Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective: Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD. Methods: Sixty-three BD patients were studied (mean +/- SD age = 38.2 +/- 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions. Results: Left rostral ACC GM volume was inversely correlated with the BIS total score (t = 3.95, p(corrected) = 0.003) and the BIS motor score (t = 5.22, p(corrected) < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance. Conclusions: Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.

Serotonin and Sensitivity to Trauma-Related Exposure in Selective Serotonin Reuptake Inhibitors-Recovered Posttraumatic Stress Disorder

Background: Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for posttraumatic stress disorder (PTSD). Serotonergic (5HT) attenuation of stress sensitivity is postulated from SSRIs` effects in other anxiety disorders, and we studied this in PTSD. Methods: Ten patients with PTSD fully recovered on SSRIs (Clinical Global Impression Scale-I 1 and 2) were enrolled in the study. Patients were tested on two occasions I week apart; in each session, they received a drink containing large neutral amino acids (LNAAs) either with (sham tryptophan depletion [STD], control) or without (acute tryptophan depletion [ATD]) tryptophan. At 5.5 hours after the drink, subjects were exposed to a trauma-related exposure challenge. Self-reports of PTSD (visual analogue scales [VAS] and the Davidson Trauma Scale [DTSI), anxiety (Spielberger State Inventory [STAI] Form Y-1), and mood (Profile of Mood States [POMS]) were obtained. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were also measured. Results: The trauma-related exposure challenge induced anxiety on both days, with more marked responses on the ATD day according to VAS, DTS, POMS, and DBP (p < .05). A trend of significance (.1 > p >.05) was observed for STAI Form Y-1, HR, and SBP. Conclusions: These data demonstrate that ATD accentuates responses to trauma-related stimuli in SSRI-recovered PTSD. They also suggest that SSRI-induced increases in serotonin function restrain PTSD symptoms, especially under provocation, supporting a role for serotonin in mediating stress resilience.

Social dysfunction in bipolar disorder: pilot study

Objective: The purpose of the present study was to assess the social skills of euthymic patients with bipolar disorder. Methods: A group of 25 outpatients with bipolar disorder type I were evaluated in comparison with a group of 31 healthy volunteers who were matched in terms of level of education, age, sex and intelligence. Both groups were assessed using a self-report questionnaire, the Brazilian Inventario de Habilidades Sociais (IHS, Social Skills Inventory). Two Wechsler Adult Intelligence Scale subtests ( Picture Arrangement and Comprehension) were also used in order to assess subject ability to analyse social situations and to make judgements, respectively. Results: Patients with bipolar disorder had lower IHS scores for the domains that assessed conversational skills/social self-confidence and social openness to new people/situations. Patients with anxiety disorders had high scores for the domain that assessed self-confidence in the expression of positive emotions. No differences were found between patients and controls in performance on the Wechsler Adult Intelligence Scale Picture Arrangement and Comprehension subtests. Conclusions: Euthymic patients with bipolar disorder present inhibited and overattentive behaviour in relation to other people and their environment. This behaviour might have a negative impact on their level of social functioning and quality of life.

Neurobiology of panic disorder: From animal models to brain neuroimaging

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG). Stressing the difference between these emotions, neuroendocrinological results indicate that the hypothalamic-pituitary-adrenal axis is activated by anticipatory anxiety, but not by panic attack nor by electrical stimulation of the rat PAG. Functional neuroimaging has shown activation of the insula and upper brain stem (including PAG), as well as deactivation of the anterior cingulated cortex (ACC) during experimental panic attacks. Voxel-based morphometric analysis of brain magnetic resonance images has shown a grey matter volume increase in the insula and upper brain stem, and a decrease in the ACC of panic patients at rest, as compared to healthy controls. The insula and the ACC detect interoceptive stimuli, which are overestimated by panic patients. It is suggested that these brain areas and the PAG are involved in the pathophysiology of panic disorder. (C) 2008 Elsevier Ltd. All rights reserved.

