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Background Clinical staging model for depression helps to better define the clinical situation of patients. The objectives of this study are: to correlate the Hetrick’s staging model of depression with the severity of depression, associated disability, and resistance to treatment in the established disease stages and to test the modification introduced by our group consisting in the introduction of a substage for recurrence from a previous episode that was stabilized with a complete remission. Methods A Cross-sectional study with 133 adult subjects having a current and primary diagnosis of Depressive disorder was developed. Patients were classified according to the model and assessed with: 17-item Hamilton Depression Scale (HAM-D), Clinical Global Impression (CGI); Global Assessment of Function (GAF); Maudsley Staging Method for treatment resistance (MSM) and Sheeham Disability Schedule (SDS). Results The variable that best contributes to the differentiation between clinical stages, in established Depression, is resistance to treatment evaluated by the MSM. Correlations between MSM and the clinical stages were statistically significant between most pairs of stages. Finally, we showed preliminary data in order to prove that a differential sub-stage for recurrent depression with and without inter-episodic remission in the current heuristic models could be a possible stage for better define depression staging model. Conclusions Resistance to treatment should be included in the definition of clinical stages in established depression. Despite the difficulty of establishing a valid model for the staging of depression, it can certainly add great value to diagnosis, therapeutic interventions and clinical research.

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.

The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.

The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development. Fondo de Investigacion Sanitaria, Instituto Salud Carlos III, Spain (PI015/01013; PI019/00126) 5.924 JCR (2020) Q1, 67/295 Biochemisty & Molecular Biology 1.455 SJR (2020) Q1, 6/68 Inorganic Chemistry No data IDRA 2020 UEM

Transcranial magnetic stimulation (TMS) is an approved intervention for treatment-resistant depression (TRD), but current targeting approaches are only partially successful. Our objectives were (1) to examine the feasibility of MRI-guided TMS in the clinical setting using a recently published surface-based, multimodal parcellation in patients with TRD who failed standard TMS (sdTMS); (2) to examine the neurobiological mechanisms and clinical outcomes underlying MRI-guided TMS compared to that of sdTMS. We used parcel-guided TMS (pgTMS) to target the left dorsolateral prefrontal cortex parcel 46. Resting-state functional connectivity (rsfc) was assessed between parcel 46 and predefined nodes within the default mode and visual networks, following both pgTMS and sdTMS. All patients (n = 10) who had previously failed sdTMS responded to pgTMS. Alterations in rsfc between frontal, default mode, and visual networks differed significantly over time between groups. Improvements in symptoms correlated with alterations in rsfc within each treatment group. The outcome of our study supports the feasibility of pgTMS within the clinical setting. Future prospective, double-blind studies of pgTMS vs. sdTMS appear warranted.

Fibromyalgia has been reported as having some clinical overlap with both depression and emotionally-unstable disorders, although both types of disorders present different cortisol suppression response to dexamethasone. In this study we investigated the hypothalamic-pituitary-adrenal system (HPA) in the fibromyalgic syndrome (FMS) using a dexamethasone suppression test (DST) of 0.25 mg designed to specifically detect cortisol hypersuppression. We studied 59 women (20 patients and 39 healthy controls) to whom the DST was administered together with a battery of psychometric tests. In our results, patients with FMS had significant lower levels of basal cortisol pre- and post-DST compared with control subjects. However, cortisol suppression rate in patients after DST was not significantly different than in controls. As other syndromes like post-traumatic stress disorder or emotionally unstable personality disorders, also related with high incidence of severe trauma, FMS patients presented significant low basal cortisol. However, they did not have cortisol hypersuppression as is commonly found in the mentioned disorders. The relation of FMS with lifetime traumas and with emotional instability should be further investigated in order to improve psychological treatment approaches for these patients.LAY SUMMARYPatients with fibromyalgic syndrome have basal hypocortisoism but no cortisol hypersuppression after dexamethasone infusion compared to control subjects, as other trauma-related syndromes.

There is increasing focus on use of resting-state functional connectivity (RSFC) analyses to subtype depression and to predict treatment response. To date, identification of RSFC patterns associated with response to electroconvulsive therapy (ECT) remain limited, and focused on interactions between dorsal prefrontal and regions of the limbic or default-mode networks. Deficits in visual processing are reported in depression, however, RSFC with or within the visual network have not been explored in recent models of depression. Here, we support prior studies showing in a sample of 18 patients with depression that connectivity between dorsal prefrontal and regions of the limbic and default-mode networks serves as a significant predictor. In addition, however, we demonstrate that including visual connectivity measures greatly increases predictive power of the RSFC algorithm (>80% accuracy of remission). These exploratory results encourage further investigation into visual dysfunction in depression, and use of RSFC algorithms incorporating the visual network in prediction of response to both ECT and transcranial magnetic stimulation (TMS), offering a new framework for the development of RSFC-guided TMS interventions in depression.

The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age- and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d>0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls.

