Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders.

BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. METHODS: To uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ. Rather than relying on a classical voxel level coordinate-based approach, our procedure extracted relevant neuroanatomical labels from text data and examined findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients/7414 controls), BD (81 studies, 3330 patients/4096 patients) and/or SZ (223 studies, 11,168 patients/11,754 controls). Permutation testing revealed commonalities and differences in hypoconnectivity and hyperconnectivity patterns across disorders. RESULTS: Hypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the three disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD. CONCLUSIONS: Findings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate between mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience.

Converting scores between the PANSS and SAPS/SANS beyond the positive/negative dichotomy.

Previous work provided conversion equations for overall indices of positive and negative symptomatology between the Positive and Negative Syndrome Scale (PANSS) and the Scales for the Assessment of Positive/Negative Symptoms (SAPS/SANS). Our objective was to provide such conversion equations for subdomains of positive and negative symptomatology in order to better account for the diversity of symptom profiles in schizophrenia. Symptoms severity was assessed using both the PANSS and SAPS/SANS in 205 patients with schizophrenia. Two exploratory factor analyses combining items from both scales were first performed separately in the positive and negative symptom domains. Positive factors were termed 'Hallucinations', 'Delusions' and 'Disorganization', while negative factors were associated with 'Expressivity', 'Amotivation' and 'Cognition', consistent with current descriptions of symptom dimensions in schizophrenia. For each factor, linear regression analyses were conducted on 80% of the data to obtain conversion equations from the PANSS to the SAPS/SANS and vice versa. Reliability was then evaluated on the 20% remaining data, with good to excellent intra-class correlation coefficients between the original and predicted scores for all but the cognition factor. These findings show that symptom severity scores can be converted with good accuracy between clinical scales beyond the positive/negative symptom dichotomy.

Medical students attitudes toward and intention to work with the underserved: a systematic review and meta-analysis.

BACKGROUND: Experts in the field of medical education emphasized the need for curricula that improve students' attitudes toward the underserved. However, some studies have shown that medical education tends to worsen these attitudes in students. We aimed at systematically reviewing the literature assessing the change in medical students' attitudes toward the underserved and intention to work with the underserved throughout medical education, the sociodemographic and educational factors associated with favorable medical student attitudes toward and/or intention to work with the underserved and the effectiveness of educational interventions to improve medical student attitudes toward and/or intention to work with the underserved. METHOD: We conducted a systematic review on MEDLINE, Scopus, and Web of Science databases. Three investigators independently conducted the electronic search. We assessed the change in medical students attitudes toward the underserved by computing a weighted mean effect size of studies reporting scores from validated scales. The research team performed a meta-analysis for the sociodemographic and educational factors associated with medical students attitudes toward and/or intention to work with the underserved. RESULTS: Fifty-five articles met the inclusion criteria, including a total of 109,647 medical students. The average response rate was 73.2%. Most of the studies were performed in the USA (n = 45). We observed a significant decline of medical students attitudes toward the underserved throughout medical education, in both US and non-US studies. A moderate effect size was observed between the first and fourth years (d = 0.51). Higher favorable medical students attitudes toward or intention to work with the underserved were significantly associated with female gender, being from an underserved community or ethnic minority, exposure to the underserved during medical education and intent to practice in primary care. Regarding educational interventions, the effectiveness of experiential community-based learning and curricula dedicated to social accountability showed the most positive outcome. CONCLUSIONS: Medical students attitudes toward the underserved decline throughout medical education. Educational interventions dedicated to improving the attitudes or intentions of medical students show encouraging but mixed results. The generalizability of our results is impeded by the high number of studies from the global-North included in the review.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

Perceived ethnic discrimination as a risk factor for psychotic symptoms: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown an elevated risk of psychotic symptoms (PS) and experiences (PEs) among ethnic minority groups, with significant variation between groups. This pattern may be partially attributable to the unfavorable socio-environmental conditions that surround ethnic minority groups. Perceived ethnic discrimination (PED) in particular has been a salient putative risk factor to explain the increased risk. METHODS: We conducted a systematic literature review and meta-analysis to assess the impact of PED on reporting PS/PEs in ethnic minorities. This review abides by the guidelines set forth by Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The included studies were obtained from the databases: Medline, PsycINFO, and Web Of Science. Sub-group analyses were performed assessing the effect of PED in different subtypes of PS, the influence of ethnicity and moderating/mediating factors. RESULTS: Seventeen studies met the inclusion criteria, and nine were used to conduct the meta-analysis. We found a positive association between PED and the occurrence of PS/PEs among ethnic minorities. The combined odds ratio were 1.77 (95% CI 1.26-2.49) for PS and 1.94 (95% CI 1.42-2.67) for PEs. We found that the association was similar across ethnic groups and did not depend on the ethnic origin of individuals. Weak evidence supported the buffering effects of ethnic identity, collective self-esteem and social support; and no evidence supported the moderating effect of ethnic density. Sensitivity to race-based rejection significantly but only slightly mediated the association. CONCLUSION: These findings suggest that PED is involved in the increased risk of PS/PEs in ethnic minority populations.

