Irritable-hostile depression: further validation as a bipolar depressive mixed state

BACKGROUND: "Hostile depression" has unofficially long been described as a depressive subtype, but since DSM-III, the affect has been made a defining characteristic of borderline personality disorder. The related affect of irritability in DSM-IV-TR subsumes various hostile nuances and is included in the stem question for mood disorders--especially for hypomanic episodes; in children, it is nonetheless a sign of depression. Then, there is the unofficial more general concept of depression with anger attacks, until recently ostensibly a "unipolar" (UP) disorder. A veritable tower of Babel indeed. In the present analyses, our aim was to extend previous research on irritable-hostile depression to more specific parameters of bipolarity and depressive mixed state (DMX). METHODS: Consecutive 348 bipolar-II (BP-II) and 254 unipolar (UP) major depressive disorder (MDD) outpatients (off psychoactive agents, including substances of abuse), were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Borderline personality, a confounding variable, rare in the FB setting, was excluded. Irritability was defined according to DSM-IV-TR, which includes various features of hostility and anger. Depressive mixed state (DMX) was defined as a major depressive episode (MDE) plus three or more concurrent intradepressive hypomanic symptoms, whether it occurred in BP-II or MDD. RESULTS: MDE with irritability was present in 59.7% (208/348) of BP-II and in 37.4% (95/254) of MDD (p=0.0000). In BP-II, MDE with, versus MDE without, irritability had significantly younger index age, higher rates of axis I comorbidity, atypical depressive features, and DMX. Upon logistic regression, we found a significant independent association between BP-II MDE with irritability and DMX. In UP, MDE with, versus without, irritability had significantly younger age and age at onset, higher rates of atypical depression, DMX, and bipolar family history. Logistic regression revealed a significant independent association between MDE with irritability and DMX. Given that we had excluded patients with borderline personality, the high prevalence of irritable-hostile depressives in this outpatient population means that hostility cannot be considered the signature of that personality. Factor analysis revealed independent "psychomotor activation" and "irritability-mental activation" factors. Odds ratios of irritability for DMX were highest in the "UP" MDD group (=12.2); for predicting DMX, irritability had the best psychometric profile of sensitivity of 66.3% and a specificity of 86.1% for this group as well. LIMITATION: We did not use specific instruments to measure irritable, hostile, and angry affects. CONCLUSIONS: These analyses show that irritable-hostile depression is distinct from agitated depression. Whether arising from a BP-II or MDD baseline, irritable-hostile depression emerges as a valid entity with strong links to external bipolar validators, such as bipolar family history. Irritable-hostile phenomenology in depression appears to be a strong clinical marker for a DMX. Irritable-hostile depression as a variant of DMX deserves the benefit of what seems to work best in practice, i.e., anticonvulsant mood stabilizers and/or atypical antipsychotics. Formal treatment studies are very much needed.     

Anxiety,stress and perfectionism in bipolar disorder

Background

Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined.

Method

Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms.

Results

Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms.

Limitations

1.

These data are cross-sectional; hence the causality implied in the mediation models can only be inferred.

2.

The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo)manic symptoms.

3.

Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic.

Conclusion

These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments.     

Genetic variants of the BDNF and DRD3 genes in bipolar disorder comorbid with anxiety disorder

Background

The high comorbidity rate between bipolar disorder (BP) and anxiety disorder (AD) has been studied in depth. This comorbidity is not as high in Han Chinese in Taiwan. Therefore, we explored the genetic effects BP comorbid with AD.

Methods

We recruited 1316 participants: 286 with BP-I, 681 with BP-II, and 349 healthy Controls. Genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

The DRD3 Ser9Gly polymorphism was associated with BP-II comorbid with AD (BPII^+AD), and the BDNF Val66Met polymorphism was associated with BP-I comorbid with AD (BPI^+AD). An interaction between the Val/Val genotype of the BDNF Val66Met and Gly/Gly polymorphism of the DRD3 Ser9Gly was found in BPII^+AD, but not in BP-II not comorbid with AD (BPI^−AD) compared with healthy Controls.

Limitation

The low comorbidity rate of AD in both BP subtypes, especially BP-I, limit generalizing our findings.

Conclusion

The involvement of the dopaminergic pathway in AD was confirmed, particularly with BP-II rather than BP-I. Because the Val/Val genotype of the BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been associated with anxiety, it seems to affect BP-I comorbid with AD without the involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of DRD3 Gly/Gly in BP-II comorbid with AD.     

