EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable outpatients

Brief batteries in schizophrenia, are needed to screen for the cognitive impact of schizophrenia. We aimed to validate and co-norm the Epidemiological Study of Cognitive Impairment in Schizophrenia (EPICOG-SCH) derived brief cognitive battery. A cross-sectional outpatient evaluation was conducted of six-hundred-seventy-two patients recruited from 234 centers. The brief battery included well-known subtests available worldwide that cover cognitive domains related to functional outcomes: WAIS-III-Letter-Number-Sequencing-LNS, Category Fluency Test-CFT, Logical-Memory Immediate Recall-LM, and Digit-Symbol-Coding-DSC. CGI-SCH Severity and WHO-DAS-S were used to assess clinical severity and functional impairment, respectively. Unit Composite Score (UCS) and functional regression-weighted Composite Scores (FWCS) were obtained; discriminant properties of FWCS to identify patients with different levels of functional disability were analyzed using receiver-operating characteristic (ROC) technique. The battery showed good internal consistency, Cronbach's alpha = 0.78. The differences between cognitive performance across CGI-SCH severity level subscales ranged from 0.5 to 1 SD. Discriminant capacity of the battery in identifying patients with up to moderate disability levels showed fair discriminant accuracy with areas under the curve (AUC) > 0.70, p < 0.0001. An FWCS mean cut-off score ≥ 100 showed likelihood ratios (LR) up to 4.7, with an LR+ of 2.3 and a LR− of 0.5. An FWCS cut-off ≥ 96 provided the best balance between sensitivity (0.74) and specificity (0.62). The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive impact of schizophrenia, and its regression-weighted Composite Score was an efficient complement to clinical interviews for confirming patients' potential functional outcomes and can be useful for monitoring cognition during routine outpatient follow-up visits

What factors should we modify to promote high functioning and prevent functional decline in people with schizophrenia?

BackgroundSince research in schizophrenia mainly focuses on deficits and risk factors, we need studies searching for high-functioning protective factors. Thus, our objective was to identify protective (PFs) and risk factors (RFs) separately associated with high (HF) and low functioning (LF) in patients with schizophrenia.MethodsWe collected information (sociodemographic, clinical, psychopathological, cognitive, and functional) from 212 outpatients with schizophrenia. Patients were classified according to their functional level (PSP) as HF (PSP &gt; 70, n = 30) and LF (PSP ≤ 50, n = 95). Statistical analysis consisted of Chi-square test, Student’s t-test, and logistic regression.ResultsHF model: variance explained: 38.4–68.8%; PF: years of education (OR = 1.227). RFs: receiving a mental disability benefit (OR = 0.062) and scores on positive (OR = 0.719), negative-expression (OR = 0.711), and negative-experiential symptoms (OR = 0.822), and verbal learning (OR = 0.866). LF model: variance explained: 42.0–56.2%; PF: none; RFs: not working (OR = 6.900), number of antipsychotics (OR = 1.910), and scores on depressive (OR = 1.212) and negative-experiential symptoms (OR = 1.167).ConclusionWe identified specific protective and risk factors for high and low functioning in patients with schizophrenia and confirmed that high functioning factors are not necessarily the opposite of those associated with low functioning. Only negative experiential symptoms are a shared and inverse factor for high and low functioning. Mental health teams must be aware of protective and risk factors and try to enhance or reduce them, respectively, to help their patients improve or maintain their level of functioning

Inverse association between negative symptoms and body mass index in chronic schizophrenia

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels

The role of genetic variability in the GABRA6, 5-HTT and BDNF genes in anxiety-related traits

Objective:  The aims of this study were to test the individual association of the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene (BDNF) and the GABAAα6 receptor subunit gene (GABRA6) with anxiety-related traits and to explore putative gene-gene interactions in a Spanish healthy sample. Method:  A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene). Results:  Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers (F = 2.96, P = 0.019). In addition, there was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met polymorphisms (F = 3.4, P = 0.009). Conclusion:  GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene-gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety-related traits

Evolution of bdnf full-length/truncated receptor ratio and cognitive/general functioning after a first episode of psychosis

