Psychosis In First-episode Patients Research Articles

Urban distance to mental healthcare units and public transport increases duration of untreated psychosis in first-episode patients.

There is a growing interest in environmental and social determinants of mental health. However, how distance to healthcare and public transportation affect illness is neglected in schizophrenia research. Here, we are interested in how the availability of mental healthcare and the ways to reach it may be associated with psychosis. We aim to investigate the association between distances to healthcare units and subway stations and duration of untreated psychosis (DUP) and greater initial severity in an antipsychotic-naïve first episode of psychosis (FEP) sample. Using 212 untreated FEP patients' data, we calculated the distances from their residences to the places of interest. Diagnoses comprehended schizophrenia spectrum disorders, depressive and bipolar affective disorders, and substance-induced disorders. Linear regressions were performed with distances as independent variables, DUP and Positive and Negative Syndrome Scale (PANSS) scores as dependent variables. Longer distance to emergency mental healthcare was related to longer DUP (95% CI: p = .034, B = 0.152) and higher total PANSS (95% CI: p = .007, B = 0.0189); longer distance to community mental healthcare units was related to longer DUP (95% CI: p = .004, B = 0.0204) and higher total PANSS (95% CI: p = .030, B = 0.152). Moreover, a longer distance to the closest subway station predicted longer DUP (95% CI: p = .019, B = 0.170). Our results indicate that poor healthcare access is related to longer DUP and higher initial PANSS scores. Future research should investigate how investments in mental health access and actions to improve public transport access could impact DUP and treatment outcomes in psychosis patients.

Routine cerebrospinal fluid parameters as biomarkers in first-episode psychosis: A prospective observational study

In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = −0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = −0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95%: 0.77–0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease.

SA51. Duration of Untreated Psychosis in First-Episode Patients

SA51. Duration of Untreated Psychosis in First-Episode Patients

The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine

Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine.

Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.

Violence and duration of untreated psychosis in first-episode patients

Violent behaviour can be a presenting sign of first-episode psychosis. Duration of untreated psychosis (DUP) has been a focus of attention because it is a potentially modifiable factor that may influence outcome. The aim was to review the literature addressing the following issues: prevalence of violence or aggression in the first episode of psychosis, violence or aggression during the periods before and after the initiation of treatment, the DUP and relation between DUP and the level of violence or aggression in first-episode psychosis. MEDLINE and PubMed databases were searched for articles using the combination of key words 'aggression' (limited to humans) and 'first episode' and 'psychosis'. Available evidence suggests that the prevalence of violent behaviour in the first episode of psychosis, particularly schizophrenia, is greater than during the later stages of the illness. First-episode psychosis is associated with an increased risk of homicide. There is some limited support for an effect of DUP length on serious violence or aggression. Violent behaviour frequently develops before the onset of first episode. Substance use disorders are additional factors that elevate the risk for violence in these patients. Earlier treatment of first episode psychosis might prevent some homicides. Personality factors and substance abuse may be more important than psychotic symptoms in the development of aggressive behaviour in patients with first-episode psychosis.

EPA-0325 – Serum s100b protein levels in first-episode psychosis

S100B is a calcium-binding protein produced by the astrocytes that has been used as a biomarker of brain inflammation. S100B has been involved in the schizophrenia pathophysiology, being considered a marker of state and prognosis. Studying the relationship between serum S100B levels and psychopathology in first-episode psychosis (FEP). At admission and discharge, serum S100B levels were measured in 20 never-medicated FEP in-patients and 20 healthy controls. Psychopathology was assessed with the PANSS (Positive and Negative Syndrome Scale). The total, positive, negative and general psychopathology scores were assessed. Results are presented as mean±sd. and S100B levels in pg./ml. At admission, patients had significantly higher serum S100B concentrations than healthy subjects (39.2±6.4 vs. 33.3±0.98, p<0.02). S100B levels increased from admission to discharge (39.2±6.4 vs. 40.0±6.8, p=0.285) but they do not reach statistical significance. There were no correlations between PANSS (total, positive, negative and general) scores and S100B at admission and discharge. Individual item by item PANSS correlations with S100B elicited a positive correlation with P5 (grandiosity) (r=0.486, p=0.030) and G5 (mannerisms/posturing) (r=0.514; p=0.02) at discharge. There also was a positive trend with G7 (motor retardation) (r=0.409; p=0.073) at discharge. FEP in-patients have significantly increased serum levels of S100B proteins, suggesting an activation of glial cells that may be associated with a neurodegenerative/inflammatory process. Apart from the study of total scale scores, the analysis of individual item is also recommended. The long-term treatment effect (one year or more) may be relevant to see their relationship to S100B levels.

