Pedro Mario Pan

Dimensions of Oppositionality in a Brazilian Community Sample: Testing the DSM-5 Proposal and Etiological Links

Objective Investigating dimensions of oppositional symptoms may help to explain heterogeneity of etiology and outcomes for mental disorders across development and provide further empirical justification for the DSM-5–proposed modifications of oppositional defiant disorder (ODD). However, dimensions of oppositionality have not previously been tested in samples outside Europe or the United States. In this study, we used a large Brazilian community sample to compare the fit of different models for dimensions of oppositional symptoms; to examine the association of psychiatric diagnoses and symptoms with dimensions of oppositionality; and to examine the associations between dimensions of oppositionality and parental history of mental disorders. Method A Brazilian community sample of 2,512 children 6 through 12 years old were investigated in this study. Confirmatory factorial analyses were performed to compare the fit of alternative models, followed by linear and logistic regression analyses of associations with psychiatric diagnosis and parental history of psychopathology. Results A three-factor model with irritable, headstrong, and hurtful dimensions fitted best. The irritable dimension showed a strong association with emotional disorders in the child (p<.001) and history of depression (p<.01) and suicidality (p<.05) in the mother. The headstrong dimension was uniquely associated with attention-deficit/hyperactivity disorder (ADHD) in the child (p<.001) and with maternal history of ADHD symptoms (p<.05). The hurtful dimension was specifically associated with conduct disorder (p< .05). Conclusions Our findings from a large community sample of Brazilian children support a distinction between dimensions of oppositionality consistent with current DSM-5 recommendations and provide further evidence for etiological distinctions between these dimensions.

High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results.

The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random =958; high risk =1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high‐risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub‐sample with “high risk” for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. Copyright

Specificity of basic information processing and inhibitory control in attention deficit hyperactivity disorder

BACKGROUND Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. METHOD We assessed 704 subjects (age 6-12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy trade-off and encoding/motor function along with variability parameters. RESULTS Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP. CONCLUSIONS Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.

Age effects on the default mode and control networks in typically developing children

BACKGROUND The investigation of neurodevelopment during late childhood and pre-adolescence has recently attracted a great deal of interest in the field of neuroimaging. One promising topic in this field is the formation of brain networks in healthy subjects. The integration between neural modules characterizes the ability of the network to process information globally. Although many fMRI-based neurodevelopment studies can be found in the literature, the analyses of very large samples (on the order of hundreds of subjects) that focus on the late childhood/pre-adolescence period and resting state fMRI are scarce, and most studies have focused solely on North American and European populations. AIMS In this study, we present a descriptive investigation of the developmental formation of the Default Mode Network and the Control Network based on a Brazilian, cross-sectional community sample of 447 typically developing subjects aged 7-15 years old. METHODS Resting state fMRI data were acquired using two MRI systems from the same manufacturer using the same acquisition parameters. We estimated the age effects on the strength of the links (between brain regions) and the network features (graph descriptors: degree and eigenvector centrality). RESULTS Our findings showed an increase in the antero-posterior connectivity in both studied networks during brain development. The graph analyses showed an increase in centrality with age for most regions in the Default Mode Network and the dorsal anterior and posterior cingulate, the right anterior insula and the left posterior temporal cortex in the Control Network. CONCLUSION We conclude that the period of 7-15 years of age is crucial for the development of both the Default Mode and Control networks, with integration between the posterior and anterior neuronal modules and an increase in the centrality measures of the hub regions.

A general psychopathology factor (P factor) in children: Structural model analysis and external validation through familial risk and child global executive function.

High rates of comorbidities and poor validity of disorder diagnostic criteria for mental disorders hamper advances in mental health research. Recent work has suggested the utility of continuous cross-cutting dimensions, including general psychopathology and specific factors of externalizing and internalizing (e.g., distress and fear) syndromes. The current study evaluated the reliability of competing structural models of psychopathology and examined external validity of the best fitting model on the basis of family risk and child global executive function (EF). A community sample of 8,012 families from Brazil with children ages 6–12 years completed structured interviews about the child and parental psychiatric syndromes, and a subsample of 2,395 children completed tasks assessing EF (i.e., working memory, inhibitory control, and time processing). Confirmatory factor analyses tested a series of structural models of psychopathology in both parents and children. The model with a general psychopathology factor (“P factor”) with 3 specific factors (fear, distress, and externalizing) exhibited the best fit. The general P factor accounted for most of the variance in all models, with little residual variance explained by each of the 3 specific factors. In addition, associations between child and parental factors were mainly significant for the P factors and nonsignificant for the specific factors from the respective models. Likewise, the child P factor—but not the specific factors—was significantly associated with global child EF. Overall, our results provide support for a latent overarching P factor characterizing child psychopathology, supported by familial associations and child EF.

Decreased centrality of subcortical regions during the transition to adolescence: A functional connectivity study

Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions.