Time course for memory dysfunction in early-life and late-life major depression: A longitudinal study from the Juntendo university mood disorder project

Background

Previous studies have demonstrated that patients with depression also have memory dysfunctions during depressive episodes. These dysfunctions partially remain immediately after remission from a depressive state; however, it is unclear whether these residual memory dysfunctions may disappear through long-term remission from depression. The present study compared patients during early-life (age<60) and late-life (age≥60) depression while in their remitted stage with healthy controls to elucidate the impact of a long-term course on memory.

Methods

Logical memory from the Wechsler Memory Scale-Revised was administered to 67 patients with major depressive disorder (MDD) (47 patients with early-life depression and residual 20 patients with late-life depression) and 50 healthy controls. MDD patients received memory assessments at the time of their initial remission and at a follow-up three years after remission.

Results

At the time of initial remission, scores for logical memory were significantly lower in both patient groups compared to matched controls. At follow-up, memory dysfunction for early-life MDD patients disappeared, whereas scores in the late-life MDD group remained significantly lower than those of matched controls.

Limitations

All patients in the present study were on antidepressant medications.

Conclusions

Our findings suggested that the progress of memory performance in late-life MDD patients may be different from early-life MDD patients.     

Risks associated with gender differences in bipolar I disorder

Background

Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial.

Methods

The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender.

Results

Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (−), excessive alcohol use (+), cyclothymic temperament (−), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+).

Limitations

The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations.

Conclusions

Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.     

Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese

Background

A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.

Methods

We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.

Results

The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06–1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.

Limitations

The relative small sample size in BD group should be considered a limitation of this study.

Conclusions

Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.     

Affective temperaments are associated with specific clusters of symptoms and psychopathology: A cross-sectional study on bipolar disorder inpatients in acute manic,mixed, or depressive relapse

Background

The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder.

Method

Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data.

Results

The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states.

Limits

Cross-sectional design; sample size.

Conclusions

Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described.     

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

BACKGROUND: Depressive mixed state (DMX), defined by hypomanic features during a major depressive episode (MDE) is under-researched. Accordingly, study aims were to find DMX prevalence in unipolar major depressive disorder (MDD) and bipolar II depressive phase, to delineate the most common hypomanic signs and symptoms during DMX, and to assess their sensitivity and specificity for the diagnosis of DMX and bipolar II. METHODS: 161 unipolar and bipolar II MDE psychotropic drug- and substance-free consecutive outpatients were interviewed during an MDE with the Structured Clinical Interview for DSM-IV. DMX was defined at two threshold levels as an MDE with two or more (DMX2), and with three or more (DMX3) simultaneous intra-episode hypomanic signs and symptoms. RESULTS: DMX2 was present in 73.1% of bipolar II, and in 42.1% of unipolar MDD (P<0.000); DMX3 was present in 46.3% of bipolar II, and in 7.8% of unipolar MDD (P<0.000). The most common hypomanic manifestations during MDE were irritability, distractibility, and racing thoughts. Irritability had the best combination of sensitivity and specificity for the diagnosis of DMX2 and DMX3. Various combinations of irritability, distractibility, and racing thoughts correctly classified the highest number of DMX2 and DMX3, and had the strongest predictive power. DMX2 had high sensitivity and low specificity for bipolar II, whereas DMX3 had low sensitivity (46.3%) and high specificity (92.1%). LIMITATIONS: Single interviewer, cross-sectional assessment, and interviewing clinician not blind to patients' unipolar vs. bipolar status. CONCLUSIONS: When conservatively defined (>or = 3 intra-episode hypomanic signs and symptoms during MDE), DMX is prevalent in the natural history of bipolar II but uncommon in unipolar MDD. These findings have treatment implications, because of growing concerns that antidepressants may worsen DMX, which in turn may respond better to mood stabilizers. These data also have methodological implications for diagnostic practice: rather than solely depending on the vagaries of the patient's memory for past hypomanic episodes, the search for hypomanic features--ostensibly elation would not be one of those--during an index depressive episode could enhance the detection of bipolar II in otherwise pseudo-unipolar patients. Strict adherence to current clinical diagnostic interview instruments (e.g. the SCID) would make such detection difficult, if not impossible.     

The ‘real world’ utility of a web-based bipolar disorder screening measure: A replication study

Background

We previously reported high acceptance of the Mood Swings Questionnaire (MSQ) bipolar disorder screening measure, as well as improved outcomes for those completing the test, leading to this independent replication study.