Ethnic minority position and migrant status as risk factors for psychotic symptoms in the general population: a meta-analysis.

Psychotic symptoms (PS) are experienced by a substantial proportion of the general population. When not reaching a threshold of clinical relevance, these symptoms are defined as psychotic experiences (PEs) and may exist on a continuum with psychotic disorders. Unfavorable socio-environmental conditions, such as ethnic minority position (EMP) and migrant status (MS), may increase the risk of developing PS and PEs. We conducted an electronic systematic review and a meta-analysis assessing the role of EMP and MS for the development and persistence of PS in the general population. Sub-group analyses were performed investigating the influence of ethnic groups, host countries, age, types of PS, and scales. Twenty-four studies met our inclusion criteria. EMP was a relevant risk factor for reporting PS [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.22-1.70) and PEs (OR 1.36, 95% CI 1.16-1.60). The greatest risk was observed in people from the Maghreb and the Middle East ethnic groups in Europe (OR 3.30, 95% CI 2.09-5.21), in Hispanic in the USA (OR 1.98, 95% CI 1.43-2.73), and in the Black populations (OR 1.85, 95% CI 1.39-2.47). We found a significant association between MS and delusional symptoms (OR 1.47, 95% CI 1.33-1.62). We found no association between EMP and persistence of PEs.EMP was associated with increased risk of reporting PS and PEs, and the risk was higher in ethnic groups facing deprivation and discrimination. We found an association between MS and delusional symptoms. These results raise questions about the precise role of socio-environmental factors along the psychosis continuum.

Effects of repeated transcranial direct current stimulation on smoking, craving and brain reactivity to smoking cues.

Recent studies have shown that transcranial direct current stimulation (tDCS) may reduce craving and smoking. However, little is known regarding brain correlates of these behavioral changes. We aimed to evaluate whether 10 sessions of tDCS modulate cigarette consumption, craving and brain reactivity to smoking cues in subjects with tobacco use disorder (TUD). In a double blind parallel-arms study, 29 subjects with TUD who wished to quit smoking were randomly assigned to receive 10 sessions of either active or sham tDCS applied with the anode over the right dorsolateral prefrontal cortex (DLPFC) and a large cathode over the left occipital region. As compared to sham, active tDCS significantly reduced smoking craving and increased brain reactivity to smoking-cues within the right posterior cingulate, as measured with a functional magnetic resonance imaging event-related paradigm. However, we failed to find a significant difference between active and sham groups regarding the self-reported number of cigarettes smoked and the exhaled carbon monoxide during one month. These findings suggested that 10 sessions of tDCS over the right DLPFC may reduce craving by modulating activity within the resisting-to-smoke network but might not be significantly more effective than sham to decrease cigarette consumption.

Examining the neural correlates of active and passive forms of verbal-spatial binding in working memory.

We designed an fMRI study to pinpoint the neural correlates of active and passive binding in working memory. Participants were instructed to memorize three words and three spatial locations. In the passive binding condition, words and spatial locations were directly presented as bound. Conversely, in the active binding condition, words and spatial locations were presented as separated, and participants were directed to intentionally create associations between them. Our results showed that participants performed better on passive binding relative to active binding. FMRI analysis revealed that both binding conditions induced greater activity within the hippocampus. Additionally, our analyses divulged regions specifically engaged in passive and active binding. Altogether, these data allow us to propose the hippocampus as a central candidate for working memory binding. When needed, a frontal-parietal network can contribute to the rearrangement of information. These findings may inform theories of working memory binding.

Cognitive deficits in individuals with methamphetamine use disorder: A meta-analysis.

BACKGROUND: Methamphetamine has long been considered as a neurotoxic substance causing cognitive deficits. Recently, however, the magnitude and the clinical significance of the cognitive effects associated with methamphetamine use disorder (MUD) have been debated. To help clarify this controversy, we performed a meta-analysis of the cognitive deficits associated with MUD. METHODS: A literature search yielded 44 studies that assessed cognitive dysfunction in 1592 subjects with MUD and 1820 healthy controls. Effect size estimates were calculated using the Comprehensive Meta-Analysis, for the following 12 cognitive domains: attention, executive functions, impulsivity/reward processing, social cognition, speed of processing, verbal fluency/language, verbal learning and memory, visual learning and memory, visuo-spatial abilities and working memory. RESULTS: Findings revealed moderate impairment across most cognitive domains, including attention, executive functions, language/verbal fluency, verbal learning and memory, visual memory and working memory. Deficits in impulsivity/reward processing and social cognition were more prominent, whereas visual learning and visuo-spatial abilities were relatively spared cognitive domains. A publication bias was observed. DISCUSSION: These results show that MUD is associated with broad cognitive deficits that are in the same range as those associated with alcohol and cocaine use disorder, as recently shown by way of meta-analysis. The prominent effects of MUD on social cognition and impulsivity/reward processing are based on a small number of studies, and as such, these results will need to be replicated. The functional consequences (social and occupational) of the cognitive deficits of methamphetamine will also need to be determined.