The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in murine brain after dopaminergic treatments. We found that Ankk1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon Ankk1 mRNA (1.004 ± 0.580-fold; t: 0.015, df: 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant Ankk1 mRNA downregulation (0.606 ± 0.057-fold; t: 2.786, df: 10, P = 0.02 and 0.588 ± 0.130-fold; t: 2.394, df: 11, P = 0.036, respectively). With respect the Ankk1 proteins profile, no effects were found after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of Ankk1 by specific pathways.

The number of large collaborative research networks in mental health is increasing. Training programs are an essential part of them. We critically review the specific implementation of a research training program in a translational Centre for Biomedical Research in Mental Health in order to inform the strategic integration of basic research into clinical practice to have a positive impact in the mental health system and society. Description of training activities, specific educational programs developed by the research network, and challenges on its implementation are examined. The Centre for Biomedical Research in Mental Health has focused on training through different activities which have led to the development of an interuniversity master's degree postgraduate program in mental health research, certified by the National Spanish Agency for Quality Evaluation and Accreditation. Consolidation of training programs within the Centre for Biomedical Research in Mental Health has considerably advanced the training of researchers to meet competency standards on research. The master's degree constitutes a unique opportunity to accomplish neuroscience and mental health research career-building within the official framework of university programs in Spain.

It has been suggested that data on positive and negative psychotic symptoms in patients with schizophrenia as assessed using different scales may be combined. For the first time, we assessed correlations between the positive syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-P) and the Scale for the Assessment of Positive Symptoms (SAPS), and between the negative syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-N) and the Scale for the Assessment of Negative Symptoms (SANS) in patients with bipolar disorder. We also aimed to confirm these correlations in patients with schizophrenia. This cross-sectional study was conducted with a group of 94 patients (40 diagnosed with bipolar disorder, 54 with schizophrenia). Assessments were carried out using the PANSS, SAPS and SANS. Large significant correlations were found between the PANSS-P and SAPS, and between the PANSS-N and SANS, in both the bipolar disorder group and the schizophrenia group. These results confirm previous findings regarding correlations between these scales in schizophrenia, and support the hypothesis that similar correlations exist in bipolar disorder. Therefore, our data support the potential usefulness in collaborative research of combining results from different scales for the assessment of psychotic symptoms in patients with bipolar disorder.

TaqIA is a polymorphismassociated with addictions and dopamine-related traits. It is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) nearby the gene for the dopamine D2 receptor (D2R). Since ANKK1 function is unknown, TaqIA-associated traits have been explained only by differences in D2R. Here we report ANKK1 studies in mouse and human brain using quantitative real-time PCR, Western blot, immunohistochemistry, and flow cytometry. ANKK1 mRNA and protein isoforms vary along neurodevelopment in the human and mouse brain. In mouse adult brain ANKK1 is located in astrocytes, nuclei of postmitotic neurons and neural precursors from neurogenic niches. In both embryos and adults, nuclei of neural precursors showsignificant variation of ANKK1 intensity.We demonstrate a correlation between ANKK1 and the cell cycle. Cell synchronization experiments showed a significant increment of ANKK1-kinase in mitotic cells while ANKK1-kinase overexpression affects G1 and M phase that were found to be modulated by ANKK1 alleles and apomorphine treatment. Furthermore, during embryonic neurogenesis ANKK1 was expressed in slow-dividing neuroblasts and rapidly dividing precursors which are mitotic cells. These results suggest a role of ANKK1 during the cell cycle in neural precursors thus providing biological support to brain structure involvement in the TaqIA-associated phenotypes., This work has been supported by the Instituto de Salud Carlos III grants PI11/0731 and PI15/01013 (J.H.), by Ministry of Economy and Competitiveness grants SAF2014-54919-R (A.G.-F.) and SAF2011-25020 (A.P.).

Inflammatory and immune processes have been implicated in the etiopathology of schizophrenia. We demonstrate the existence of immune function alteration, assessed by serum cytokine's levels, not only in schizophrenia patients but also in their unaffected first-degree relatives. This finding may provide a new data for considering cytokines as schizophrenic disease biomarkers. © 2012 Elsevier Ireland Ltd.

The study aims to identify psychopathologic variables in cannabis-induced psychosis and recent-onset primary psychoses using the Symptom Checklist-90-R and the Psychiatric Research Interview for Substance and Mental Disorders. A sample of 181 subjects with psychotic symptoms and cannabis use referred to the psychiatry inpatient units of 3 university general hospitals were assessed. The final sample included 50 subjects with a diagnosis of cannabis-induced psychotic disorder (CIPD) and 104 subjects with primary psychotic disorders. Using receiver operating characteristic curves, the most efficient psychopathologic variables for classifying CIPD were interpersonal sensitivity, “depression,” phobic anxiety, and Scale to Assess Unawareness of Mental Disorders subscales. The area under the receiver operating characteristic curve of the model including depression and “misattribution” scores was 96.78% (95% confidence interval, 94.43-99.13). Depressive symptoms could be used to distinguish CIPD from other primary psychotic disorders. Clinical variables related to “neurotic” symptoms could be involved in the susceptibility to cannabis-induced psychosis.

