Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Corollary discharge function in healthy controls: Evidence about self-speech and external speech processing.

As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyse this corollary discharge phenomenon (agency and ownership), we registered the event-related potentials of 42 healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership) and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared with the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience) and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).

The CACNA1C and the ZNF804A genes are among the most relevant schizophrenia GWAS findings. Recent evidence shows that the interaction of these genes with the schizophrenia diagnosis modulates brain functional response to a verbal fluency task. To better understand how these genes might influence the risk for schizophrenia, we aimed to study the interplay between CACNA1C and ZNF804A on working memory brain functional correlates. The analyses included functional and behavioural N-back task data (obtained from an fMRI protocol) and CACNA1C-rs1006737 and ZNF804A-rs1344706 genotypes for 78 healthy subjects and 78 patients with schizophrenia (matched for age, sex and premorbid IQ). We tested the effects of the epistasis between these genes as well as of the three-way interaction (CACNA1C × ZNAF804A × diagnosis) on working memory-associated activity (N-back: 2-back vs 1-back). We detected a significant CACNA1C × ZNAF804A interaction on working memory functional response in regions comprising the ventral caudate medially and within the left hemisphere, the superior and inferior orbitofrontal gyrus, the superior temporal pole and the ventral-anterior insula. The individuals with the GWAS-identified risk genotypes (CACNA1C-AA/AG and ZNF804A-AA) displayed a reduced working memory modulation response. This genotypic combination was also associated with opposite brain activity patterns between patients and controls. While further research will help to comprehend the neurobiological mechanisms of this interaction, our data highlight the role of the epistasis between CACNA1C and ZNF804A in the functional mechanisms underlying the pathophysiology of schizophrenia.

Anomalous self-experiences are related to general cognition deficits in schizophrenia.

Anomalous self-experiences (ASEs) are prevalent in schizophrenia, but its underpinnings are not completely understood. Given the likely complex substrate of the experience of the self, neurocognitive functions requiring coordinate cerebral activity may relate to ASEs. Moreover, cognitive deficits functioning may be involved in the link between self-experience disturbances and some aspects of social dysfunction in schizophrenia. We have assessed ASEs in 41 schizophrenia patients (11 first episodes) using the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE), and the general cognition using the Brief Assessment of Cognition in Schizophrenia (BACS). Besides, social cognition was assessed using two complementary tools Meyer, Salovey and Caruso Emotional Intelligence Test (MSCEIT) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia). The results revealed that Self-awareness/presence and Somatization IPASE scores were inversely explained by motor speed in the BACS; Consciousness IPASE scores were inversely explained by problem solving performance in the BACS. These data reveal a significant relationship between certain domains of general cognition and anomalous self-experiences, that may be useful in further investigation on the substrates of ASEs.

A cost utility analysis alongside a cluster-randomised trial evaluating a minor ailment service compared to usual care in community pharmacy.

BACKGROUND: Minor ailments are "self-limiting conditions which may be diagnosed and managed without a medical intervention". A cluster randomised controlled trial (cRCT) was designed to evaluate the clinical, humanistic and economic outcomes of a Minor Ailment Service (MAS) in community pharmacy (CP) compared with usual care (UC). METHODS: The cRCT was conducted for 6 months from December 2017. The pharmacist-patient intervention consisted of a standardised face-to-face consultation on a web-based program using co-developed protocols, pharmacists' training, practice change facilitators and patients' educational material. Patients requesting a non-prescription medication (direct product request) or presenting minor ailments received MAS or UC and were followed-up by telephone 10-days after the consultation. The primary economic outcomes were incremental cost-utility ratio (ICUR) of the service and health related quality of life (HRQoL). Total costs included health system, CPs and patient direct costs: health professionals' consultation time, medication costs, pharmacists' training costs, investment of the pharmacy and consultation costs within the 10 days following the initial consultation. The HRQoL was obtained using the EuroQoL 5D-5L at the time of the consultation and at 10-days follow up. A sensitivity analysis was carried out using bootstrapping. There were two sub-group analyses undertaken, for symptom presentation and direct product requests, to evaluate possible differences. RESULTS: A total of 808 patients (323 MAS and 485 UC) were recruited in 27 CPs with 42 pharmacists (20 MAS and 22 UC). 64.7% (n = 523) of patients responded to follow-up after their consultation in CP. MAS patients gained an additional 0.0003 QALYs (p = 0.053). When considering only MAS patients presenting with symptoms, the ICUR was 24,733€/QALY with a 47.4% probability of cost-effectiveness (willingness to pay of 25,000€/QALY). Although when considering patients presenting for a direct product request, MAS was the dominant strategy with a 93.69% probability of cost-effectiveness. CONCLUSIONS: Expanding community pharmacists' scope through MAS may benefit health systems. To be fully cost effective, MAS should not only include consultations arising from symptom presentation but also include an oversight of self-selected products by patients. MAS increase patient safety through the appropriate use of non-prescription medication and through the direct referral of patients to GP. TRIAL REGISTRATION: ISRCTN, ISRCTN17235323 . Registered 07/05/2021 - Retrospectively registered.