Methods

Individuals accessing the web-based MSQ provided baseline and 3-month follow-up data assessing depression and hypo/manic severity, quality of life and overall functioning, while we evaluated any subsequent actions. A total of 670 participants scoring above MSQ cut-off but not previously diagnosed as having a bipolar disorder were studied, with three principal sample sub-sets derived: 141 who ‘took no action’, 394 who took action but did not receive a confirmed clinical diagnosis of bipolar disorder, and 135 who took action and had a bipolar diagnosis confirmed by their health professional.

Results

As reported in the initial study, the MSQ was viewed as informative by participants. All three sample sub-sets improved on key study measures—with those receiving a confirmed bipolar diagnosis (and thus most likely to have management plans modified) reporting the greatest improvement.

Limitations

Web-based recruitment risked an unrepresentative sample of individuals with bipolar disorder; sample members may have been biased by high levels of cooperativeness; the MSQ's psychometric properties in community web-based samples remain unestablished.

Conclusions

Results were strikingly consistent with those quantified in the initial study. Findings—including high acceptance and a superior outcome for those who had a bipolar diagnosis clinically confirmed following a ‘positive’ screen—provide further support for the ‘real world’ utility of the MSQ screening measure for bipolar disorder.     

Validity and reliability of a rating scale on subjective cognitive deficits in bipolar disorder (COBRA)

Background

Discrepancies between bipolar patients' reports and neuropsychological testing have been described and replicated. Unfortunately, no valid, specific, user-friendly, brief instrument is available to measure cognitive deficits as reported by these patients. The main aim of this study was to validate a novel instrument named the “cognitive complaints in bipolar disorder rating assessment” (COBRA). Second, we investigated the relationship between the COBRA, objective cognitive measures and illness course variables.

Method

The total sample (N=215) included 91 bipolar disorder patients and 124 healthy controls. The psychometric properties of the COBRA (e.g. internal consistency, concurrent validity, discriminative validity, factorial analyses, ROC curve and feasibility) were analyzed. A complete neuropsychological battery was used as objective cognitive assessment.

Results

The COBRA had one-factor structure with very high internal consistency (Cronbach's alpha=0.913). A high convergent validity was indicated by a strong correlation with the Frankfurt Complaint Questionnaire (ro=0.888, p<0.001). Bipolar patients experienced greater cognitive complaints compared to control group suggesting a discriminative validity of the instrument. Significant correlations were found between the COBRA and some objective cognitive measures. Furthermore, higher COBRA scores were associated with bipolar II subtype, residual depressive symptoms, hypomanic episodes and total episodes.

Limitations

The cross-sectional design of the study, the influence of medication and severity of patients included.

Conclusions

The COBRA showed to be a useful instrument to assess overall cognitive complaints in bipolar disorder with very satisfactory psychometric properties. Cognitive complaints were partially correlated with memory and executive function measures and with issues that may increase the subjective perception of cognitive deficits, such as subthreshold depressive symptoms and number of episodes.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

Association of exercise with quality of life and mood symptoms in a comparative effectiveness study of bipolar disorder

Background

Individuals with bipolar disorder lead a sedentary lifestyle associated with worse course of illness and recurrence of symptoms. Identifying potentially modifiable predictors of exercise frequency could lead to interventions with powerful consequences on the course of illness and overall health.

Methods

The present study examines baseline reports of exercise frequency of bipolar patients in a multi-site comparative effectiveness study of a second generation antipsychotic (quetiapine) versus a classic mood stabilizer (lithium). Demographics, quality of life, functioning, and mood symptoms were assessed.

Results

Approximately 40% of participants reported not exercising regularly (at least once per week). Less frequent weekly exercise was associated with higher BMI, more time depressed, more depressive symptoms, and lower quality of life and functioning. In contrast, more frequent exercise was associated with experiencing more mania in the past year and more current manic symptoms.

Limitations

Exercise frequency was measured by self-report and details of the exercise were not collected. Analyses rely on baseline data, allowing only for association analyses. Directionality and predictive validity cannot be determined. Data were collected in the context of a clinical trial and thus, it is possible that the generalizability of the findings could be limited.

Conclusion

There appears to be a mood-specific relationship between exercise frequency and polarity such that depression is associated with less exercise and mania with more exercise in individuals with bipolar disorder. This suggests that increasing or decreasing exercise could be a targeted intervention for patients with depressive or mood elevation symptoms, respectively.     

Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background

Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method

Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results

Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations

Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions

There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.     

Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder,major depressive disorder,and schizophrenia: A 10-year nationwide population-based prospective cohort study

Background

The high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study.

Method

Using a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia.

Results

The identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3±14.0, 46.5±13.7, and 45.9±12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155–2.507) and schizophrenia (HR of1.793, 95% CI: 1.532–2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107–2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002–1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls.

Conclusions

This first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.     

Predictors of relapse in patients with major depressive disorder in a 52-week,fixed dose,double blind,randomized trial of selegiline transdermal system (STS)

Objective

We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment.

Method

After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24 h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥14 and a CGI-S score of ≥3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse.

Results

For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis.

Conclusions

While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD.     

Impact of self-reported juvenile abuse on treatment outcome in patients with major depressive disorder

Background

We assessed the impact of juvenile abuse (emotional, physical, or sexual) on response to treatment in adults with major depressive disorder (MDD) suboptimally responsive to antidepressant therapy.

Methods

A post hoc analysis explored the relationship between self-reported history of juvenile abuse and response to risperidone or placebo augmentation during a 6-week double-blind study period in patients with MDD suboptimally responsive to a previous adequate trial of antidepressant monotherapy.

Results

Overall, only one clinical measure showed a small, but statistically significant difference in outcome between patients with abuse versus without abuse (HRSD-17). In patients reporting abuse (n=141), improvement with risperidone versus placebo augmentation was greater on several measures: HRSD-17 total and 2 subscale scores, responder rates, Q-LES-Q, and PaRTS-D. In patients without abuse (n=127), only two measures showed significant improvement: HRSD-17 subscale and PaRTS-D. Responder rates (HRSD-17) were: 40.9% (risperidone) versus 23.1% (placebo; p=0.01; odds ratio=2.7) in those with abuse, and 41.0% versus 34.4% (p=0.39; odds ratio=1.4) in those without. Adverse events rates were: 37.0% (risperidone) and 54.4% (placebo) in patients with abuse, and 56.3% and 55.6% in those without.

Limitations

Analysis not preplanned. Validated questionnaire not used to determine abuse status.

Conclusions

Self-reported juvenile abuse history may impact response to risperidone augmentation therapy in adults with MDD suboptimally responsive to antidepressants. Abuse status may reduce placebo response and reporting of adverse events.     

Dissociation of regional activity in the default mode network in first-episode,drug-naive major depressive disorder at rest

Background

Major depressive disorder (MDD) is associated with altered neural activity in the default mode network (DMN). In the present study, we used a fractional amplitude of low-frequency fluctuations (fALFF) approach to directly investigate the features of spontaneous brain activity of the DMN in patients with the first-episode, drug-naive MDD at rest.

Methods

Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects participated in the study. The fALFF and independent component analysis (ICA) approaches were utilized to analyze the data.

Results

Patients with MDD exhibited a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the left dorsal medial prefrontal cortex (MPFC) and decreased fALFF in the left parahippocampal gyrus (PHG). The increased fALFF values of the left dorsal MPFC were positively correlated to the Hamilton Rating Scale for Depression (HRSD) scores.

Conclusions

Our results first suggested that there was a dissociation pattern of resting-state fALFF in the DMN in patient with MDD, which highlighted the importance of the DMN in the pathogenesis of MDD.     

Psychostimulants for managing unipolar and bipolar treatment-resistant melancholic depression: A medium-term evaluation of cost benefits

Background

We earlier reported an open study of 50 unipolar and bipolar treatment resistant depressed patients indicating that psychostimulants may have differential superiority for the melancholic depressive sub-type. We designed an extension study to examine cost benefits of psychostimulants more closely for those only with melancholic depression.

Method

The sample comprised patients clinically diagnosed with melancholic depression who had failed to respond to and/or experienced significant side-effects with at least two antidepressants. Data were collected for 61 unipolar and 51 bipolar II patients receiving a psyschostimulant for a mean interval of 69 weeks. Benefits and side-effects were assessed.

Results

Effectiveness ratings were similar across unipolar and bipolar sub-sets. Psychostimulants were judged as ‘very’ effective for 20% of patients and ‘somewhat’ effective for 50%. Forty percent judged the psychostimulant as being ‘as effective’ or as ‘superior’ to previously prescribed antidepressants, and worthy of being maintained. Significant side-effects were experienced by 40% of patients, requiring medication to be ceased in 12%. Twenty percent of the bipolar patients experienced a worsening of highs.

