Javier Vázquez-Bourgon

Catechol-O-methyltransferase Val158Met polymorphism and negative symptoms after acute antipsychotic treatment in first-episode non-affective psychosis.

Genetic factors play an important role in the understanding of clinical response to antipsychotic treatments. We aimed to assess the effect of the catechol-O-methyltransferase (COMT) genotype in the short-term (6 weeks) clinical response of 161 first-episode psychosis patients. COMT genotype was not related to clinical response at 6 weeks. Val homozygote patients showed higher negative symptoms than Met homozygote patients. The COMT Val158 genotype seems to be related to the severity of negative symptoms rather than to clinical response.

A Disrupted-in-Schizophrenia 1 Gene Variant is Associated with Clinical Symptomatology in Patients with First-Episode Psychosis.

Objective DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis. Methods Two hundred and thirteen Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Results Patients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers. Conclusion DISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorder.

Effect of DISC1 polymorphisms on the long-term course of neurocognitive deficits in non-affective psychosis

Neurocognitive deficits are core symptoms of schizophrenia that determine a poorer outcome. High variability in the progression of neuropsychological deficits in schizophrenia has been described. It is still unknown whether genetic variations can affect the course of cognitive deficits. Variations in the Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with neurocognitive deficits. This study investigated the association between 3 DISC1 polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped. Cognitive function was assessed at baseline and after 3 years of initiating treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects. Patients carrying the A allele of rs1000731 exhibited a significant improvement in Working Memory and Attention domains, and the homozygosity of the A allele of rs821616 showed a significant improvement in Motor Dexterity performance over 3 years of follow-up. In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.

Cross-Modal Recruitment of Auditory and Orofacial Areas During Sign Language in a Deaf Subject

BACKGROUND Modern sign languages used by deaf people are fully expressive, natural human languages that are perceived visually and produced manually. The literature contains little data concerning human brain organization in conditions of deficient sensory information such as deafness. CASE DESCRIPTION A deaf-mute patient underwent surgery of a left temporoinsular low-grade glioma. The patient underwent awake surgery with intraoperative electrical stimulation mapping, allowing direct study of the cortical and subcortical organization of sign language. We found a similar distribution of language sites to what has been reported in mapping studies of patients with oral language, including 1) speech perception areas inducing anomias and alexias close to the auditory cortex (at the posterior portion of the superior temporal gyrus and supramarginal gyrus); 2) speech production areas inducing speech arrest (anarthria) at the ventral premotor cortex, close to the lip motor area and away from the hand motor area; and 3) subcortical stimulation-induced semantic paraphasias at the inferior fronto-occipital fasciculus at the temporal isthmus. CONCLUSIONS The intraoperative setup for sign language mapping with intraoperative electrical stimulation in deaf-mute patients is similar to the setup described in patients with oral language. To elucidate the type of language errors, a sign language interpreter in close interaction with the neuropsychologist is necessary. Sign language is perceived visually and produced manually; however, this case revealed a cross-modal recruitment of auditory and orofacial motor areas.

Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone

Abstract Background Different effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine (n=62) and followed-up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy. Results The overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (χ2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2=9.617; P=.008) and increased sleep duration (χ2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines. Conclusions First-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

Age of onset of Cannabis use and cognitive function in first-episode non-affective psychosis patients: Outcome at three-year follow-up

