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.

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.

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.