Childhood maltreatment and adult proinflammatory status in patients with major depression.

BACKGROUND: An increasing body of research considers the immunological effects of major depression. It remains an open question, whether depression itself acts in an immunomodulatory fashion or whether other factors related to depression result in these immunological effects. Regardless, major depression is often the result of early life stress, the implications of which are not satisfactorily understood. SUBJECTS AND METHODS: Early life stress was retrospectively evaluated in 25 depressed inpatients via the CTQ (Childhood Trauma Questionnaire). Its impact on immunological biomarkers (fibrinogen, SAA, CRP, adiponectin, TNF-α, resistin, and sE-selectin) in adulthood was assessed via multiple regression analyses. Parental bonding was assessed via the PBI (Parental bonding questionnaire), severity of depression with the HDRS-17 (Hamilton-Depression-Rating Scale). RESULTS: Nearly all patients had experienced a parental style of affectionless control. Physical neglect significantly predicted fibrinogen levels (R(2)=0.42, adjusted R(2)=0.27, ß=0.56, p=0.04). Severity of depression was not associated with immune markers. CONCLUSION: Childhood maltreatment was linked to fibrinogen levels in our sample. Thus, inflammation may be an important mechanism mediating the adverse effects of early life stress on adult health in patients with major depression.

Pathways linking early life stress, metabolic syndrome, and the inflammatory marker fibrinogen in depressed inpatients.

BACKGROUND: Previous research has shown that metabolic syndrome as well as early life stress can account for immunoactivation (e.g. in the form of altered fibrinogen levels) in patients with major depression. This study aims at assessing the relationship between components of metabolic syndrome, early life stress and fibrinogen levels, taking the severity of depression into consideration. SUBJECTS AND METHODS: Measures of early life stress and signs of metabolic syndrome were collected in 58 adult inpatients diagnosed with depression. The relationships between the factors were assessed by means of path analyses. Two main models were tested: the first model with metabolic syndrome mediating between early life stress and fibrinogen levels and the second model without the mediating effect of metabolic syndrome. RESULTS: The first model was not supported by our data (χ²=7.02, df=1, p=0.008, CFI=0.00, NNFI=-9.44, RMSEA=0.50). The second model however provided an excellent fit for the data (χ²=0.02, df=1, p=0.90, CFI=1.00, NNFI=2.71, RMSEA=0.00). Extending the models by introducing severity of depression into them did not yield good indices of fit. CONCLUSIONS: The developmental trajectory between early life stress and inflammation appears not to be mediated by metabolic syndrome associated factors in our sample. Possible reasons including severity and type of early life stress, as well as potential epigenetic influences are discussed.

Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study.

OBJECTIVE: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks. RESULTS: After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS. CONCLUSIONS: Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram.

Psychopharmacological treatment status in outpatients with bipolar disorder: a clinical survey in Germany.

OBJECTIVE: The objective of this epidemiological study was to evaluate the current treatment status as well as the acceptance of medication and satisfaction with life in outpatients with bipolar disorder in Germany. METHODS: Data for this cross-sectional epidemiologic survey was collected between February 15th, 2006 and May 31st, 2006. Three hundreds six bipolar euthymic outpatients under routine treatment conditions were included in the study. Forty one practicing psychiatrists used a clinical interview to evaluate the current treatment status, acceptance of current medication, and current life satisfaction. RESULTS: The majority of patients suffered from "pure" bipolar-II-disorder (50.6%), followed by 23.0% with "pure" bipolar-I-disorder. Apart from these patients, 12.9% of all participants had a history of mixed episodes and 5.6% a history of rapid cycling. Mean duration of bipolar disorder was 10.6 years. The majority of patients (54.3%) received psychopharmacological monotherapy. Combination therapy was administered in 45.9% of the patients, 39.3% receiving two agents, and 6.6% three agents. Antidepressants (64.1%) were the most common combination medications. Monotherapy was used preferably in bipolar-I- (62.7%) and bipolar-II-disorders (56.2%), combination therapy predominantly in patients with a history of mixed episodes (57.7%) and rapid cycling (55.0%). Half of the patients (49.2%) were able to hold an occupation. 84.2% of all patients were satisfied with their medication. Overall, patients evaluated their life satisfaction between "good" and "satisfactory" (2.69 according to German school grades where 1 is the highest and 6 the lowest mark). Patients receiving lithium, valproate or antidepressants as monotherapy rated above the mean, patients with combination therapy, carbamazepine monotherapy or medications summarized as "others" rated below the mean. CONCLUSION: Most of the German outpatients received a pharmacotherapy that is recommended in the guidelines of bipolar disorder. The use of (atypical) antipsychotics was low. Conversely, the incidence of treatment with tricyclic antidepressants (not guideline compatible), was observed to be relatively high. Irrespective of their medication, in Germany patients with bipolar disorder show a high acceptance of their pharmacotherapy, and rate their life satisfaction as high. Nonetheless, half of the evaluated patients were not able to pursue a profession. Besides the disease age, gender and family life e.g., child care may also play a confounding role regarding the unemployment statistics.

Inflammatory biomarkers in 70 depressed inpatients with and without the metabolic syndrome.

OBJECTIVE: Chronic subclinical inflammation may be associated with the metabolic syndrome as well as with depression. We examined the impact of the metabolic syndrome on concentrations of inflammatory biomarkers in major depression. METHOD: Data for 70 inpatients with major depressive disorder (diagnosed according to ICD-10 and DSM-IV), and with or without the metabolic syndrome, were assessed 4 to 5 weeks after admission to the clinic of the Department of Psychiatry, Charité-University Medicine, Berlin, between 2005 and 2007. The metabolic syndrome was defined according to the criteria of the International Diabetes Federation (2005). Immunologic biomarkers assessed included adiponectin, resistin, serum amyloid A (SAA), C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble E-selectin, and CD40 ligand (CD40L). Severity of depression was measured with the 17-item Hamilton Depression Rating Scale. RESULTS: After regressional correction for confounding variables and covariates, a 2-factorial analysis of variance (metabolic syndrome x time) revealed that the metabolic syndrome's presence affected adiponectin (F(43,1) = 5.56; P < .05) and IL-6 levels (F(25,1) = 6.80; P < .05) significantly. There was also a trend for effects on fibrinogen levels (F(47,1) = 3.66; P = .06). CONCLUSIONS: This is the first study to evaluate the putative additive effect of the metabolic syndrome on a panel of 9 inflammatory biomarkers in depression. Our findings support an additive effect on some (adiponectin, IL-6, and trendwise for fibrinogen) markers. Patients with the metabolic syndrome and major depression are at higher risk for more frequent and more severe cardiovascular side effects than their counterparts without the metabolic syndrome.