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

Background: The synchronized activity of distributed neural assemblies ­ reflected in the electroencephalogram (EEG) ­ underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored. Methods: We assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 werein their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters. Results: We found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory. Limitations: All patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes. Conclusion: Spectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.

Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task.

A deficit in task-related functional connectivity modulation from electroencephalogram (EEG) has been described in schizophrenia. The use of measures of neuronal connectivity as an intermediate phenotype may allow identifying genetic factors involved in these deficits, and therefore, establishing underlying pathophysiological mechanisms. Genes involved in neuronal excitability and previously associated with the risk for schizophrenia may be adequate candidates in relation to functional connectivity alterations in schizophrenia. The objective was to study the association of two genes of voltage-gated ion channels (CACNA1C and KCNH2) with the functional modulation of the cortical networks measured with EEG and graph-theory parameter during a cognitive task, both in individuals with schizophrenia and healthy controls. Both CACNA1C (rs1006737) and KCNH2 (rs3800779) were genotyped in 101 controls and 50 schizophrenia patients. Small-world index (SW) was calculated from EEG recorded during an odd-ball task in two different temporal windows (pre-stimulus and response). Modulation was defined as the difference in SW between both windows. Genetic, group and their interaction effects on SW in the pre-stimulus window and in modulation were evaluated using ANOVA. The CACNA1C genotype was not associated with SW properties. KCNH2 was significantly associated with SW modulation. Healthy subjects showed a positive SW modulation irrespective of the KCNH2 genotype, whereas within patients allele-related differences were observed. Patients carrying the KCNH2 risk allele (A) presented a negative SW modulation and non-carriers showed SW modulation similar to the healthy subjects. Our data suggest that KCNH2 genotype contributes to the efficient modulation of brain electrophysiological activity during a cognitive task in schizophrenia patients.

Topography of activation deficits in schizophrenia during P300 task related to cognition and structural connectivity.

BACKGROUND: The study of cerebral underpinnings of schizophrenia may benefit from the high temporal resolution of electromagnetic techniques, but its spatial resolution is low. However, source imaging approaches such as low-resolution brain electromagnetic tomography (LORETA) allow for an acceptable compromise between spatial and temporal resolutions. METHODS: We combined LORETA with 32 channels and 3-Tesla diffusion magnetic resonance (Dmr) to study cerebral dysfunction in 38 schizophrenia patients (17 first episodes, FE), compared to 53 healthy controls. The EEG was acquired with subjects performing an odd-ball task. Analyses included an adaptive window of interest to take into account the interindividual variability of P300 latency. We compared source activation patters to distractor (P3a) and target (P3b) tones within- and between-groups. RESULTS: Patients showed a reduced activation in anterior cingulate and lateral and medial prefrontal cortices, as well as inferior/orbital frontal regions. This was also found in the FE patients alone. The activation was directly related to IQ in the patients and controls and to working memory performance in controls. Symptoms were unrelated to source activation. Fractional anisotropy in the tracts connecting lateral prefrontal and anterior cingulate regions predicted source activation in these regions in the patients. CONCLUSIONS: These results replicate the source activation deficit found in a previous study with smaller sample size and a lower number of sensors and suggest an association between structural connectivity deficits and functional alterations.

