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.     

Mood and metabolic consequences of sleep deprivation as a potential endophenotype’ in bipolar disorder

It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression–dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression–dejection and anger–hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression–dejection, anger–hostility, and confusion–bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first-degree relatives of patients with bipolar disorder.     

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.     

Body-image dissatisfaction is strongly associated with chronic dysphoria

Background

Individual depressive symptoms may contribute to the risk of chronic depression. This study aimed to explore which symptoms predict chronic dysphoria, a hallmark of depression.

Methods

1057 participants from the population-based Young Finns study were examined for four times during a 16-year period. Those with a modified Beck’s Depression Inventory score in the upper third at all four screenings were considered to have chronic dysphoria (n=135). Participants with only one high depression score formed the reference group of transient dysphoria (n=179). Individual items of the Inventory were analyzed in terms of their association with dysphoria status and chronicity, controlling for potential confounding factors, such as personality assessed using the Temperament and Character Inventory.

Results

Body-image dissatisfaction was strongly associated with chronically elevated dysphoria (Bonferroni-corrected p=0.006). The degree of body-image dissatisfaction was associated with the probability for chronic dysphoria in a dose–response manner, with the estimated probability ranging from 0.01 to 0.60 as a function of item response. The association remained after adjustments for a wide range of personality characteristics.

Limitations

The study relied on self-reports of mood and personality, and lacked information on external opinion on participants appearances. The requirement of full time-series data may have resulted in attrition-related bias.

Conclusions

Body-image dissatisfaction was a strong predictor of chronic depression characterized by dysphoria. This finding suggests that dysfunctional attitude towards oneself might represent a potentially important target for cognitive therapies and preventive interventions.     

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.     

Differences in functional connectivity in major depression versus bipolar II depression

Background

Objective methods of differentiating unipolar versus bipolar depression would enhance our ability to treat these disorders by providing more accurate diagnoses. One first step towards developing diagnostic methodology is determining whether brain function as assessed by functional MRI (fMRI) and functional connectivity analyses might differentiate the two disorders.

Methods

Fourteen subjects with bipolar II depression and 26 subjects with recurrent unipolar depression were studied using fMRI and functional connectivity analyses.

Results

The first key finding of this study was that functional connectivity of the right posterior cingulate cortex differentiates bipolar II and unipolar depression. Additionally, results suggest that functional connectivity of this region is associated with suicidal ideation and depression severity in unipolar but not bipolar II depression.

Limitations

The primary limitation is the relatively small sample size, particularly for the correlational analyses.

Conclusions

The functional connectivity of right posterior cingulate cortex may differential unipolar from bipolar II depression. Further, connectivity of this region may be associated with depression severity and suicide risk in unipolar but not bipolar depression.     

Time course of recovery showing initial prefrontal cortex changes at 16 weeks,extending to subcortical changes by 3 years in pediatric bipolar disorder

Objective

Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD).

Methods

Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge.

Results

At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum.

Limitations

Small sample size renders the present findings preliminary.

Conclusions

Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.     

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

Objectives

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods

Participants included 55 adults (age 18–65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1–3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).

Results

Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.

Conclusions

While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.     

Behavioral Activation System (BAS) differences in bipolar I and II disorder

Background

A growing body of evidence supports the Behavioral Activation System (BAS) dyresgulation model of bipolar disorder, however its application to bipolar II disorder is limited. The current study examines its potential relevance to bipolar I and II disorders. We specifically sought to determine whether bipolar sub-types would differ in terms of BAS sensitivity, and examined for differential prospective relationships between BAS sensitivity and bipolar I and II symptom expression.

Method

Participants were recruited from the Sydney-based Black Dog Institute. Diagnostic groups were derived on the basis of agreement between clinician and DSM-IV diagnoses from structured interviews. Baseline measures of BAS sensitivity, mood symptoms and anxiety were completed. Self-rated mood was assessed over a 6-month period. Clinician-rated mood status was re-assessed at follow-up to determine the predictive utility of BAS scores.

Results

The sample comprised 151 bipolar participants (69 bipolar I, 82 bipolar II). BAS-Drive and Reward Responsiveness scores were significantly higher in bipolar I disorder participants. BAS sub-scale scores were uniquely positively associated with mood variability in bipolar I and II disorder. BAS-Drive and Reward Responsiveness scores were positively associated with bipolar I hypo(mania), and with the former also positively associated with bipolar II depression. BAS scores did not predict bipolar I or II mood episode status at 6-month follow-up.

Limitations

BAS sensitivity was self-reported; inability to establish independence of BAS scores from residual symptoms; lack of controlling for medication effects; inability to determine the influence of life events; length of follow-up period may have not been sufficient to evaluate the predictive utility of BAS sensitivity for mood episodes or detect course of illness differences across bipolar sub-types.

Conclusions

Differences in BAS sensitivity and associations with mood variability were quantified in bipolar I and II disorder, suggesting the need for tailored treatments for these separate conditions. Further investigation of the role of the BAS in bipolar sub-types is warranted.     

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.