Introdução: Durante as fases críticas do desenvolvimento embriológico, o organismo encontra-se num estado de vulnerabilidade a interferências externas. Assim, o presente estudo tem por objetivo avaliar os impactos da restrição proteica durante a lactação na morfologia renal da prole. Métodos: Utilizou-se ratos adultos da linhagem Wistar, que foram induzidos ao cruzamento. Considerou-se o nascimento como o dia 0 e as matrizes foram divididas em dois grupos (dietas normoproteica - NP - e hipoproteica - LP). No dia 21, os animais sofreram eutanásia e os rins foram preparados para análise histológica. Resultados: Evidenciou-se nos animais do grupo LP que o ganho de peso foi 63,33% menor, o número de glomérulos exibiu uma redução de 32,99% (P<0.0001), o comprimento glomerular apresentou uma diminuição de 12,70% (P<0.001) e a área total glomerular teve uma redução de 18,12% (P<0.01), quando comparados com o grupo NP. Conclusão: A restrição proteica materna durante o período de lactação provoca injúrias ao desenvolvimento renal da prole, evidenciadas pela menor contagem de glomérulos e menores dimensões das estruturas renais nos animais submetidos a essa dieta.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

In dit hoofdstuk gaan we naar de psychiatrisch beelden en de beschrijving van de verschillende syndromen.

Background: We investigated the efficacy of an intensive 1-week behavioral therapy program focusing on agoraphobia for panic disorder patients with agoraphobia (PDA).Design and methods: The study design was a case-control study. Main outcome measure was the agoraphobia score of the Fear Questionnaire (FQ-AGO). The outcomes on the FQ-AGO of a 1-week intensive therapy (96 patients) and a twice-weekly therapy (98 patients) were compared.Results: Agoraphobia improved significantly in both groups, 1 week and 3 months after therapy. Effect size for changes in the 1-week intensive therapy on the FQ-AGO was 0.75.Limitations: Limitations are use of antidepressants, no placebo group, and no long term follow-up.Conclusion: Behavioral therapy for agoraphobia can be shortened significantly if intensified without affecting therapy outcome, thus allowing patients a more rapid return to work and resumption of daily activities. (C) 2014 Elsevier B.V All rights reserved.

Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed. (C) 2015 Elsevier Ltd. All rights reserved.

This study was intended to assess the extent to which the low-expression allele of the serotonin transporter gene promoter predicts better response to exposure-based behavior therapy in patients with panic disorder with agoraphobia (PDA). Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior therapy program and provided saliva samples to extract genomic DNA and classify individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in avoidance behavior in PDA following treatment. After controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression genotypes showed a more favorable response to exposure therapy two weeks following treatment, compared to the other patients. This study suggests a genetic contribution to treatment outcome following behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PDA.

BACKGROUND:The biological basis of uncued panic attacks is not yet understood. An important theory concerning the nature and cause of panic disorder is the 'suffocation false alarm theory'. This alarm is supposed to be over-sensitive in panic disorder patients and can be triggered by CO2. No neurobiological substrate has been identified for such an alarm. The present study investigates differences in brain activation in panic patients, healthy individuals and experienced divers in response to CO2, representing three groups with descending sensitivity to CO2.METHOD:Brain activation was measured with functional magnetic resonance imaging. Subjects breathed through a mouthpiece delivering a continuous flow of 100% oxygen for two minutes, followed by a hypercapnic gas mixture (7% CO2) for the next two minutes. Statistical analysis was performed using SPM8.RESULTS:There was a significant main effect of group in response to the CO2. Patients show increased brainstem activation in response to hypercapnia compared to controls and divers. Subjective feelings of breathing discomfort were positively correlated with brain activation in the anterior insula in all groups.CONCLUSION:This is the first study showing that the behavioural response to CO2 that characterises panic disorder patients is likely due to increased neural sensitivity to CO2 at brainstem level.

Background: Acute exercise has shown to reduce the effects of experimental panic provocation in healthy volunteers and in patients with panic disorder. Recent evidence suggests that when larger amounts of CO2 are inhaled, a large proportion of healthy subjects can also develop an affective response consistent with definitions of a panic attack. Our aim was to test whether exercise can show antipanic effects in healthy subjects when exposed to higher concentrations of CO2. Methods: Thirtyone healthy subjects, on four separate occasions in a randomized Latin square design, performed either moderate/hard or very-light exercise immediately followed by either a single or a double 35% CO2/65% O-2 inhalation. Results: Compared to very-light exercise, when subjects performed moderate/hard exercise they reported a reduction in panic symptoms on the Panic Symptom List and the Visual Analogue Scale of Fear but no difference on the Visual Analogue Scale of Discomfort after a double CO2 inhalation. After a single CO2 inhalation, reductions were only seen on the Panic Symptom List. Conclusions: After intense exercise, subjects had less panic symptoms when exposed 35% CO2, particularly after a double inhalation. Depression and Anxiety 29:155-158, 2012. (C) 2011 Wiley Periodicals, Inc.

It has been well established that the inhalation of Carbon Dioxide (CO2) can induce in humans an emotion closely replicating spontaneous panic attacks, as defined by current psychiatry nosology. The purpose of this review is to provide a critical summary of the data regarding CO2's psychopharmacological properties and underlying mechanisms. The authors review the literature on the human and animal response for the exposure of exogenous CO2 focusing on five points of interest: 1) the early history of the use of CO2 as an anesthetic and therapeutic agent, 2) the subjective effects of breathing CO2 at different concentrations in humans, 3) the use of CO2 in experimental psychiatric research as an experimental model of panic, 4) the pharmacological modulation of CO2-induced responses, and 5) the putative neurobiological mechanisms underlying the affective state induced by CO2. The authors conclude with an evolutionary-inspired notion that CO2 might act as an agent of a primal emotion serving a homeostatic function, in the control of respiration and acid-base balance.

Investigating and understanding gene–environment interaction (G × E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia–hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes ( n =42 genes) met the criteria for a link to ischemia–hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia–hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G × E interactions in clinical genetic and translational neuroscience studies.

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges.

Sex differences on the WISC-R (Wechsler Intelligence Scale for Children-Revised) are examined in a sample of 1258 11 year olds in Mauritius. Boys obtained a significantly higher Full Scale IQ by 5.8 IQ points. Boys obtained a higher Performance IQ by 6.5 IQ points and a higher Verbal IQ by 1.0 IQ points. On the subtests, girls obtained a significantly higher mean on Coding while boys obtained significantly higher means on Similarities, Picture Completion, Block Design, Object Assembly and Mazes. There was no significant sex difference on Digit Span. Two methods were adopted for determining whether boys had an advantage on Spearman's g. First, calculated from the first principal component of a principal components analysis, boys had an advantage on Spearman's g of 6.15 IQ points. Second, using the method of entering the sex difference on each of the subtests as point-biserial correlations, including these in the full matrix of subtest correlations for factor analysis and examining the factor loading of sex on g produced a correlation between sex and g of .224, the equivalent of a sex difference of 6.9 IQ points. Thus the sex difference on the Full Scale IQ was found to be a good approximate measure of the difference in g. The pattern of sex differences in Mauritius is compared with that in eight other countries and found to be generally similar, although the boys' advantage is greater in Mauritius than elsewhere. The variance in boys is slightly greater than in girls, but is only significant for Block Design.

Background: There has been a growing scientific interest on the interface between exercise and psychiatric disorders. However, there is a lack of self-report instruments to assess levels of physical activity adapted to Brazilian Portuguese. Objective: To translate, assess the semantic equivalence of the Habitual Physical Activity Questionnaire and perform a non-psychometric pre-test with subjects (n = 30) from the Brazilian population, with different educational backgrounds. Methods: The cross-cultural adaptation process consisted of two translations and back translations performed by two independent evaluators; an evaluation of the versions and the development of a synthetic version; and a commented pretest of the questionnaire. Results: For each item of the instrument, the results of the four stages are reported. Most of the participants (91%) did not present any difficulties comprehending the items of the instrument. Further studies should be addressed to determine the adequacy of using this instrument in the less-educated population. We recommend that less instructed subjects be supervised while responding the questionnaire. Discussion: The use of two translations versions, their critical appraisal and the assessment of the target population conceives more safety to the process of semantic equivalence. Sardinha A, et al. / Rev Psiq Clín. 2010;37(1):16-22 Key-words: Cross-cultural adaptation, physical activity, exercise, semantic equivalence, translation.

Background: There has been a growing scientific interest on the interface between exercise and psychiatric disorders. However, there is a lack of self-report instruments to assess levels of physical activity adapted to Brazilian Portuguese. Objective: To translate, assess the semantic equivalence of the Habitual Physical Activity Questionnaire and perform a non-psychometric pre-test with subjects (n = 30) from the Brazilian population, with different educational backgrounds. Methods: The cross-cultural adaptation process consisted of two translations and back translations performed by two independent evaluators; an evaluation of the versions and the development of a synthetic version; and a commented pretest of the questionnaire. Results: For each item of the instrument, the results of the four stages are reported. Most of the participants (91%) did not present any difficulties comprehending the items of the instrument. Further studies should be addressed to determine the adequacy of using this instrument in the less-educated population. We recommend that less instructed subjects be supervised while responding the questionnaire. Discussion: The use of two translations versions, their critical appraisal and the assessment of the target population conceives more safety to the process of semantic equivalence.

Inhalation of an increased concentration of carbon dioxide (CO 2 ) has been shown to induce a state of negative affect in healthy subjects that is closely related to the clinical phenomenon of panic. It has been suggested that the vulnerability to CO 2 is moderated by differences in serotonin (5-HT) activity, caused by a functional polymorphism in the promoter region of the 5-HT transporter (5-HTTLPR) gene. Our aim was to examine the relationship between bi- and tri-allelic 5-HTTLPR genotype and the affective response to different dosages of inhaled CO 2 in healthy volunteers. Ninety-six subjects performed a double inhalation of four mixtures containing, respectively, 0%, 9%, 17.5% and 35% CO 2 , following a double-blind, cross-over, randomized design. Affective responses were measured with a visual analogue scale for fear and the Panic Symptom List. 5-HTTLPR genotype was expressed as LL, SL and SS. Subjects with the SL and SS genotype reported less fear than LL subjects. A significant interaction effect was found between genotype and CO 2 dosage: the SS genotype showed lower fear scores than the LL genotype, particularly in the 17.5% CO 2 dose condition. The present study suggests that the dose-dependent fear reaction to CO 2 is moderated by a polymorphism in the 5-HT transporter gene, particularly at intermediate CO 2 dosages. It also underscores the usefulness of the introduction of an intermediate phenotype related to panic to reveal an underlying genetic vulnerability otherwise staying elusive. These results are in line with current theories on the role of 5-HT in both panic and respiration.

Great success in HCV therapy was achieved by the development of direct-acting antivirals (DAA). However, the unsolved issues such as high cost and genotype dependency drive us to pursue additional therapeutic agents to be used instead or in combination with DAA. The cationic peptide p41 is one of such candidates displaying submicromolar anti-HCV potency. By electrostatic coupling of p41 with anionic poly(amino acid)-based block copolymers, antiviral peptide nanocomplexes (APN) platform was developed to improve peptide stability and to reduce cytotoxicity associated with positive charge. Herein, we developed a facile method to prepare galactosylated Gal-APN and tested their feasibility as liver-specific delivery system. In vitro, Gal-APN displayed specific internalization in hepatoma cell lines. Even though liver-targeted and non-targeted APN displayed comparable antiviral activity, Gal-APN offered prominent advantages to prevent HCV association with lipid droplets and suppress intracellular expression of HCV proteins. Moreover, in vivo preferential liver accumulation of Gal-APN was revealed in the biodistribution study. Altogether, this work illustrates the potential of Gal-APN as a novel liver-targeted therapy against HCV.

The recent advent of genome‐wide mass‐marker technology has resulted in renewed optimism to unravel the genetic architecture of psychotic disorders. Genome‐wide association studies have identified a number of common polymorphisms robustly associated with schizophrenia, in ZNF804A, transcription factor 4, major histocompatibility complex, and neurogranin. In addition, copy number variants (CNVs) in 1q21.1, 2p16.3, 15q11.2, 15q13.3, 16p11.2, and 22q11.2 were convincingly implicated in schizophrenia risk. Furthermore, these studies have suggested considerable genetic overlap with bipolar disorder (particularly for common polymorphisms) and neurodevelopmental disorders such as autism (particularly for CNVs). The influence of these risk variants on relevant intermediate phenotypes needs further study. In addition, there is a need for etiological models of psychosis integrating genetic risk with environmental factors associated with the disorder, focusing specifically on environmental impact on gene expression (epigenetics) and convergence of genes and environment on common biological pathways bringing about larger effects than those of genes or environment in isolation (gene–environment interaction). Collaborative efforts that bring together expertise in statistics, genetics, epidemiology, experimental psychiatry, brain imaging, and clinical psychiatry will be required to succeed in this challenging task.

Background: A disproportionately large number of persons with panic disorder (PD) smoke cigarettes compared to people in the general population and individuals with other anxiety disorders. Clinical and epidemiological data suggest that cigarette smoking increases the risk for the development and maintenance of PD. The carbon dioxide (CO2) challenge is well established as experimental model for panic. The present study seeks to examine whether cigarette smoking has an influence on laboratory elicited panic in PD patients.Methods: In total 92 subjects (46 smokers and 46 non-smokers) with PD, according to the DSM-IV criteria, were compared. All subjects received a baseline clinical assessment and underwent a 35% CO2 challenge. Response to the challenge was evaluated via the Panic Symptom List and the Visual Analogue Fear Scale.Results: The two samples did not differ on baseline anxiety level. Smokers had a significantly higher increase in panic symptoms in response to the challenge compared to non-smokers (p = 0.04).Limitations: This type of study does not provide information concerning the underlying mechanisms of the link between smoking and panic. Study limitations include lack of formal assessment of personality and of inter-rater reliability.Conclusions: The present findings are consistent with the idea that smoking facilitates panic in PD subjects. This may have clinical implications, as quitting smoking could become one of the relevant steps in the treatment of PD patients. (C) 2009 Elsevier B.V. All rights reserved.