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Depression and bipolar disorder differences, tinnitus treatment online - .

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Bipolar disorder is a high prevalent, chronic, recurrent illness with devastating consequences when untreated because of high rates of morbidity and mortality. To be able to distinguish between bipolar and unipolar depression is crucial, as the treatment of both conditions differs considerably. Unipolar and bipolar depression were first described by Leonhard9 and this distinction was validated by Angst,10 Perris,11 and Winokur and coworkers12 who showed that clinical, familial, and course features supported the nosological differentiation between both forms. The percentage of patients initially identified with “unipolar” depression who experience manic episodes varies widely across studies, but may be as high as 50%.43 To identify those unipolar patients who, in the long-term, “become” bipolar patients is another way of obtaining more information about bipolar depression. A great number of individuals with the so-called soft or subsyndromal states belong to the bipolar spectrum by virtue of their positive family histories, their pharmacological response, and their tendency to progress to full clinical disorder.49 Based on a sample of patients with bipolar II disorder and major depressive disorder, Benazzi and Akiskal24 aimed to identify validated bipolar markers.
Based on the fact that some clinical characteristics are more common in both bipolar depression andmajor depressive disorder, respectively, or are observed in unipolar depressed patients who “convert” to bipolar disorder over time, Mitchell et al50 have suggested a probabilistic approach. This approach uses a set of sociodemographic and clinical variables to establish which patients with depression are more or less likely to have an underlying bipolar disorder, and it is based on differences between subjects with bipolar disorder and major depressive disorder other than the presence or absence of manic symptoms.41 Therefore, the assessment of the presence of (hypo)manic symptoms would be complemented by other aspects related to the clinical history to make an accurate diagnosis. As previously mentioned, Solomon et al48 suggested a preliminary screen for bipolar disorder in patients with a depressive episode bymeans of assessing the presence of delusions during the current episode of major depression, the number of prior episodes of major depression, and a family history of major depression or mania. The influence of subsyndromal depression on psychosocial functioning and on futuremood recurrences points to the need to introduce treatments with the aim of achieving full remission. A better knowledge of the characteristics that permit discrimination between unipolar and bipolar disorder, together with a good anamnesis complemented with information from family members and a higher use of screening tools, could facilitate an increase in the detection of bipolar disorder in patients with depression. A recent study56 showed that the MDQ yielded a positive screen rate of bipolar patients with a diagnosis of unipolar disorder and a current depressive episode. A contentious issue is whether (hypo)mania that occurs during treatment of “unipolar” depression is, following DSM-IV, an antidepressant-induced mood disorder or, as suggested by some experts, the precipitation of an underlying bipolar disorder.
Despite depression being the most frequent presentation of bipolar disorder associated with high morbidity and mortality, it has been a neglected field of research.
The authors of this study would like to thank the CIBERSAM, and appreciate the support of the Generalitat de Catalunya for the Bipolar Disorders Group (2009 SGR 1022). The 'face' of bipolar disorder to many is mania; however, the 'down side' is truly the depressed phase. Differentiating major depressive disorder (MDD) from depression in bipolar disorder (BPD), particularly BPD II, can be a challenge. In conjunction with a clinical evaluation, evidence-based validated measures can be helpful to clinicians in both the initial assessment and the long-term management of bipolar depression. Data shows that combined olanzapine and fluoxetine leads to more symptomatic improvement than does olanzapine or placebo alone.
Other mood stabilizers such as lithium and valproate have not demonstrated efficacy in acute treatment of bipolar depression.
It is estimated that up to a one-third of patients with bipolar disorder do not respond to treatments in naturalistic studies and this is considered to be a conservative estimate.3,36 Many patients who receive adequate pharmacotherapy still may have lengthy and debilitating periods of subthreshold depressive symptoms after major episodes. These pervasive but subthreshold depressive symptoms have been associated with social and occupational impairment.37 There is little evidence to date that offers any effective strategies for patients who do not respond to first-line treatments.
Family-focused therapy develops communication skills and problem solving skills in caregivers and the patients.
Interpersonal and social rhythm therapy, is an adaptation of the interpersonal psychotherapy for depression and approaches interpersonal problems through problem-solving by encouraging patients to regulate and maintain daily routines and sleep and wake rhythms.58 In a large (n=175) randomized clinical trial,58 acutely manic, mixed, or depressed patients with bipolar I disorder were assigned to weekly interpersonal and social rhythm therapy, or to equally intensive clinical management, both with pharmacotherapy. The approach to psychoeducation in mental health care has been based on utilizing established curricula that emphasize an awareness of illness, treatment adherence, early detection of recurrences, and sleep and wake regularity. Timely assessment of bipolar disorder in patients who present with major depressive symptoms is critical.
