Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Cotard syndrome without depressive symptoms in a schizophrenic patient

Cotard Syndrome without Depressive Symptoms in a Schizophrenic Patient

Insatisfação com a imagem corporal após a cirurgia bariátrica: um estudo comparativo entre a cirurgia de revisão e primária

Dissertação de mestrado integrado em Psicologia (área de especialização em Psicologia Clínica e da Saúde)

Qualidade de vida após um ano da cirurgia bariátrica

Dissertação de mestrado integrado em Psicologia

Momentos de inovação: emergência e evolução das protonarrativas em terapia narrativa

Dissertação de mestrado em Psicologia Aplicada

Predictors of dropout in a controlled clinical trial of psychotherapy for moderate depression

A significant number of psychotherapy clients remain untreated, and dropping out is one of the main reasons. Still, the literature around this subject is incoherent. The present study explores potential pre-treatment predictors of dropout in a sample of clients who took part in a clinical trial designed to test the efficacy of narrative therapy for major depressive disorder compared to cognitive-behavioral therapy. Logistic regression analysis showed that: (1) treatment assignment did not predict dropout, (2) clients taking psychiatric medication at intake were 80% less likely to drop out from therapy, compared to clients who were not taking medication, and (3) clients presenting anxious comorbidity at intake were 82% less likely to dropout compared to those clients not presenting anxious comorbidity. Results suggest that clinicians should pay attention to depressed clients who are not taking psychiatric medication or have no comorbid anxiety. More research is needed in order to understand this relationship.

Exploring female mice interstrain differences relevant for models of depression

Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8?weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

“PhenoWorld”: a new multidimensional strategy for studying behaviour in rodents

Tese de Doutoramento em Ciências da Saúde

Stress-triggered synaptic malfunction: a gate along the path from depressionto dementia

Tese de Doutoramento em Ciências da Saúde.

The effect of high-fat diet on rat’s mood, feeding behavior and response to stress

An association between obesity and depression has been indicated in studies addressing common physical (metabolic) and psychological (anxiety, low self-esteem) outcomes. Of consideration in both obesity and depression are chronic mild stressors to which individuals are exposed to on a daily basis. However, the response to stress is remarkably variable depending on numerous factors, such as the physical health and the mental state at the time of exposure. Here a chronic mild stress (CMS) protocol was used to assess the effect of high-fat diet (HFD)-induced obesity on response to stress in a rat model. In addition to the development of metabolic complications, such as glucose intolerance, diet-induced obesity caused behavioral alterations. Specifically, animals fed on HFD displayed depressive- and anxious-like behaviors that were only present in the normal diet (ND) group upon exposure to CMS. Of notice, these mood impairments were not further aggravated when the HFD animals were exposed to CMS, which suggest a ceiling effect. Moreover, although there was a sudden drop of food consumption in the first 3 weeks of the CMS protocol in both ND and HFD groups, only the CMS-HFD displayed an overall noticeable decrease in total food intake during the 6 weeks of the CMS protocol. Altogether, the study suggests that HFD impacts on the response to CMS, which should be considered when addressing the consequences of obesity in behavior.

The positive effect on ketamine as a priming adjuvant in antidepressant treatment.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.

Depressão em pacientes HIV positivos: a realidade de um hospital português

Aims: Depression is the most common psychiatric disorder among people infected with HIV. This study aims to characterize the Hospital of Joaquim Urbano population of HIV-infected patients’ profile regarding depressive symptoms and whether they correlate with the analytical parameters most frequently evaluated in the context of infection by this virus – HIV viral load, CD4+ count and CD4+ percentage. Methods: We conducted an observational descriptive and analytical study. The participants’ level of depressive symptoms was assessed with the Beck Depression Inventory. The medical and psychiatric history and the analytical values of viral load, CD4+ count and CD4+ percentage were obtained by consulting the participants’ clinical processes. Results: A prevalence of 65.5% in HIV-infected patients’ depressive symptoms was found, with a considerable high percentage of subjects presenting with severe symptoms (32.7%). No associations between the depressive symptoms’ levels and CD4+ count, CD4+ percentage or viral load were found. However, depressive symptoms were associated with substance abuse and education level. Conclusions: The high prevalence of depressive symptoms found in this study reinforces the importance of monitoring this type of symptoms in HIV-infected subjects. The fact that there have been no associations between depressive symptoms and the analytical parameters evaluated is in line with previous studies.

Paternal Adjustment and Paternal Attitudes Questionnaire: Antenatal and postnatal portuguese versions

The Paternal Adjustment and Paternal Attitudes Questionnaire (PAPA) was designed to assess paternal adjustment and paternal attitudes during the transition to parenthood. This study aimed to examine the psychometric characteristics of the Portuguese versions of the PAPA-Antenatal (PAPA-AN) and -Postnatal (PAPA-PN) versions. A nonclinical sample of 128 fathers was recruited in the obstetrics outpatient unit, and they completed both versions of the PAPA and selfreport measures of depressive and anxiety symptoms during pregnancy and the postpartum period, respectively. Good internal consistency for both PAPA-AN and PAPA-PN was found. A three-factor model was found for both versions of the instrument. Longitudinal confirmatory factor analysis revealed a good model fit. The PAPA-AN and PAPA-PN subscales revealed good internal consistency. Significant associations were found between PAPA (PAPA-AN and PAPA-PN) and depressive and anxiety symptoms, suggesting good criterion validity. Both versions also showed good clinical validity, with optimal cutoffs found. The present study suggested that the Portuguese versions of the PAPA are reliable multidimensional self-report measures of paternal adjustment and paternal attitudes that could be used to identify fathers with adjustment problems and negative attitudes during the transition to parenthood.

Breastfeeding and depression: a systematic review of the literature

Background: Research has separately indicated associations between pregnancy depression and breastfeeding, breastfeeding and postpartum depression, and pregnancy and postpartum depression. This paper aimed to provide a systematic literature review on breastfeeding and depression, considering both pregnancy and postpartum depression. Methods: An electronic search in three databases was performed using the keywords: “breast feeding”, “bottle feeding”, “depression”, “pregnancy”, and “postpartum”. Two investigators independently evaluated the titles and abstracts in a first stage and the full-text in a second stage review. Papers not addressing the association among breastfeeding and pregnancy or postpartum depression, non-original research and research focused on the effect of antidepressants were excluded. 48 studies were selected and included. Data were independently extracted. Results: Pregnancy depression predicts a shorter breastfeeding duration, but not breastfeeding intention or initiation. Breastfeeding duration is associated with postpartum depression in almost all studies. Postpartum depression predicts and is predicted by breastfeeding cessation in several studies. Pregnancy and postpartum depression are associated with shorter breastfeeding duration. Breastfeeding may mediate the association between pregnancy and postpartum depression. Pregnancy depression predicts shorter breastfeeding duration and that may increase depressive symptoms during postpartum. Limitations: The selected keywords may have led to the exclusion of relevant references. Conclusions: Although strong empirical evidence regarding the associations among breastfeeding and pregnancy or postpartum depression was separately provided, further research, such as prospective studies, is needed to clarify the association among these three variables. Help for depressed pregnant women should be delivered to enhance both breastfeeding and postpartum psychological adjustment.