Is infection a major risk factor for preeclampsia?

Recently in an open population-based program composed of 15 354 pregnant women in Colombia we applied a biopsychosocial risk model, which permitted us to identify pregnant women at high risk of preeclampsia. 1443 (9.4%) of patients at high risk for developing preeclampsia received 450 mg of linoleic acid, and 1.5 g/day of calcium. Bacteriuria was identified in 1766 (11.5%) and vaginal infections in 2150 (14.0%) of the pregnant women. These women received oral antibiotics for 10 days. The incidence of low birthweight, preterm delivery and preeclampsia were reduced by 53% (6.2% vs 13.2%), 64.7% (1.8% vs 5.1%), and 52.5% (3.8% vs 8.0%) respectively, when compared with the incidence of the preceding five years. We believe that these dramatic reductions were due to early identification of risk factors, administration of nutritional supplements and principally by treatment of asymptomatic infections. Unfortunately, because of the study design it is not possible to confirm that infection was the major risk factor for preeclampsia in our population. However, we hypothesize that chronic subclinical infections may cause increased maternal cytokine levels sufficient to affect vascular endothelial function, and so prime individuals for the subsequent development of preeclampsia. This hypothesis can be tested in a more appropriately designed clinical trial to assess whether there is a relationship between infection, inflammation and preeclampsia.     

Peptidoglycan: a major aetiological factor for psoriasis?

Peptidoglycan (PG), a major cell-wall component of Gram-positive bacteria, has been detected within antigen-presenting cells in various inflammatory conditions, including psoriasis. The additional presence of T-helper 1 cells specific for streptococcal or staphylococcal PG in psoriasis skin lesions implicates PG as an important T-cell stimulator for the disease. PG is a major target for the innate immune system, and associations between genetic polymorphisms of recognition receptors for PG and various auto-inflammatory diseases have been identified. The location of these genes within four linkage sites for psoriasis raises the possibility that an altered innate recognition of PG might contribute to the enhanced T-cell response to the bacterial antigen. These observations suggest that PG is a major aetiological factor for psoriasis and emphasize the importance of PG in bacterial-infection-induced inflammatory disease.     

Does major depressive disorder with somatic delusions constitute a distinct subtype of major depressive disorder with psychotic features?

BackgroundAmong patients with major depression with psychotic features, little is known about the extent to which those with and without somatic delusions differ.MethodsThe first 183 participants in the STOP-PD study were divided into two groups based on the presence or absence of somatic delusions and were compared on multiple demographic and clinical characteristics.ResultsIn the multivariate analysis, those with somatic delusions reported more somatic symptoms, rated their health as worse, and were less likely to have persecutory delusions.ConclusionsBased on the methods we used, we could not detect meaningful differences between subjects with and without somatic delusions. This suggests that the presence of irrational somatic ideation does not define a distinct clinical subgroup among patients with psychotic depression. This finding needs to be replicated.     

Functioning after a major depressive episode: complete or incomplete recovery?

BACKGROUND: Numerous studies have shown improved functioning after a depression, but often substantial limitations at follow-up remained. The goal of this study is to examine (1) whether functioning returns to pre-morbid levels after a major depressive episode (MDE), (2) predictors of incomplete functional recovery, and (3) how these functional levels relate to those in a non-depressed sample. METHODS: Data were derived from the Netherlands Mental Health Survey and Incidence Study, a prospective general population study with three waves. Psychopathology was measured with the Composite International Diagnostic Interview (CIDI) and functioning with the Short-Form-36 Health Survey (SF-36). One hundred and sixty-five individuals who met criteria for MDE between baseline and third wave, but not in the 12 months preceding baseline and third wave were selected. RESULTS: Mean post-morbid levels of functioning did not differ from pre-morbid levels although this level still differed significantly from the non-depressed sample. Sixty to eighty-five percent of the respondents did better or showed no change on different scales after recovery from MDE. Co-morbid substance use disorder and anxiety disorder, presence of somatic illness, external mastery, low social support and high baseline functioning were predictors of worsened functioning. LIMITATIONS: Lay interviewers used fully structured diagnostic interviews to determine MDE and functioning was measured using self-report. CONCLUSIONS: In general, people who recover from a MDE will also recover from functional impairments. The most important predictors of incomplete functional recovery are clinical and social in nature whereas personality and demographic characteristics are less important.     