The puzzling question of inhibitory control in Tourette syndrome: A meta-analysis.

Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive behaviors might arise from inhibitory deficits. However, conflicting findings regarding TS patients' inhibitory performance in neuropsychological tasks have been reported throughout the literature. Therefore, this meta-analysis aimed to evaluate inhibitory control through neuropsychological tasks, and to analyze the factors modulating inhibitory deficits. To this end, a literature search was performed through MEDLINE and PsycINFO, to retrieve studies including neuropsychological tasks that assessed inhibitory control in TS patients. Of the 4020 studies identified, 61 were included in the meta-analysis, for a total of 1717 TS patients. Our analyses revealed a small to medium effect in favor of inhibitory deficits in TS patients. This effect was larger in TS+ADHD patients, but pure TS patients also showed some inhibitory deficits. Therefore, deficits in inhibitory control seem to be an inherent component of TS, and are exacerbated when ADHD is concomitant.

Abnormal prefrontal and parietal activity linked to deficient active binding in working memory in schizophrenia.

Working memory deficits have been widely reported in schizophrenia, and may result from inefficient binding processes. These processes, and their neural correlates, remain understudied in schizophrenia. Thus, we designed an FMRI study aimed at investigating the neural correlates of both passive and active binding in working memory in schizophrenia. Nineteen patients with schizophrenia and 23 matched controls were recruited to perform a working memory binding task, in which they were instructed to memorize three letters and three spatial locations. In the passive binding condition, letters and spatial locations were directly presented as bound. Conversely, in the active binding condition, words and spatial locations were presented as separated, and participants were instructed to intentionally create associations between them. Patients exhibited a similar performance to the controls for the passive binding condition, but a significantly lower performance for the active binding. FMRI analyses revealed that this active binding deficit was related to aberrant activity in the posterior parietal cortex and the ventrolateral prefrontal cortex. This study provides initial evidence of a specific deficit for actively binding information in schizophrenia, which is linked to dysfunctions in the neural networks underlying attention, manipulation of information, and encoding strategies. Together, our results suggest that all these dysfunctions may be targets for neuromodulation interventions known to improve cognitive deficits in schizophrenia.

Tone-matching ability in patients with schizophrenia: A systematic review and meta-analysis.

CONTEXT: Patients with schizophrenia display abnormalities in pitch discrimination of non-verbal tones as revealed by the Tone-Matching Task (TMT). It may lead to deficits in higher-order cognitive functions and clinical symptoms. OBJECTIVES: We conducted a systematic review and meta-analysis pooling data about TMT score differences between patients with schizophrenia and healthy controls, to evaluate the deficit's effect size, and to develop reliable knowledge about pitch processing impairment and its pejorative impact. METHOD: Relevant publications were identified by a systematic search of PubMed and EMBASE databases. Then, we excluded non-relevant studies for the meta-analysis. Effect size for percent of correct responses to the TMT was expressed as standardized mean difference (SMD). RESULTS: Eighteen of 167 identified studies met eligibility criteria for review, of which 10 were included in the meta-analysis. Our meta-analysis showed that the effect size for the percent of correct response to the TMT between patients (N=371) and controls (N=342) was large: SMD=1.17 [95% CI: 0.926-1.418] (z-value=9.338 and p-value<0.001). Meta-analysis showed moderate heterogeneity between studies (Q(9)=17.22, p=0.04, I2=47.74%). The relationship between tone-matching impairment and clinical symptoms of schizophrenia remains heterogeneous across studies. Some authors observed significant correlations between tone-matching performance and a number of higher-order cognitive abilities. CONCLUSION: This review and meta-analysis highlights a large significant disturbance in tone-matching ability in patients as compared with controls. The study of basic auditory processing opens promising perspectives for pathophysiological modelling of the disorder and therapeutic issues.

Is there a binding deficit in working memory in patients with schizophrenia? A meta-analysis.

In schizophrenia (SZ), a specific binding deficit in working memory (WM) has not yet been demonstrated, given that studies with various methodologies were conducted and the results obtained were heterogeneous. Thus, a meta-analysis of 10 WM studies was performed. Effect sizes were calculated for binding and control conditions. Analyses disclosed significantly lower scores in SZ patients relative to controls for both binding and control conditions. In addition, analyses revealed no greater impairments for the binding condition than for the control condition in SZ patients. Our meta-analysis suggests that there is no specific deficit of binding in WM in SZ.