Time discrimination and change detection could share a common brain network: findings of a task-based fMRI study.

Introduction: Over the past few years, several studies have described the brain activation pattern related to both time discrimination (TD) and change detection processes. We hypothesize that both processes share a common brain network which may play a significant role in more complex cognitive processes. The main goal of this proof-of-concept study is to describe the pattern of brain activity involved in TD and oddball detection (OD) paradigms, and in processes requiring higher cognitive effort. Methods: We designed an experimental task, including an auditory test tool to assess TD and OD paradigms, which was conducted under functional magnetic resonance imaging (fMRI) in 14 healthy participants. We added a cognitive control component into both paradigms in our test tool. We used the general linear model (GLM) to analyze the individual fMRI data images and the random effects model for group inference. Results: We defined the areas of brain activation related to TD and OD paradigms. We performed a conjunction analysis of contrast TD (task > control) and OD (task > control) patterns, finding both similarities and significant differences between them. Discussion: We conclude that change detection and other cognitive processes requiring an increase in cognitive effort require participation of overlapping functional and neuroanatomical components, suggesting the presence of a common time and change detection network. This is of particular relevance for future research on normal cognitive functioning in the healthy population, as well as for the study of cognitive impairment and clinical manifestations associated with various neuropsychiatric conditions such as schizophrenia.

'Effectiveness of a remote nutritional intervention to increase the adherence to the Mediterranean diet among recovered depression patients'.

BACKGROUND: There is substantial evidence supporting that remote interventions are useful to change dietary habits. However, the effect of a remote intervention based on Mediterranean diet (MD) in depressive patients has been less explored. OBJECTIVE: This study aims to assess the effectiveness of a remotely provided Mediterranean diet-based nutritional intervention in the context of a secondary prevention trial of depression. METHODS: The PREDIDEP study was a 2-year multicenter, randomized, single-blinded trial designed to assess the effect of the MD enriched with extra virgin olive oil (EVOO) on the prevention of depression recurrence. The intervention group received usual care for depressed patients and remote nutritional intervention every three months which included phone contacts and web-based interventions; and the control group, usual care. At baseline and at 1-year and 2-year follow-up, the 14-item MD Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire (FFQ) were collected by a dietitian. Mixed effects linear models were used to assess changes in nutritional variables according to the group of intervention. The trial was registered at ClinicalTrials.gov NCT03081065. RESULTS: Compared with control group, the MD intervention group showed more adherence to MD (between-group difference: 2.76; 95% CI 2.13-3.39; p < 0.001); and a healthier diet pattern with a significant increase in the consumption of olive oil (p < 0.001), and a significant reduction in refined cereals (p = 0.031) after 2 years of intervention. CONCLUSIONS: The remote nutritional intervention increases adherence to the MD among recovered depression patients.Trial registration: ClinicalTrials.gov identifier: NCT03081065.

Schizophrenia and Hospital Admissions for Cardiovascular Events in a Large Population: The APNA Study.

(1) Background: Patients with schizophrenia have higher mortality, with cardiovascular diseases being the first cause of mortality. This study aims to estimate the excess risk of hospital admission for cardiovascular events in schizophrenic patients, adjusting for comorbidity and risk factors. (2) Methods: The APNA study is a dynamic prospective cohort of all residents in Navarra, Spain. A total of 505,889 people over 18 years old were followed for five years. The endpoint was hospital admissions for a cardiovascular event. Direct Acyclic Graphs (DAG) and Cox regression were used. (3) Results: Schizophrenic patients had a Hazard Ratio (HR) of 1.414 (95% CI 1.031-1.938) of hospital admission for a cardiovascular event after adjusting for age, sex, hypertension, type 2 diabetes, dyslipidemia, smoking, low income, obesity, antecedents of cardiovascular disease, and smoking. In non-adherent to antipsychotic treatment schizophrenia patients, the HR was 2.232 (95% CI 1.267-3.933). (4) Conclusions: Patients with schizophrenia have a higher risk of hospital admission for cardiovascular events than persons with the same risk factors without schizophrenia. Primary care nursing interventions should monitor these patients and reduce cardiovascular risk factors.

Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain.

BACKGROUND: We analyzed the relationship between the prevalence of schizophrenia and the season of birth and gestation during a period of an influenza pandemic. METHODS: Cross-sectional analysis of a prospective population-based cohort of 470,942 adults. We fitted multivariant logistic regression models to determine whether the season of birth and birth in an influenza-pandemic year (1957, 1968, 1977) was associated with schizophrenia. RESULTS: 2077 subjects had been diagnosed with schizophrenia. Logistic regression identified a significantly greater prevalence of schizophrenia in men than in women (OR = 1.516, CI 95% = 1.388-1.665); in those born in the winter or spring than in those born in the summer or autumn (OR = 1.112, CI 95% = 1.020-1.212); and in those born in a period of an influenza pandemic (OR = 1.335, CI 95% = 1.199-1.486). The increase in risk was also significant when each influenza pandemic year was analyzed separately. However, neither month of birth nor season of birth, when each of the four were studied individually, were associated with a statistically significant increase in that risk. CONCLUSIONS: The winter-spring period and the influenza pandemics are independent risk factors for developing schizophrenia. This study contradicts many previous studies and thus revitalizes a locked debate in understanding the neurodevelopmental hypothesis of this disorder.

An fMRI Study Using a Combined Task of Interval Discrimination and Oddball Could Reveal Common Brain Circuits of Cognitive Change.

Recent functional neuroimaging studies suggest that the brain networks responsible for time processing are involved during other cognitive processes, leading to a hypothesis that time-related processing is needed to perform a range of tasks across various cognitive functions. To examine this hypothesis, we analyze whether, in healthy subjects, the brain structures activated or deactivated during performance of timing and oddball-detection type tasks coincide. To this end, we conducted two independent signed differential mapping (SDM) meta-analyses of functional magnetic resonance imaging (fMRI) studies assessing the cerebral generators of the responses elicited by tasks based on timing and oddball-detection paradigms. Finally, we undertook a multimodal meta-analysis to detect brain regions common to the findings of the two previous meta-analyses. We found that healthy subjects showed significant activation in cortical areas related to timing and salience networks. The patterns of activation and deactivation corresponding to each task type partially coincided. We hypothesize that there exists a time and change-detection network that serves as a common underlying resource used in a broad range of cognitive processes.

Eating Disorder Awareness Campaigns: Thematic and Quantitative Analysis Using Twitter.

BACKGROUND: Health awareness initiatives are frequent but their efficacy is a matter of controversy. We have investigated the effect of the Eating Disorder Awareness Week and Wake Up Weight Watchers campaigns on Twitter. OBJECTIVE: We aimed to examine whether the Eating Disorder Awareness Week and Wake Up Weight Watchers initiatives increased the volume and dissemination of Twitter conversations related to eating disorders and investigate what content generates the most interest on Twitter. METHODS: Over a period of 12 consecutive days in 2018, we collected tweets containing the hashtag #wakeupweightwatchers and hashtags related to Eating Disorder Awareness Week (#eatingdisorderawarenessweek, #eatingdisorderawareness, or #EDAW), with the hashtag #eatingdisorder as a control. The content of each tweet was rated as medical, testimony, help offer, awareness, pro-ana, or anti-ana. We analyzed the number of retweets and favorites generated, as well as the potential reach and impact of the hashtags and the characteristics of contributors. RESULTS: The number of #wakeupweightwatchers tweets was higher than that of Eating Disorder Awareness Week and #eatingdisorder tweets (3900, 2056, and 1057, respectively). The content of tweets was significantly different between the hashtags analyzed (P<.001). Medical content was lower in the awareness campaigns. Awareness and help offer content were lower in #wakeupweightwatchers tweets. Retweet and favorite ratios were highest in #wakeupweightwatchers tweets. Eating Disorder Awareness Week achieved the highest impact, and very influential contributors participated. CONCLUSIONS: Both awareness campaigns effectively promoted tweeting about eating disorders. The majority of tweets did not promote any specific preventive or help-seeking behaviors.

