Methodological approaches to situational analysis in global mental health: a scoping review.

Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.

Managing the risks of mood symptoms with LNG-IUS: a clinical perspective.

INTRODUCTION: Lack of awareness of reproductive hormone-related mood changes in the general population or limited acknowledgement of their existence by health care providers regularly contribute to fears or misconceptions about the link between hormonal contraception and potential mood changes. Recent media discussion linked the levonorgestrel intrauterine system (LNG-IUS 20 µg/d) to elevated cortisol levels and the possibility of panic attacks, anxiety, mood changes, sleep disturbance and restlessness. Efficacy of the LNG-IUS is based primarily on local effects but systemic effects, including a potential increase in mood symptoms, are a known risk and reflected in the product labelling for all LNG-IUS products. OBJECTIVE: There is a need to improve communication to the public and health care providers around potential risk of mood disorders in order to facilitate 'informed choice' amongst women considering an LNG-IUS as their contraceptive method and directly address the fears of women currently using an LNG-IUS. RESULTS: We propose a simple and brief, step-by-step process that can be embedded within current counselling that explores and clarifies the potential risk of developing mood symptoms prior to placement of LNG-IUS. It also addresses concerns from women using an LNG-IUS who either present with mood symptoms or are concerned about potential onset. CONCLUSION: Mood symptoms with use of LNG-IUS are uncommon; however, all women, including those who may experience an increased sensitivity to certain progestins, should be counselled appropriately to raise awareness of the potential risk within an informed discussion around effectiveness, benefits and possible adverse events.

Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi.

Depression affects 10-15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring.

Meningitis determined by oligosymptomatic dengue virus type 3 infection: report of a case.

Dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. Neurological manifestations such as encephalitis, myelitis, Guillain-Barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. Meningitis is a rare complication. We report the case of a 24-year-old woman who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with a normal glucose value and negative bacterial and fungal cultures. The etiology of meningitis was confirmed by positive dengue PCR in the serum. This case report highlights dengue infection as a potential cause of meningitis in endemic areas. Also, meningitis can be the first manifestation of the infection. Dengue should be investigated even in the absence of a typical picture of the infection.

Neurologic dengue manifestations associated with intrathecal specific immune response.

BACKGROUND: Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index. OBJECTIVES: To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance. METHODS: CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barré syndrome. RESULTS: All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies. CONCLUSIONS: Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.

Dengue infection: neurological manifestations and cerebrospinal fluid (CSF) analysis.

Neurological manifestation is considered a rare complication of dengue infection. Neurological and cerebrospinal fluid (CSF) findings of 13 patients with dengue infection were studied. Seven patients had encephalitis, two had myelitis and four showed Guillain-Barré syndrome (GBS). No alteration in CSF was found from 57% of those with encephalitis. Patients with GBS and myelitis showed a CSF-blood barrier dysfunction. The differences in the CSF may be related to the location of the lesion and multiple mechanisms of the disease in the nervous system.

Insomnia in women: an overlooked epidemic?

Insomnia is a common and significant healthcare problem, and affects a large percentage of women seen by general practitioners, obstetrician-gynecologists and mental health professionals. Specific risk factors for insomnia may be gender-related, including higher prevalence rates of depression and anxiety among women, environmental and social factors, as well as reproductive-related factors (e.g., peri-menstrual difficulties and menopause-related symptoms). Sleep problems interfere significantly with daytime functioning and overall well-being, and may lead to serious clinical consequences. Treatment options include benzodiazepines, non-benzodiazepines, nonprescription sleep aids, and non-pharmacologic interventions such as sleep hygiene measures. This article reviews the existing literature on the prevalence, clinical characteristics of insomnia in women, and highlights some of the treatment options available. Healthcare providers should be aware of the variety of pharmacologic and non-pharmacologic options for treatment of insomnia and, in particular, be able to weigh their efficacy against the risks of side effects and next-day sedation.

Sex- and age-related differences in major depressive disorder with comorbid anxiety treated with fluoxetine.

OBJECTIVE: To examine sex- and age-related differences of treatment outcome in a cohort of outpatients with major depressive disorder (MDD), with and without comorbid anxiety, treated with fluoxetine. METHODS: Outpatients with a SCID-diagnosis of MDD aged 18 to 65 years were treated openly with fluoxetine (20 mg/day) for 8 weeks. The 17-item Hamilton Depression Rating Scale (HAM-D-17) was administered at baseline, and at weeks 2, 4, 6 and 8. Remission of MDD was defined as a HAM-D-17 score < or =7 at week 8. Rates of remission and change of depressive symptoms of MDD were compared among women aged < 45 years and > or =45 years. The analyses were then repeated in men. The presence of comorbid anxiety disorders was included in the prediction model for change of depressive symptoms of MDD across age and sex. RESULTS: 176 women and 153 men were included in this analysis. Remission of MDD occurred in 57.1% and 50% of younger and older women respectively. Similar rates were present in men (57.2% and 49.1%, respectively). Age did not predict remission of depression or change of depressive symptoms of MDD, in both women and men. Anxious and non-anxious subtypes of depression did not present sex- or age-related differences in treatment outcome. CONCLUSION: In this cohort of outpatients with MDD, we observed no sex- or age-related differences in response to an 8-week treatment with the SSRI fluoxetine. Similarly, there were no age-related differences among women with anxious and non-anxious subtype of depression.