Relations between structural and EEG-based graph metrics in healthy controls and schizophrenia patients.

Our aim was to assess structural and functional networks in schizophrenia patients; and the possible prediction of the latter based on the former. The possible dependence of functional network properties on structural alterations has not been analyzed in schizophrenia. We applied averaged path-length (PL), clustering coefficient, and density (D) measurements to data from diffusion magnetic resonance and electroencephalography in 39 schizophrenia patients and 79 controls. Functional data were collected for the global and theta frequency bands during an odd-ball task, prior to stimulus delivery and at the corresponding processing window. Connectivity matrices were constructed from tractography and registered cortical segmentations (structural) and phase-locking values (functional). Both groups showed a significant electroencephalographic task-related modulation (change between prestimulus and response windows) in the global and theta bands. Patients showed larger structural PL and prestimulus density in the global and theta bands, and lower PL task-related modulation in the theta band. Structural network values predicted prestimulus global band values in controls and global band task-related modulation in patients. Abnormal functional values found in patients (prestimulus density in the global and theta bands and task-related modulation in the theta band) were not predicted by structural data in this group. Structural and functional network abnormalities respectively predicted cognitive performance and positive symptoms in patients. Taken together, the alterations in the structural and functional theta networks in the patients and the lack of significant relations between these alterations, suggest that these types of network abnormalities exist in different groups of schizophrenia patients.

Variation at NRG1 genotype related to modulation of small-world properties of the functional cortical network.

Functional brain networks possess significant small-world (SW) properties. Genetic variation relevant to both inhibitory and excitatory transmission may contribute to modulate these properties. In healthy controls, genotypic variation in Neuregulin 1 (NRG1) related to the risk of psychosis (risk alleles) would contribute to functional SW modulation of the cortical network. Electroencephalographic activity during an odd-ball task was recorded in 144 healthy controls. Then, small-worldness (SWn) was calculated in five frequency bands (i.e., theta, alpha, beta1, beta2 and gamma) for baseline (from -300 to the stimulus onset) and response (150-450 ms post-target stimulus) windows. The SWn modulation was defined as the difference in SWn between both windows. Association between SWn modulation and carrying the risk allele for three single nucleotide polymorphisms (SNP) of NRG1 (i.e., rs6468119, rs6994992 and rs7005606) was assessed. A significant association between three SNPs of NRG1 and the SWn modulation was found, specifically: NRG1 rs6468119 in alpha and beta1 bands; NRG1 rs6994992 in theta band; and NRG1 rs7005606 in theta and beta1 bands. Genetic variation at NRG1 may influence functional brain connectivity through the modulation of SWn properties of the cortical network.

Noise power associated with decreased task-induced variability of brain electrical activity in schizophrenia.

In schizophrenia, both increased baseline metabolic and electroencephalographic (EEG) activities as well as decreased task-related modulation of neural dynamics have been reported. Noise power (NP) can measure the background EEG activity during task performance, and Shannon entropy (SE) is useful for quantifying the global modulation of EEG activity with a high temporal resolution. In this study, we have assessed the possible relationship between increased NP in theta and gamma bands and decreased SE modulation in 24 patients with schizophrenia and 26 controls over the parietal and central regions during a P300 task. SE modulation was calculated as the change from baseline to the active epoch (i.e., 150-550 ms following the target stimulus onset). Patients with schizophrenia displayed statistically significant higher NP values and lower SE modulation than healthy controls. We found a significant association between gamma NP and SE in all of the participants. Specifically, a NP increase in the gamma band was followed by a decrease in SE change. These results support the notion that an excess of gamma activity, unlocked to the task being performed, is accompanied by a decreased modulation of EEG activity in schizophrenia.

Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients.

Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior-frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks.

Association between electroencephalographic modulation, psychotic-like experiences and cognitive performance in the general population.

