Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Factors associated with involuntary admissions among patients with substance use disorders and comorbidity: a cross-sectional study.

BACKGROUND: To investigate factors associated with involuntary admissions to hospital pursuant to a social services act of patients with substance use disorder by comparing the socio-demographic characteristics, substance use, and psychiatric comorbidities with voluntarily admitted patients. METHODS: This cross-sectional study compared two groups admitted to combined substance use disorder and psychiatry wards. Sixty-five patients were involuntarily admitted pursuant to the Social Services Act and 137 were voluntarily admitted. The International Classification of Diseases and Related Health Problems was used for diagnostic purposes regarding substance use disorders, type and severity of psychiatric problems, and level of functioning. Socio-demographic variables were measured using the European Addiction Severity Index, and the Symptom Checklist-90-R instruments were used to evaluate the range of psychological problems and psychopathological symptoms. Logistic regression was performed to investigate the relationship between involuntary admissions and patients characteristics. RESULTS: Patients who had been involuntarily admitted were more likely to be females, had utilized public welfare services more often, presented more severe substance use patterns, and had a history of more frequent visits to physicians for somatic complaints in the last 6 months, they also had fewer comorbid mental disorders. Still, considerable burdens of comorbid substance use disorders and mental disorders were observed both among involuntary and voluntary admitted patients. CONCLUSIONS: More attention is required for involuntarily admitted patients in order to meet the needs associated with complex and mixed disorders. In addition, treatment centers should offer diagnostic options and therapy regarding substance use, psychiatric and somatic disorders.

Depression trajectories and cytokines in schizophrenia spectrum disorders - A longitudinal observational study.

Depression occurs frequently in all phases of schizophrenia spectrum disorders. Altered activity in the immune system is seen in both depression and schizophrenia. We aimed to uncover depressive trajectories in a sample of 144 adult individuals with schizophrenia spectrum disorders followed for one year, in order to identify possible cytokine profile differences. Patients were assessed longitudinally with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), where a score above 6 predicts depression. The serum cytokine concentrations for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p70 and IL-17A were measured using immunoassays. Latent growth curve models, multilevel models and latent class growth analysis (LCGA) were applied. The LCGA model supported three latent classes (trajectories) with differing CDSS profiles during the one-year follow-up: a high CDSS group (40.8 % of participants), a moderate CDSS group (43.9 %) and a low CDSS group (15.3 %). Five single PANSS items predicted affiliation to depressive trajectory: hallucinations, difficulty in abstract thinking, anxiety, guilt feelings and tension. In the high CDSS group, despite diminishing psychotic symptoms, depressive symptoms persisted throughout one year. The pro-inflammatory cytokines IFN-γ, IL-1ß and TNF-α were differentially distributed between the depressive trajectories, although levels remained remarkably stable throughout 12 months. Significant changes were found for the anti-inflammatory cytokine IL-10 at baseline with an accompanying difference in change over time. More research is required to optimize future treatment stratification and investigate the contribution of inflammation in depressed patients with schizophrenia spectrum disorders.

A comparison of adolescent- and adult-onset first-episode, non-affective psychosis: 2-year follow-up.

This study aimed to compare 2-year outcome among individuals with early-onset (EO; <18 years) versus adult-onset (AO) first-episode, non-affective psychosis. We compared clinical and treatment characteristics of 43 EO and 189 AO patients 2 years after their inclusion in a clinical epidemiologic population-based cohort study of first-episode psychosis. Outcome variables included symptom severity, remission status, drug abuse, treatment utilization, cognition and social functioning. At baseline, EO patients were more symptomatically compromised. However, these initial baseline differences were no longer significant at the 2-year follow-up. This study challenges the findings of a larger and older literature base consisting primarily of non-comparative studies concluding that teenage onset indicates a poor outcome. Our results indicate that adolescent-onset and adult-onset psychosis have similar prognostic trajectories, although both may predict a qualitatively different course from childhood-onset psychosis.

Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis.

BACKGROUND: A potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. OBJECTIVES: To examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. METHODS: In a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. RESULTS: For all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. CONCLUSION: Treatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01446328; URL: http://www. CLINICALTRIALS: gov/.

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study.

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.

The International Study on General Practitioners and Early Psychosis (IGPS).

