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Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences.
We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases.
The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms.
Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.
A significant proportion of depressed patients will experience multiple episodes of depression throughout their lifetimes, and, in recent years, attention has been paid to the identification of risk factors associated with a recurrent course of major depression. Residual depressive symptoms following acute phase therapy appears to be the most important clinical risk factor leading to recurrence. However, advances in empirically-supported treatment algorithms and guidelines, and in pharmacotherapy and psychotherapy, provide physicians with the tools necessary to improve short- and long-term outcomes in the treatment of depression. Additionally, recent developments in genetic and psychological vulnerability research have sought to further improve outcomes by identifying markers in patients who may likely experience multiple depressive episodes.
This chapter deals with the diagnosis of mood disorders. The adoption of a lumping strategy for mood disorders, particularly for classifying depressive disorders, reflects the perspective of depression as a unitary construct that represents a final common pathway derived from a variety of etiological and pathophysiological sources, which accounts for the shared clinical features seen in the heterogeneous groups of depressive disorders. A diagnosis of a major depressive episode (MDE) is made by recognizing the characteristic syndrome of symptoms that cluster together during the same period of time. The hallmark of manic and hypomanic episodes is a discrete period of abnormally elevated, euphoric, expansive, or irritable mood that persists for at least a week in the case of mania or at least 4 days in the case of hypomania. Major depressive disorder is characterized by one or more major depressive episodes.
Disaster preparedness is an area of major concern for the medical community that has been reinforced by recent world events. The emergency healthcare system must respond to all types of disasters, whether the incidents occur in urban or rural settings. Although the barriers and challenges are different in the rural setting, common areas of preparedness must be explored.
This study sought to answer several questions, including: (1) What are rural emergency medical services (EMS) organizations training for, compared to what they actually have seen during the last two years?; (2) What scale and types of events do they believe they are prepared to cope with?; and (3) What do they feel are priority areas for training and preparedness?
Data were gathered through a multi-region survey of 1,801 EMS organizations in the US to describe EMS response experiences during specific incidents as well as the frequency with which these events occur. Respondents were asked a number of questions about local priorities.
A total of 768 completed surveys were returned (43%). Over the past few years, training for commonly occurring types of crises and emergencies has declined in favor of terrorism preparedness. Many rural EMS organizations reported that events with 10 or fewer victims would overload them. Low priority was placed on interacting with other non-EMS disaster response agencies, and high priority was placed on basic staff training and retention.
Maintaining viable, rural, emergency response capabilities and developing a community-wide response to natural or man-made events is crucial to mitigate long-term effects of disasters on a local healthcare system. The assessment of preparedness activities accomplished in this study will help to identify common themes to better prioritize preparedness activities and maximize the response capabilities of an EMS organization.
Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose–response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored.
Plasma drug concentrations and clinical response were measured in two groups of hospitalised depressed patients, who received amitriptyline or Imipramine double-blind, in a dosage of 250 mg for four weeks. Virtually no significant linear or curvilinear relationships were found between any plasma measure and any measure of clinical response. Modest but significant direct relationships were found between age and concentration of parent drugs but not demethylated metabolites. Blood drug level measurement therefore appears to be of little value in monitoring drug treatment of depressed in-patients.
Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.
A preceding paper has reviewed the history, background, and rationale for this collaborative effort exploring the biologic basis of the affective disorders. This paper details the ‘flow’ of a subject through the experimental protocol, the instrumentation used to obtain the clinical and behavioural data, and the biologic methodologies employed in the analysis of the body fluids. Data management and analysis techniques developed for this study are also examined.
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