Prediction of patient contacts by cognition in schizophrenia

Objective: To investigate the correlations between cognitive function and clinical outcome variables. Method: Patients diagnosed for the first time with schizophrenia between January 2004 and June 2010 were cognitively tested in conjunction with diagnostic procedures. Cognitive test data were connected to Danish healthcare registers and patients were followed in the registers from their first contact with psychiatric in- and outpatient care until October 2011. Results: Patients had impaired attention, processing speed and executive function as measured by Trail Making Test part B; their executive functions, as measured by the Wisconsin Card Sorting Test (WCST), and working memory, as measured by Rigshospitalet’s digit span test, were unaffected as compared to norms. The admission rate, from schizophrenia diagnosis to the end of the study, was predicted by Trail Making Test part A, Rey’s Auditory Verbal Learning Test (RAVLT), RAVLT (total learning), RAVLT (memory), d2 Test of Attention (total) and d2 type 2 error (error of commission), independent of gender, age and schizophrenia subtype. The length of hospitalization after the schizophrenia diagnosis was mainly determined by the schizophrenia subtype (schizophrenia simplex: incidence rate ratio (IRR) 0.24; 95% confidence interval (CI) 0.15–0.40, p &lt; 0.001). Diagnosis was secondarily determined by deficits in attention and executive function, Trail Making Test part B, d2 Test of Attention (total), d2 type 1 error (error of omission), d2 type 2 error, and also by age and substance use disorder. The outpatient contact rate from schizophrenia diagnosis to the end of the study was predicted by d2 Test of Attention, Trail Making Test part A, and d2 type 2 error. The annual rate of criminal conviction, institutionalization and social retirement pension was mainly predicted by substance misuse. Conclusion: Cognitive function only predicted hospitalization and outpatient contacts to a minor degree in a cohort of newly diagnosed patients with schizophrenia. </jats:sec

Pharmacological Characterization of [³H]ATPCA as a Substrate for Studying the Functional Role of the Betaine/GABA Transporter 1 and the Creatine Transporter

The betaine/γ-aminobutyric acid (GABA) transporter 1 (BGT1) is one of the four GABA transporters (GATs) involved in the termination of GABAergic neurotransmission. Although suggested to be implicated in seizure management, the exact functional importance of BGT1 in the brain is still elusive. This is partly owing to the lack of potent and selective pharmacological tool compounds that can be used to probe its function. We previously reported the identification of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA), a selective substrate for BGT1 over GAT1/GAT3, but also an agonist for GABA_A receptors. With the aim of providing new functional insight into BGT1, we here present the synthesis and pharmacological characterization of the tritiated analogue, [³H]­ATPCA. Using traditional uptake assays at recombinant transporters expressed in cell lines, [³H]­ATPCA displayed a striking selectivity for BGT1 among the four GATs (<i>K</i>_m and <i>V</i>_max values of 21 μM and 3.6 nmol ATPCA/(min × mg protein), respectively), but was also found to be a substrate for the creatine transporter (CreaT). In experiments with mouse cortical cell cultures, we observed a Na⁺-dependent [³H]­ATPCA uptake in neurons, but not in astrocytes. The neuronal uptake could be inhibited by GABA, ATPCA, and a noncompetitive BGT1-selective inhibitor, indicating functional BGT1 in neurons. In conclusion, we report [³H]­ATPCA as a novel radioactive substrate for both BGT1 and CreaT. The dual activity of the radioligand makes it most suitable for use in recombinant studies