BACKGROUND: In much of the world, general practitioners (GPs) are the health professionals most frequently initially contacted when a young person is developing psychosis. However little is known about their expertise in assessing psychosis and its risk. METHODS: To assess the diagnostic patterns and treatment practices related to psychosis of GPs working in a range of health care systems, questionnaires were mailed to 12,516 randomly selected GPs in seven countries: Canada, Australia, New Zealand, England, Norway, Austria and the Czech Republic. Sites were defined as gatekeeping or non-gatekeeping, based on the primary care health system in effect at each site. A gatekeeping system (GK) is one which mandates that patients see a GP before in order to be referred to a specialist. By contrast, in a non-gatekeeping (nGK) system, individuals can seek help directly from specialists without authorization by a GP. RESULTS: Twenty-two percent (n=2784) GPs responded to the mailed questionnaire. They reported low prevalence of early psychosis seen in general practice. Using awareness of functional decline as a prognostic sign as a proxy, gatekeeping (GK) GPs were found to be superior in their knowledge of the signs and symptoms of early psychosis than were non-gatekeeping GPs. GP's with less knowledge as to early psychosis were more likely to refer individuals with suspected psychosis to specialists. GP's reported a preference for access to specialized outpatient services as compared with obtaining continuous medical education relevant to early psychosis. The duration of maintenance treatment recommended by GP's was less than that recommended in international guidelines. GP's also underestimated the risk for relapse after a first episode of psychosis. CONCLUSIONS: As GPs were largely unaware of features of early psychosis, such as functional decline, this should be the target of educational programs for GP's. However, the incidence of psychosis is low and GP's express a preference for access to appropriate referral over continuing medical education. Therefore, the development of specialized services for the assessment and care of patients who are in the early stages of developing schizophrenia may be warranted.

The key to reducing duration of untreated first psychosis: information campaigns.

UNLABELLED: The TIPS early intervention program reduced the duration of untreated psychosis (DUP) in first-episode schizophrenia from 16 to 5 weeks in a health care sector using a combination of easy access detection teams (DTs) and a massive information campaign (IC) about the signs and symptoms of psychosis. This study reports what happens to DUP and presenting schizophrenia in the same health care sector when the IC is stopped. METHODS: Using an historical control design, we compare 2 cohorts of patients with first-episode Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, non-affective psychosis at admission to treatment. The first cohort (N = 108) was recruited from January 1997 to December 2000, using an IC to raise awareness about recognizing psychosis to the public, the schools, and to general practitioners. The second cohort (N = 75) was recruited from January 2002 to June 2004 with no-IC. Easy access DTs were available to both cohorts. RESULTS: In the no-IC period, DUP increased back up to 15 weeks (median) and fewer patients came to clinical attention through the DTs. No-IC patients were diagnosed less frequently with schizophreniform disorder, more Positive and Negative Syndrome Scale positive and total symptoms, and poorer Global Assessment of Functioning (symptom) Scale scores. CONCLUSIONS: Intensive education campaigns toward the general public, the schools, and the primary health care services appear to be an important and necessary part of an early detection program. When such a campaign was stopped, there was a clear regressive change in help-seeking behavior with an increase in DUP and baseline symptoms.

First-episode psychosis: diagnostic stability over one and two years.

BACKGROUND: Diagnostic stability is important for daily clinical work and planning of treatment. The aims of this study were to measure diagnostic stability in a clinical epidemiologic sample and to identify markers of change in diagnosis. SAMPLING AND METHODS: Diagnostic stability and change were measured in a sample of 301 patients with first-episode psychosis from four national health care sectors in Norway and Denmark at baseline, 1 and 2 years. RESULTS: Diagnostic stabilities were high for schizophrenia and schizoaffective disorder (85-99%), low for schizophreniform disorder (16-19%), and intermediate for other diagnoses. Diagnostic change from schizophreniform to schizophrenia was frequent in year 1 (72%). Characteristics discriminating schizophreniform patients keeping their diagnosis (i.e. having recovered within 6 months with no relapse) from those developing schizophrenia at 1 year were female gender, better childhood premorbid functioning, shorter duration of untreated psychosis and more severe general psychotic symptoms, especially excitation. CONCLUSIONS: Findings provide validation for the DSM-IV categories within the schizophrenic spectrum. The limitations of the study were: the raters were not blind to baseline assessments; patients with longer duration of untreated psychosis were more likely to refuse participation; not all patients were assessed at 1- and 2-year follow-up, but the attrition was rather low.

The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse.

