD: Depressive symptoms and medication were studied in 85 consecutive acute myocardial infarction patients during 18 months follow-up. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). RESULTS: The proportion of patients with depressive symptoms (BDI >/= 10) was 21.2% while in hospital, 30.0% at 6 months and 33.9% at 18 months. At 18 months, none of the patients were receiving adequate antidepressive medication. There were eight patients with BDI scores corresponding to moderate/severe depression (BDI >/= 19). Six of these patients were receiving benzodiazepine medication and two of them had been treated in the mental health care system after the myocardial infarction. CONCLUSION: There seems to be considerable problems in the diagnosis and/or treatment of depression after myocardial infarction.

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

BACKGROUND: Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. AIMS: To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. METHOD: Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. RESULTS: Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. CONCLUSIONS: Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.