Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents

AbstractBackground Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. Methods Eighty-two Depressed and 24 healthy female adolescents, aged 12 to 17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. Results At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalized after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. Limitations In the follow-up section, a limited number of post-CBT patients were recruited. Conclusions To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.

Effect of antidepressants on melatonin metabolite in depressed patients

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Symptomatic expression of depression among Jewish adolescents: effects of gender and age

Background Depression symptomatology was assessed with the Beck Depression Inventory (BDI) in a sample of Jewish adolescents, in order to compare the frequency and severity of depression with non-Jewish adolescents as well as examine gender difference of the expression of depressive symptomatology. Method Subjects comprised 475 students from Jewish private schools, aged 13-17 years, who were compared with an age-matched non-Jewish sample (n = 899). Kendall`s definition was adopted to classify these adolescents according to level of depressive symptoms. The frequency of depression was calculated for ethnicity, gender and age strata. Discriminant analysis and principal component analysis were performed to assess the importance of depression-specific and non-specific items, along with the factor structure of the BDI, respectively. Results The overall mean score on the BDI in the Jewish and the non-Jewish sample was 9.0 (SD = 6.4) and 8.6 (SD = 7.2), respectively. Jewish girls and boys had comparable mean BDI scores, contrasting with non-Jewish sample, where girls complained more of depressive symptoms than boys (p < 0.001). The frequency of depression, adopting a BDI cutoff of 20, was 5.1% for the Jewish sample and 6.3% for the non-Jewish sample. The frequency of depression for Jewish girls and boys was 5.5% (SE = 1.4) and 4.6% (SE = 1.5), respectively. On the other hand, the frequency of depression for non-Jewish girls and boys was 8.4% (SE = 1.2) and 4.0% (SE = 1.0), respectively. The female/male ratio of frequency of BDI-depression was 1.2 in the Jewish sample, but non-Jewish girls were twice (2.1) as likely to report depression as boys. Discriminant analysis showed that the BDI highly discriminates depressive symptomatology among Jewish adolescents, and measured specific aspects of depression. Factor analysis revealed two meaningful factors for the total sample and each gender (cognitive-affective dimension and somatic dimension), evidencing a difference between Jewish boys and Jewish girls in the symptomatic expression of depression akin to non-Jewish counterparts. Conclusions Ethnic-cultural factor might play a role in the frequency, severity and symptomatic expression of depressive symptoms in Jewish adolescents. The lack of gender effect on depression, which might persist from adolescence to adulthood among Jewish people, should be investigated in prospective studies.

Culturally-sensitive complaints of depressions and anxieties in women

Background: Current classifications of Mental Disorders are centered on Westernized concepts and constructs. Cross-cultural sensitivity emphasizes culturally-appropriate translations of symptoms and questions, assuming that concepts and constructs are applicable.Methods: Groups and individual psychiatrists from various cultures from Asia, Latin America, North Africa and Eastern Europe prepared descriptions of main symptoms and complaints of treatment-seeking women in their cultures, which are interpreted by clinicians as a manifestation of a clinically-relevant dysphoric disorder. They also transliterated the expressions of DSM IV criteria of main dysphoric disorders in their cultures.Results: In many non-western cultures the symptoms and constructs that are interpreted and treated as dysphoric disorders are mostly somatic and are different from the Western-centered DSM or ICD systems. In many cases the DSM and ICD criteria of depression and anxieties are not even acknowledged by patients.Limitations: the descriptive approach reported here is a preliminary step which involved local but Westernized clinicians-investigators following a biomedical thinking. It should be followed by a more systematic-comprehensive surveys in each culture.Conclusions: Westernized concepts and constructs of mental order and disorders are not necessarily universally applicable. Culturallysensitive phenomena, treatments and treatment responses may be diversified. Attempts at their cross-cultural harmonization should take into consideration complex interactional multi-dimensional processes. (c) 2006 Elsevier B.V. All rights reserved.

Clinical features associated to refractory obsessive-compulsive disorder

Some patients with obsessive-compulsive disorder (OCD) exhibit an unsatisfactory reduction in symptom severity despite being treated with all the available therapeutic alternatives. The clinical variables associated with treatment-refractoriness in OCD are inconsistently described in the literature.Methods: To investigate factors associated with treatment-reftactoriness of patients with OCD, we conducted a case-control study, comparing 23 patients with treatment-refractory OCD to 26 patients with treatment-responding OCD.Results: the factors associated with refractoriness of OCD were higher severity of symptoms since the onset of OCD (P < 0.001), chronic course (p=0.003), lack of a partner (p=0.037), unemployment (p=0.025), low economic status (p=0.015), presence of obsessive-compulsive symptoms of sexual/religious content (p=0.043), and higher scores on family accommodation (P < 0.001). Only the three latter variables remained significantly associated with treatment-reftactoriness after regression analyses. Limitations: small sample size, the biases and drawbacks inherent to a case-control study, and the inclusion criteria used to define the study groups may have limited the generalisation of the results.Conclusion: A major strength of this study is the systematic and structured evaluation of a vast array of variables related to the clinical expression of OCD, including epigenetic factors and ratings derived from instruments evaluating family accommodation. The presence of sexual/religious symptoms, low economic status and high modification on family function due to OCD were independently associated with, treatment-refractoriness. Future longitudinal studies are warranted to verify if these variables represent predictive factors of treatment non-response. (c) 2006 Elsevier B.V. All rights reserved.