Brain plasticity has demonstrated to play a role in the pathophysiology of schizophrenia. Cognitive deterioration in these patients can be prevented by ensuring the adequate functioning of signaling pathways associated with brain plasticity. As BDNF exerts its action through receptors, in this study, we hypothesized that levels of some BDNF receptors during a first episode of psychosis (FEP) would correlate with the cognitive and global functioning of patients in the long term. We also hypothesized that the improvement of the ratio of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors, and the predominance of the full-length isoform would be associated with better cognition and functioning. Peripheral levels of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors were assessed in a sample of 97 FEP patients and 97 matched healthy controls. TrKB-FL/TrKB-T ratio(hereinafter, FL/T) was calculated for each patient. Cognitive and global functioning was measured at inclusion and at two years. A high baseline FL/T ratio was found to be related to a better cognitive function (global cognition, verbal memory, working memory and premorbid IQ). Cognitive performance at disease onset and at two years improved when the levels of the ratio were higher than one, with functional BDNF receptor (TrKB-FL) exceeding the value of the truncated isoform (TrKB-T). In addition the increase in the FL/T ratio during the two years of follow-up had positive effects on global functioning. This may be due either to a reduction in TrKB-T or to an increase in TrKB-FL, or both. In conclusion FL / T ratio was related to general functioning and cognition in the long-term

The influence of oxytocin and prolactin during a first-episode of psychosis: the implication of sex differences, clinical features and cognitive performance

Background: Approximately 3% of the population suffers a first episode of psychosis (FEP), and a high percentage of these patients subsequently relapse. Because the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment, and outcome of such events and to define new therapeutic targets. Here we analyzed the plasma oxytocin and prolactin levels during an FEP, assessing their correlation with clinical and cognitive features. Methods: The oxytocin and prolactin in plasma was measured in 120 FEP patients and 106 healthy controls, all of whom were subjected to a clinical and neuropsychological assessment. Most patients were under antipsychotics. Statistical analyses aimed to identify factors associated with the FEP and to search for associations between the variables. This study is preliminary and exploratory because the P-values were not corrected for multiple comparisons. Results: FEP patients had less oxytocin, more prolactin, and a poor premorbid IQ, and they performed worse in sustained attention. Male patients with higher prolactin levels experienced more severe psychotic symptoms and required higher doses of antipsychotics. Low oxytocin was associated with poor sustained attention in women, whereas low oxytocin and high prolactin in men correlated with better performance in sustained attention. Conclusion: Low oxytocin, high prolactin, and poor premorbid IQ and sustained attention are factors associated with an FEP, representing potential therapeutic targets in these patients. These biological factors and cognitive domains might play an important role during a FEP, which could help us to develop new strategies that improve the outcomes of this disorder and that should perhaps be gender specific

The Influence of Oxytocin and Prolactin During a First Episode of Psychosis: The Implication of Sex Differences, Clinical Features, and Cognitive Performance

Background Approximately 3% of the population suffers a first episode of psychosis (FEP), and a high percentage of these patients subsequently relapse. Because the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment, and outcome of such events and to define new therapeutic targets. Here we analyzed the plasma oxytocin and prolactin levels during an FEP, assessing their correlation with clinical and cognitive features. Methods The oxytocin and prolactin in plasma was measured in 120 FEP patients and 106 healthy controls, all of whom were subjected to a clinical and neuropsychological assessment. Most patients were under antipsychotics. Statistical analyses aimed to identify factors associated with the FEP and to search for associations between the variables. This study is preliminary and exploratory because the P-values were not corrected for multiple comparisons. Results FEP patients had less oxytocin, more prolactin, and a poor premorbid IQ, and they performed worse in sustained attention. Male patients with higher prolactin levels experienced more severe psychotic symptoms and required higher doses of antipsychotics. Low oxytocin was associated with poor sustained attention in women, whereas low oxytocin and high prolactin in men correlated with better performance in sustained attention. Conclusion Low oxytocin, high prolactin, and poor premorbid IQ and sustained attention are factors associated with an FEP, representing potential therapeutic targets in these patients. These biological factors and cognitive domains might play an important role during a FEP, which could help us to develop new strategies that improve the outcomes of this disorder and that should perhaps be gender specific

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients