Clarissa Trzesniak

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder ☆

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFC). Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyrus. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD.

Is the Full Version of the AUDIT Really Necessary? Study of the Validity and Internal Construct of Its Abbreviated Versions

BACKGROUND This study was aimed at assessing the psychometric qualities of the abbreviated versions of the Alcohol Use Disorders Identification Test (AUDIT-3, AUDIT-4, AUDIT-C, AUDIT-PC, AUDIT-QF, FAST, and Five-Shot) and at comparing them to the 10-item AUDIT and the CAGE in 2 samples of Brazilian adults. METHODS The validity and internal consistency of the scales were assessed in a sample of 530 subjects attended at an emergency department and at a Psychosocial Care Center for Alcohol and Drugs. The Structured Clinical Interview for DSM-IV was used as the diagnostic comparative measure for the predictive validity assessment. The concurrent validity between the scales was analyzed by means of Pearsons correlation coefficient. RESULTS The assessment of the predictive validity of the abbreviated versions showed high sensitivity (of 0.78 to 0.96) and specificity (of 0.74 to 0.94) indices, with areas under the curve as elevated as those of the AUDIT (0.89 and 0.92 to screen for abuse and 0.93 and 0.95 in the screening of dependence). The CAGE presented lower indices: 0.81 for abuse and 0.87 for dependence. The analysis of the internal consistency of the AUDIT and its versions exhibited Cronbachs alpha coefficients between 0.83 and 0.94, while the coefficient for the CAGE was 0.78. Significant correlations were found between the 10-item AUDIT and its versions, ranging from 0.91 to 0.99. Again, the results for the CAGE were satisfactory (0.77), although inferior to the other instruments. CONCLUSIONS The results obtained in this study confirm the validity of the abbreviated versions of the AUDIT for the screening of alcohol use disorders and show that their psychometric properties are as satisfactory as those of the 10-item AUDIT and the CAGE.

Social anxiety disorder: what are we losing with the current diagnostic criteria?

Filho AS, Hetem LAB, Ferrari MCF, Trzesniak C, Martín‐Santos R, Borduqui T, de Lima Osório F, Loureiro SR, Busatto Filho G, Zuardi AW, Crippa JAS. Social anxiety disorder: what are we losing with the current diagnostic criteria?

Are cavum septum pellucidum abnormalities more common in schizophrenia spectrum disorders? A systematic review and meta-analysis

Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher incidence of cavum septum pellucidum (CSP), which is consistent with a neurodevelopmental model for this disorder. In this meta-analytic review, we describe and discuss the main CSP MRI findings in schizophrenia spectrum disorders (SSDs) to date. We adopted as keywords cavum and schizophrenia or psychosis, and the inclusion criteria were articles in English, with samples of SSD patients compared to healthy subjects, which used MRI to assess CSP, without time limit. From 18 potential reports, fifteen were eligible to be part of the current review. These studies included 1054 patients with SSD and 866 healthy volunteers. Six out of 15 studies pointed to a higher prevalence of CSP of any size in SSD patients, while five out of 15 showed that subjects with SSD had a greater occurrence of a large CSP than healthy individuals. However, the meta-analysis demonstrated that only the incidence of a large CSP was significantly higher in SSD relative to healthy comparisons (odds ratio=1.59; 95%CI 1.07-2.38; p=0.02). Overall our results suggest that only a large CSP is associated with SSD while a small CSP may be considered a normal neuroanatomical variation. Our review revealed a large degree of variability in the methods employed across the MRI studies published to date, as well as evidence of publication bias. Studies in large, community-based samples with greater standardization of methods should clarify the true significance of CSP in SSD.

Social anxiety disorder women easily recognize fearfull, sad and happy faces: The influence of gender

BACKGROUND It has been suggested that individuals with social anxiety disorder (SAD) are exaggeratedly concerned about approval and disapproval by others. Therefore, we assessed the recognition of facial expressions by individuals with SAD, in an attempt to overcome the limitations of previous studies. METHODS The sample was formed by 231 individuals (78 SAD patients and 153 healthy controls). All individuals were treatment naïve, aged 18-30 years and with similar socioeconomic level. Participants judged which emotion (happiness, sadness, disgust, anger, fear, and surprise) was presented in the facial expression of stimuli displayed on a computer screen. The stimuli were manipulated in order to depict different emotional intensities, with the initial image being a neutral face (0%) and, as the individual moved on across images, the expressions increased their emotional intensity until reaching the total emotion (100%). The time, accuracy, and intensity necessary to perform judgments were evaluated. RESULTS The groups did not show statistically significant differences in respect to the number of correct judgments or to the time necessary to respond. However, women with SAD required less emotional intensity to recognize faces displaying fear (p=0.002), sadness (p=0.033) and happiness (p=0.002), with no significant differences for the other emotions or men with SAD. CONCLUSIONS The findings suggest that women with SAD are hypersensitive to threat-related and approval-related social cues. Future studies investigating the neural basis of the impaired processing of facial emotion in SAD using functional neuroimaging would be desirable and opportune.

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate (NMDA) transmission plays a pivotal role in the neuropathophysiology of schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising approaches to the treatment of schizophrenia. The aim of this article is to review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R). This review also includes a discussion and translation of neuroscience into schizophrenia therapeutics. Although the precise mechanism of action of minocycline in the brain remains unclear, there is evidence that it blocks the neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA signaling pathways. We, therefore, hypothesize that the effects of minocycline on the brain may be partially modulated by the NMDA-R or related mechanisms. Thus, we have included a review of minocycline neuroscience. The search was performed in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of glycine and D-cycloserine trials were conflicting regarding effectiveness on the negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a potential effect on negative symptoms and on cognitive deficits. Sarcosine data indicated a considerable improvement as adjunctive therapy. Finally, minocycline add-on treatment appears to be effective on a broad range of psychopathology in patients with schizophrenia. The differential modulation of NMDA-R neurosystems, in particular synaptic versus extrasynaptic NMDA-R activation and specific subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection. Thus, psychotropics modulating NMDA-R neurotransmission may represent future monotherapy or add-on treatment strategies in the treatment of schizophrenia.

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania:

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by d-amphetamine (d-AMPH). In the first model (reversal treatment), rats received saline or d-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or d-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the d-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the d-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Neuroimaging in specific phobia disorder: a systematic review of the literature

OBJECTIVE Specific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP. METHOD A literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy. RESULT The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated. CONCLUSION In spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP.

Validity of a Brazilian version of the Zung self-rating depression scale for screening of depression in patients with Parkinson's disease☆

INTRODUCTION Parkinsons disease (PD) is a neurodegenerative disorder with prominent motor manifestations and many other non-motor symptoms that significantly decrease quality-of-life and are frequently under-recognized, for example depression. OBJECTIVE To study the validity of a Brazilian version of the Zung Self-rating Depression Scale (SDS) for the diagnosis of depression in patients with PD. METHODS We evaluated 78 consecutive non demented patients over the age of 40 with diagnosis of PD at a Movement Disorders Outpatient Clinic, who could read and understand questionnaires. They completed the SDS and the Geriatric Depression Scale with 15 items (GDS-15). The diagnosis of depression was made after a structured clinical interview based on DSM-IV criteria for the diagnosis of major depression (SCID-CV). RESULTS The prevalence of major depression was 23.1%. Cronbachs alpha was 0.73 and the area under the ROC curve was 0.93 for the SDS. The score index of 55 had a sensitivity of 88.9% and a specificity of 83.3% for the diagnosis of depression. The total scores of the SDS and GDS-15 were highly correlated (0.652, p < 0.0001) and correlated weakly with the scores of a motor scale. DISCUSSION The SDS is a valid tool for screening depression in patients with PD since the specific SDS index of 55 is adopted. Two shortened versions could be used with good results.

Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study

BACKGROUND Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). METHOD FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. RESULTS We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction. CONCLUSIONS Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.