AIM: An association between deficit of electroencephalographic (EEG) modulation during an odd-ball task and psychotic symptoms has been described in clinical samples, in agreement with the proposed role for altered salience in psychosis. To discard the possible influence of medication, the relationship between psychotic-like experiences and EEG modulation in the general population was explored. METHODS: EEG and psychotic-like experiences were assessed in 194 healthy subjects during a P300 paradigm. EEG modulation was assessed as changes from pre-stimulus to response windows in spectral entropy (SE, a measurement of signal irregularity), median frequency (MF, a quantifier of the frequency distribution of oscillatory activity) and theta, alpha, beta-1, beta-2 and gamma relative power (RP, a summary of the distribution of spectral components). RESULTS: A significant widespread decrease in SE and MF from baseline to response was found, with a significant increase in RP for theta and a decrease for higher frequency bands, supporting an increase in EEG regularity and a slowing of brain oscillations during the response. Furthermore, a significant association was found between SE modulation and distress of negative psychotic-like experiences, as well as between verbal memory and RP modulation for beta-1. Performance in verbal fluency was associated with the increase in theta RP during the response. CONCLUSION: EEG irregularity of healthy subjects decreased at the expense of a larger contribution of theta RP and a decreased contribution of fast frequency bands. Subjects with smaller modulation showed poorer cognitive scores and greater distress of negative psychotic-like experiences.

Decreased entropy modulation of EEG response to novelty and relevance in schizophrenia during a P300 task.

The analysis of the interaction between novelty and relevance may be of interest to test the aberrant salience hypothesis of schizophrenia (SCH). In comparison with other neuroimaging techniques, such as functional magnetic resonance imaging, electroencephalography (EEG) provides high temporal resolution. Therefore, EEG is useful to analyze transient dynamics in neural activity, even in the range of milliseconds. In this study, EEG activity from 31 patients with SCH and 38 controls was analyzed using Shannon spectral entropy (SE) and median frequency (MF). The aim of the study was to quantify differences between distractor (i.e., novelty) and target (i.e., novelty and relevance) tones in an auditory oddball paradigm. Healthy controls displayed a larger SE decrease in response to target stimulus than in response to distractor tones. SE decrease was accompanied by a significant and widespread reduction of MF (i.e., a significant slowing of EEG activity). In comparison with controls, patients showed a significant reduction of changes in SE in response to both target and distractor tones. These differences were also observed in patients that only received a minimal treatment prior to EEG recording. Furthermore, significant changes in SE were inversely correlated to positive and total symptoms severity for SCH patients. Our findings support the notion that SCH is associated with a reduced response to both novelty and relevance during an auditory P300 task.

Gamma power and cognition in patients with schizophrenia and their first-degree relatives.

BACKGROUND: Gamma oscillations are essential for functional neural assembly formation underlying higher cerebral functions. Previous studies concerning gamma band power in schizophrenia have yielded diverse results. METHODS: In this study, we assessed gamma band power in minimally treated patients with schizophrenia, their first-degree relatives and healthy controls during an oddball paradigm performance, as well as the relation between gamma power and cognitive performance. RESULTS: We found a higher gamma power in the patient group than in the healthy controls at the P3, P4, Fz, Pz and T5 sites. Compared with their relatives, gamma power in the patients was only marginally higher over P3 and P4. We found a nearly significant inverse association between gamma power at F4 and Tower of London performance in the patients, as well as a significant inverse association between gamma power at T5 and verbal memory and working memory scores in the relatives. CONCLUSION: These results support higher total gamma power in association with schizophrenia and its inverse association with cognitive performance in patients and their first-degree relatives.

Decreased spectral entropy modulation in patients with schizophrenia during a P300 task.