Insight and suicidality in first‐episode psychosis: understanding the influence of suicidal history on insight dimensions at first presentation

Lack of insight is a cardinal feature of psychosis with crucial implications for outcome. Concerns have been raised regarding a link between insight and suicidality. This study aimed to test the relationship between suicidal behaviour preceding first-episode psychosis (FEP) and insight dimensions at treatment onset. A total of 112 FEP inpatients were recruited. Suicidal events prior to admission were recorded. Insight was assessed multidimensionally with the Schedule for the Assessment of Insight - Expanded version shortly after admission. Suicidal and non-suicidal patients were compared regarding scores on 'total insight' and three insight domains: 'awareness of mental illness', 'relabeling of psychotic experiences as abnormal' and 'compliance'. This analysis was also adjusted for a set of sociodemographic, clinical, neurocognitive and psychopathological variables. Bivariate analyses demonstrated a direct association between previous suicidality and all insight domains. However, these associations did not survive multivariable regression models, which demonstrated gender (female), shorter duration of untreated psychosis (DUP) and psychopathological symptoms - depression and disorganization - to mediate the influence of suicidal history on insight, and therefore to underlie the latter. Insight dimensions in FEP patients are influenced by having suicidal antecedents through some mediating variables such as gender, DUP and depression. Further prospective studies are needed to clarify the potential implications of these findings on the management of insight in FEP. As suicidal history is associated with greater levels of both depression and insight at first presentation, these three variables might be useful in predicting further suicidal events.

Brief Psychiatric Rating Scale — Excited Component (BPRS-EC) and neuropsychological dysfunction predict aggression, suicidality, and involuntary treatment in first-episode psychosis

ObjectiveAggression, suicidality and involuntary treatment constitute severe clinical problems in first-episode psychosis (FEP). Although there are studies on prevalence and clinical predictors of these conditions, little is known on the influence of psychopathology and neuropsychological dysfunction. Method152 FEP inpatients were prospectively assessed using the Brief Psychiatric Rating Scale (BPRS) and a neuropsychological examination covering the domains ‘processing speed’, ‘concentration and attention’, ‘executive function’, ‘working memory’, ‘verbal memory’, ‘verbal comprehension’, ‘logical reasoning’, ‘global cognition’, and ‘general intelligence’. Clinical data were collected retrospectively in a structured file audit trial. ResultsPatients were aged 24.5±4.9years, and 112 (74%) were male. At admission, 13 (9%) patients presented with severe aggression, and 28 (18%) with severe suicidality. 31 patients (20%) received involuntary treatment. In multivariate analyses, aggression was predicted by BPRS-Excited Component (BPRS-EC; p=.001), suicidality was predicted by BPRS-EC (p=.013) and general intelligence (p=.016), and predictors for involuntary treatment were BPRS-EC (p=.001) and neuropsychological dysfunction in the domain ‘concentration and attention’ (p=.016). ConclusionPsychopathology and neuropsychological functioning independently predict dangerous behavior in FEP patients. Some correlations with neuropsychology (e.g., of aggression with concentration/attention) are absent in multivariate analyses and may thus constitute a proxy of psychopathological features. In addition to clinical data, BPRS-EC can be used as a predictor of dangerous behavior. Patients with severe aggression and suicidality show different patterns of neuropsychological dysfunction, indicating that suicidality should not be conceptualized as subtype of aggressive behavior.