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

Lobo A, Lopez-Anton R, Santabarbara J, de-la-Camara C, Ventura T, Quintanilla MA, Roy JF, Campayo AJ, Lobo E, Palomo T, Rodriguez-Jimenez R, Saz P, Marcos G. Incidence and lifetime risk of dementia and Alzheimer’s disease in a Southern European population. Objective: To calculate both the incidence rates and the lifetime risk (LTR) of dementia and Alzheimer’s disease (AD). Methods: A two-phase case-finding procedure was implemented in a cohort of 4057 cognitively intact individuals 55+ years of age living in Zaragoza, Spain, and followed-up at 2.5 and 4.5 years. Age- and sex-specific incidence rates were calculated. A mortality-adjusted, multivariate model was used to document LTRs. Results: The incidence rate of dementia continued to rise after the age of 90 years, but was slightly lower than in North and West European studies. Only a tendency for an increased LTR with age was observed. Thus, LTR was 19.7% for a 65-year-old woman and 20.4% at the age of 85 years, the corresponding figures for AD being 16.7% and 17.6%. The LTR of AD was higher in women and was about twice as high among illiterate individuals when compared with individuals with higher educational levels. Conclusions: The incidence rate of dementia in this Southern European city was slightly lower than in previous studies in North-West Europe. LTR of dementia and AD seems to be slightly increased with age. The association of illiteracy with higher LTR of AD is intriguing.

Objective To evaluate the prevalence, clinical features, and comorbidities of restless legs syndrome (RLS) among psychogeriatric patients in an out-patient clinical setting. Methods Cross-sectional study of a sample of 100 non-demented psychogeriatric outpatients that were assessed for the presence of RLS using the Revised International Restless Legs Syndrome Study Group criteria and other support criteria. Medical and psychiatric illnesses, drug treatments, and other risk factors for RLS were documented. Results Prevalence of definite RLS in our sample was 11.11% with an additional prevalence of 10.10% of possible RLS. None of these patients had received a diagnosis of RLS previously. RLS was associated with major depressive disorder and with hypertension, but not with other previously described risk factors as female gender, some medical conditions, or psychoactive drug treatments. Conclusions RLS is a frequent condition in psychogeriatric patients, especially among those with depression, and is commonly underdiagnosed and undertreated. Clinicians should routinely ask for RLS symptoms when assessing their patients in their regular clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.

A number of findings suggest that inflammation plays a role in the pathophysiology of schizophrenia. Taking into account a physiological balance between pro- and anti-inflammatory mediators, we measured the plasma levels of cyclooxygenase-derived mediators and other key pro- and anti-inflammatory transcription factors in peripheral blood mononuclear cells (PBMC). Forty healthy subjects and 46 treated chronic schizophrenic patients with an acutely exacerbated condition who met DSM-IV criteria were included. COX by-products prostaglandin E2 (PGE2) and 15d-prostaglandin J2 (15d-PGJ2) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPARγ) as well as nuclear factor kappaB (NFκB) activity in nuclear extracts from PBMC and expression of its inhibitory subunit IκBα in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE2 than age-matched controls (p=0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ2 were lower (p=0.004), correlating with a lower expression of its nuclear target, PPARγ in nuclear extracts from PBMC (p=0.001). Although no changes in NFκB activity were observed between patients and healthy controls, the expression of its inhibitory protein IκBα was lower in the patients compared to the controls (p=0.027). These findings suggest that schizophrenia is associated with a systemic imbalance in the plasma levels of pro-inflammatory/anti-inflammatory prostaglandins in favor of the former. Furthermore, the expression and activity of anti-inflammatory PPARγ are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients.

Cognitive function in schizophrenia has been associated with different sociodemographic and clinical variables. Substance use disorder (SUD) history has also been associated with cognition in schizophrenia; however, contradictory results have been found regarding its influence on cognitive function. Our aim was to study the relationship between executive function and a) age, b) duration of illness, c) number of psychotic episodes, d) positive symptoms, and e) negative symptoms, in a sample of schizophrenic patients, and secondly to study whether these relationships persisted after stratification of the sample according to the presence or absence of SUD history. A final sample of 203 schizophrenic patients were evaluated for psychotic symptoms using the PANSS, and assessed using a neuropsychological battery to calculate a composite executive function score. Linear regression analyses were performed, with this executive score as the dependent variable, and age, duration of illness, number of psychotic episodes, positive PANSS score and negative PANSS score as independent variables. For the total sample, the regression model showed three variables to be significant predictors of the executive score: age (p=0.004), number of episodes (p=0.027), and PANSS negative score (p=0.003). However, once the sample was stratified, the regression model showed age (p=0.011) and number of episodes (p=0.011) to be predictor variables for the executive score in the group of schizophrenic patients with SUD history, while age (p=0.028) and PANSS negative score (p=0.006) were predictors in the group of schizophrenic patients without such history. These findings highlight the importance of considering SUD history in studies of cognitive function in schizophrenia.