Temperament traits and remission of depression: A naturalistic six-month longitudinal study.

BACKGROUND: The aim of this naturalistic longitudinal study was to add evidence regarding the potential of Cloninger's temperament traits (novelty seeking, harm avoidance, reward dependence and persistence) for predicting the effect of pharmacological treatment on the rates of therapeutic response and remission. METHODS: The study was based on 200 outpatients with unipolar depressive disorders of different severity and course of illness, and extended up to 6 months of follow-up. Patients were assessed in their temperament with the Tridimensional Personality Questionnaire (TPQ) and their condition was classified (in course and severity) according to the International Classification of Diseases, Tenth revision (ICD-10) diagnostic criteria for research. Patients were blindly rated (concerning other predicting variables) on the improved Clinical Global Impression-Severity scale for depression (iCGI-S) at baseline, 6 weeks, 3 months and 6 months. Outcome measures at the last observation carried forward were therapeutic response (reduction of ≥50% in the last iCGI-S) and remission (last iCGI-S = 0), which were available for 187 patients. RESULTS: Remission was independently and directly associated with length of follow-up, and inversely with the baseline iCGI-S score and harm avoidance (patients in the high tertile had a 2.7 likelihood of non-remission in comparison with those in the low tertile); persistence was found to have a complex, V-shape relationship with remission. Within a sub-sample of more severe cases (n = 118), having higher harm avoidance scores, a more favorable outcome was associated with higher reward dependence and the non-smoking condition. LIMITATIONS: With a naturalistic, non-experimental design, the sample may not be representative of the general population. CONCLUSIONS: Temperament traits may help predict outcome in patients treated for depression.

Aberrant timing and oddball detection in Schizophrenia: findings from a signed differential mapping meta-analysis.

Schizophrenia (SZ) is associated with deficits in both temporal and salience processing. The underlying neurological dysfunctions in both processes, which are interrelated and share neuroanatomical bases, remain poorly understood. The principal objective of this study was to elucidate whether there are any brain regions that show abnormal response during timing and oddball tasks in patients with SZ. To this end, we conducted a signed differential mapping (SDM) meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing abnormal responses elicited by tasks based on the oddball paradigm in patients with SZ. We conducted a similar SDM meta-analysis of neuroimaging studies of timing tasks in SZ. Finally, we undertook a multimodal meta-analysis to detect the common findings of the two previous meta-analyses. We found that SZ patients showed hypoactivation in cortical and subcortical areas related to timing. The dysfunction observed during timing tasks partially coincided with deficiencies in change-detection functions (particularly in the case of preattentional processing in the mismatch negativity response). We hypothesize that a dysfunctional timing/change detection network underlies the cognitive impairment observed in SZ.

Increasing Interest of Mass Communication Media and the General Public in the Distribution of Tweets About Mental Disorders: Observational Study.

BACKGROUND: The contents of traditional communication media and new internet social media reflect the interests of society. However, certain barriers and a lack of attention towards mental disorders have been previously observed. OBJECTIVE: The objective of this study is to measure the relevance of influential American mainstream media outlets for the distribution of psychiatric information and the interest generated in these topics among their Twitter followers. METHODS: We investigated tweets generated about mental health conditions and diseases among 15 mainstream general communication media outlets in the United States of America between January 2007 and December 2016. Our study strategy focused on identifying several psychiatric terms of primary interest. The number of retweets generated from the selected tweets was also investigated. As a control, we examined tweets generated about the main causes of death in the United States of America, the main chronic neurological degenerative diseases, and HIV. RESULTS: In total, 13,119 tweets about mental health disorders sent by the American mainstream media outlets were analyzed. The results showed a heterogeneous distribution but preferential accumulation for a select number of conditions. Suicide and gender dysphoria accounted for half of the number of tweets sent. Variability in the number of tweets related to each control disease was also found (5998). The number of tweets sent regarding each different psychiatric or organic disease analyzed was significantly correlated with the number of retweets generated by followers (1,030,974 and 424,813 responses to mental health disorders and organic diseases, respectively). However, the probability of a tweet being retweeted differed significantly among the conditions and diseases analyzed. Furthermore, the retweeted to tweet ratio was significantly higher for psychiatric diseases than for the control diseases (odds ratio 1.11, CI 1.07-1.14; P<.001). CONCLUSIONS: American mainstream media outlets and the general public demonstrate a preferential interest for psychiatric diseases on Twitter. The heterogeneous weights given by the media outlets analyzed to the different mental health disorders and conditions are reflected in the responses of Twitter followers.

