Esther Setién-Suero

Homocysteine and cognition: A systematic review of 111 studies.

BACKGROUND Elevated plasma homocysteine ​​(Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected. METHODS We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed. RESULTS We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline. DISCUSSION Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.

Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study.

This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as “The Reading the Mind in the Eyes” (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM.

Low-density lipoprotein cholesterol and suicidal behaviour in a large sample of first-episode psychosis patients

Abstract Objectives: Our aims were to confirm the relationship between lipid and lipoprotein concentrations and suicidal behaviour in first-episode psychosis (FEP) patients. Methods: Suicidal behaviour was explored in a large FEP sample (N = 383). Baseline lipid profile was compared between those who attempted or completed suicide and those who not presented suicidal behaviour. Results: Low-density lipoprotein cholesterol (LDL-c) (OR = 0.99, 95% CI= 0.98–1.00) and depressive symptoms (OR = 1.15, 95% CI = 1.06–1.24) were significantly related with suicidal behaviour. Conclusions: Lipid profile test may be considered in the assessment of suicide risk in psychosis and LDL-c an important biological marker.

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.

S173. GREY MATTER VOLUME DEFFICITS IN PATIENTS WITH A FIRST EPISODE NON-AFFECTIVE PSYCHOSIS AND SUICIDE RELATED BEHAVIOUR

Abstract Background Suicide represents the main cause of premature dead in first episode psychosis (FEP) patients. However, our understanding of suicidal behaviour in this population is limited. During the last decade, several works have related suicidal behaviour in FEP patients with structural abnormalities in frontal and temporal areas as well as specific structures such as hippocampus, insula and amygdala. The main aim of this work was to analyse the possible structural brain abnormalities associated with suicide-related-behaviour in a large sample of FEP patients. Methods We use a voxel-based morphometry (VBM) analysis in 146 FEP individuals: 24 FEP with and 122 without suicidal behaviour. All images were taken in the same 3T Phillips scanner. The CAT 12 toolbox, which is implemented in SPM12 was used for VBM analysis of the data. A two-sample t-test was set with sex, age, handedness, total intracraneal volume and global disability score as nuisance covariables. We applied threshold-free cluster enhancement (TFCE) with 5000 permutations and corrected for multiple comparisons (FWE) at p<0.05. Results A gradual reduction of grey matter volume related to presence of suicide-related-behaviour was found in frontal area, specifically in superior frontal gyrus, middle frontal gyrus, precentral gyrus, inferior frontal gyrus and orbital gyrus. In addition, significant reduction was found in middle temporal gyrus as well as in posterior cingulate gyrus and precuneus. Discussion Our results are in line with previous works which related suicidal behaviours with reduced frontal regions. Frontal areas are involved in: i) cognitive analysis; ii) foresight and weighing consequences of behaviour; iii) considering future and making predictions; iv) impulse control; v) delaying gratification; vi) inhibiting inappropriate behaviour; vii) initiating appropriate behaviour. Reestructuraria esta frase asi: On the other hand, precuneus is involved in: i) episode memories; ii) reflective self-awareness; iii) executive function; and iv) it is activated during judgements. Finally, cingulate gyrus has been strongly associated with emotional responses to pain, regulation of aggressive behaviour and decision making. Finally, middle temporal gyrus appears to play an important role in retrieving semantic information. This study provides some insights about brain abnormalities associated with suicide-related-behaviours in FEP patients. In particular, the areas reported in this study are related with important functions such as impulsivity, emotional processing information, responses to pain and aggressiveness which are strongly associated with suicide-related-behaviours. Further studies are necessary to replicate the relevance of these structures in suicidal behaviour in FEP patients.

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.

F124. SEX DIFFERENCES IN OUTCOME IN FIRST EPISODE PSYCHOSIS PATIENTS: A 10-YEAR FOLLOW-UP STUDY

Abstract Background Specialized early intervention programs are efficient in treating patients with a first episode of psychosis (FEP) at least after 2 years. However, few studies have examined long-term outcomes, and particularly prognostic implications of the sex of FEP patients. Methods We aimed to investigate long-term neuropsychological and functional outcomes in female and male 10 years after the first presentation of a non-affective psychotic episode. One hundred sixty-five FEP patients, 73 women and 92 men were assessed for sociodemographic, clinical and neuropsychological information. Results Differences in outcome between female and male based on baseline, 1-year, 3-year and 10-year follow-up information were substantial, showing women better outcomes on several variables. Schizophrenia diagnosis was significantly more frequent in men (82% vs. 62%; p = 0.01). Women were more likely than men married (45% vs. 24%; p = 0.01) and having children (41% vs. 13%); p < 0.001). Significant differences arose for social function (F= 5.469; p = 0.022) and processing speed (F = 12.66; p < 0.001). There was also some weak evidence (albeit not quite statistically significant at p < 0.05) for negative symptoms and global neurocognitive function. Discussion Women who suffered a first episode of psychosis have better functional and neurocognitive outcomes compared to men. This differential outcome profile is important for clinicians to consider sex specific therapeutic approaches.

