Selection bias in clinical studies of first-episode psychosis: A follow-up study

Objectives: Selection bias is a concern in studies on psychotic disorders due to high dropout rates and many eligibility criteria for inclusion. We studied how representative the first-episode psychosis study sample in the Turku Early Psychosis Study (TEPS) was.Methods: We screened 3772 consecutive admissions to the clinical psychiatric services of Turku Psychiatry, Finland, between October 2011 and June 2016. A total of 193 subjects had first-episode psychosis and were suitable for TEPS. Out of 193 subjects, 101 participated (PA) and 92 did not participate (NPA) in TEPS due to refusal or contact problems. We retrospectively used patient register data to study whether NPA and PA groups differed in terms of clinical outcomes during 1-year follow-up.Results: In overall sample, the NPA group had a significantly higher rate of discontinuation of clinical treatment than the PA group (48.9 % vs 29.7 %, p = 0.01). In the hospital-treated subsample chi-square tests did not indicate statistically significant differences between the NPA and PA groups in the rate of involuntary care (69.7 % vs 62.7 %, p = 0.34), coercive measures (36.0 % vs 22.7 %, p = 0.06), and readmissions during the follow-up (41.5 % vs 33.8 %, p = 0.31), respectively.Conclusion: The differences in clinical outcomes and treatment characteristics in the non-participating and participating groups were relatively modest. The results do not support a major sample selection bias that would complicate the interpretation of results in this first-episode psychosis study.</p

Amygdala subnucleus volumes in psychosis high-risk state and first-episode psychosis

Structural and functional abnormalities of the amygdala in schizophrenia have been well documented. Post-mortem studies suggest that the lateral nucleus is particularly affected in schizophrenia. It is not known whether the amygdala subnuclei are differently affected at the time of the first-episode psychosis or already at high-risk state.75 first-episode psychosis patients (FEP), 45 clinical high-risk patients (CHR) and 76 population controls participated in this cross-sectional case-control study. Participants underwent T1-weighted 3T MRI scans, from which the amygdala was segmented using a newly developed automated algorithm. Because early adverse events increase risk for psychosis and affect the amygdala, we also tested whether experiences of childhood maltreatment associate with the putative amygdala subnuclei abnormalities.Compared to the population controls, FEP had smaller volumes of the lateral, and basal nuclei. In CHR, only the lateral nucleus was significantly smaller compared to the control subjects. Experience of childhood maltreatment was inversely associated with lateral nucleus volumes in FEP but not in CHR.These results show that the lateral and basal nuclei of the amygdala are already affected in FEP. These volumetric changes may reflect specific cellular abnormalities that have been observed in post-mortem studies in schizophrenia in the same subnuclei. Decreased volume of the lateral nucleus in CHR suggest that a smaller lateral nucleus could serve as a potential biomarker for psychosis risk. Finally, we found that the lateral nucleus volumes in FEP may be sensitive to the effects of childhood maltreatment.</p

Short-term functional outcome in psychotic patients: results of the Turku early psychosis study (TEPS)

Background Functional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N). Methods Altogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA. Results During follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning. Conclusions In patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis.</p

Psykoosipotilaiden toimintakyvyn ennuste ja sitä ennustavat tekijät

TAUSTA. Tavoitteenamme oli tutkia luonnollisessa tutkimusasetelmassa psykoosin ja psykoosiriskin vuoksi ensi kertaa hoitoon tulleiden potilaiden toimintakyvyn ennustetta ja siihen vaikuttavia tekijöitä.AINEISTO JA MENETELMÄT. Tutkimusaineisto koostui 130 psykoosi- ja 107 psykoosiriskipotilaasta, joille tehtiin alkuhaastattelun jälkeen seurantahaastattelu yhdeksän ja 18 kuukauden kuluttua. Seurannan perusteella muodostettiin hyvän ja huonon ennusteen ryhmät, joita selitettiin logistisella regressioanalyysillä.TULOKSET JA PÄÄTELMÄT. Psykoosi- ja riskipotilaiden toimintakyvyn ennusteissa ei ollut eroa. Hyvä ennuste yhdistyi naissukupuoleen, lapsuuden sosiaalisuuteen, koulumenestykseen ja vähäisiin traumakokemuksiin sekä hyvään koulutustasoon ja työtilanteeseen. Oireista tunneköyhyys ja ajattelun hajanaisuus liittyvät huonoon ennusteeseen. Monimuuttuja-analyysissä naimattomuus, lapsuuden traumakokemukset ja heikko koulumenestys, huono työtilanne sekä tunneköyhyys ja ajattelun hajanaisuus ennustivat huonoa toimintakykyä. Koulutuksen ja työteon tukemiseen liittyvät kuntoutustoimenpiteet ovat keskeisiä pyrittäessä parantamaan psykoosipotilaiden ja psykoosiriskissä olevien potilaiden toimintakykyä.</p

Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (rho = 0.20) and disorganization (rho = 0.23), and with worse verbal performance (rho = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [C-11]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V-T) of [C-11]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells

Staging of Schizophrenia with the Use of PANSS: An International Multi-Center Study

Introduction: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method.Methods: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed.Results: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients.Discussion: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.<br /

Elevated serum chemokine CCL22 levels in first-episode psychosis : associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p <0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (rho = 0.20) and disorganization (rho = 0.23), and with worse verbal performance (rho = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [C-11]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V-T) of [C-11]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.Peer reviewe

Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study

Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 +/- 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P &lt; .001) and lower rates of negative symptoms (P &lt; .01) and higher depression/anxiety measures (P &lt; .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples