Perinatal and neonatal factors and mental disorders in children and adolescents: looking for the contributions of the early environment to common and dissociable aspects of psychopathology.

High rates of co-occurrence of mental disorders have been hypothesized to represent a result of common susceptibility to overall psychopathology. The purpose of this study is to test the hypothesis that commonalities among psychiatric disorders might be partially driven by sharable perinatal and neonatal environmental factors for mental disorders. Participants were 6-14 years of age children and their parents. Primary caregivers provided data on perinatal and neonatal information assessed retrospectively (n = 2231). Psychiatric disorders diagnoses were assessed using the Development and Well Being Behavior Assessment (DAWBA). We used bifactor models to disentangle common from dissociable aspects of psychopathology. These models allow modeling psychiatric disorders as the result of a common domain of psychopathology (p-factor) and three dissociable domains (fear, distress, and externalizing symptoms). Associations were tested using linear and tobit regression models. The p-factor was associated with male sex, low socioeconomic status, gestational smoking, gestational drinking, low levels of maternal education and presence of mental disorder in the mother. Associations with specific factors also emerged suggesting some risk factors might also have some role for fear, distress and externalizing factors. Our study supports the hypothesis that overall susceptibility to psychopathology might be partially driven by sharable perinatal and neonatal factors.

Longitudinal associations between positive attributes and psychopathology and their interactive effects on educational outcomes.

Psychopathology is associated with impaired learning and early termination of schooling, whereas positive attributes are associated with better educational outcomes. However, it is important to understand if and how psychopathology and positive attributes longitudinally impact each other so we could shed light on where to intervene to promote educational outcomes through these constructs. A large prospective school-based community cohort of youths (5-15 years of age, 45% female) were assessed and followed up for 3 years (n = 2010; 80% retention). We assessed the longitudinal impact of positive attributes (Youth Strength Inventory) and psychopathology (bifactor model of Strengths and Difficulties Questionnaire) using a cross-lagged panel model. We also used generalized mixed effects models to investigate how these both constructs predict school dropout and literacy, adjusting for confounders and testing their interaction. Positive attributes negatively predicted, and were negatively predicted by, the general factor of psychopathology and conduct problems in the cross-lagged panel model. Positive attributes (OR = 0.57, 95% CI [0.44, 0.73], p < 0.001) and specific conduct symptoms (OR = 2.33, 95% CI [1.64, 3.33], p < 0.001) predicted school dropout, whereas the general factor of psychopathology predicted lower literacy ability (ß = - 0.08, 95% CI [- 0.11, - 0.05], p < 0.001). However, the protective association of positive attributes on school dropout decreases as the general factor of psychopathology increases. These findings provide new evidence that positive attributes and psychopathology mutually influence each other over development and have interactive effects on educational outcomes.

Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Evaluation of Ongoing Participation of People with Schizophrenia in a Mutual Support Group as a Complementary Intervention to Outpatient Psychiatric Treatment.

This study aims to evaluate a group of people with schizophrenia undergoing outpatient treatment and who participate in a mutual support intervention, compared to another group of people with the same diagnosis, but attending only the usual outpatient treatment. This is a prospective study, with two measurements between six months. The mutual support group was initially composed of 16 people and the treatment as usual group was composed of 15 people. Clinical (medication adherence and functioning) and Recovery (hope, well-being, recovery and internalized stigma) outcomes were assessed. Nonparametric tests were used to verify differences in measurements between groups and between two moments. A higher level of internalized stigma and a decrease in the adherence to drug treatment in the treatment as usual group were verified. When comparing the pre-post difference between groups, there was a greater increase in adherence to drug treatment in the mutual support group. Our data point to more favorable results in the mutual support group, showing that ongoing participation in these groups is an important tool for the recovery process and for the treatment itself.

Heterotypic trajectories of dimensional psychopathology across the lifespan: the case of youth-onset attention deficit/hyperactivity disorder.