CHRONIC LITHIUM TREATMENT PREVENT ANXIETY-LIKE BEHAVIOR RELATED TO DIETARY RESTRICTION

Caloric intake reduction has been considered as the major experimental manipulation able to increase longevity in experimental models. Therefore, its effects upon cognition and mood like behavior are poorly explored. On the other hand, Li(+) is a re-emergent therapeutic drug used to treat mood disorders, mainly bipolar disorder, with antipanic and antidepressant actions. On the hypothesis that lithium treatment could attenuate the negatives effects of stress on Central Nervous Systems (CNS), we evaluated the role of chronic lithium treatment on anxiety-like behaviors in animals submitted to stress by chronic moderated feed restriction (FR). Male wistar rats were divided into four groups (n = 7-8/group) according to dietary and drug manipulation: ad libitum (AL) with unlimited access to standard rat diet, lithium treatment ( AL + Li) which received approximately 50 mg/Kg animal/day of LiCl solved in water and ad libitum diet, FR that were fed with equivalent to 70% of total rat diet consumed by AL group, and FR + Li which received diet corresponding to FR and Li administration. After 12 weeks of drug and FR manipulation, anxiety like behavior was evaluated in elevated plus mazes (EPM). Chronic lithium treatment prevent the anxiogenic like effect of FR ( open time, F(3,30) = 3.588; P = 0.0265; percentage of open entries, F(3,30) = 6.004; P= 0.00029; and open time at the first min, 2.35; F(3,30) = 4.937; P = 0.0073, Duncan test P < 0.05) compared to AL diet. Ours results adding to evidences that moderate feed restriction my increase anxiety-like behavior; also suggest that chronic lithium treatment may be attenuated this effects.

GABAA receptor β3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population

GABAergic systems have been implicated in the pathogenesis of anxiety, depression and insomnia. These symptoms are part of the core and comorbid psychiatric disturbances in post-traumatic stress disorder (PTSD) In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABAA receptor beta3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) was GI, the alleles were divided into GI and non-GI groups. On the total score of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, social dysfunction and depression subscales, patients with the GI non-GI genotype had a significantly higher score when compared to either the G1G1 genotype (alpha = 0.01) or the non-GI non-GI genotype (alpha = 0.05). No significant difference was found between the G1G1 and non-Gl non-G1 genotypes. When the GI non-G1 heterozygotes were compared to the combined G1G1 and non-GI non-GI homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P = 0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P = 0.006), anxiety/insomnia (P = 0.003), social dysfunction (P = 0.054) and depression (P = 0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major (GI) allele confers higher levels of somatic symptoms, anxiety/insomnia, social dysfunction and depression than found in homozygosity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Acute generalized exanthematous pustulosis (AGEP). Case report

Acute Generalized Exanthematous Pustulosis (AGEP) is a drug-induced dermatosis characterized by an acute episode of sterile pustules over erythematous-edematous skin. It is accompanied by an episode of fever, which regresses a few days after discontinuation of the drug that caused the condition or as a result of corticosteroid treatment. The main triggering drugs are antibiotics, mainly beta-lactam ones. Other medications, such as antifungal agents, non steroid anti-inflammatory drugs, analgesics, antiarrhythmic, anticonvulsant and antidepressant drugs, may also be responsible. Histologically, it is characterized by the existence of vasculitis, associated with non-follicular subcorneal pustules. A case of a Caucasian female outpatient unit of Dermatology with AGEP, who presented with generalized pustulosis lesions after the use of cephalosporin for urinary infection is related. The diagnosis was confirmed by the clinical and pathological correlations, the resolution of the dermatosis after discontinuation of the drug and use of systemic corticosteroid treatment, and the recurrence of the disorder after the introduction of a similar drug. The importance of the recognition of this drug-induced dermatosis is given by its main differential clinical and histological diagnoses: generalized pustular psoriasis and subcorneal pustulosis.

Effects of Aerobic Exercise on Anxiety Disorders: A Systematic Review

Anxiety disorders are the most common psychiatric disorders observed currently. It is a normal adaptive response to stress that allows coping with adverse situations. Nevertheless, when anxiety becomes excessive or disproportional in relation to the situation that evokes it or when there is not any special object directed at it, such as an irrational dread of routine stimuli, it becomes a disabling disorder and is considered to be pathological. The traditional treatment used is medication and cognitive behavioral psychotherapy, however, last years the practice of physical exercise, specifically aerobic exercise, has been investigated as a new non-pharmacological therapy for anxiety disorders. Thus, the aim of this article was to provide information on research results and key chains related to the therapeutic effects of aerobic exercise compared with other types of interventions to treat anxiety, which may become a useful clinical application in a near future. Researches have shown the effectiveness of alternative treatments, such as physical exercise, minimizing high financial costs and minimizing side effects. The sample analyzed, 66.8% was composed of women and 80% with severity of symptoms anxiety as moderate to severe. The data analyzed in this review allows us to claim that alternative therapies like exercise are effective in controlling and reducing symptoms, as 91% of anxiety disorders surveys have shown effective results in treating. However, there is still disagreement regarding the effect of exercise compared to the use of antidepressant symptoms and cognitive function in anxiety, this suggests that there is no consensus on the correct intensity of aerobic exercise as to achieve the best dose-response, with intensities high to moderate or moderate to mild.