Patterns of alcohol use between genders: A cross-cultural evaluation

Introduction: Alcohol use by men and women is very much influenced by social habits and customs. Cultural peculiarities and biological differences between the sexes require more focused and standardized studies. The objective was to systematize information on patterns of alcohol use between the sexes.Method: A literary review (1972-2004) identified 96 publications (Lilacs, Scielo, Medline) and some related books.Results and conclusions: Men drank more and presented more problems (legal, family, social, clinical, traumas and mortality) associated with alcohol use; the consequences of alcohol use in developing countries with low death rates is even higher. Women can face more discrimination by using alcohol as well as worse health problems when they abuse drinking (liver, pancreas, and central and peripheral nervous system problems, psychiatric comorbidity, etc.); sexual abuse is more commonly associated with women than discussing the different responses to treatment. As for social roles/responsibilities exercised by women, there are indications that marriage, employment, and children have a good influence, discouraging alcohol use, while divorce, unemployment, and no children contribute to higher consumption. For both sexes, religion was a protective factor for alcohol use; acculturation was a strong influence in the pattern of alcohol use, and alcohol worsened the evolution of existing psychiatric disorders. (c) 2006 Elsevier B.V. All rights reserved.

Social phobia in obsessive-compulsive disorder: Prevalence and correlates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hospital-dia: para quem e para quê?

OBJETIVO: Estudar prospectivamente a população internada em um hospital-dia (HD) em relação a fatores que poderiam influenciar na melhora e na duração da internação. MÉTODOS: Foram entrevistados, para obtenção de dados sociodemográficos e avaliação da evolução, 34 pacientes internados no Hospital-Dia da Faculdade de Medicina de Botucatu, Unesp, durante um ano. O diagnóstico psiquiátrico foi avaliado pela CIDI (Composite International Diagnostic Interview), a sintomatologia psiquiátrica pela BPRS (Brief Psychiatric Rating Scale) e a incapacitação psicossocial pela DAS (Psychiatric Disability Assessment Schedule). Todos os pacientes foram acompanhados, e seus familiares, entrevistados. RESULTADOS: Predominaram mulheres (76%), jovens (61,8%), sem vínculo conjugal (71%), sem trabalho (82,4%), com diagnóstico de transtornos afetivos (44,1%) e com internações psiquiátricas prévias (44%). Apenas quatro (12%) pacientes apresentavam uma síndrome maior segundo BPRS. Houve considerável incapacitação psicossocial dos pacientes em alguns papéis sociais. Maior renda per capita foi um fator associado à melhor evolução. As internações duraram em média 74 dias. Pacientes com internações prévias tenderam a permanecer menos tempo no HD. CONCLUSÕES: Portadores de transtornos afetivos e quadros não-psicóticos geralmente não necessitam de internação por período integral em hospital psiquiátrico. Contudo, os pacientes deste estudo tiveram um elevado número de internações psiquiátricas prévias, provavelmente por necessitarem de um nível de atendimento além das possibilidades dos ambulatórios. Entretanto, pacientes com maior número de internações -- em tese mais graves -- tenderam a permanecer menos tempo no HD, o que suscita dúvidas quanto à sua adesão a serviços abertos, bem como aos possíveis fatores facilitadores dessa adesão. em um momento de crescimento expressivo no número de serviços de internação parcial no Brasil, como nos últimos anos, mais estudos são necessários a fim de esclarecer para quem e para quê são destinados esses serviços.

Avaliação da sintomatologia afetiva e cognitiva de adolescentes epilépticos

The present work aimed to study the relationship between epileptic condition and psychological activity. The purpose of this investigation was to identify cognitive complaints and affective disturbs, like depressive disorders, and to compare both with epileptic condition. Forty epileptic adolescents, aged from 13 to 19 years old were analyzed. These patients were a consecutive series of males and females attending the Neuroepilepsy Center from the Universidade Estadual de Campinas, SP, and from lower social-economic background. The methodological procedures included specific questionnaires (a open and a assertive kind), and the Zung Self-rating Depression Scale. Cognitive alterations like thinking slowness or memorizing complaints in many patients, and affective disorders like depressive disturbs in 82.5% were the basic findings. The results also showed association between frequency of seizures and depressive disturbs; and between chronicity of epileptic condition and depressive disturbs. The discussion of these data suggests a relationship of epileptic condition with psychological reactions. We concluded that it is necessary to elevate the self-concept of these depressive patients in order to reduce their psychic suffering.