BACKGROUND: Recent studies have demonstrated the existence of a distinct late-onset attention deficit/hyperactivity disorder (ADHD) trajectory. Our objective is to test if there are distinct ADHD trajectories regarding age of onset from childhood to adolescence and to compare clinical manifestations, cognitive functions and genetic risk for ADHD among distinct longitudinal groups. METHOD: Nine hundred and twenty four children and adolescents from the community participated in the study. We compared clinical, cognitive features and genetic risk among four groups of participants: (a) childhood-limited, (b) youth-onset, (c) childhood-onset with youth persistence, and (d) community comparisons without ADHD. Symptomatic and diagnostic assessments were performed using the Development and Well-Being Behavior Assessment, the Strengths and Difficulties Questionnaire, and the Child Behavior Checklist. Cognitive functions were measured using a battery of standardized tests. Genetic risk for ADHD was calculating using summary statistics from the Psychiatric Genomics Consortium. RESULTS: Half of the adolescents (52%) with ADHD had their symptom onset in adolescence. The impairment level of this group in adolescence is similar to the persistent group. Despite not having ADHD, the youth-onset group already presented in childhood more symptoms from other domains of psychopathology, higher shared variance in psychiatric symptomatology (p-factor), school impairment, and executive dysfunctions than community comparisons. Furthermore, the youth-onset group presented lower levels of genetic risk for ADHD compared to other cases. CONCLUSIONS: A significant proportion of adolescents with ADHD were youth-onset cases and presented similar impairment levels as those cases with early-onset ADHD. The presence of cognitive impairments and higher levels of clinical symptoms in the youth-onset group already at childhood speaks in favor of a heterotypic trajectory of psychopathology suggesting that youth-onset ADHD might be an artificial consequence of categorizing dimensional psychopathology into discrete diagnostic groups.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

Cross-Sectional and Longitudinal Associations of Temperament and Mental Disorders in Youth.

Here we evaluate the cross-sectional and longitudinal associations between temperament and mental disorders in adolescents. Temperament was assessed in a cohort of 1540 youths by the revised self-report Early Adolescence Temperament Questionnaire (EATQ-R) at baseline and confirmatory factor analyses were used to test the best empirical model. Mental disorders were assessed by parental interview using the Development and Well-Being Behavior Assessment at baseline and at 3-year follow-up. Participants were grouped into Typically Developing Comparisons, Phobias, Distress, Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD). Logistic regression models tested the effects of temperament on incidence and remission of mental disorders. The bifactor model of EATQ-R presented the best fit. Distress, ADHD and DBD have lower levels of effortful control in baseline. Adjusted longitudinal analysis showed that effortful control predicted lower incidence of Phobias (OR 0.74; p = 0.018), distress (OR 0.74; p = 0.014) and DBD (OR 0.68; p = 0.037). Temperament factors did not predicted remission rates.

The association between psychotic experiences and traumatic life events: the role of the intention to harm.

BACKGROUND: Previous work showed traumatic life events (TLE) with intention to harm, like bullying and abuse, to be more strongly associated with psychotic experiences (PE) than other types of trauma, like accidents. However, this association is subject to reporting bias and can be confounded by demographic characteristics and by differences in dose of exposure across different trauma categories. We studied the association between TLE with and without intention to harm and PE, taking into account potential confounders and biases. METHODS: A total of 2245 children and adolescents aged 6-14 years were interviewed by psychologists. The interview included the presence of 20 PE (both self-report and psychologist evaluation). In addition, parents provided information on child exposure to trauma, mental health and PE. RESULTS: Results showed no significant association between TLE without intention to harm only and PE for the three methods of assessment of PE (self-report, parent report and psychologist rating). On the other hand, there was a positive association between PE and TLE in groups exposed to traumatic experiences with intention to harm (with intention to harm only and with and without intention to harm). Results remained significant after controlling for demographic and clinical confounders, but this positive association was no longer significant after adjusting for the number of TLE. CONCLUSIONS: TLE with intention to harm display a stronger association with PE than TLE without intention to harm, and this difference is likely reducible to a greater level of traumatic exposure associated with TLE with intention to harm.

Fine motor ability and psychiatric disorders in youth.

Impaired fine motor ability has been linked to several domains of psychopathology. However, studies validating the specificity of this association among several categorical psychiatric disorders are still needed. The aim of this study was to assess differences in fine motor ability performance among four non-overlapping groups of psychiatric disorders and a group of typical developing comparisons (TDC). Our sample consisted of 2035 subjects aged 6-14-year-old. Diagnoses of psychiatric disorders were performed with the Development and Well-Being Assessment (DAWBA). Five non-overlapping groups without comorbidity were formed: phobic disorders (n = 101), distress disorders (n = 82), attention deficit hyperactivity disorder (ADHD) (n = 133), oppositional defiant disorder/conduct disorder (ODD/CD) (n = 52) and one group of typical developing comparisons (TDC) (n = 1667). Fine motor ability was evaluated by three tasks: sequential finger-thumb opposition, Oseretsky, and pronation/supination tests. Each task was assessed by total time to perform the movement and levels of accuracy, fluency, symmetry, precision, and coordination. We found that, when compared to TDC, the ADHD group performed more poorly in total fine motor ability (mean difference = - 0.28; p = 0.014), time to complete the task (mean difference = 0.36; p < 0.001), accuracy (mean difference = - 0.30; p = 0.005), fluency (mean difference = - 0.26; p = 0.03), symmetry (mean difference - 0.25; p = 0.04), precision (mean difference = - 0.26; p = 0.026), and coordination (mean difference = - 0.25; p = 0.042). The ADHD group also took more time to complete the task than the ODD/CD group (mean difference = 0.45; p = 0.037). No other significant between-group differences were found. Additional analyses showed those differences were statistically significant for all ADHD dimensions. Our results suggest that children with ADHD present impairments in all aspects of fine motor abilities compared to TDC, a difference not found in other psychiatric disorders.

New evidence in support of staging approaches in schizophrenia: Differences in clinical profiles between first episode, early stage, and late stage.

Few studies have examined the progression of symptom dimensions in schizophrenia patients over the course of the illness. The objective of this study was to investigate whether clinical and psychopathological differences exist between first-episode schizophrenia (FES) and multiple-episode patients in an inpatient setting. Patients (N=203) were evaluated using the Positive and Negative Syndrome Scale (PANSS) over time. Five different generalized estimating equations were built for the PANSS factors using the following as covariates: sex, patient's age, assessment time point (i.e., moment of patient's evaluation, with a minimum of two and a maximum of four assessments throughout the study timeframe). The FES group was used as the reference to which the groups with up to five years of illness and more than five years of illness were compared. Remission rates and treatment resistance (TRS) rates were also compared. Generalized estimating equations were used to allow for different numbers of assessments over the study period. Patients with FES showed significantly milder severity in positive, disorganized, and hostility factors. Also, FES patients were more likely to achieve remission (P=0.002) and had lower rates of TRS (P=0.001). First-episode schizophrenia seems to be the critical period to improve outcome, as multiple-episode patients were similar in clinical characteristics regardless of illness duration.

Default mode network maturation and psychopathology in children and adolescents.

BACKGROUND: The human default mode (DMN) is involved in a wide array of mental disorders. Current knowledge suggests that mental health disorders may reflect deviant trajectories of brain maturation. METHOD: We studied 654 children using functional magnetic resonance imaging (fMRI) scans under a resting-state protocol. A machine-learning method was used to obtain age predictions of children based on the average coefficient of fractional amplitude of low frequency fluctuations (fALFFs) of the DMN, a measure of spontaneous local activity. The chronological ages of the children and fALFF measures from regions of this network, the response and predictor variables were considered respectively in a Gaussian Process Regression. Subsequently, we computed a network maturation status index for each subject (actual age minus predicted). We then evaluated the association between this maturation index and psychopathology scores on the Child Behavior Checklist (CBCL). RESULTS: Our hypothesis was that the maturation status of the DMN would be negatively associated with psychopathology. Consistent with previous studies, fALFF significantly predicted the age of participants (p < .001). Furthermore, as expected, we found an association between the DMN maturation status (precocious vs. delayed) and general psychopathology scores (p = .011). CONCLUSIONS: Our findings suggest that child psychopathology seems to be associated with delayed maturation of the DMN. This delay in the neurodevelopmental trajectory may offer interesting insights into the pathophysiology of mental health disorders.

The effectiveness of acupuncture as a treatment for tinnitus: a randomized controlled trial using (99m)Tc-ECD SPECT.

OBJECTIVE: Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. METHODS: This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. RESULTS: No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. CONCLUSIONS: ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. KEY POINTS: • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

A cross-sectional study to compare levels of psychiatric morbidity between young people and adults exposed to violence in a large urban center.

BACKGROUND: Teenagers and young adults are more exposed to violence and traumatic events than adults, and these factors can be associated with mental disorders. This paper aims at investigating whether young people are more exposed to violence and traumatic events and to compare pattern of mental disorders with adults. METHODS: Cross-sectional study using the Composite International Diagnostic Interview, conducted between 2007 and 2008 with a randomly selected sample of 15 to 75 year-old residents of São Paulo, Brazil. RESULTS: Two thousand five hundred thirty-six participants were divided into two groups: 1096 (43.2 %) young people (15 to 24 years), and 1440 (56.8 %) adults (25 to 75 years). 12-month exposure to traumatic events was higher among young people (32.1 % vs. 20.6 %; p < 0.001). Assaultive violence was reported by 13.4 % of young people and 8.6 % of adults (p = 0.012); 20.1 % of young people and 13 % of adults reported suffering other injury or shocking events (p < 0.001); sudden death/life threatening illness of a close person was declared by 6.1 % of young people and 3.2 % of adults (p = 0.017). Prevalence of alcohol related disorders was higher among young people (5.4 % vs. 2.5 %; P = 0.032); depressive disorders were more prevalent among adults (9.0 % vs. 4.7 %; P = 0.004). Alcohol related disorders were associated to assaultive violence among young people (OR = 3.4; 95 % CI = 1.36 to 8.52; p = 0.004) and adults (OR = 2.38; 95 % CI = 1.23 to 4.61; p = 0.002). Phobic/anxiety disorders were associated to other injury or shocking events among young people (OR = 1.28; 95 % CI = 0.67 to 2.44; p = 0.025). Major depressive disorder was associated to assaultive violence among young people (OR = 2.27; 95 % CI = 1.09 to 4.74; p = 0.004) and adults (OR = 1.28; 95 % CI = 0.85 to 1.93; p = 0.009). CONCLUSION: Exposure to violence and traumatic events was higher among young people. Alcohol related disorders, depression and phobic/anxiety disorders were significantly higher among young people exposed to traumatic events. Despite the study design, high exposure to violence and traumatic events in this age group can be considered important factors in triggering mental disorders in this vulnerable age period.

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.

Temporal stability of network centrality in control and default mode networks: Specific associations with externalizing psychopathology in children and adolescents.

Abnormal connectivity patterns have frequently been reported as involved in pathological mental states. However, most studies focus on "static," stationary patterns of connectivity, which may miss crucial biological information. Recent methodological advances have allowed the investigation of dynamic functional connectivity patterns that describe non-stationary properties of brain networks. Here, we introduce a novel graphical measure of dynamic connectivity, called time-varying eigenvector centrality (tv-EVC). In a sample 655 children and adolescents (7-15 years old) from the Brazilian "High Risk Cohort Study for Psychiatric Disorders" who were imaged using resting-state fMRI, we used this measure to investigate age effects in the temporal in control and default-mode networks (CN/DMN). Using support vector regression, we propose a network maturation index based on the temporal stability of tv-EVC. Moreover, we investigated whether the network maturation is associated with the overall presence of behavioral and emotional problems with the Child Behavior Checklist. As hypothesized, we found that the tv-EVC at each node of CN/DMN become more stable with increasing age (P < 0.001 for all nodes). In addition, the maturity index for this particular network is indeed associated with general psychopathology in children assessed by the total score of Child Behavior Checklist (P = 0.027). Moreover, immaturity of the network was mainly correlated with externalizing behavior dimensions. Taken together, these results suggest that changes in functional network dynamics during neurodevelopment may provide unique insights regarding pathophysiology.

Effects of risperidone on cytokine profile in drug-naïve first-episode psychosis.

BACKGROUND: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder. METHODS: The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls. RESULTS: We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms. CONCLUSIONS: In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary.

Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia?

OBJECTIVE: Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness. METHODS: One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%. RESULTS: Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age. CONCLUSION: Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.