The Expanded Endocannabinoid System Contributes to Metabolic and Body Mass Shifts in First-Episode Schizophrenia: A 5-Year Follow-Up Study.

Alterations in the expanded endocannabinoid system (eECS) and cell membrane composition have been implicated in the pathophysiology of schizophrenia spectrum disorders. We enrolled 54 antipsychotic (AP)-naïve first-episode psychosis (FEP) patients and 58 controls and applied a targeted metabolomics approach followed by multivariate data analysis to investigate the profile changes in the serum levels of endocannabinoids: 2-arachidonoylglycerol (2-AG) and anandamide, endocannabinoids-like N-acylethanolamines (NAEs: linoleoylethanolamide, oleoylethanolamide, and palmitoylethanolamide), and their dominating lipid precursor's phosphatidylcholines. Biomolecule profiles were measured at the onset of first-episode psychosis (FEP) and 0.6 years and 5.1 years after the initiation of AP treatment. The results indicated that FEP might be characterized by elevated concentrations of NAEs and by decreased 2-AG levels. At this stage of the disease, the NAE-mediated upregulation of peroxisome proliferator-activated receptors (PPARs) manifested themselves in energy expenditure. A 5-year disease progression and AP treatment adverse effects led to a robust increase in 2-AG levels, which contributed to strengthened cannabinoid (CB1) receptor-mediated effects, which manifested in obesity. Dynamic 2-AG, NAEs, and their precursors in terms of phosphatidylcholines are relevant to the description of the metabolic shifts resulting from the altered eECS function during and after FEP.

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease.

The primary objective of this study was to evaluate how schizophrenia (SCH) spectrum disorders and applied antipsychotic (AP) treatment affect serum level of amino acids (AAs) and biogenic amines (BAs) in the early course of the disorder. We measured 21 different AAs and 10 BAs in a sample of antipsychotic (AP)-naïve first-episode psychosis (FEP) patients (n = 52) at baseline, after 0.6-year as well as after 5.1-year treatment compared to control subjects (CSs, n = 37). Serum levels of metabolites were determined with AbsoluteIDQ p180 kit using flow injection analysis tandem mass spectrometry and liquid chromatography technique. Elevated level of taurine and reduced level of proline and alpha-aminoadipic acid (alpha-AAA) were established as metabolites with significant change in AP-naïve FEP patients compared to CSs. The following 0.6-year treatment restored these alterations. However, further continuous 5.1-year AP treatment changed the metabolic profile substantially. Significantly elevated levels of asparagine, glutamine, methionine, ornithine and taurine, alongside with decreased levels of aspartate, glutamate and alpha-AAA were observed in the patient group compared to CSs. These biomolecule profile alterations provide further insights into the pathophysiology of SCH spectrum disorders and broaden our understanding of the impact of AP treatment in the early stages of the disease.

The course of cognitive functioning after first-episode of psychosis: A six month follow-up study.

Our aim with the present study was to evaluate rank-order and mean-level cognitive functioning stability among first-episode psychosis (FEP) patients, measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB), over a six month period. We also aimed to examine longitudinal measurement invariance and identify factors-such as age, gender, educational level, treatment and psychopathological change scores-potentially linked to cognitive change among patients. In addition, correlations between objectively measured and subjectively evaluated cognitive functioning were estimated. Neuropsychological assessments were administered to 85 patients after the initial stabilisation of their psychosis; 82 of the patients were retested. Subjectively perceived cognitive functioning was measured using a subscale derived from the Estonian version of the Subjective Well-Being Under Neuroleptic Scale (SWN-K-E). On average, executive functioning and processing speed improved significantly, while memory test scores decreased significantly, over time. Very high rank-order stability (r=0.80 to 0.94, p<0.001) was observed with all measured ability scores. Confirmatory factor analysis revealed the loadings of a single (broad ability) factor model were equal across both measurement occasions, but the lack of intercept invariance suggested that mean-level comparisons are more appropriately carried out at a subtest level. On average psychopathology scores and antipsychotics doses declined over time, with the latter also significantly correlating with better executive functioning. Gender was a significant moderator of some domains of cognitive performance, and decline tended to be somewhat more pronounced for women. The results also indicated the lack of any relationship between objective and subjective measurements of cognitive functioning.