The aim was to determine the post-onset longitudinal course of cognitive functioning in first-episode psychoses and to examine how premorbid adjustment, duration of untreated psychosis (DUP), and clinical variables such as relapse are associated with that course. Consecutive patients with a DSM-IV diagnosis of non-organic psychosis coming to their first treatment in the health care areas under study were included. Ultimately, 207 patients were assessed neuropsychologically at baseline, 138 were reassessed one year later, and 111 two years later. Five dimensions were identified through principal component analysis of eight neuropsychological (NP) test results: Working Memory (WM), Executive Function (EF), Verbal Learning (VL), Impulsivity (Im), and Motor Speed (MS). No major changes were found in the level of neurocognitive functioning from baseline to the 1-year and 2-year follow-ups. Patients with good initial levels of premorbid academic functioning had consistently better scores on WM at all three time points. No association was found between DUP and the longitudinal course of neurocognitive function. Significant associations occurred between better WM and VL at 1 and 2 years and fewer relapses during the first year, but not the second. Most NP deficits are in place by onset of psychosis and are stable over two years. Milder WM deficits are associated with higher premorbid academic functioning. More severe deficits in WM and VL are associated with more relapses during the first year. It is unclear whether NP deficits cause relapse, relapse causes NP deficits, or both are manifestations of a third deteriorative process.

Multifamily group treatment in a program for patients with first-episode psychosis: experiences from the TIPS project.

Psychoeducational multifamily group treatment based on the McFarlane model was implemented for adult patients experiencing a first episode of psychosis and for the families of 301 patients. Patients were participants in a research project in Norway and Denmark. Of 301 patients 246 were invited to participate and 147 agreed. Patients' reluctance to participate increased with age. Most had to wait between six and 12 months until a sufficient number was gathered to start a group. Treatment was well received by patients and families. Care should be taken to prevent a long delay before group commencement at this stressful period in the lives of patients and families.

One-year effect of changing duration of untreated psychosis in a single catchment area.

BACKGROUND: There is highly replicated positive correlation between longer duration of untreated psychosis and poorer outcome. AIMS: To study the effect of early intervention in first psychosis on one-year outcome using an historical quasi-experimental design. METHOD: We compare the outcome of two samples of first-episode psychosis from the same healthcare district at different time periods. The historical control sample was assessed during 1993-1994, before the establishment of a system for early detection of psychosis. The experimental sample is the early detection sample in the Early Treatment and Intervention in Psychosis study assessed during 1997-2000. RESULTS: At 1-year follow-up, the early detection group was younger, had a smaller fraction of individuals with schizophrenia, had less severe negative and general symptoms and had more friends in the past year than the historical control group. No differences were found in clinical course (remission, relapse, continuously psychotic) or positive symptoms, but more patients in the early detection sample were treated as outpatients without hospitalisation. CONCLUSIONS: Early detection of schizophrenia in one healthcare sector is associated with less severe deterioration at 1 year.

Early detection of the first episode of schizophrenia and suicidal behavior.

OBJECTIVE: The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts. METHOD: The authors examined consecutive patients with nonorganic, nonaffective psychosis who sought initial treatment at psychiatric treatment units in four catchment areas: two that had an early detection program and two that did not. RESULTS: The rate of severe suicidality (plans or attempts) was significantly higher in subjects from communities without the early detection program relative to those from early detection communities, even after adjustments for known predictors of suicidality. CONCLUSION: Early detection programs that bring patients into treatment at lower symptom levels may reduce suicidality risk at first treatment contact.

Substance abuse in first-episode non-affective psychosis.

Abuse of alcohol and drugs is an important and clinically challenging aspect of first-episode psychosis. Only a few studies have been carried out on large-sized and reliably characterized samples. These are reviewed, and the results are compared with a sample of 300 first-episode psychosis patients recruited for the TIPS (Early Treatment and Identification of Psychosis) study from Norway and Denmark. Prevalence rates from the literature vary from 6% to 44% for drugs and 3% to 35% for alcohol. In our sample, 23% abused drugs and 15% abused alcohol during the last 6 months. When compared to non-abusers, the drug-abusing group is characterized by the following: male gender, younger age, better premorbid social, poor premorbid academic functioning, and more contact with friends in the last year before onset. Alcohol abusers were the oldest group and they had the least contact with friends. A group of patients abusing both drugs and alcohol had poor premorbid academic functioning from early childhood. Overall, drug and alcohol abuse are highly prevalent in contemporary first-episode psychosis samples. In our study, substance abuse comorbidity did not generate differences on diagnosis, duration of untreated psychosis, psychiatric symptoms, or global functioning at onset/baseline. The premorbid profiles of the substance abusers were clearly different from the non-abusers. Drug abusers, in particular, were more socially active both premorbidly and during the year preceding the start of treatment.