Bipolar disorder is a serious emotional disorder marked by periods of depression and manic and normal (euthymia) moods. The latter hypothesis regarding dysregulated genes is particularly intriguing, as bipolar disorder has a strong genetic basis. To test this hypothesis, we conducted a study in which genomewide gene expressions were measured in peripheral blood cells for 24 bipolar disorder patients.
We collected samples from depressed and manic bipolar patients and analyzed them for RNA (gene expression) using the Affymetrix GeneChip® Human Gene 1.0 ST Array. Genomewide gene expression profiles were generated for manic (N = 12) and depressed (N = 12) subjects and resulted in gene expression data for 20,093 genes.
Results for the 10 most significant genes and 10 most significant pathways from GSEA are shown in Tables 1 and 2. On examination of the functions of these genes from the GeneCards® database and from the data available from the top 10 pathways recognized to be different between mania and depression, it appeared that genes involved in cell division and the cellular cytoskeleton were the most different between the two groups. Another interesting finding was that many of the genes identified were associated with neurological illnesses such as neuropathy, epilepsy and dysautonomia, while others were associated with different types of cancers. It also has been shown that many cancer cells become autonomous and are not influenced by circadian rhythms, as normal cells are (Fu et al, 2002).
Several studies have reported that the long-term course of the illness is dominated by depressive rather than manic symptoms, with a direct negative impact on patient functioning. About 15% of severe bipolar patients die by suicide1 and the percentage of patients who attempt suicide more than once is even higher.
This distinction is necessary in order to ensure accurate and early diagnosis, and to improve the pharmacological treatment of depression and understand the biology involved in each condition. By definition, (hypo)mania plays an essential role in the understanding of the bipolar condition of a mood disorder. They observed that manic symptoms during depression demarcated a more severe and psychopathologically complex clinical state.
When the predictors are analyzed, they are quite similar to those aspects described in cross-sectional comparative studies between unipolar and bipolar depression.
Except for greater acuteness, severity, and psychotic symptomatology, bipolar I converters were similar to major depressive disorder nonconverters.
Lower age at onset (before 21 years), higher major depressive episode recurrence, mixed depression, and bipolar family history were significantly more common in bipolar II disorder. Instead of proposing a categorical diagnostic distinction between bipolar and unipolar depressive disorder, they recommend a likelihood approach as follows (see Table II). The Hypomania Checklist (HCL-32)57 can also help to identify the hypomanic component of depressive episodes and increase the detec- tion rate of both bipolar disorder and minor bipolar disorders.
A high increase in the number of patients who would be considered bipolar if the duration criteria of hypo(manic) symptoms were more flexible has also been reported.58 Therefore, major depressive disorder seems to be overdiagnosed at the expense of bipolar disorder.
It doesn't really work that way and there is an imbalance in the results based on the minting of the coin, age, use, and many other factors. The Mood Disorder Questionnaire (MDQ) was developed specifically to help clinicians differentiate unipolar depression from bipolar depression.10 It comprises 15 questions that can be easily administered in an office setting.
Kessing and colleagues studied patients with bipolar disorder (n=158) who were randomized to either a specialized mood disorder clinic that offered combined intervention with evidence-based pharmacological treatment and group psychoeducation or a standard treatment outpatient clinic and followed for 2.5 years.
Evidence-based models of psychotherapy include cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, group psychoeducation, and systematic care management. Over 1 year, patients in intensive therapy recovered more rapidly and were more likely to be clinically well in any study month than those in brief treatment. In a study of euthymic bipolar I and bipolar II, patients were randomly assigned to pharmacotherapy along with 21 sessions of structured group psychoeducation or 21 sessions of an unstructured support group.
Evidence-based screening tools such as the MDQ can assist clinicians in making a diagnosis of bipolar depression. Hypomania with and without Dysphoria: comparison of comorbidity and clinical characteristics of respondents from a national community sample.

Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression.
Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. The Mood Disorder Questionnaire: A Simple, Patient-Rated Screening Instrument for Bipolar Disorder.
Bipolar I, bipolar II, and nonbipolar major depression among the relatives of affectively ill probands. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Highlights of prescribing information for Symbyax (olanzapine and fluoxetine hydrochloride) capsules. Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study). Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.
Lurasidone Monotherapy For The Treatment Of Bipolar I Depression: Results of a 6-week, Double-Blind, Placebo-Controlled Study. Lurasidone adjunctive to lithium or valproate for the treatment of bipolar depression: results of a 6-week, double-blind, placebo-controlled study. Effect of lurasidone on metabolic indices in bipolar i depression: data from monotherapy and adjunctive studies. Changes in Cardiometabolic Parameters and Metabolic Syndrome Status in Patients with Schizophrenia Switching from other antipsychotics to lurasidone.
Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. Efficacy and safety of adjunctive oral ziprasidone for acute treatment of depression in patients with bipolar I disorder: a randomized, double-blind, placebo-controlled trial. Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials.
Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN primary care database 1995-2009. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: results of a large, multisite study.
Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Evidence-based guidelines for treating bipolar disorder: revised second edition--recommendations from the British Association for Psychopharmacology. Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial.
The integration of measurement and management for the treatment of bipolar disorder: a STEP-BD model of collaborative care in psychiatry.
Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood. Common and specific elements of psychosocial treatments for bipolar disorder: a survey of clinicians participating in randomized trials. A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder.
Effects of psychoeducational intervention for married patients with bipolar disorder and their spouses.
Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial.
Family-focused treatment versus individual treatment for bipolar disorder: results of a randomized clinical trial. Relapse prevention in patients with bipolar disorder: cognitive therapy outcome after 2 years. Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Moreover, changes of gene expression have been shown to be related to circadian and seasonal rhythms.
In the comparison of gene expression in peripheral lymphocytes between manic and depressive patients, a number of genes had significantly different expression.
This is a novel molecular finding regarding differences between the neurobiology of depression and mania. Recent research has shown that cell division is closely linked to circadian rhythms and that molecular mechanisms of circadian rhythms provide information regarding changes in other cellular metabolic processes (Hong et al, 2014). The relationship of some of the genes identified in this study to some forms of cancer may therefore be an indicator of disruption of circadian rhythm molecular mechanisms involved in the pathophysiology of bipolar disorder. Anand is Vice Chair for Research at Cleveland Clinic’s Center for Behavioral Health and directs the Mood and Emotional Disorders Across the Life Span (MEDALS) program. Join clinicians and researchers from Cleveland Clinic’s Neurological Institute in this open forum for discussion of the latest advances in patient care, research, and technology — specifically for healthcare professionals. Despite its high morbidity and mortality, it is a field of research that has been neglected until recent years.
It would reduce the economic burden and improve the health and quality of life of these patients. Although major depressive disorder is classified separately from bipolar disorder, the criteria for unipolar and bipolar depression are identical, and emphasis is placed upon the euphoric condition and not upon differences in the depressive episodes.13 However, the impact of antidepressant treatment is different, clear for unipolar patients, unclear and sometimes self-defeating for bipolar patients, increasing the risks of (hypo)manic switch or rapid cycling. Sometimes, especially when dealing with a bipolar disorder type II, diagnosis can be difficult when hypomanic episodes are not clearly detected. Although there are no pathognomonic characteristics specific to bipolar depression compared with unipolar depressive disorder, when both conditions have been analyzed, some clinical and epidemiological differences can be described (Table I). In a retrospective study published in 1976, Dunner and colleagues44 found that up to 21% of type I and type II bipolar patients had previously been hospitalized due to “unipolar depression.” Akiskal et al45 proposed eight criteria predictive of the “bipolarization” of a depression, and suggested calling “pseudounipolar depression” the episodes that will show its bipolarity afterwards. Early onset was the most discriminative feature of this major depressive disorder subgroup at possible higher risk of shifting to bipolar disorder. Failure to identify minor elated states leads to misdiagnosis of bipolar spectrum patients as unipolar.
Using a broader concept and a more comprehensive screening of bipolarity, Zimmermann et al31 have suggested that major depressive disorder is a heterogeneous concept including a large group with subthreshold bipolar disorder. There are areas of overlap between both forms of depression, although some differences have also been found.

A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Time spent with symptoms in a cohort of bipolar disorder outpatients in Spain: a prospective, 18-month follow- up study. Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: results of a large, multsite study. Differential effect of number of previous episodes of affective disorder on response to lithium or divalproex in acute mania.
Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes. Differential outcome of bipolar patients receiving antidepressant monotherapy versus combination with an antimanic drug.
Clinical features of bipolar depression versus major depressive disorder in large multicenter trials.
Delineating bipolar II mixed states in the Ravenna-San Diego collaborative study: the relative prevalence and diagnostic significance of hypomanic features during major depressive episodes.
Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD.
Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity.
Co-occurrence of disturbed sleep and appetite loss differentiates between unipolar and bipolar depressive episodes. A population- based analysis of distinguishers of bipolar disorder from major depressive disorder. Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression- polarity (SAD-P).
Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study. Screening for bipolar disorder in a Spanish sample of outpatients with current major depressive episode. Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar- II,minor bipolar disorders and hypomania. Deconstructing bipolar disorder: a critical review of its diagnostic validity and a proposal for DSM-V and ICD-11. Interestingly, other antipsychotics such has aripiprazole29* and ziprasidone30* have failed to demonstrate efficacy in bipolar depression over placebo.
Effects extended to relationship functioning and life satisfaction.51 There were no differences among the three intensive modalities in symptoms or psychosocial functioning over 1 year. While there were no differences in time-to-recovery between the groups in the acute phase, patients who received interpersonal and social rhythm therapies during the acute phase had longer times to recurrence and better vocational functioning in the maintenance phase than did patients who received treatment as usual. Treatment of bipolar depression can be complex and requires a more sophisticated approach than major depressive disorder.
Changes in brain circuitry oscillations, neurochemical changes and even switching on and off of genes have been proposed. Therefore, dysregulated gene expression may underlie the mood phases seen in bipolar disorder. KEGG Pathway and Biological Process Gene Ontology (BP: GO) Pathway (downloaded from the Broad Institute’s Molecular Signatures Database) were additionally used for pathway analysis. As seen in Table 1, most of the genes were protein coding, and one involved in signal transduction (phosphoinositide-3-kinase) was among the top 10 significantly different genes.
A high percentage of bipolar patients are initially misdiagnosed as having unipolar depressive disorder.
It also could help clarify whether bipolar depression and major depressive disorder are separate diagnostic entities or whether they belong to the same illness spectrum as different manifestations of the same underlying disorder. They found the following predictors: treatment-induced hypomania, family history of bipolar disorder, strong inheritability, depression with hypersomnia and motor retardation, psychotic depression, continuous multigenerational familial transmission, postpartum onset and early onset (before age 25).
This profile was associated with early age at onset of major depressive disorder and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes.
The authors suggested that early age at onset of depression represents a marker of a genetically based recurrent or polyphasic mood disorder. The distinction between bipolar and unipolar depression would assist in making an accurate and early diagnosis, in improving treatment, and in reaching a better understanding of each condition which, in turn, would contribute to improving illness outcome.
Results of the national depressive and manicdepressive association 2000 survey of individuals with bipolar disorder. Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report. There is surprisingly little evidence to guide clinicians and the viable psychopharmacological options are different than in MDD. This mistake carries significant negative consequences for the treatment of this population and for outcomes.
All the risks mentioned could be lowered by means of an early diagnosis and prophylactic treatment. Bipolar II switchers had a more protracted and tempestuous course with shorter well intervals. The new editions of the forthcoming diagnostic classifications will face the challenge of improving the discriminant validity of bipolar and unipolar depressions.
Combined pharmacological and non-pharmacological strategies appear to be an optimal approach to treatment. Therefore, it is essential to establish an accurate distinction between bipolar and unipolar depression in order to make an accurate and early diagnosis, leading to improvements in treatment and course of illness. Overall, descriptions of temperamental instability during major depressive disorder episodes provided useful clinical information for predicting which depressed patients will switch to bipolar II. New treatments will also need to be tested in the two indications, hopefully providing a final answer to the unsolved question of the efficacy and safety of antidepressants in bipolar depression. This could also help clarify whether bipolar depression and major depressive disorder are separate diagnostic entities or belong to the same illness spectrum. The high prevalence of comorbidities in bipolar patients has a negative impact on prognosis and sometimes also makes an accurate diagnosis more difficult to establish. Meanwhile, the best way to discriminate between unipolar and bipolar depression is the course and outcome of the condition. This review aims to analyze the differences between unipolar and bipolar depression and identify possible predictors that may influence the “conversion” from unipolar depression to bipolar disorder. The most frequent misdiagnosis includes substance-use disorders, anxiety disorders, personality disorders, and attention deficit hyperactivity disorder.22,23 To sum up, bipolar depression, which is often related to comorbidity, disability and mortality, is still largely unknown and frequently underestimated, which may engender a more severe course of the illness. To what extent both disorders are merely different course patterns of one condition is still a matter of debate.

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