Cardio-respiratory symptoms in panic disorder: a contribution from cognitive-behaviour therapy

Objective: To compare patients with panic disorder with agoraphobia treated with cognitive-behavioural therapy (CBT) associated with the medication with patients treated only with medication and verify the behaviour of the cardio-respiratory symptoms of both groups. Methods: Randomized sample in the Psychiatry Institute of the Federal University of Rio de Janeiro, divided in two groups of 25 participants each. Group 1 undertook 10 weekly sessions of CBT with one hour of duration each together with medication. Group 2, Control, were administered medication that only consisted of tricyclic anti-depressants and selective inhibitors of the re-uptake of serotonin. Evaluation instruments were applied at the beginning and to the end of the interventions. Results: According to the applied scales, group 1 showed statistically more significant results than group 2, with: reduction of panic attacks, cardio-respiratory symptoms, anticipatory anxiety, agoraphobia avoidance and fear of bodily sensations. Conclusion: Exposures (in vivo and interoceptive), especially for induction symptom exercises and relaxation, were considered essential to prepare patients with panic disorder to handle future cardio-respiratory symptoms and panic attacks with agoraphobia.

Anxiety and depression symptoms in women and men from early pregnancy to 3-months postpartum: parity differences and effects

This study aimed to investigate both anxiety and depression symptoms from early pregnancy to 3-months postpartum, comparing women and men and first and second-time parents. Methods: A sample of 260 Portuguese couples (N=520), first or second-time parents, recruited in an Obstetrics Out-patients Unit, filled in the State-Anxiety Inventory (STAI-S) and the Edinburgh Post-Natal Depression Scale (EPDS) at the 1st, 2nd and 3rd pregnancy trimesters, childbirth, and 3-months postpartum. Results: A decrease in anxiety and depression symptoms from early pregnancy to 3-months postpartum was found in both women and men, as well as in first and second-time parents. Men presented less anxiety and depression symptoms than women, but the same pattern of symptoms over time. Second-time parents showed more anxiety and depression symptoms than first-time parents and a different pattern of symptoms over time: an increase in anxiety and depression symptoms from the 3rd trimester to childbirth was observed in first-time parents versus a decrease in second-time parents. Limitations: The voluntary nature of the participation may have lead to a selection bias; women and men who agreed to participate could be those who presented fewer anxiety and depression symptoms. Moreover, the use of self-report symptom measures does not give us the level of possible disorder in participants. Conclusions: Anxiety and depression symptoms diminish from pregnancy to the postpartum period in all parents. Patterns of anxiety and depression symptoms from early pregnancy to 3-months postpartum are similar in women and men, but somewhat different in first and second time parents. Second-time parents should also be considered while studying and intervening during pregnancy and the postpartum.

Patients presenting with somatic complaints in general practice: depression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors.

BACKGROUND: Mental disorders in primary care patients are frequently associated with physical complaints that can mask the disorder. There is insufficient knowledge concerning the role of anxiety, depression, and somatoform disorders in patients presenting with physical symptoms. Our primary objective was to determine the prevalence of depression, anxiety, and somatoform disorders among primary care patients with a physical complaint. We also investigated the relationship between cumulated psychosocial stressors and mental disorders. METHODS: We conducted a multicentre cross-sectional study in twenty-one private practices and in one academic primary care centre in Western Switzerland. Randomly selected patients presenting with a spontaneous physical complaint were asked to complete the self-administered Patient Health Questionnaire (PHQ) between November 2004 and July 2005. The validated French version of the PHQ allowed the diagnosis of mental disorders (DSM-IV criteria) and the analyses of exposure to psychosocial stressors. RESULTS: There were 917 patients exhibiting at least one physical symptom included. The rate of depression, anxiety, and somatoform disorders was 20.0% (95% confidence interval [CI] = 17.4% to 22.7%), 15.5% (95% CI = 13.2% to 18.0%), and 15.1% (95% CI = 12.8% to 17.5%), respectively. Psychosocial stressors were significantly associated with mental disorders. Patients with an accumulation of psychosocial stressors were more likely to present anxiety, depression, or somatoform disorders, with an increase of 2.2 fold (95% CI = 2.0 to 2.5) for each additional stressor. CONCLUSIONS: The investigation of mental disorders and psychosocial stressors among patients with physical complaints is relevant in primary care. Psychosocial stressors should be explored as potential epidemiological causes of mental disorders.

Patients presenting with somatic complaints in general practice : dépression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors

RAPPORT DE SYNTHÈSE Introduction En médecine de premier recours, les plaintes physiques sont fréquemment associées à des troubles dépressifs, anxieux et somatoformes et peuvent les masquer. Il est fréquemment reporté que ces troubles mentaux ont tendance à être insuffisamment diagnostiqués. Par ailleurs, peu d'études ont été conduites en médecine de premier recours concernant la possible association entre facteurs de stress psychosociaux et troubles dépressifs, anxieux et somatoformes. Objectifs Les objectifs étaient de déterminer la prévalence des troubles dépressifs, anxieux et somatoformes chez des patients consultant avec une plainte physique en médecine de premier recours, ainsi que d'explorer la possible association entre ces troubles mentaux et des facteurs de stress psychosociaux. Méthodes Nous avons conduit une étude transversale, multicentrique parmi vingt et un cabinets médicaux en Suisse Romande et la Policlinique Médicale Universitaire de Lausanne. Les sujets étaient sélectionnés aléatoirement parmi des patients qui avaient présenté spontanément au moins une plainte physique et qui avaient consulté lors d'une demi- journée de consultation considérée pour l'étude. Les patients inclus ont rempli l'auto- questionnaire Patient Health Questionnaire (PHQ) entre novembre 2004 et juillet 2005. Nous avons utilisé la version française et validée du PHQ qui permet le diagnostic des principaux troubles mentaux selon les critères du DSM-IV et l'analyse de l'exposition aux facteurs de stress psychosociaux. Résultats Neuf cent dix-sept patients se présentant avec au moins une plainte physique ont été inclus. Le taux de troubles dépressifs, anxieux et somatoformes a été de 20,0% (intervalle de confiance [IC] à 95% = 17,4%-22,7%), 15,5% (IC 95% = 13,2%- 18,0%) et 15,1% (IC 95% = 12,8%~17,5%), respectivement. Les facteurs de stress psychosociaux ont été significativement associés aux troubles mentaux. Les patients avec une accumulation de facteurs de stress psychosociaux ont été le plus souvent déprimés, anxieux ou ont manifesté des troubles somatoformes, avec une augmentation par un facteur 2,2 (IC 95% = 2,0-2,5) pour chaque facteur additionnel. Conclusions Bien que la relation entre facteurs de stress psychosociaux et trouble dépressif soit bien établie, cette étude montre qu'il existe un lien entre ces facteurs de stress et les troubles dépressifs, anxieux et somatoformes. L'investigation de ces troubles mentaux chez des patients consultant avec un symptôme physique en médecine de premier recours est pertinente. D'autres explorations sont nécessaires pour investiguer le bénéfice potentiel d'une prise en charge intégrée des facteurs de stress psychosociaux sur la diminution des plaintes physiques et des troubles mentaux chez les patients que suivent les médecins de premier recours.

Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response.

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

Associations of Serum Uric Acid and SLC2A9 Variant with Depressive and Anxiety Disorders: A Population-Based Study.

BACKGROUND: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. METHODS: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. RESULTS: Men reported significantly higher levels of SUA compared to women (357±74 µmol/L vs. 263±64 µmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. CONCLUSIONS: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.

Fear and anxiety at the basis of adolescent externalizing and internalizing behaviors: a case study.

Juvenile delinquency is rarely associated with success in psychotherapeutic treatment. Up until now, few data have been recorded regarding possible overlaps or common features of conduct disorders with anxiety disorders. This case report of a delinquent adolescent's presenting an obsessive-compulsive disorder discusses possible underlying common features of externalizing and internalizing disorders, mainly in terms of fear and anxiety regulation. The successful psychotherapy is discussed with regard to efficient psychological assessment and treatment of delinquent adolescents, and it underlies the importance of detailed analysis of psychopathology in cases of juvenile delinquency.