Early detection of first-episode psychosis: the effect on 1-year outcome.

UNLABELLED: Early intervention is assumed to improve outcome in first-episode psychosis, but this has not been proven. OBJECTIVE: To study whether 1-year outcome will be better in a health care sector with early detection (ED) of psychosis compared with sectors with no early detection (no-ED). DESIGN: A quasi-experimental study with ED in 2 experimental sectors and no-ED in 2 control sectors. ED was achieved through low-threshold ED teams and information campaigns about psychosis for the public, schools, and primary health care providers. The ED and no-ED health care areas offered an equivalent assessment and treatment program during the first year. Two hundred and eighty-one patients were included; 88% were reassessed after 1 year. RESULTS: The ED-area patients (N = 141) had a median duration of untreated psychosis of 5 weeks at baseline compared with 16 weeks for patients in the no-ED area (N = 140). Positive and general symptoms, global assessment of functioning, quality of life, time to remission, and course of psychosis at 1 year after the start of treatment were not different between ED and no-ED groups. Outcome was significantly better for the ED area for negative symptoms. CONCLUSIONS: The ED, no-ED differences at baseline become attenuated by 1 year but not the difference in negative symptoms, suggesting secondary prevention in this domain of psychopathology. However, this possibility requires further testing by follow-up and replication.

Obstacles to care in first-episode psychosis patients with a long duration of untreated psychosis.

AIM: This qualitative study is a sub-study of the early 'Treatment and Intervention in Psychosis Study' (TIPS-2), a program for early intervention strategies for people experiencing a first episode of psychosis. We aimed to improve knowledge about factors that prevent or delay patients with a long duration of psychosis from accessing psychiatric health-care services at an earlier illness stage and their personal views on the impact of ongoing informational campaigns (ICs) on help-seeking behaviour. METHOD: Following an interpretative-phenomenological approach, eight consecutive TIPS-2 patients with duration of untreated psychosis lasting for more than 6 months were interviewed. The interviews were analysed using a meaning condensation procedure. RESULTS: Five main themes were identified: (i) participants' failure to recognize symptoms of psychosis; (ii) difficulties expressing their experiences; (iii) concerns about stigma; (iv) poor psychosis detection skills among health-care professionals; and (v) participants' lack of awareness or understanding of ICs. CONCLUSIONS: The five themes identified may suggest that despite exposure to the targeted ICs, participants were unable to recognize or understand the severity of their symptoms. Further, although family members or others sometimes recognized the initial symptoms of psychosis development, these symptoms were attributed to reasons other than psychosis. Participants reported that health-care personnel also had trouble identifying emerging signs of psychosis. The ICs need to be carefully crafted to relay information to people who do not consider themselves as currently experiencing signs of psychosis.

"Everyone Needs a Friend Sometimes" - Social Predictors of Long-Term Remission In First Episode Psychosis.

Background: Predictors of long-term symptomatic remission are crucial to the successful tailoring of treatment in first episode psychosis. There is lack of studies distinguishing the predictive effects of different social factors. This prevents a valid evaluating of their independent effects. Objectives: To test specific social baseline predictors of long-term remission. We hypothesized that first, satisfaction with social relations predicts remission; second, that frequency of social interaction predicts remission; and third, that the effect of friend relationship satisfaction and frequency will be greater than that of family relations satisfaction and frequency. Material and Methods: A sample of first episode psychosis (n = 186) completed baseline measures of social functioning, as well as clinical assessments. We compared groups of remitted and non-remitted individuals using generalized estimating equations analyses. Results: Frequency of social interaction with friends was a significant positive predictor of remission over a two-year period. Neither global perceived social satisfaction nor frequency of family interaction showed significant effects. Conclusions: The study findings are of particular clinical importance since frequency of friendship interaction is a possibly malleable factor. Frequency of interaction could be affected through behavioral modification and therapy already from an early stage in the course, and thus increase remission rates.

Reducing the duration of untreated first-episode psychosis: effects on clinical presentation.

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.