Neurodevelopmental risk factors have assumed a critical role in prevailing notions concerning the etiopathogenesis of neuropsychiatric disorders. Staging, diagnostic elements at which phase of disease is determined, provides a means of conceptualizing the degree and extent of factors affecting brain development trajectories, but is concurrently specified through the particular interactions of genes and environment unique to each individual case. For present purposes, staging perspectives in neurodevelopmental aspects of the disease processes are considered from conditions giving rise to neurodevelopmental staging in affective states, adolescence, dopamine disease states, and autism spectrum disorders. Three major aspects influencing the eventual course of individual developmental trajectories appear to possess an essential determinant influence upon outcome: (i) the type of agent that interferes with brain development, whether chemical, immune system activating or absent (anoxia/hypoxia), (ii) the phase of brain development at which the agent exerts disruption, whether prenatal, postnatal, or adolescent, and (iii) the age of expression of structural and functional abnormalities. Clinical staging may be assumed at any or each developmental phase. The present perspective offers both a challenge to bring further order to diagnosis, intervention, and prognosis and a statement regarding the extreme complexities and interwoven intricacies of epigenetic factors, biomarkers, and neurobehavioral entities that aggravate currents notions of the neuropsychiatric disorders.

The prevailing utility, and indeed necessity, of clinical staging models applied in considerations of neuropsychiatric disease progressions is discussed from the perspectives of schizophrenia spectrum disorders and affective disorders, cannabis in schizopsychotic disorder, incidences of affect and psychosis, staging disorders in aging and the indices and prevalence of apathy. There would appear to be a strong current consensus that the pursuit of clinical staging of these and other brain disease states has contributed a systematic conceptual instrument to facilitate the better understanding, diagnosis, prognosis and treatment as derived from a multitude of genetic predispositions, symptoms and syndromes, early-onset and prodromal phases, recurrences and relapses, that have complicated the situation of the patient. Through a staging determination of the disorder, elements of diagnosis will describe the progression of symptoms/syndromes through pre-onset, prodromal, first-episode, recurrences and relapses, and treatment resistance thereby facilitating the eventual prognosis, intervention alternatives and treatment. This approach varies from observations of individuals at early stages of development (infancy, childhood, adolescece) to early middle age, in the case of diseases expressed through the aging processes. Essentially, the major contribution of the staging model may lie in the early identification, diagnosis, and treatments of disorders that afflict the brain and central nervous system.

Epigenetics, or alterations in the phenotype or gene expression due to mechanisms other than changes in the underlying DNA sequence, reflects the sensitivity and responsiveness of human and animal brains in constantly varying circumstances regulating gene expression profiles that define the biomarkers and present the ultimate phenotypical outcomes, such as cognition and emotion. Epigenetics is associated with functionally relevant alterations to the genome in such a fashion that under the particular conditions of early, adolescent, and adult life, environmental signals may activate intracellular pathways that remodel the "epigenome," triggering changes in gene expression and neural function. Thus, genetic influences in neuropsychiatric disorders that are subject to clinical staging, epigenetics in schizophrenia, epigenetic considerations in the expression of sensorimotor gating resulting from disease conditions, biomarkers of drug use and addiction, current notions on the role of dopamine in schizophrenia spectrum disorders, and the discrete interactions of biomarkers in persistent memory were to greater or lesser extents reflected upon. The relative contributions of endophenotypes and epistasis for mediating epigenetic phenomena and the outcomes as observed in the analysis of biomarkers appear to offer a multitude of interactive combinations to further complicate the labyrinthine machinations of diagnosis, intervention, and prognosis.

Polymorphisms of DRD2 and ANKK1 have been associated with psychiatric syndromes where there is believed to be an underlying learning process deficit such as addiction, post-traumatic stress disorder and psychopathy. We investigated the effects of the DRD2 C957T and ANKK1 TaqIA single nucleotide polymorphism (SNP), which have been associated with psychopathic traits in alcoholic patients, on fear conditioning and aversive priming in healthy volunteers. We found that the DRD2 C957T SNP, but not the ANKK1 TaqIA SNP, was associated with both differential conditioning of the skin conductance response and the aversive priming effect. There were no differences between the genotype groups with respect to the extinction of the skin-conductance conditioned response. These results suggest that the C957T SNP could be related to learning differences associated with the risk of developing psychiatric disorders in individuals that are carriers of the C homozygous genotype. Our genetic data raise the possibility that the dopaminergic system functional variations determined by this SNP could affect fear learning.

Background Taq IA, the most widely analyzed genetic polymorphism in addictions, has traditionally been considered a gene marker for association with D2 dopamine receptor gene ( DRD2 ). Taq IA is located in the coding region of the ANKK1 gene that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein nonetheless had yet to be identified. This study examined the ANKK1 expression pattern as a first step to uncover the biological bases of Taq IA-associated phenotypes. Methods Northern blot and quantitative reverse-transcriptase polymerase chain reaction analyses were performed to analyze the ANKK1 mRNA. To study ANKK1 protein expression, we developed two polyclonal antibodies to a synthetic peptides contained in the putative Ser/Thr kinase domain. Results We demonstrate that ANKK1 mRNA and protein were expressed in the adult central nervous system (CNS) in human and rodents, exclusively in astrocytes. Ankk1 mRNA level in mouse astrocyte cultures was upregulated by apomorphine, suggesting a potential relationship with the dopaminergic system. Developmental studies in mice showed that ANKK1 protein was ubiquitously located in radial glia in the CNS, with an mRNA expression pick around embryonic Day 15. This time expression pattern coincided with that of the Drd2 mRNA. On induction of differentiation by retinoic acid, a sequential expression was found in human neuroblastoma, where ANKK1 was expressed first, followed by that of DRD2 . An opposite time expression pattern was found in rat glioma. Conclusions Spatial and temporal regulation of the expression of ANKK1 suggest an involvement of astroglial cells in Taq IA-related neuropsychiatric phenotypes both during development and adult life.