Postpartum onset obsessive-compulsive disorder: diagnosis and management.

The postpartum period is associated with an increased risk of developing obsessive-compulsive disorder (OCD) in women. Postpartum onset OCD is often undiagnosed and untreated resulting in serious consequences for the patient, her family and the newborn. The symptoms of postpartum onset OCD may consist of obsessional intrusive thoughts about harming the newborn without compulsions or with both obsessions and compulsions. In this review, the phenomenology of postpartum onset OCD is described as well as strategies for screening and diagnosis. The review also characterizes the differences between postpartum onset OCD and postpartum depression and postpartum psychosis and explores strategies for managing postpartum onset OCD patients. Issues regarding pharmacologic treatment of OCD in breastfeeding mothers are also reviewed.

Characteristics of women with premenstrual dysphoric disorder (PMDD) who did or did not report history of depression: a preliminary report from the Harvard Study of Moods and Cycles.

We examined the characteristics of 33 women with a diagnosis of premenstrual dysphoric disorder (PMDD) who did (n = 19) or did not (n = 14) report a history of major depression. Five hundred thirteen older premenopausal women (ages 36-44) from a community-based sample completed a prospective evaluation of PMDD with daily records. The diagnosis of PMDD was confirmed in 33 women (6.3%), and 14 subjects met criteria for PMDD with no history of depression. Demographic characteristics, cigarette smoking, and menstrual and reproductive history of subjects with PMDD who did or did not report a history of depression were compared. Women with PMDD and no history of depression were more educated and more frequently had a marital disruption (p < 0.05). No significant differences were observed with respect to reproduction-related characteristics or past cigarette smoking. These preliminary data suggest the existence of characteristics particularly related to women who meet criteria for PMDD and have no history of depression. Given the significant psychosocial impairment commonly associated with PMDD symptoms and the existing data that support its classification and adequate treatment as a distinct clinical entity, further studies are needed to better identify predictors of this syndrome unrelated to a lifetime history of depression.

Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17beta-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women. METHODS: Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17beta-estradiol (100 microgram) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores. RESULTS: Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17beta-estradiol compared with 5 (20%) in the placebo group (P =.001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups. CONCLUSION: Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.

The perimenopause, depressive disorders, and hormonal variability.

CONTEXT: Several investigations have postulated that the perimenopause may represent a period of increased psychiatric vulnerability, particularly for mood disorders. This review characterizes the perimenopause, including biological changes, the influence of psychosocial factors and the most common clinical manifestations. Clinic-based studies and community-based surveys addressing the prevalence of depressive symptoms in perimenopausal women are critically reviewed. We also discuss the potential greater vulnerability to mood disturbance during the perimenopause in response to hormonal variability. A therapeutic algorithm for management of depressive symptoms in middle-aged perimenopausal women is also presented. The role of estrogen in the treatment of perimenopausal depressive symptoms is particularly discussed. In addition, we review the existing data regarding the potential efficacy of estrogen as an antidepressant agent (monotherapy, augmentation strategy or prophylaxis). DESIGN: Narrative review.

An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy.

Treatment of major depression in menopausal women is controversial. Estrogen replacement therapy (ERT) treats mild depression but may not treat more severe depression in this population. Antidepressants are recommended as treatment for major depression in menopausal women, but the specific efficacy of antidepressants has not been examined in menopause-associated depression. Twenty-two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 score < or =7 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p < 0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers. Subjects responded well to mirtazapine regardless of whether their depression preceded ERT use or developed after ERT was initiated. Therapeutic response also appeared independent of menopausal status (perimenopausal vs. postmenopausal), ERT preparation, and concomitant use of medroxyprogesterone. Mirtazapine is an effective treatment for major depression in perimenopausal and postmenopausal women whose depression precedes ERT use and does not respond to ERT or whose depression develops after ERT is initiated.

Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial.

BACKGROUND: Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during stress, depressive symptoms) that may cause deleterious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH) therapy. AIM: To evaluate the impact of a clinical intervention with rh-GH therapy on GH- deficient adults. METHOD: The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week) in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. RESULTS: Rh-GH was significant better than placebo at 6th month (p < 0.05), producing increased serum Insulin like growth factor-I (IGF-I) levels, reduced body mass index (BMI) and body fat, increased lean body mass and water, reduced waist/hip ratio and increased energy expenditure. The rh-GH therapy was also significantly better than placebo on depressive features as measured by the Hamilton Depression Scale (17-items) (p = 0.0431) and the Beck Depression Inventory (p = 0.0431). Neuropsychological evaluations showed significant improvements in measures of Attention: Digit Backward (p = 0.035), Verbal Fluency (FAS) (p = 0.02) and Cognitive Efficiency (WAIS-R tests): Vocabulary (p = 0.027), Picture Arrangements (p = 0.017), and Comprehension (p = 0.01) following rh-GH therapy. CONCLUSION: The clinical, psychiatric, and neuropsychological impairments of untreated GH-deficient adults can be decreased by rh-GH therapy.

[Benzodiazepines: patterns of use, tolerance and dependence]. / Benzodiazepínicos: padrões de uso, tolerância e dependência.

The authors review recent studies on benzodiazepine, the most largely used drug for insomnia and anxiety. In this paper are summarized: the development, patterns of use and abuse, mechanism of action, development of differential tolerance to its many effects, and the phenomena of withdrawal and dependence on the benzodiazepines.