Salivary cortisol response to psychosocial stress in patients with first-episode psychosis.

AIM: To analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group. METHODS: We performed a cross-sectional analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool. RESULTS: Patients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test. CONCLUSION: Patients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.

Integration of complementary biomarkers in patients with first episode psychosis: research protocol of a prospective follow up study.

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

Significantly lower right middle cerebral artery blood flow velocity in the first episode of psychosis during neurocognitive testing.

BACKGROUND: Changes in cerebral hemodynamics have been reported in schizophrenia and proposed as underlying the cognitive deficits seen in patients. The objective of our study was to compare changes of the cerebral blood flow velocity (BFV) during neurocognitive tasks between the patients with the first episode of psychosis and healthy controls. SUBJECTS AND METHODS: We recruited 46 patients with the first episode of psychosis (FEP), admitted to the University Hospital Centre Zagreb during 2016-2017 and 41 control subjects. Transcranial Doppler ultrasonography monitoring of BFV in both middle cerebral arteries was recorded during 25-minute long neurocognitive assessment with Phonemic Verbal Fluency test, Trial Making Test B and Stroop test. Between every consecutive test resting periods were recorded. RESULTS: After the adjustment for age, sex and education by quantile regression, patients with FEP had significantly lower BFV in middle cerebral arteries during the 3rd (Δ-15, Δ%-28% p=0.023) and 4th task (Δ-15, Δ%-28% p=0.031) of the Stroop test and the 1st task of Foot tapping test (Δ -16, Δ% -30% p=0.034). We observed significantly lower changes of right middle cerebral artery BFV in FEP between two consecutive tests in all four tasks of the Phonemic verbal fluency test, 1st and 2nd task of the Stroop test and Trail making test, and the1st task of Foot tapping test; and of the left artery between first three tasks of the Phonemic verbal fluency test, the last one of the Phonemic verbal fluency test and all first three tasks of the Stroop test. CONCLUSIONS: Decreased middle BFV during the execution of particular neurocognitive tasks in patients with FEP, compared to control subjects might indicate impaired hemodynamic function in the prefrontal/parietal brain areas, and possibly provide an explanation of some of the observed neurocognitive deficits in patients with the first episode of psychosis.

Changes of neurocognitive status in patients with the first-episode psychosis after 18 months of treatment-A prospective cohort study.

Neurocognitive symptoms exert the most influence on treatment outcomes over the course of schizophrenia, starting from the first-episode of psychosis (FEP) onwards. Our aim was to analyze the neurocognitive status of FEP compared to healthy controls (HC), and its change after 18 months of treatment. We performed a study in a sample of 159 patients with FEP and 100 HC. We followed the patients up for 18 months after initial assessment with a battery of neurocognitive tests. We observed statistically significant improvement in the majority of neurocognitive tests after 18 months, but several tests of specific neurocognitive domains (verbal memory, language functions, executive functions) did not show significant differences between the two assessments. The results for the majority of tests obtained from patients with FEP after 18 months of treatment showed significant deterioration compared with HC. Although our study showed significant improvement of baseline neurocognitive deficits in FEP with treatment, this varied across domains and overall performance remained below that of HC. Thus, while it seems that treatment of FEP may help to delay or restore neurocognitive deterioration, it is unclear whether specific areas of neurocognitive deterioration (e.g. verbal domain) would benefit from more time or specific treatment approaches.

Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis.

INTRODUCTION: We analyzed the association of cannabinoid receptor CNR1 genotypes with changes in neurocognitive performance in patients with first-episode psychosis (FEP) after 18 months of treatment. Our secondary aim was to analyze the association of CNR1 genotypes with changes of perceived levels of stress. METHODS: We enrolled a sample of 159 patients with FEP from two Croatian psychiatric hospitals between 2014 and 2017. Patients were assessed at baseline and after 18 months. We analyzed the associations of changes in neurocognitive test results and the perceived levels of stress with CNR1 polymorphic loci (rs7766029 and rs12720071) in 121 patients. RESULTS: In the analysis adjusted only for baseline neurocognitive test scores, carriers of rs7766029 CC genotype had significantly (with false discovery rate, FDR < 15%) higher improvement in verbal memory (Wechsler, Wechsler 30') and attention (Digit span F) compared with other participants. In such analysis, rs12720071 carriers of AG genotype had significantly (FDR < 15%) higher improvement in executive functions (Block design), but lower improvement in language functions than AA carriers. In the fully adjusted analysis for age, sex, cannabis use and negative symptoms, only the association of rs7766029 genotypes with the change in the Weschler 30' score was significant (FDR < 15%). In the analysis adjusted only for the baseline neurocognitive tests' scores, both rs7766029 and rs12720071 genotypes were significantly associated with the change in perceived levels of stress (FDR < 15%). In the fully adjusted analysis, only the association with rs7766029 genotype remained significant. CONCLUSIONS: The rs7766029 CNR1 variants may moderate changes in neurocognitive performance as well as in perceived levels of stress of patients with FEP over time.