Antidepressivo em ratos com insuficiência aórtica pode modificar a expressão gênica de ocitocina e vasopressina centrais?

Aortic regurgitation (AR) leads to a left ventricle dilation and hypertrophy in response to a chronic volume overload. It is still very frequent in developing countries, for instance Brazil, and often as secondary to rheumatic fever. Usually, chronic AR is generally well tolerated for many years, when with the heart dilated the patient searches for treatment. Bidirectional association with depression and cardiovascular disease has been described. Selective serotonin reuptake inhibitors (SSRI) are widely prescribed to treat several affective disorders, especially for cardiovascular patients since they decrease arrhythmia probability. These SSRI improves cardiac function in rats submitted to stress protocols. Preliminary study from our laboratory showed that following 4 weeks of treatment with one SSRI (paroxetine) in subchronic AR rats there was a decreased in daily sodium intake and an improvement in systolic function. An increase in the central oxytocinergic transmission may be involved in this peripheral improvement to the heart. The investigations about the mechanisms underlying this improvement are necessary. Therefore the aims of this project is investigate the effects of 4 weeks of treatment of paroxetine, a SSRI, in rats with a subchronic AR over the central central gene expression of oxytocin and vasopressin using a reverse transcription polymerase chain reaction (RT-PCR)

Motor Activity and Depression Severity in Adolescent Outpatients

Objectives: The present study investigated the association between motor activity and severity of depression in 6 depressed adolescent outpatients. Method: Motor activity was assessed by actigraphy and the severity of depression was assessed weekly using the CDRS-R. The levels of motor activity were analyzed by considering activity parameters. Results: Among the parameters of motor activity studied, the mean total activity, the mean 24-hour activity levels, the mean waking activity, and the mean activity level between 12:00 and 18:00 h were inversely correlated with severity of depression. The means of the 10 most active hours tended toward a negative correlation with the depressive severity score. Conclusion: The results seem to suggest an association between motor activity level and severity of depression in adolescents. Nevertheless, in order to reach a more conclusive understanding, it would be necessary to replicate this study using a larger number of individuals as well as a longer observation period. Copyright (C) 2009 S. Karger AG, Basel

COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes

Background: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val(158)Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val(158)Met on FER during manic and depressive episodes in BD patients and in healthy controls. Materials and methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer "angry" and "happy" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on "disgust" and "angry" faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. ClinicalTrials.gov Identifier: NCT00969. (C) 2011 Elsevier B.V. All rights reserved.

Does Lithium Prevent Alzheimer's Disease?

Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.

DIFFERENTIAL INVOLVEMENT OF DORSAL RAPHE SUBNUCLEI IN THE REGULATION OF ANXIETY- AND PANIC-RELATED DEFENSIVE BEHAVIORS

A wealth of evidence indicates that the dorsal raphe nucleus (DR) is not a homogenous structure, but an aggregate of distinctive populations of neurons that may differ anatomically, neurochemically and functionally. Other findings suggest that serotonergic neurons within the mid-caudal and caudal part of the DR are involved in anxiety processing while those within the lateral wings (IwDR) and ventrolateral periaqueductal gray (vIPAG) are responsive to panic-evoking stimuli/situations. However, no study to date has directly compared the activity of 5-HT and non-5HT neurons within different subnuclei of the DR following the expression of anxiety- and panic-related defensive responses. In the present investigation, the number of doubly immunostained cells for Fos protein and tryptophan hydroxylase, a marker of serotonergic neurons, was assessed within the rat DR, median raphe nucleus (MRN) and PAG following inhibitory avoidance and escape performance in the elevated T-maze, behaviors associated with anxiety and panic, respectively. Inhibitory avoidance, but not escape, significantly increased the number of Fos-expressing serotonergic neurons within the mid-caudal part of the dorsal subnucleus, caudal and interfascicular subnuclei of the DR and in the MRN. Escape, on the other hand, caused a marked increase in the activity of non-5HT cells within the IwDR, vIPAG, dorsolateral and dorsomedial columns of the PAG. These results strongly corroborate the view that different subsets of neurons in the DR are activated by anxiety- and panic-relevant stimuli/situations, with important implications for the understanding of the pathophysiology of generalized anxiety and panic disorders. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.