Binge drinking is a common pattern of alcohol use in the US. However, no studies have evaluated the effectiveness of brief interventions targeting only binge drinkers.Randomized controlled clinical trial with a 12-month follow-up period conducted from March 1, 2003 to March 1, 2006 in Spain. Of a screened population of 15,325 patients seeking routine medical care from their primary care providers, patients who met inclusion criteria were randomized into an experimental group (n=371) or a control group (n=381). The primary outcome measures were the frequency of binge drinking episodes and weekly alcohol intake.There were no significant differences at baseline between groups in alcohol use and demographic variables. At the end of the 12-month follow-up period, there were significant reductions in binge-drinking status (52.2% vs 67.2%, P.001), number of episodes of binge drinking (1.14 vs 1.56, P.001), number of drinks weekly (19.2 vs 22.4, P.001), and frequency of excessive alcohol intake in 7 days (47.9% vs 66.6%, P.001).This study provided evidence that screening and brief counseling delivered by a primary care physician as part of regular health care significantly reduced binge drinking episodes in binge drinkers.

Twin, family and recent molecular studies support the hypothesis of genetic overlapping between schizophrenia and bipolar disorder. Brain structural features shared by both psychiatric disorders might be the phenotypic expression of a common genetic risk background. Interleukin-1 (IL-1) cluster (chromosome 2q13) genetic variability, previously associated with an increased risk both for schizophrenia and for bipolar disorder, has been also associated with gray matter (GM) deficits, ventricular enlargement and hypoactivity of prefrontal cortex in schizophrenia. The aim of the present study was to analyze the influence of IL-1 cluster on brain morphology in bipolar disorder. Genetic variability at IL-1B and IL-1RN genes was analyzed in 20 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) bipolar patients. Magnetic resonance imaging (MRI) measurements were obtained for whole-brain GM and white matter, dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus, hippocampus and lateral ventricles. MRI data were corrected for age and cranial size using regression parameters from a group of 45 healthy subjects. A -511C/T polymorphism (rs16944) of IL-1B gene was associated with whole-brain GM deficits (P = 0.031) and left DLPFCGM deficits (P = 0.047) in bipolar disorder patients. These findings support the hypothesis of IL-1 cluster variability as a shared genetic risk factor contributing to GM deficits both in bipolar disorder and in schizophrenia. Independent replication in larger samples would be of interest to confirm these results.

Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurodevelopmental components, demonstrate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cognitive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, 'healthy' young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed.

Several avenues of investigation through which the 'labyrinths' of schizopsychotic diagnosis may be examined, are offered by the consideration of the 'beacons' of symptom-profiles and biomarkers. Neurodevelopmental issues and risk assessment, neurocognitive factors of predictive necessity, supersensitivity in neurotransmitter systems, the implications of prodromal expressions of the disorder, functional dysconnectivity arising from prefrontal to diverse regional patterns and circuits with a neurodevelopmental origin, and heritable gene characteristics are viewed against the backdrop of the schizophrenia spectrum disorders. The associations between adolescent-adult use of cannabis, on the one hand, and, alternatively, the prevalence of chromosomal abnormalities, e.g., GRIK4 and NPAS3, and mental retardation, on the other hand, with the symptom-profiles of schizopsychosis provide further evidence of emerging biomarkers of biological inheritance factors. The involvement of dopamine D1 and D2 receptors, particularly in prefrontal region, with regard to functional integrity of cognitive systems is reviewed. It would appear that considerations of these disorders imply that one essential hub around which much of the neuropathology revolves may be observed in the various expressions of the cognitive and structural insufficiency.

ResumenObjetivos.El estudio de la concentración de N-acetil-aspartato (NAA) proporciona datos interesantes sobre las alteraciones corticales en las enfermedades psicóticas. Aunque la reducción de la concentración de NAA en la corteza cerebral es un resultado habitual en la esquizofrenia crónica, es menos constante en la enfermedad bipolar. Por otra parte, es probable que los valores de NAA puedan ser diferente en hombres y mujeres con esquizofrenia.Métodos.Mediante con espectroscopia por resonancia magnética protónica ('H MRS) calculamos las concentraciones de NAA en la corteza prefrontal de dos grupos de hombres, uno con esquizofrenia (n = 11) y otro con trastorno bipolar (n = 13) de similar duración y los comparamos con una muestra de hombres sanos que usamos como grupo control (n = 10). Además, comparamos el grado de desviaciones estructurales de los volúmenes normales de sustancia gris (SG) y líquido cefalorraquídeo (LCR) en la corteza prefrontal dorsolateral.Resultados.Comparados con los controles, los pacientes con esquizofrenia y trastorno bipolar tuvieron un cociente NAA/creatina más bajo, y sólo el grupo de pacientes con esquizofrenia mostró un aumento de LCR en la región prefrontal dorsolateral. No hubo ninguna diferencia entre los grupos en el cociente colina/creatina.Conclusiones.Estos datos sugieren que la disminución de NAA en la región prefrontal pueda ser similar en la esquizofrenia y en el trastorno bipolar, al menos, en estados crónicos. Sin embargo, el LCR cortical puede aumentar significativamente en pacientes con esquizofrenia.

Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the "brain reward cascade," especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

Aims.In a background of interest in staging models in psychiatry, we tested the validity of a simple staging model of cognitive impairment to predict incident dementia.Method.A large community sample of adults aged ≥55 years (N = 4803) was assessed in the baseline of a longitudinal, four-wave epidemiological enquiry. A two-phase assessment was implemented in each wave, and the instruments used included the Mini-Mental Status Examination (MMSE); the History and Aetiology Schedule and the Geriatric Mental State-AGECAT. For the standardised degree of cognitive impairment Perneczky et al's MMSE criteria were applied. A panel of psychiatrists diagnosed cases of dementia according to DSM-IV criteria, and cases and sub-cases of dementia were excluded for the follow-up waves. Competing risk regression models, adjusted by potential confounders, were used to test the hypothesised association between MMSE levels and dementia risk.Results.Out of the 4057 participants followed up, 607 (14.9%) were classified as ‘normal’ (no cognitive impairment), 2672 (65.8%) as ‘questionable’ cognitive impairment, 732 (18.0%) had ‘mild’ cognitive impairment, 38 (0.9%) had ‘moderate’ cognitive impairment and eight (0.2%) had ‘severe’ impairment.Cognitive impairment was associated with risk of dementia, the risk increasing in parallel with the level of impairment (hazard ratio: 2.72, 4.78 and 8.38 in the ‘questionable’, ‘mild’ and ‘moderate’ level of cognitive impairment, respectively).Conclusions.The documented gradient of increased risk of dementia associated with the severity level of cognitive impairment supports the validity of the simple staging model based on the MMSE assessment.

Background: Different neuropsychological studies have shown schizophrenic patients to have executive function deficits, as illustrated by their performance in neuropsychological tasks such as the Wisconsin Card Sorting Test (WCST); certain studies have described a relationship between these deficits and negative symptoms. Schizophrenic patients also exhibit a high lifetime prevalence (40–50%) of comorbid substance use disorders (SUDs). However, little attention has been paid to this comorbidity (dual diagnosis) in studies associating executive functions and negative symptoms. Sampling and Methods: Our objective is to investigate the relationship between performance in the WCST and psychopathology as measured by the Positive and Negative Syndrome Scale (PANSS) in a sample of 65 male schizophrenic patients with a history of SUDs (Sch SUD+) and in a sample of 48 male schizophrenic patients without such history (Sch SUD–). Results: In the Sch SUD– group, patients who completed 4 or more categories in the WCST (‘good performers’) obtained a mean score of 21.2 ± 8.8 on the negative subscale of the PANSS, compared with a mean score of 27.8 ± 8.6 in those who completed 3 or less (‘poor performers’); these differences were statistically significant (p = 0.015). In the Sch SUD+ group, however, no association was found between WCST performance and the PANSS negative subscale score. Conclusions: The presence of a history of comorbid SUDs should be taken into consideration in studies investigating executive functions and negative symptoms in schizophrenia.

ObjectivesA study of N-acetyl-aspartate (NAA) can provide data of interest about cortical alterations in psychotic illnesses. Although a decreased NAA level in the cerebral cortex is a replicated finding in chronic schizophrenia, the data are less consistent for bipolar disease. On the other hand, it is likely that NAA values in schizophrenia may differ in men and women.MethodsWe used proton magnetic resonance spectroscopy (1H MRS) to examine NAA levels in the prefrontal cortex in two groups of male patients, one with schizophrenia (n = 11) and the other with bipolar disorder (n = 13) of similar duration, and compared them to a sample of healthy control males (n = 10). Additionally, we compared the degree of structural deviations from normal volumes of gray matter (GM) and cerebrospinal fluid (CSF) in the dorsolateral prefrontal cortex.ResultsCompared to controls, schizophrenia and bipolar patients presented decreased NAA to creatine ratios, while only the schizophrenia group showed an increase in CSF in the dorsolateral prefrontal region. There were no differences in choline to creatine ratios among the groups.ConclusionsThese data suggest that the decrease in NAA in the prefrontal region may be similar in schizophrenia and bipolar disorder, at least in the chronic state. However, cortical CSF may be markedly increased in schizophrenia patients.