Antidepressant combination for major depression in incomplete responders—a systematic review

BackgroundAntidepressant combination has been suggested as a strategy to increase treatment efficacy. The objective of this study was to perform a systematic review and meta-analysis of studies that assessed the effect of antidepressant combination for major depression in patients with incomplete response to an initial antidepressant.MethodsStudies were retrieved from PubMed (1966–February, 2012), Cochrane Library (–February, 2012), Embase (1980–February, 2012), PsycINFO (1980–February, 2012), Lilacs (1982–February, 2012), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. Included studies had an open label phase in which an initial antidepressant was used for the treatment of major depression and a double blind phase for the incomplete responders that compared monotherapy with the first antidepressant versus the association of a second antidepressant to the first one.ResultsOut of the 4,884 studies retrieved, only five satisfied the inclusion criteria. The total number of patients included was 483. Only two small trials reported benefits of adding a second antidepressant to the initial antidepressant. Dropouts due to side effects were not reported in three studies. Meta-analysis was not performed due to the small number of studies, the inconsistency in the direction of effect and the possible instability of effect size. Only limited kinds of combination, involving mianserin, mirtazapine and desipramine were studied. Some properties of the first two drugs such as the anxiolytic, sedative, and orexigenic effects, can mimic depression improvement.LimitationsPublication bias cannot be ruled out. Only one study included a monotherapy arm with the antidepressant used for augmentation of the first antidepressant.ConclusionsThe practice of using a combination of antidepressants for major depression in incomplete responders is not warranted by the literature.     

Gray colored glasses: Is major depression partially a sensory perceptual disorder?

Background

Major depression is a neuropsychiatric disorder that can involve profound dysregulation of mood. While depression is associated with additional abnormalities besides reduced mood, such as cognitive dysfunction, it is not well established that sensory perception is also altered in this disorder (aside from in psychotic depression). Recent studies have shown that visual processing, in as early a stage as the retina, is impaired in depression. This paper examines the hypothesis that major depression can involve alterations in sensory perception.

Methods

A Pubmed literature search investigated several lines of evidence: innervation of sensory cortex by serotonin and norepinephrine; antidepressant drugs and depression itself affecting processing of facial expressions of emotion; electroencephalography (EEG) studies of depressed persons and antidepressant drugs; involvement of the serotonergic 5HT2A receptor in both depression and hallucinogenic drug action; psychotic depression involving sensory distortions; dopamine possibly playing a role in depression; and the antidepressant effect of blocking the NMDA receptor with ketamine.

Results

Data from each of these lines of evidence support the hypothesis that major depression can involve sensory perceptual alterations.

Conclusions

Loss of interest in one's daily activities and inability to experience pleasure, also known as anhedonia, in major depression may in part be mediated by sensory abnormalities, whereby normal sensory perceptions are no longer present to activate reward circuitry.

Limitations

The data supporting the hypothesis tend to be associative, so further confirmation of the hypothesis awaits additional controlled experiments.     

Brain-derived neurotrophic factor: a bridge between major depression and Alzheimer's disease?

Cognitive impairment is common in major depression (MD) patients, with these individuals incurring increased risk for development of Alzheimer's disease (AD). Further, depressive symptoms are common in AD patients. This apparent convergence suggests pathogenic factors common to AD and MD. Since decreased brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is related to both AD and MD, the author suggests that BDNF could be a bridge between AD and MD, explaining both the depressive symptoms in AD, and, cognitive impairment in MD. Evidence supporting this hypothesis suggests that early antidepressants treatment for aged MD patients may decrease the risk of AD, and agents that increase central BDNF may offer an alternative treatment for MD patients with cognitive impairment and/or for AD sufferers with depressive symptoms.     

Is there evidence for a male depressive syndrome in inpatients with major depression?

BACKGROUND: The question is investigated whether atypical depressive symptoms such as irritability, anger attacks, aggressiveness or abusive behavior, which are hypothesized to indicate a hypothetical male depressive syndrome are more prevalent in male than in female inpatients with unipolar major depression. METHODS: Data were obtained from 2411 patients who had been consecutively admitted to the Department of Psychiatry of the Ludwig-Maximilians-University of Munich. Psychopathological symptoms had been assessed by a standardized documentation system (AMDP). RESULTS: Neither frequency nor mean scores of most of the symptoms describing a male depressive syndrome differed between males and females. There were no gender differences in symptoms with respect to severity of depression, first hospitalization and duration of illness. However, gender differences emerged when regarding symptom patterns by factor analysis. Limitations: Only inpatients were studied, and comorbidity was not considered. CONCLUSIONS: The hypothesis of a male depressive syndrome needs further research, focusing on the gradual development of (masked) depression by men in mainly non-clinical samples.     