Association of Serum Brain-Derived Neurotrophic Factor and Duration of Untreated Psychosis in First-Episode Patients with Schizophrenia

Background/Aims: The brain-derived neurotrophic factor (BDNF) levels in serum and the central nervous system are altered in patients with schizophrenia, suggesting that changes in the expression of BDNF might contribute to the disease pathophysiology. Long duration of untreated psychosis (DUP) has been associated with poorer prognosis in patients with schizophrenia. Such a relationship of untreated psychosis to outcome may indicate a neurodegenerative process and may have important implications for understanding the pathophysiology of schizophrenia. Methods: In this study, we investigated the association between serum BDNF levels and DUP in a sample of drug-naïve patients in their first episode of schizophrenia (FEP). We investigated serum BDNF levels in a sample of 37 drug-naïve FEP patients and 21 matched healthy subjects. Results: The serum BDNF level in the sample of FEP was significantly reduced compared to the healthy subjects (18.87 ± 8.23 vs. 29.2 ± 7.73 ng/ml, t = 4.76, d.f. = 57, p = 0.01). A negative correlation was found between serum BDNF levels and DUP in the group of patients (r = –0.346, p = 0.036). Conclusions: Our findings indicate that low serum BDNF levels at the onset of schizophrenia were associated with a long DUP and this could reflect an acute neurodegenerative reaction during the untreated phase of psychosis.

Impaired MMN/P3a complex in first-episode psychosis: Cognitive and psychosocial associations

Mismatch negativity (MMN) is a neurophysiological indicator of the brain's ability to extract relevant information from an irrelevant background. The P3a orienting response often accompanies MMN in deviance detection paradigms. Both MMN and P3a have been described as reliable biomarkers of schizophrenia. MMN/P3a impairments are associated with deficits in verbal memory and attentional switching, reflecting dysfunctions in the temporal and frontal systems, respectively. It remains unresolved whether MMN/P3a are robust biomarkers of psychosis in first-episode patients. Thirty-four young people (18 to 30 years) were assessed in this study; 17 first-episode psychosis (FEP) patients were compared to 17 healthy controls. To elicit MMN/P3a, a two-tone passive auditory oddball paradigm with 8% duration deviants was used; event-related potentials were recorded at frontal, central and temporal (mastoid) sites. Neuropsychological assessments included processing speed, attentional switching, simple attention, and verbal learning and memory. Social functioning and quality of life measures were also obtained. The FEP group showed significantly reduced MMN amplitudes compared to controls. The FEP group also showed significantly reduced P3a amplitudes at frontal and central sites compared with controls. As expected, the FEP group also showed significant deficits in attention and verbal learning/memory. Correlational analyses found strong associations between fronto-central MMN/P3a peak amplitude and cognitive/psychosocial functioning. This study provides evidence of early neurobiological markers in young people with FEP. These findings suggest that MMN/P3a impairments are present at early stages of psychosis and that fundamental pre-attentive/deviance detection deficits may mark the beginning of progressive underlying changes with illness onset. Such deficits in FEP appear to have important links with higher-order cognitive and psychosocial functioning.

Association of Pre-Onset Cannabis, Alcohol, and Tobacco Use With Age at Onset of Prodrome and Age at Onset of Psychosis in First-Episode Patients

Several reports suggest that cannabis use is associated with an earlier age at onset of psychosis, although not all studies have operationalized cannabis use as occurring prior to onset of symptoms. This study addressed whether pre-onset cannabis use, alcohol use, and tobacco use are associated with an earlier age at onset of prodromal and psychotic symptoms. Effects of the progression of frequency of use were examined through time-dependent covariates in survival analyses. First-episode patients (N=109) hospitalized in three public-sector inpatient psychiatric units underwent in-depth cross-sectional retrospective assessments. Prior substance use and ages at onset of prodromal and psychotic symptoms were determined by standardized methods, and analyses were conducted using Cox regression modeling. Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis-use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males. Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.

Intensive-Treatment Gains Lost by Five-Year Follow-Up

Intensive-Treatment Gains Lost by Five-Year Follow-Up

Worsening of Symptoms Prevented by Early Detection

Worsening of Symptoms Prevented by Early Detection

Schizophrenia Scientist Comes Full Circle

Schizophrenia Scientist Comes Full Circle