Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs). According to multivariate analysis, antipsychotic-naïve FEP patients had significantly higher levels of taurine and spermine, whereas values of proline (Pro), alpha-aminoadipic acid (alpha-AAA), kynurenine (Kyn), valine (Val), tyrosine (Tyr), citrulline (Citr), tryptophan (Trp), and histidine (His) were diminished compared to CSs. Increased levels of taurine and spermine, as well as reduced levels of alpha-AAA and Kyn probably reflect the compromised function of N-methyl-D-aspartate (NMDA) receptors in patients. The decreased levels of Pro (AA modulating the function of glutamate decarboxylase) likely reflect the imbalanced function of gamma-aminobutyric acid (GABA) system in the brain of FEP patients. The alterations in ratio between Tyr and phenylalanine (Phe) can be taken as a sign of compromised function of dopaminergic system. These metabolic shifts were reinstated by 7-month antipsychotic treatment. Serum metabolic profiles can be regarded as important indicators to investigate clinical course of SCH and treatment response.
Results of this study demonstrate that the structure of underlying cognitive abilities as measured by a selection of CANTAB tests is not the same for healthy individuals and FEP patients, with patients displaying widespread cognitive impairment.
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.
Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.
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.
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