Abnormalities in sleep patterns in individuals at risk for psychosis and bipolar disorder

AIM To compare patterns of sleep and the presence of sleep disturbances in individuals in at-risk mental states (ARMS) for psychosis and bipolar disorder (BD) with a healthy control (HC) group. METHODS This was a comparative study involving 20 individuals in ARMS for psychosis or BD, according to the Comprehensive Assessment of At-Risk Mental States, and 20 age- and sex-matched healthy controls. Quality of sleep in the previous month was assessed using the Pittsburgh Sleep Quality Index, diurnal somnolence was evaluated using The Epworth Sleepiness Scale, and chronotype was determined using the Questionnaire of Morningness/Eveningness (QME). All of the participants underwent polysomnography (PSG) during the entire night for two consecutive nights. The first night aimed to adapt the subject to the environment, and only the data from the second night were used for the analysis. RESULTS Compared with the HC group, individuals in the ARMS group reported significantly worse sleep quality, as measured by the Pittsburgh Sleep Quality Index. Both groups had scores consistent with daytime sleepiness on the Epworth Sleepiness Scale, and there were no differences with regard to chronotype between the groups, with a predominance of the indifferent type in both groups. In the PSG assessment, we observed increased Sleep Latency (SL) and increased Rapid Eye Movement Sleep Onset Latency (REMOL) in the ARMS group, compared to the HC group. CONCLUSION The results of this study indicated that sleep abnormalities could be found early in the course of mental diseases, even in at-risk stages, and support the further investigation of their predictive value in the transition to psychosis and BD.

Early intervention for bipolar disorder: current imperatives, future directions

OBJECTIVES The objective of this article is to discuss the rationale/background for early intervention in bipolar disorder. METHOD Narrative review. RESULTS There are often significant delays before the diagnosis of bipolar disorder is made and effective management initiated. Growing evidence from both preclinical and clinical literature points to a clear need for improved early identification and early intervention in bipolar disorder. Increasing efforts are being applied to the identification of those at high risk of onset of bipolar disorder. It is hoped that identification of an early prodrome of illness will allow preventative measures to be taken. CONCLUSIONS There is a clear rationale for improved early identification and early intervention in bipolar disorder.

Peripheral immuno-inflammatory abnormalities in ultra-high risk of developing psychosis

BACKGROUND Immuno-inflammatory imbalances have been documented in schizophrenia, but very little is known about the immunological changes prior to the onset of disease. OBJECTIVE This work aimed to compare serum levels of pro- and anti-inflammatory cytokines in young subjects at ultra-high risk (UHR) of developing psychosis with age- and sex-matched healthy controls. METHODS A total of 12 UHR and 16 age- and sex-matched healthy controls (HC) subjects were enrolled in this study. Clinical profile was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS), Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and Global Assessment of Functioning (GAF) scale. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, IFN-γ, and IL-17 were measured by flow cytometry using the Th1/Th2/Th17 cytometric bead array. RESULTS Compared with the healthy control group, patients in UHR showed increased IL-6 levels (Z=-2.370, p=0.018) and decreased IL-17 levels in serum (Z=-1.959, p=0.050). Levels of IL-17 positively correlated to the values in GAF symptoms (rho=0.632, p=0.028). CONCLUSION Our results suggest that immunological imbalances could be present in the early stages of psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Income inequality and mental illness-related morbidity and resilience: a systematic review and meta-analysis

BACKGROUND Studies of the association between income inequality and mental health have shown mixed results, probably due to methodological heterogeneity. By dealing with such heterogeneity through a systematic review and meta-analysis, we examine the association between income inequality, mental health problems, use of mental health services, and resilience (defined as the ability to cope with adversity). METHODS We searched the Global Health, PsychARTICLES, PsycINFO, Social Policy and Practice, Embase and MEDLINE databases up to July 6, 2016, for quantitative studies of the association of income inequality with prevalence or incidence of mental disorders or mental health problems, use of mental health services, and resilience. Eligible studies used standardised instruments at the individual level, and income inequality at the aggregated, contextual, and ecological level. We extracted study characteristics, sampling, exposure, outcomes, statistical modelling, and parameters from articles. Because several studies did not provide enough statistical information to be included in a meta-analysis, we did a narrative synthesis to summarise results with studies categorised as showing either a positive association, mixed results, or no association. The primary outcome in the random-effects meta-analysis was mental health-related morbidity, defined as the prevalence or incidence of any mental health problem. This study is registered with PROSPERO, number CRD42016036377. FINDINGS Our search identified 15 615 non-duplicate references, of which 113 were deemed potentially relevant and were assessed for eligibility, leading to the inclusion of 27 studies in the qualitative synthesis. Nine articles found a positive association between income inequality and the prevalence or incidence of mental health problems; ten articles found mixed results, with positive association in some subgroups and non-significant or negative association in other subgroups; and eight articles found no association between income inequality and mental health problems. Of the nine articles included in our meta-analysis, one reported a positive association between income inequality and mental health problems, six reported mixed results, and two reported no association. Pooled Cohens d effect sizes for the association between income inequality and any mental disorder or mental health problems were 0·06 (95% CI 0·01-0·11) for any mental disorder, and 0·12 (0·05-0·20) for depressive disorders. Our meta-regression analysis showed that none of the factors considered (sample size, contextual level at which income inequality was assessed, quality assessment, type of instruments, and individual income as control variable) explained heterogeneity between studies (I2 89·3%; p<0·0001). Only one study investigated the association between income inequality and resilience; it found greater income inequality was associated with higher prevalence of depression only among individuals with low income. The only study of the role of income inequality as a determinant of the use of mental health services reported no association. INTERPRETATION Income inequality negatively affects mental health but the effect sizes are small and there is marked heterogeneity among studies. If this association is causal and growing income inequality does lead to an increase in the prevalence of mental health problems, then its reduction could result in a significant improvement in population wellbeing. FUNDING None.