BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.
- MeSH
- kognitivní poruchy etnologie MeSH
- lidé MeSH
- mozek patologie MeSH
- poruchy spojené s užíváním psychoaktivních látek MeSH
- prognóza * MeSH
- prospektivní studie MeSH
- recidiva MeSH
- rizikové faktory MeSH
- schizofrenie * dějiny diagnóza epidemiologie etiologie farmakoterapie klasifikace patologie rehabilitace terapie MeSH
- společenské stigma MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Uvedený príspevok k problematike stereochémie liečiv je pokusom o zvýraznenie dôležitosti stereo-chemického ponímania farmakológie a o zviditeľnenie pokrokov „chirálnej farmakológie“ v rámcisúčasných poznatkov o selektívnych účinkoch liečiv. Neexistujú jednoduché riešenia v problematike„racemáty–versus–enantioméry“ a každá látka musí byť chápaná a testovaná individuálne, t.j. naprincípe case–by–case. Pre mnoho súčasne dostupných racemátov je pomerne málo poznatkovo farmakologických, toxikologických a farmakokinetických vlastnostiach ich individuálnych enan-tiomérov, alebo o vplyve veku, zdravotného stavu, pohlavia a genetických faktorov na biologickúdostupnosť a odpoveď organizmu na liečivo. Dodatočné testovanie enantiomérov v praxi používa-ných racemátov môže viesť k objavom nových indikácií pôvodného liečiva, zlepšiť jeho klinicképoužitie a vyústiť k zvýšeniu jeho bezpečnosti a účinnosti. Ak je to tak, v tom prípade sú „chirálneúvahy“ vo farmakológii dvojnásobne hodné problémov, ktoré so sebou prinášajú.
The present contribution to the problems of the stereochemistry of drugs is an attempt at stressingthe importance of a stereochemical view of pharmacology and at informing about the advances of„chiral pharmacology“ within the framework of the contemporary knowledge of selective effects ofdrugs. There are no simple solutions in the „racemates versus enantiomers“ problems and eachsubstance must be considered and tested individually, i.e. on the case–by–case principle. For manyracemates available at present there exist relatively few items of knowledge concerning thepharmacological, toxicological and pharmacokinetic properties of their individual enantiomers, orconcerning the influence of age, health condition, sex and genetic factors on biological availabilityand response of the organism to the drug. Additional testing of the enantiomers of the racematesused in practice can lead to the discovery of new indications of the original drug, improve its clinicaluse and result in increasing its safety and efficacy. If it is so, in this case the „chiral meditations“in pharmacology are double worth the problems they pose.
