Laura Béchard-Evans

Predictors of rate and time to remission in first-episode psychosis : a two-year outcome study

BACKGROUND The evidence regarding the independent influence of duration of untreated psychosis (DUP) on rate and time to remission is far from unequivocal. The goal of the current study was to examine the role of predictors for rate and time to remission in first-episode psychosis (FEP). METHOD The differential effect of age, gender, age of onset, duration of untreated psychosis (DUP), duration of untreated illness (DUI), pre-morbid adjustment, co-morbid diagnosis of substance abuse and adherence to medication on the rate of and time to remission were estimated using a logistic and Poisson regression, and survival analysis respectively, in FEP patients. RESULTS In a sample of 107 FEP patients 82.2% achieved remission over a period of 2 years after a mean of 10.3 weeks (range 1-72). Regression analysis, based on complete data on all variables of interest (n=80), showed status of remission to be positively influenced by better pre-morbid adjustment (RR 0.57, 95% CI 0.34-0.95, p<0.05), later age of onset (RR 1.09, 95% CI 1.05-1.13, p<0.0001), higher level of adherence to medication (RR 1.96, 95% CI 1.38-2.76, p<0.001) and shorter DUI (RR 0.99, 95% CI 0.997-0.999, p<0.005). Time to remission was influenced by age of onset (HR 1.04, 95% CI 1.00-1.08, p<0.04) and adherence to medication (HR 1.58, 95% CI 1.11-2.23, p<0.01). CONCLUSIONS Improving adherence to medication early in the course of treatment may be an important intervention to improve short-term outcome.

Determinants of help-seeking and system related components of delay in the treatment of first-episode psychosis

INTRODUCTION Knowledge about factors that influence different components of duration of untreated psychosis (DUP) is important for designing interventions to reduce DUP. METHOD We tested associations between help-seeking and referral components of DUP (DUP-H and DUP-R, respectively) and the following predictor variables: age, gender, ethnicity, living arrangement, pre-morbid adjustment, age at onset of psychosis, diagnosis, level of symptoms, type of first and total number of mental health contacts prior to and after the onset of psychosis in a sample of 98 first-episode psychosis patients (FEP). RESULTS Longer DUP-HS was significantly associated with earlier age at onset, diagnosis of schizophrenia spectrum psychosis and poor pre-morbid adjustment during adolescence. Longer DUP-R was associated with earlier age at onset and first help-seeking contact having been made with a non-medical professional. CONCLUSIONS Relatively non-malleable patient characteristics are likely to influence delay in help-seeking while more malleable systemic characteristics influence delay associated with referral for specialized treatment.

Early Predictors of Nonadherence to Antipsychotic Therapy in First-Episode Psychosis

Objective: To examine the hypothesis that poorer social and family support, identifiable at the onset of treatment, is associated with nonadherence in the first 6 months of treatment of patients with first-episode psychosis (FEP), independent of other patient-related factors. Method: Consecutive patients (n = 100) admitted to a specialized early intervention service for FEP who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for either a schizophrenia spectrum disorder or an affective psychosis were evaluated monthly for 6 months regarding their adherence to medications. Using sociodemographic and illness-related factors, including social and family support, as independent variables and adherence as the dependent variable, univariate analyses were followed by logistic regression. Results: Fifty-six patients (54.9%) were adherent (76% to 100% of doses taken) and 46 (45.1%) nonadherent (less than 76% of doses taken). Nonadherent patients were less likely to have received a good level of social support (χ2 = 5.89, df = 1, P = 0.02), as rated by their respective case manager, and more likely to be single (Fisher exact test, P = 0.019) and to have refused medication at the first offer of treatment (χ2 = 19.70, df = 1, P = 0.001). Using logistic regression, both the level of social support (OR = 3.552, P = 0.03) and early medication acceptance (OR = 11.092, P < 0.001) were significant as predictors of adherence. Conclusion: These results suggest the significance of social and family support in achieving adherence to medications very early in the course of treatment of FEP, in addition to the influence of early acceptance or rejection of medication.

Factors influencing relapse during a 2-year follow-up of first-episode psychosis in a specialized early intervention service.

BACKGROUND Differential association of risk factors associated with relapse following treatment of first-episode psychosis (FEP) have not been studied adequately, especially for patients treated in specialized early intervention (SEI) services, where some of the usual risk factors may be ameliorated. METHOD Consecutive FEP patients treated in an SEI service over a 4-year period were evaluated for relapse during a 2-year follow-up. Relapse was based on ratings on the Scale for Assessment of Positive Symptoms (SAPS) and weekly ratings based on the Life Chart Schedule (LCS). Predictor variables included gender, duration of untreated psychosis (DUP), total duration of untreated illness (DUI), age of onset, pre-morbid adjustment, co-morbid diagnosis of substance abuse during follow-up and adherence to medication. Univariate analyses were followed by logistic regression for rate of relapse and survival analysis with the Cox proportional-hazards regression model for time to relapse as the dependent variables. RESULTS Of the 189 eligible patients, 145 achieved remission of positive symptoms. A high rate of medication adherence (85%) and relatively low relapse rates (29.7%) were observed over the 2-year follow-up. A higher relapse rate was associated with a co-morbid diagnosis of substance abuse assessed during the follow-up period [odds ratio (OR) 2.84, 95% confidence interval (CI) 1.24-6.51]. The length of time to relapse was not associated with any single predictor. CONCLUSIONS Specialized treatment of substance abuse may be necessary to further reduce risk of relapse even after improving adherence to medication.

Sex differences in the cortisol response to awakening in recent onset psychosis

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.

Investigating cognitive deficits and symptomatology across pre-morbid adjustment patterns in first-episode psychosis

BACKGROUND Cognitive deficits in schizophrenia are well established and are known to be present during the first episode of a psychotic disorder. In addition, consistent heterogeneity within these impairments remains unexplained. One potential source of variability may be the level of pre-morbid adjustment prior to the onset of first-episode psychosis (FEP). METHOD Ninety-four FEP patients and 32 healthy controls were assessed at baseline on several neuropsychological tests comprising six cognitive domains (verbal memory, visual memory, working memory, processing speed, reasoning/problem-solving and attention) and an abbreviated version of the full IQ. A global neurocognitive domain was also computed. Pre-morbid adjustment patterns were divided into three distinct groups: stable-poor, stable-good and deteriorating course. RESULTS Based on a cut-off of 0.8 for effect size, the stable-poor pre-morbid adjustment group was significantly more impaired on most cognitive domains and full IQ compared to the deteriorating group, who were more severely impaired on all measures compared to the stable-good group. The type of cognitive deficit within each subgroup did not differ and the results indicate that a global neurocognition measure may reliably reflect the severity of cognitive impairment within each subgroup. CONCLUSIONS Pre-morbid adjustment patterns prior to onset of psychosis are associated with severity but not type of cognitive impairment. Patients in the stable-poor group are generally more impaired compared to the deteriorating group, who are, in turn, more impaired than the stable-good group.

Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis

BACKGROUND Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results. METHOD Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol. RESULTS Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size). CONCLUSIONS Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.