Meta-analysis of functional magnetic resonance imaging studies of timing and cognitive control in schizophrenia and bipolar disorder: Evidence of a primary time deficit.

Schizophrenia (SZ) and Bipolar Disorder (BD) are associated with deficits in both timing and cognitive control functions. However, the underlying neurological dysfunctions remain poorly understood. The main goal of this study was to identify brain structures activated both by increases in cognitive activity and during timing tasks in patients with SZ and BD relative to controls. We conducted two signed differential mapping (SDM) meta-analyses of functional magnetic resonance imaging studies assessing the brain response to increasing levels of cognitive difficulty: one concerned SZ, and the other BD patients. We conducted a similar SDM meta-analysis on neuroimaging of timing in SZ (no studies in BD could be included). Finally, we carried out a multimodal meta-analysis to identify common brain regions in the findings of the two previous meta-analyses. We found that SZ patients showed hypoactivation in timing-related cortical-subcortical areas. The dysfunction observed during timing partially coincided with deficits for cognitive control functions. We hypothesize that a dysfunctional temporal/cognitive control network underlies the persistent cognitive impairment observed in SZ.

Atypical antipsychotics normalize low-gamma evoked oscillations in patients with schizophrenia.

The symptoms of schizophrenia might be mediated by a cortical network disconnection which may disrupt the cortical oscillatory activity. Steady-state responses are an easy and consistent way to explore cortical oscillatory activity. A chirp-modulated tone (increasing the frequency of the modulation in a linear manner) allows a fast measure of the steady-state response to different modulation rates. With this approach, we studied the auditory steady-state responses in two groups of patients with schizophrenia (drug-naive and treated with atypical antipsychotic drugs), in order to assess the differences in their responses with respect to healthy subjects, and study any potential effect of medication. Drug-naive patients had reduced amplitude and inter-trial phase coherence of the response in the 30-50Hz range, and reduced amplitude of the response in the 90-100Hz range, when compared to controls. In the treated patients group, the response in the 30-50Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90-100Hz range remained as in the drug-naive group. These results suggest that gamma activity impairment in schizophrenia is a complex phenomenon that affects a wide band of frequencies and may be influenced by antipsychotic treatment.

Geniuses of medical science: Friendly, open and responsible, not mad.

Recent studies based on biography analysis provide support for the notion that the prevalence of mental illness in the creative geniuses of art, literature and science is higher than it is in more ordinary folk. However, this relationship between madness and genius, which was also addressed by the classical philosophers, has been generalized to all branches of professional endeavour. Whilst it may hold true for illustrious personalities of the fine arts, we found that the relationship proves inappropriate to the biographies of ten individuals renowned in history for their innovative contributions to medical science. Furthermore, examination of these ten biographies invites the hypothesis that certain personality traits - especially, agreeableness, conscientiousness and openness to new experience - can act to enhance creativity and protect against mental illness.

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network.

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile.

Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis.

BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response. METHODS: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study's original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model. RESULTS: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02-1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024-0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65). CONCLUSIONS: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics.

Time perception networks and cognition in schizophrenia: a review and a proposal.