Is postnatal depression a distinct subtype of major depressive disorder? An exploratory study

Postnatal depression (PND) has an estimated prevalence of 6.5 to 12.9%. In addition to the direct consequences for women, PND also interferes with the maternal-infant interaction, contributing to long-term cognitive and emotional impairments in exposed offspring. It is unclear how PND differs from major depressive disorder (MDD) more generally, and if PND represents a distinct subtype of depression. We explored whether women with a history of PND have specific differences in brain activation associated with sex hormone changes during the late luteal phase of the menstrual cycle, compared to parous women with either a past history of MDD outside of the postnatal period, or an absent history of MDD (‘never depressed’). Thirty mothers (history of PND (n = 10), history of MDD (n = 10), and ‘never depressed’ (n = 10)) underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) acquisition during an emotional faces task. Amygdala activity was analysed using a region of interest (small volume correction) approach. There was a significant reduction in BOLD response to positive emotional faces in the right amygdala in women with a history of PND compared to women with a history of MDD. A similar but non-significant trend was found in the left amygdala in women with a history of PND compared to ‘never depressed’ women. Our findings support the hypothesis that women with vulnerability to PND represent a distinct subgroup of women with a differential sensitivity to changes in sex hormones. Further, albeit highly tentative, they provide a putative biomarker that could assist in detection of women at-risk to PND.

     

The treatment of psychotic major depression: is there a role for adjunctive psychotherapy?

BACKGROUND: Psychotic depression is a relatively prevalent mood disorder associated with greater symptom severity, a poorer course of illness and higher levels of functional impairment compared with nonpsychotic depression. Separate lines of investigation suggest that various forms of cognitive-behavioral therapy are efficacious for treating severe forms of nonpsychotic depression as well as primary psychotic disorders. However, there currently are no empirically supported psychotherapies specifically designed for treating psychotic depression. METHOD: We review the efficacy of current somatic treatments for the disorder and discuss the limited data to date on potentially useful psychotherapeutic approaches. In particular, we describe the clinical improvement observed in a subgroup of hospitalized patients with psychotic depression treated with Acceptance and Commitment Therapy as part of a larger clinical trial. RESULTS: Pilot results demonstrated that Acceptance and Commitment Therapy was associated with clinically significant reductions in acute symptom severity and impairment compared with treatment as usual. CONCLUSION: The findings suggest that patients with psychotic depression can benefit from psychotherapy. Clinical and research recommendations in this area are presented.     

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.     

Does the BAFF dysregulation play a major role in the pathogenesis of systemic lupus erythematosus?

Given the prominent role currently assigned to B lymphocytes in systemic lupus erythematosus, it is not surprising that the B cell activity factor belonging to the tumor necrosis factor family (BAFF) is involved in its pathogenesis. This cytokine is produced in excess, and inserted into its receptors on the surface of circulating B cells. Up-regulation of BAFF is most likely to lead to breach of tolerance by aberrant survival of B cells directed to the self. Trials aimed at blocking BAFF have thus been set out. Yet the results are awaited.     

Is the type of remission after a major depressive episode an important risk factor to relapses in a 4-year follow up?

BACKGROUND: Rates of relapse and predictive relapse factors were studied over more than 4 years in a sample of Spanish outpatients with DSM-III-R criteria for unipolar major depressive episode. METHODS: A final sample of 139 outpatient was followed monthly in a naturalistic study. The Structured Clinical Interview for DSM-III-R was used. Phases of evolution were recorded using the Hamilton Depression Rating Scale, applying the Frank criteria. Survival analysis, Kaplan-Meier product limit and proportional hazards models were used. RESULTS: A higher rate of relapses was observed in the partial remission group (91.4%) compared to the complete remission one (51.3%). The four factors with predictive relapse value were: "partial remission versus complete remission", "the intensity of clinical symptoms", "the age" and "the number of previous depressive episodes". The existence of partial remission was the most powerful predictive factor. LIMITATIONS: The decreasing sample size during the follow-up and the difficulty in warranting the treatment compliance. CONCLUSIONS: At medium term, relapse rates for a major depressive episode are high. Partial remission after a depressive episode seems to be an important predictive factor for relapses in a 4-year follow-up. CLINICAL RELEVANCE: Not reaching complete remission is a strong risk factor for relapses in a 4-year follow up study.     

Is the female preponderance in major depression secondary to a gender difference in specific anxiety disorders?

BACKGROUND: While a female preponderance in unipolar depression is a consistent finding in community-based studies, determinants remain speculative. This study aimed to examine whether a female preponderance in certain anxiety disorders drives a gender difference in depression. METHOD: The relevant data from the National Comorbidity Study (NCS) are analysed. RESULTS: We observed a biphasic pattern in the emergence of a female preponderance in the depressive and anxiety disorders, with an initial pre-pubertal or early adolescent onset, and after attenuation in early to middle adulthood, re-emergence in mid- to late-adulthood. Analyses focused on determinants of the initial female preponderance. Female gender, presence of an anxiety disorder and variable ages of onset in the anxiety disorder all contributed to the increased chance of an initial depressive episode. Some specificity in linking the onset of depressive temporally in early adolescence with two anxiety disorders was demonstrated, specifically generalized anxiety disorder and panic disorder. CONCLUSIONS: The separate anxiety disorders and their age of onset had variable links with depression, but female gender remained a significant predictor of depression after accounting for the effects of prior anxiety.