Spectral entropy (SE), also known as Shannon entropy, is a useful parameter for quantifying the global regularity of the electroencephalographic (EEG) signal. Hence, it is of interest in the assessment of the electrophysiological correlates of cognitive processing in schizophrenia. However, to date, SE has been barely used in studies comparing resting EEG recordings between patients and controls. In this work, we compared SE between resting baseline [-250 0] ms and active task [150 550] ms windows of a P300 task in 31 patients with schizophrenia and 38 controls. Moreover, we also calculated the median frequency (MF) and relative power in each frequency band for these windows to assess the correlates of the possible SE differences. Controls showed a significant (p < 0.0029) SE decrease (i.e., meaning higher signal regularity) from baseline to the active task window at parietal and central electrode sites. This SE decrease from baseline to active conditions was significantly lower in patients. In controls, this SE decrease was accompanied by a statistically significant decrease in MF (i.e., a significant slowing of the EEG activity), not observed in patients. In this latter group, the difference in SE between resting baseline and active task windows was inversely correlated to positive and total symptoms scores, as measured with the positive and negative symptoms scale. Our data support the relevance of SE in the study of cerebral processing in schizophrenia.

Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia.

AIMS: The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia. METHODS: We explored the relation between cognitive performance and regional GM volumes using voxel-based morphometry (VBM), in order to discover if the association between gamma noise power (an electroencephalography measurement of background activity in the gamma band) and cognition is observed through structural deficits related to the disease. Noise power, magnetic resonance imaging and cognitive assessments were obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy controls. RESULTS: In comparison with controls, patients showed GM deficits at posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and left inferior dorsolateral prefrontal regions. Patients exhibited a direct association between performance in working memory and right temporal (superior and inferior gyri) GM densities. They also displayed a negative association between right anterior cerebellum volume and gamma noise power at the frontal midline (Fz) site. CONCLUSION: A structural deficit in the cerebellum may be involved in gamma activity disorganization in schizophrenia. Temporal structural deficits may relate to cognitive dysfunction in this illness.

Contribution of baseline body mass index and leptin serum level to the prediction of early weight gain with atypical antipsychotics in schizophrenia.

AIM: This study investigated whether biochemical parameters add predictive information concerning risk for weight gain associated with treatment with atypical antipsychotics (AP) to that provided by baseline weight. METHODS: Weight changes were assessed in 25 patients with schizophrenia after 3-6 months of treatment. These patients were started on AP monotherapy owing to a first psychotic episode or resumed treatment after at least a 6-month period of abandonment. Anthropometric and biochemical data were collected and analyzed as predictors of early weight change. RESULTS: The baseline biochemical and anthropometric data were not significantly higher in the patients than in the healthy participants. During follow up, the patients had significant increases in body mass index and total cholesterol and apolipoprotein B level. The baseline weight and leptin level were predictive of weight gain during follow up, with an inverse association in both cases. CONCLUSION: Baseline weight and leptin level may help to assess the risk of early weight gain with AP.

Cognitive outcome and gamma noise power unrelated to neuregulin 1 and 3 variation in schizophrenia.

BACKGROUND: Neuregulins are a family of signalling proteins that orchestrate a broad range of cellular responses. Four genes encoding Neuregulins 1-4 have been identified so far in vertebrates. Among them, Neuregulin 1 and Neuregulin 3 have been reported to contribute to an increased risk for developing schizophrenia. We hypothesized that three specific variants of these genes (rs6994992 and rs3924999 for Neuregulin 1 and rs10748842 for Neuregulin 3) that have been related to this illness may modify information processing capacity in the cortex, which would be reflected in electrophysiological parameters (P3b amplitude or gamma noise power) and/or cognitive performance. METHODS: We obtained DNA from 31 patients with schizophrenia and 23 healthy controls and analyzed NRG1 rs6994992, NRG1 rs3924999 and NRG3 rs10748842 promoter polymorphisms by allelic discrimination with real-time polymerase chain reaction (PCR). We compared cognitive outcome, P300 amplitude parameters and an electroencephalographic measure of noise power in the gamma band between the groups dichotomized according to genotype. RESULTS: Contrary to our hypothesis, we could not detect any significant influence of variation in Neuregulin 1/Neuregulin 3 polymorphisms on cognitive performance or electrophysiological parameters of patients with schizophrenia. CONCLUSIONS: Despite our findings, we cannot discard that other genetic variants and, more likely, interactions between those variants and with genetic variation related to different pathways may still influence cerebral processing in schizophrenia.