This study evaluated the effects of a putative activator of brain reward circuitry on outcomes in a 1-y prospective comprehensive outpatient clinical program. As part of the Gene Narcotic Attenuation Program, Haveos (Synaptamine)(TM) was administered for the treatment of substance use disorder. Seventy-six patients (45 males and 31 females; mean age, 33 y [standard deviation, 7.0]) who had been given a diagnosis of serious substance use disorder were recruited. After exclusion of 15 patients who dropped out before the end of the study, self-reported craving decreased from program entrance to 12 wk (visual analog scale whereby 0 represents no craving and 5, the strongest craving) for 61 compliant patients (mean decrease, 2.85, 95% confidence interval [CI], 2.65, 3.05); this improvement was significant (P

The neuronal substrates underlying aspects of comorbidity in brain disease states may be described over psychiatric and neurologic conditions that include affective disorders, cognitive disorders, schizophrenia, obsessive-compulsive disorder, substance abuse disorders as well as the neurodegenerative disorders. Regional and circuitry analyses of biogenic amine systems that are implicated in neural and behavioural pathologies are elucidated using neuroimaging, electrophysiological, neurochemical, neuropharmacological and neurobehavioural methods that present demonstrations of the neuropathological phenomena, such as behavioural sensitisation, cognitive impairments, maladaptive reactions to environmental stress and serious motor deficits. Considerations of neuronal alterations that may or may not be associated with behavioural abnormalities examine differentially the implications of discrete areas within brains that have been assigned functional significance; in the case of the frontal lobes, differential deficits of ventromedial and dorsolateral prefrontal cortex may be associated with different aspects of cognition, affect, remission or response to medication thereby imparting a varying aspect to any investigation of comorbidity.

Substance abuse is a frequent comorbid condition with other psychiatric disorders including schizophrenia and depression. These disorders may share a common substrate at the neurotransmitter or neurocircuit level. One candidate is hypofunction of the glutamate system. Several lines of evidence suggest that N-methyl-D-aspartate (NMDA) receptors may hypofunction in schizophrenia. Thus, NMDA receptor antagonists are schizophrenogenic; postmortem and imaging results point to reduced NMDA receptor function in schizophrenic brains; a number of genes that have been linked to schizophrenia code for proteins that influence NMDA function; and there is preliminary evidence that pro-NMDA drugs may be therapeutic in the treatment of schizophrenia. One of the most effective therapeutics for the treatment of substance abuse in schizophrenic people is clozapine, and clozapine may act at the glycine modulatory site to enhance NMDA receptor function. This preliminary line of evidence may link schizophrenia and drug abuse to a common neurochemical base, subnormal NMDA receptor function. People with schizophrenia and drug abusers similarly show deficits in tasks known to be sensitive to ventromedial prefrontal cortical damage, and both groups show decreased activation in the ventral striatum during reward anticipation in functional magnetic resonance imaging studies. These observations implicate common prefrontal cortical-striatal circuits and their modulation by hippocampal projections in schizophrenia and substance abuse. Withdrawal from substance abuse and depression both have been linked to changes in the function of several neurotransmitters including serotonin, dopamine and glutamate. These findings suggest possible common substrates and novel therapeutic approaches. Further studies are needed to fully characterize the neurocircuits and transmitters involved in various psychiatric disorders and their possible common elements in comorbid drug abuse.

There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. Recently, we evaluated a complex named Synaptamine [Haveos (SG8839R)]. The main difference with an older studied variant and the latest variant is the inclusion of a proprietary form of Rhodiola rosea, a known catechol-O-methyl-transferase inhibitor (COMT) to potentially enhance the activity of presynaptic released dopamine. In this regard, based on the current literature we hypothesize that manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, is dependent upon gene polymorphisms. In this regard we hypothesize that carrying the LL genotype with low COMT activity should as theorized, increase the reward induced by substance-induced dopamine release and may indeed increase the propensity to type 1 alcoholism and possibly other drugs that activate the dopaminergic system. Thus when alcohol is present in low COMT LL genotype, increasing COMT activity, not inhibiting it should assist in the reduction of social consumption or abuse. Alternatively, under physiological conditions (no psychoactive substances present (e.g. alcohol) carrying the DRD2 A1 allele with associated low D2 receptors should, as theorized, increase craving behavior because of a low or hypodopaminergic state causing the individual to seek out substances that increase the release of dopamine for subsequent activation of unbound D2 sites in the nucleus accumbens. Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimin) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse.