Timing is an essential function for the survival of many living organisms. Despite its significance, it is relatively under-researched, particularly in schizophrenia. We examined neurophysiological, neuropathological, imaging and genetic studies of both healthy subjects and subjects suffering from schizophrenia in relation to time perception as measured by interval timing. We found that the data from studies in healthy populations indicate that time perception may be inter-linked with numerous other cognitive functions and share common brain networks. The same networks are implicated in the pathophysiology of schizophrenia. There is also evidence that several neurotransmitter systems, particularly the dopaminergic D2 system, are involved in interval timing. Patients with schizophrenia have been shown to suffer from a distorted sense of time, which has an impact on their cognitive function and results in both positive and negative symptoms. Therefore, genes involved in interval timing can be considered candidate genes for distorted cognition in schizophrenia. We discuss the hypothesis that time perception dysfunction is a primary cognitive dysfunction in schizophrenia.

Meta-analysis of functional neuroimaging studies indicates that an increase of cognitive difficulty during executive tasks engages brain regions associated with time perception.

OBJECTIVES: We hypothesize that time perception and executive functions are interrelated and share neuroanatomical basis, and that fluctuations in levels of cognitive effort play a role in mediating that relation. The main goal of this study was to identify brain structures activated both by increases in cognitive activity and during time perception tasks. METHODS: We performed a multimodal meta-analysis to identify common brain regions in the findings of (a) an SDM meta-analysis of neuroimaging studies assessing the brain response to increasing levels of cognitive difficulty, and (b) an ALE meta-analysis on neuroimaging of time perception (Ortuño, Guillén-Grima, López-García, Gómez, & Pla, 2011. Schizophr. Res., 125(2-3), 129-35). RESULTS AND CONCLUSIONS: Consistent with results of previous, separate meta-analyses, the current study supports the hypothesis that there exists a group of brain regions engaged both in time perception tasks and during tasks requiring cognitive effort. Thus, brain regions associated with working memory and executive functions were found to be engaged during time estimation tasks, and regions associated with time perception were found to be engaged by an increase in the difficulty of non-temporal tasks. The implication is that temporal perception and cognitive processes demanding cognitive control become interlinked when there is an increase in the level of cognitive effort demanded.

Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit-hyperactivity disorder and bipolar disorder.

BACKGROUND: As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP. MATERIALS AND METHODS: We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used. RESULTS: Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p=0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p>0.05). CONCLUSIONS: The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders. LIMITATIONS: Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.

Structural brain abnormalities in first-episode psychosis: differences between affective psychoses and schizophrenia and relationship to clinical outcome.

OBJECTIVES: Several studies have described volumetric brain abnormalities in first-episode psychosis. The extent to which these differ in patients with schizophrenia and affective psychoses, or are related to subsequent clinical outcome, is unclear. We examined volumetric magnetic resonance imaging (MRI) abnormalities in young patients with a first episode of psychosis, and compared these volumetric abnormalities in patients with schizophrenia versus affective psychosis. We then assessed whether baseline MRI abnormalities in the entire sample predicted subsequent clinical outcome. METHODS: A total of 28 adolescent patients with first-episode psychosis and 20 age-matched healthy volunteers were scanned using a 1.5 T scanner. MRI data were processed and analysed using voxel-based morphometry (VBM). We assessed clinical outcome three years after the initial scan. RESULTS: Patients had smaller grey matter (GM) volumes than controls in frontal, insular, parietal, and cerebellar cortex. Patients with an affective psychosis had greater GM volume in the right posterior cingulate than both controls and patients with schizophrenia, but less GM volume in the left cerebellum and insula. In the sample as a whole, smaller right hippocampus GM volume was associated with poor clinical outcome at three-year follow-up. CONCLUSIONS: Volumetric brain abnormalities are evident in young adults presenting with a first episode of both affective psychoses and schizophrenia, but there are also significant differences between these two patient groups. Clinical outcome after the first episode may be related to the severity of volumetric abnormalities at presentation.