Late-onset-psychosis: cognition.

BACKGROUND: The objectives of the study were to characterize and compare the cognitive profile and natural evolution of patients presenting late-onset psychotic symptoms (LOPS: onset ≥ 50 years old) to those of elderly patients (≥ 50 years old) with life-long/early-onset schizophrenia (EOS: onset <40 years old). METHODS: Neuropsychological profiles of 15 LOPS patients were compared to those of 17 elderly EOS patients and to those of two control groups (n = 11/group). The evolution of the two patient groups was compared using an independent diagnostic consensual procedure involving a geriatric psychiatry physician/clinician and a neuropsychologist blinded to the initial psychiatric diagnosis. RESULTS: EOS presented significant memory and executive impairments when compared to controls but there was no significant difference between LOPS and their controls when age and education were taken into account. However, a detailed inspection of normative data suggests more executive impairments in LOPS than in EOS. The clinical judgment of experts was in favour of significant cognitive deficits with or without dementia in most LOPS (82.3%-94.1%) and EOS (80.0%-93.3%) patients. Regarding evolution, mild cognitive impairment (MCI) and vascular cognitive impairment (VCI) were the most common clinical diagnoses made by geriatric psychiatry physicians/clinicians for the LOPS (40%). In addition, 20% of LOPS versus 5.9% of EOS patients met the diagnostic criteria for dementia by consensus of the experts. Cerebral abnormalities were confirmed (CT scan; SPECT) in 73.3% of LOPS patients. CONCLUSION: The present results suggest cognitive deficits (mostly of executive functions) and vascular and neurodegenerative vulnerability in LOPS. Further studies with larger samples are needed to confirm the present findings.

Clinical characterization of late- and very late-onset first psychotic episode in psychiatric inpatients.

OBJECTIVES: The goals of this study were to investigate the prevalence and initial symptoms of the late-onset schizophrenia (LOS: >40 years) and very-late-onset schizophrenia-like psychosis (VLOSLP: >60 years) nosological groups proposed by the International Late-Onset Schizophrenia Group. DESIGN: This was a retrospective, cross-sectional, chart review study. SETTING: The study was conducted at Centre Hospitalier Robert-Giffard (CHRG), Quebec City, Canada. PATIENTS: The medical records of inpatients from the CHRG who presented with psychotic symptoms were analyzed. MEASUREMENTS: Positive and negative symptoms were scored using the SAPS and SANS. Groups' symptoms were compared using chi(2), Fisher's exact tests, t tests, and exact Mann-Whitney tests. An exact conditional logistic regression analysis was performed to determine which clinical characteristics were the most predictive of the groups' classification. RESULTS: Among the 1,767 unique, first-admission medical records reviewed, 23 (1.3%) inpatients developed their first psychotic symptoms at the age of 40-59 years old (LOS), and 13 (0.7%) at the age of 60 years and above (VLOSLP). LOS patients were more apathetic and presented more abnormal psychomotor activity than the VLOSLP. Persecutory delusions, auditory hallucinations, inappropriate social behavior, formal thought disorders and anhedonia were frequent in the two groups. A logistic regression model including psychomotor abnormalities was statistically relevant to predict the belonging to LOS group. CONCLUSION: LOS and VLOSLP are rare. Abnormal psychomotor activity can properly differentiate VLOSLP and LOS. The nosological model proposed by the International Late-Onset Schizophrenia Group is at least partially supported by the present data.

Human uridine diphosphate-glucuronosyltransferase UGT2B7 conjugates mineralocorticoid and glucocorticoid metabolites.

Mineralocorticoid and glucocorticoid hormones are metabolized as glucuronide conjugates. Using labeled [(14)C]uridine diphosphate glucuronic acid and microsomal preparations from human embryonic kidney 293 cells stably expressing the different human and monkey uridine diphosphate glucuronosyltransferase (UGT)2B enzymes, it is demonstrated that the two human allelic variants UGT2B7H((268)) and UGT2B7Y((268)) conjugate aldosterone, its A-ring reduced metabolites (5alpha-dihydroaldosterone and 3alpha,5beta-tetrahydroaldosterone), and both 5alpha- and 5beta-tetrahydrocortisone epimers. The two variants of UGT2B4 also glucuronidate tetrahydroaldosterone, whereas all enzymes tested were inefficient to produce cortisol glucuronide derivatives. Kinetic analyses reveal that UGT2B7 polymorphisms glucuronidate mineralocorticoids with a 5.5- to 20-fold higher affinity than glucocorticoids. For the first time, a significant difference between the two allelic variants of UGT2B7 is described, because UGT2B7H((268)) possesses an 11-fold higher aldosterone glucuronidation efficiency (ratio Vmax((app.))/Km((app.))) than UGT2B7Y((268)). RT-PCR experiments demonstrate the expression of UGT2B7 in human kidney and in renal proximal tubule epithelial cells, suggesting that mineralocorticoids and glucocorticoids are metabolized in their target tissue. Measurement of aldosterone glucuronidation and normalization with the UGT2B protein contents in monkey tissues demonstrate that liver and kidney glucuronidate this hormone with a similar velocity. Immunohistochemical studies performed in monkey kidney cortex reveal a restrictive expression of UGT2B proteins in the epithelial cells of the proximal tubules. Because expression of the mineralocorticoid receptor was detected in the distal tubule epithelial cells, the present data suggest a two-cell mechanism of aldosterone action and metabolism in the kidney.

Isolation and characterization of the monkey UGT2B30 gene that encodes a uridine diphosphate-glucuronosyltransferase enzyme active on mineralocorticoid, glucocorticoid, androgen and oestrogen hormones.

The present study reports the genomic organization and the characterization of a novel cynomolgus monkey UDP-glucuronosyltransferase (UGT) enzyme, UGT2B30. UGT enzymes are microsomal proteins that catalyse the transfer of the glucuronosyl group from UDP-glucuronic acid (UDPGA) to a wide variety of lipophilic compounds, namely hormonal steroids. The 15 kb UGT2B30 gene amplified by PCR showed a genomic organization similar to those encoding UGT2B human enzymes. The cDNA encoding UGT2B30 was isolated from a cynomolgus monkey prostate cDNA library, and the deduced amino acid sequence showed an identity of 94% with UGT2B19, a monkey isoform previously characterized. Stable expression of UGT2B30 protein in human kidney 293 (HK293) cells was assessed by Western-blot analysis and its conjugating activity was screened using 39 potential substrates. The UGT2B30 enzyme is active on many compounds of different classes, including testosterone, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol, androsterone, oestradiol, tetrahydroaldosterone and tetrahydrocortisone, with glucuronidation efficiencies (V(max)/K(m) ratios) ranging from 0.6 to 8.8 microl x min(-1) x mg of protein(-1). Reverse-transcriptase-PCR analysis revealed that the UGT2B30 transcript is expressed in several tissues, including prostate, testis, mammary gland, kidney, adrenals and intestine. The relative activity of UGT2B30 in comparison with other simian UGT2B isoforms, as well as its large variety of substrates, strongly suggest that this enzyme is essential to inactivation of several steroids.