Fundamento y objetivo La enzima catecol-O-metiltransferasa (COMT) interviene de un modo significativo en la regulacion del sistema dopaminergico, especialmente en la corteza prefrontal. Estudios previos han evaluado la asociacion entre la actividad enzimatica de la COMT y la esquizofrenia, aunque los resultados no han sido concluyentes. El gen COMT contiene un polimorfismo funcional que ocasiona, en la posicion 158 del peptido, el cambio de valina por metionina y la modificacion de la actividad enzimatica, de forma que la COMT -valina muestra una capacidad de degradacion postsinaptica de la dopamina significativamente superior a la COMT -metionina. El objetivo de este trabajo es realizar un estudio de asociacion genetica con el polimorfismo funcional Val 158 Met del gen COMT en pacientes con esquizofrenia y en controles sanos espanoles. Pacientes y metodo Se ha realizado un estudio de casos y controles con una muestra de 177 pacientes y 141 controles. Los pacientes del estudio –115 varones y 62 mujeres, con una edad entre 27 y 49 anos; media (desviacion estandar) de 38 (10,7) anos– se incluyeron consecutivamente segun acudieron a las consultas del Servicio de Psiquiatria del Hospital Universitario 12 de Octubre y si cumplian criterios DSM-IV (cuarta edicion del Diagnostic and Statistical Manual of Mental Disorders) para esquizofrenia (n = 162) o trastorno esquizoafectivo (n = 15). Asimismo, se incluyo a 141 controles evaluados, sanos y libres de enfermedad medica o psiquiatrica –92 varones y 49 mujeres, con una edad entre 26 y 47 anos, media de 36 (9,4) anos–. La identificacion del genotipo se llevo a cabo por medio de tecnicas de genetica molecular humana que asociaron la reaccion en cadena de la polimerasa del ADN al estudio de la conformacion de la hebra simple del ADN ( single strand conformational polymorphism ; SSCP) del polimorfismo Val 158 Met de COMT . Resultados No se encontraron diferencias significativas en las frecuencias de los alelos para este polimorfismo al comparar controles y pacientes. Sin embargo, en el analisis por genotipos y desde un modelo de herencia recesivo (Val/Val frente a Val/Met y Met/Met), se detecto una posible tendencia a la significacion. Nuestros resultados no permiten confirmar la posible contribucion de variaciones del gen COMT en la etiopatogenia de la esquizofrenia, pero ofrecen indicios que permiten sospechar su participacion en algunos grupos concretos de pacientes. Conclusiones Con los resultados obtenidos en este estudio, la posible contribucion del gen COMT en la etiopatogenia de la esquizofrenia no puede descartarse. El debate sobre el posible efecto del polimorfismo Val 158 Met de COMT en la esquizofrenia se mantendria abierto; de ahi la necesidad de reproducir los estudios en muestras mayores que permitan analisis estratificados de subgrupos de pacientes.

The Annunciation from the Monastery of Santo Domingo of Caleruega, founded by Alfonso X the Wise, has remained virtually forgotten by the Spanish historiography. Isolated behind the walls of the cloister, the sculpture group presents a particularity that hasn’t been properly analyzed for too long: the Virgin is pregnant. The amount of recorded examples of the same nature shows that this kind of representations was common in some kingdoms of the Iberian Peninsula during the Late Middle Ages. From an essentially iconographic perspective, but without giving up further approaches, this paper provides an in-depth study on the singularity of the Annunciation from Caleruega. At the same time, it becomes the starting point for a comprehensive analysis of this variant of the Angelic Salutation.

Objective In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimer's disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM-5 (DSM-5-MCI) and Petersen's (P-MCI) criteria. Method A population representative cohort of 4057 dementia-free individuals 55+ years of age was followed up at 2.5 and 4.5 years in Zaragoza, Spain (ZARADEMP). Using the Geriatric Mental State- AGECAT for assessment, research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. ‘Conversion rate’ (CR), ‘annual conversion rate’ (ACR), and incidence rate (IR) were calculated along with incidence rate ratio (IRR) to compare the performance of the intermediate cognitive definitions. Results At 4.5-year follow-up, in individuals aged 65+ years, ACRs for non-cases, P-MCI, and DSM-5-MCI were 0.8, 1.9 and 3.4, respectively, for global dementia. The IRRs were 2.9 and 5.3 for P-MCI and DSM5-MCI, respectively, being the non-cases the reference category. The corresponding values were slightly lower for AD. Conclusion Conversion rate to dementia and AD was higher using DSM-5-MCI criteria than using Petersen's criteria. However, prediction of the construct still has some way to go, as most MCI individuals did not convert at 4.5-year follow-up.

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.

Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps

Previous studies have generally found a relationship between negative and cognitive symptoms in schizophrenia. The present study investigated the relationship between the 5 PANSS factors of a recent consensus model developed by NIMH researchers, and cognitive performance as assessed with the MATRICS Consensus Cognitive Battery (MCCB) in 80 patients with schizophrenia using correlation and regression analyses. The PANSS Cognitive factor showed a small to moderate significant association with MCCB Speed of processing, Working memory, Verbal learning, the Neurocognitive composite score, and the Overall composite score. Notably, however, no relationship was found between the PANSS Negative factor and any of the MCCB scores. The Positive, Excited and Depressed factors also did not show associations with the MCCB. These results highlight the need for refined assessment instruments and support the relative independence of cognition from other domains of psychopathology, including negative symptoms, in patients with schizophrenia.

ResumenEl polimorfismo TaqIA vinculado al gen del receptor D2 de dopamina se ha asociado con el alcoholismo. El propósito de este trabajo es estudiar la atención y el control inhibitorio mediante el test de ejecución continua y la tarea de detención en una muestra de 50 pacientes varones alcohólicos españoles divididos en dos grupos segύn la presencia del alelo TaqIA1 en su genotipo. Nuestros resultados muestran que los alcoholicos portadores del alelo TaqIA1 presentan atención sostenida más baja y menos control inhibitorio que los pacientes sin ese alelo.