Limitations

The study was uncontrolled and retrospective, no formal rater-completed or patient-completed interval measures of severity were completed, while diagnostic judgments about melancholic depression and bipolar disorder were clinically judged.

Conclusions

This open study suggests that psychostimulants may be efficacious antidepressant options for managing unipolar and bipolar melancholia, often seemingly having very rapid onset and generally requiring only low doses, and arguing the need for controlled studies in melancholic patients.     

The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum

BACKGROUND: Presently it is a hotly debated issue whether unipolar and bipolar disorders are categorically distinct or lie on a spectrum. We used the ongoing Ravenna-San Diego Collaboration database to examine this question with respect to major depressive disorder (MDD) and bipolar II (BP-II). METHODS: The study population in FB's Italian private practice setting comprised consecutive 650 outpatients presenting with major depressive episode (MDE) and ascertained by a modified version of the Structured Clinical Interview for DSM-IV. Differential assignment of patients into MDD versus BP-II was made on the basis of discrete hypomanic episodes outside the timeframe of an MDE. In addition, hypomanic signs and symptoms during MDE (intra-MDE hypomania) were systematically assessed and graded by the Hypomania Interview Guide (HIG). The frequency distributions of the HIG total scores in each of the MDD, BP-II and the combined entire sample were plotted using the kernel density estimate. Finally, bipolar family history (BFH) was investigated by structured interview (the Family History Screen). RESULTS: There were 261 MDD and 389 BP-II. As in the previous smaller samples, categorically defined BP-II compared with MDD had significantly earlier age at onset, higher rates of familial bipolarity (mostly BP-II), history of MDE recurrences (>or=5), and atypical features. However, examining hypomania scores dimensionally, whether we examined the MDD, BP-II, or the combined sample, kernel density estimate distribution of these scores had a normal-like shape (i.e., no bimodality). Also, in the combined sample of MDE, we found a dose-response relationship between BFH loading and intra-MDE hypomania measured by HIG scores. LIMITATIONS: Although the interviewer (FB) could not be blind to the diagnostic status of his private patients, the systematic rigorous interview process in a very large clinical population minimized any unintended biases. CONCLUSIONS: Unlike previous studies that have examined the number of DSM-IV hypomanic signs and symptoms both outside and during MDE, the present analyses relied on the more precise hypomania scores as measured by the HIG. The finding of a dose-response relationship between BFH and HIG scores in the sample at large strongly suggests a continuity between BP-II and MDD. Our data indicate that even in those clinically depressed patients without past hypomanic episodes (so-called "unipolar" MDD), such scores are normally rather than bimodally distributed during MDE. Moreover, the absence of a 'zone of rarity' in the distribution of hypomanic scores in the combined total, MDD and BP-II MDE samples, indicates that MDD and BP-II exist on a dimensional spectrum. From a nosologic perspective, our data are contrary to what one would expect from a categorical unipolar-bipolar distinction. In practical terms, intra-MDE hypomania and BFH, especially in recurrent MDD, represent strong indicators of bipolarity.     

Iowa gambling task performance in euthymic bipolar I disorder: A meta-analysis and empirical study

Background

The Iowa Gambling Task (IGT) has been recommended as an index of reward sensitivity, which is elevated in bipolar disorder. We conducted a meta-analysis of IGT performance in euthymic bipolar I disorder compared with control participants. Findings indicated that people with bipolar disorder make more risky choices than control participants, though the effect is small (g=0.35). It is not clear which of the many processes involved in IGT performance are involved in producing the observed group difference.

Methods

Fifty-five euthymic people with bipolar disorder and 39 control participants completed the IGT. The Expectancy Valence Model was used to examine differences in IGT. We also examined whether variation in IGT performance within the bipolar group was related to current mood, illness course, impulsivity, or demographics.

Results

Bipolar and control groups did not differ on the total number of risky choices, rate of learning, or any of the parameters of the Expectancy Valence Model. IGT performance in bipolar disorder was not related to any of the examined individual differences.

Limitations

It is possible that there are group differences that are too small to detect at our sample size or that are not amenable to study via the Expectancy Valence Model.

Conclusions

We were unable to identify group differences on the IGT or correlates of IGT performance within bipolar disorder. Though the IGT may serve as a useful model for decision-making, its structure may make it unsuitable for behavioral assessment of reward sensitivity independent of punishment sensitivity.