S124. RECOVERY TRAJECTORIES IN FIRST EPISODE PSYCHOSIS PATIENTS: THE ROLE OF TIMING

Abstract Background Prevent symptom relapse and promote functional recovery are the two main goals of early intervention services in first episode of psychosis. Identify patterns of recovery will be important in developing and implementing targeted recovery focused interventions. The goal of this study was to explore trajectories of recovery following a first episode of psychosis. Methods A sample of 373 FEP patients was followed over 3 years. Recovery profiles in terms of symptomatic and functional remission were explored. Relapses during follow-up were considered. Results Four recovery trajectories were identified: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery more likely have less severe baseline negative symptoms (OR= 2.092; 95% CI = 0.99–4.419) and not be diagnosed with schizophrenia (OR= 2.242; 95% CI = 1.015–4.954); short DUP (OR= 2.152; 95% CI = 0.879–5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954–5.457) increased the likelihood of good unstable recovery; less severe baseline negative symptoms (OR= 3.851; 95% CI = 1.422–10.435) and single status (OR= 4.307; 95% CI = 1.014–18.293) increased the likelihood of a poor unstable recovery when these three trajectories were compared with a poor stable recovery. Poor unstable trajectory was significantly associated with a high relapse rate (73%). Discussion Our results shed light on identifying different recovery profiles in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly attending the role of timing in the design of interventions.

F81. AGE OF ONSET OF CANNABIS USE AND COGNITIVE FUNCTION IN FIRST EPISODE NON-AFFECTIVE PSYCHOSIS PATIENTS: 3-YEAR FOLLOW-UP OUTCOME

Abstract Background In recent years, the effect of cannabis use on cognitive functions in patients with psychosis has been widely studied, but results are somewhat contradictory. On the other hand, it has also been studied the relevance of the age of onset of consume, suggesting that the early age of onset of consumption may be related to a greater cognitive impairment. Methods 349 patients with a first episode of non-affective psychosis were studied. Patients were classified in cannabis users and non-users. Users were divided according to their age at the beginning of use of cannabis in: early-onset (age<16) and late-onset (≥16 years-old). Differences between groups at baseline were studied 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) started consuming before 16 years of age and 60.7% (N=82) did so at age 16 of after. No differences were found between early-onset and late-onset groups on cognitive domains. However, cannabis users (early and late) showed significantly worse performance in processing speed than non-users. Longitudinal analises revealed that the groups of early-onset, late-onset and non-users of cannabis, had different evolution in processing speed domain and in the global cognitive functioning. Discussion The main findings of this study were that, although there were differences between patients who used cannabis and those who did not, minimal differences aroused between the early-onset and late-onset cannabis users. With respect to longitudinal analyses, we must be careful with their interpretation, since although a priori we found a significant group by time interaction (early-onset, late-onset, and non-users) in some domain, when the cannabis use at 3-year follow-up was considered, results did not show any significance, this reveals that cannabis users (early-onset and late-onset) and non-cannabis users did not differ in the degree of change in their cognitive functions, regardless of whether or not the patients had maintained consumption during the first 3-year of disease progression.

T72. VERBAL MEMORY AND VOXEL BASED MORPHOMETRY IN FIRST EPISODE NON-AFFECTIVE PSYCHOSIS: A PROCESS ORIENTED APPROACH

Abstract Background Deficits in auditory-verbal memory have been reported by the vast majority of published research in schizophrenia and also detected in first episode psychosis (FEP), confirming they are already present at the early stages of the illness. However, the specific neurocognitive constructs underlying defective verbal memory and their neuroanatomical correlates remains poorly understood in schizophrenia spectrum disorders patients. Methods Data on the Rey Auditory Verbal Learning Test (RAVLT), a widely used verbal memory measure that provides a range of performance indexes to evaluate distinct memory processes including: a) acquisition/learning b) sensitivity to interference c) retrieval; d) retention or rate of forgetting; e) and retrieval efficiency was available for 388 FEP patients and 184 healthy controls (HC). In 218 FEP patients and 146 HC, structural magnetic resonance imaging data were analysised using Voxel based morphometry (VBM) toolbox. Results The FEP group showed significantly lower results on acquisition/learning, delayed recall as well as higher rates of forgetting. They also exhibited a significant sensitivity to retroactive but not proactive interference. We also found significant correlations between bilateral frontal lobe morphometry and proactive interference as well as between right frontal lobe morphometry and retroactive interference. Rate of forgetting was significantly correlated with right occipital cortex morphometry. Those with higher rates of forgetting and proactive and retroactive interference demonstrated further gray matter reductions in frontal and occipital cortical areas. Discussion The application of a process oriented approach to the neuropsychological evaluation of verbal memory allows a finer-grained analysis of the neurocognitive constructs underlying defective verbal memory in FEP. The results suggest specific relationships between different neuroanatomical structures and discrete memory processes with these structures playing an important role in verbal memory deficits found in FEP.