BACKGROUND In recent years, the effects of cannabis use on cognitive functions in patients with psychosis have been widely studied. Recently, special emphasis has been placed on the impact of age at the onset of consumption on cognition in these patients. METHOD 349 patients with a first episode of non-affective psychosis were studied. Patients were classified as cannabis users and non-users. Users were divided, according to their age when they began using cannabis, into: early-onset (age < 16) and late-onset (age ≥ 16) users. Differences between groups at baseline were studied based on sociodemographic, clinical, and cognitive variables. The groups were longitudinally (3-year) compared on cognitive variables. RESULTS Out of the 349 patients included in this study, 38.7% (N = 135) were cannabis users. Of them, 39.3% (N = 53) were early-onset and 60.7% (N = 82) were late-onset cannabis users. No baseline differences were found between the early-onset and late-onset groups on cognitive domains. Longitudinally, only patients who had withdrawn from cannabis use during follow-up showed a significant improvement in verbal memory. CONCLUSION Our results did not show differences between the early-onset group and the other two groups in long-term cognitive performance, even if they kept consuming cannabis during the first three years of disease progression. Further studies are needed to elucidate the true relationship between early-onset cannabis use and cognitive function in patients with a first episode of psychosis.

T175. A 10-YEAR LONGITUDINAL STUDY OF GREY MATTER VOLUME IN FIRST EPISODE OF NON-AFFECTIVE PSYCHOSIS

Abstract Background Structural abnormalities in First Episode of Non- Affective Psychosis (FEP) are shown to be present at the time of onset of the illness. Although there are multiple cross-sectional studies in chronic patients there is no clear evidence how these alterations progress years after the appearance of the first episode. Methods Data for the present investigation were obtained from an ongoing epidemiological and longitudinal intervention programme of first-episode psychosis (PAFIP) conducted at the Marqués de Valdecilla University Hospital (HUMV), Spain. Images for 62 FEP patients and 47 healthy controls were acquired at baseline and 10 year follow-up on the same 1.5-T whole-body scanner (SIGNA, GE, Milwaukee, WS, USA). Three-dimensional T1-weighted images, using a spoiled gradient-recalled acquisition in the steady state (GRASS) (SPGR) sequence, were acquired in the coronal plane with the following parameters: TE=5 msec, TR =24 msec, NEX=2, rotation angle =45°, FOV= 26 x 19.5 cm, slice thickness =1.5 mm and a matrix of 256 x 192. Structural imaging data for each subject was analyzed using serial longitudinal Statistical Parametric Mapping software (SPM12). After segmenting the mid-point average and multiply the result by the jacobian maps, DARTEL was applied to spatially normalise de diferences. T-test between both groups was performed, allowing voxel-wise comparison of progressive structural change. All results were p<0.05 FWE corrected. Results FEP patients exhibited progressive bilateral atrophy of the anterior cingulate bilaterally, the right inferior orbital, middle and superior frontal giri, left precentral and postcentral giri and cerebellum. We found no areas were grey matter was greater in controls than in patients. Discussion In this study we analyze a well characterized sample of patients with a first episode of non-affective psychosis in the first weeks after onset and 10 years later. Our results confirm that, apart from the grey matter volume reduction presented at baseline, patients show a progressive grey matter loss in anterior cingulate, frontal and parietal lobes as well as cerebellum.

F101. CANNABIS USE AND HEPATIC STEATOSIS IN PSYCHOSIS: RESULTS FROM A 3-YEAR LONGITUDINAL STUDY

Abstract Background Metabolic alterations are common in patients suffering from psychosis. The rise in glycemic lipids may be related to and observed increased in the prevalence of hepatic steatosis measured by the Fatty Liver Index. However, we have recently reported a probable protective effect of cannabis smoking on weight gain and related metabolic alterations in a sample of patients drug-naïve suffering from a first episode of psychosis. We aimed to explore the effect of cannabis smoking on hepatic steatosis in a sample of first-episode non-affective psychosis patients. Methods Anthropometric measurements, glycemic and lipid parameters, and liver steatosis index (FLI), were obtained at baseline and after 3 years of having initiated treatment. Patients were divided into two groups depending on self-reported cannabis use (cannabis users and non-users). Results Cannabis users presented at baseline lower FLI (F=4.26, p=0.040) than non-users. These differences were also observed after 3 years of treatment (F=6.61, p=0.011). Discussion Our results support the hypothesis that cannabis has a protective effect against hepatic steatosis. However, before being transferred to clinical practice, this study should be replicated, using larger samples.