Association between childhood dimensions of attention deficit hyperactivity disorder and adulthood clinical severity of bipolar disorders.

BACKGROUND: Clinical features of attention deficit hyperactivity disorder can be frequently observed in cases with bipolar disorders and associated with greater severity of bipolar disorders. Although designed as a screening tool for attention deficit hyperactivity disorder, the Wender Utah Rating Scale could, given its factorial structure, be useful in investigating the early history of impulsive, inattentive or mood-related symptoms among patients with bipolar disorders. METHODS: We rated the Wender Utah Rating Scale in 276 adult bipolar disorder cases and 228 healthy controls and tested its factorial structure and any associations with bipolar disorder phenomenology. RESULTS: We confirmed a three-factor structure for the Wender Utah Rating Scale (' impulsivity/temper', ' inattentiveness' and ' mood/self-esteem'). Cases and controls differed significantly on Wender Utah Rating Scale total score and sub-scale scores ( p-values < 10-5). About 23% of bipolar disorder cases versus 5% of controls were classified as ' WURS positive' (odds ratio = 5.21 [2.73-9.95]). In bipolar disorders, higher Wender Utah Rating Scale score was associated with earlier age at onset, severity of suicidal behaviors and polysubstance misuse; multivariate analyses, controlling for age and gender, confirmed the associations with age at onset ( p = 0.001) and alcohol and substance misuse ( p = 0.001). CONCLUSION: Adults with bipolar disorders who reported higher levels of childhood symptoms on the Wender Utah Rating Scale presented a more severe expression of bipolar disorders in terms of age at onset and comorbidity. The Wender Utah Rating Scale could be employed to screen for attention deficit hyperactivity disorder but also for ' at-risk behaviors' in adult bipolar disorder cases and possibly for prodromal signs of early onset in high-risk subjects.

Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment.

OBJECTIVE: Duration of untreated illness represents a potentially modifiable component of any diagnosis-treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. METHOD: In a well-characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined. RESULTS: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant-induced mania). CONCLUSION: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD-II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

[Cognitive disturbances and bipolar depression]. / Troubles cognitifs et dépression bipolaire.

The existence of cognitive deficits during the acute phases of bipolar disorder (manic, depressive, hypomanic or mixed episodes) has long been demonstrated and by numerous studies. The existence of cognitive deficits during euthymic periods has been much less studied. In addition, these studies are hampered by several methodological difficulties (small sample sizes, confounding factors influencing cognitive performance such as residual symptoms, comorbidities, age.. not considered). More recently, several studies have clearly documented the existence of memory deficits (especially, verbal), attention and executive function during euthymic periods in bipolar patients. In addition, several prospective studies and meta-analyses suggest that these deficits independent predictors of the functional. Thus the development of specific cognitive remediation programs is a major stake. These deficits may be markers of vulnerability to bipolar disorder, but may also reflect the cognitive « toxicity ¼ of major mood episodes.

Affect intensity measure in bipolar disorders: a multidimensional approach.

BACKGROUND: Emotional dysregulation, characterized by high levels of both arousal and intensity of emotional responses, is a core feature of bipolar disorders (BDs). In non-clinical populations, the 40-item Affect Intensity Measure (AIM) can be used to assess the different dimensions of emotional reactivity. METHODS: We analyzed the factor structure of the AIM in a sample of 310 euthymic patients with BD using Principal Component Analysis and examined associations between AIM sub-scale scores and demographic and illness characteristics. RESULTS: The French translation of the AIM demonstrated good reliability. A four-factor solution similar to that reported in non-clinical samples (Positive Affectivity, Unpeacefulness [lack of Serenity], Negative Reactivity, Negative Intensity), explained 47% of the total variance. Age and gender were associated with Unpeacefulness and Negative reactivity respectively. 'Unpeacefulness' was also positively associated with psychotic symptoms at onset (p=0.0006), but negatively associated with co-morbid substance misuse (p=0.008). Negative Intensity was positively associated with social phobia (p=0.0005). LIMITATIONS: We cannot definitively exclude a lack of statistical power to classify all AIM items. Euthymia was carefully defined, but a degree of 'contamination' of the self-reported levels of emotion reactivity may occur because of subsyndromal BD symptoms. It was not feasible to control for the possible impact of on-going treatments. CONCLUSIONS: The AIM scale appears to be a useful measure of emotional reactivity and intensity in a clinical sample of patients with BD, suggesting it can be used in addition to other markers of BD characteristics and sub-types.

Clinical features associated with trait-impulsiveness in euthymic bipolar disorder patients.

BACKGROUND: A strong association has been reported between trait-impulsiveness and bipolar disorder (BD). Much attention has been focused on this association, but subgroup analysis has generated conflicting results, raising questions about the role of trait-impulsiveness in suicidal behavior and substance misuse in bipolar patients. METHOD: We compared Barratt Impulsiveness Scale-10 scores between 385 euthymic bipolar patients and 185 healthy controls. We then investigated possible association between impulsiveness scores and the following clinical characteristics: suicide attempt (SA), lifetime alcohol/cannabis misuse, rapid cycling and mixed episodes. RESULTS: Bipolar patients and healthy controls had significantly different BIS-10 total score and subscores (motor, attentional and nonplanning impulsiveness) (all p values <0.0001). No association was observed between BIS-10 total score, personal history of SA, number of SA, age at first SA and history of violent SA. Higher BIS-10 total scores were associated with alcohol misuse (p=0.005), cannabis misuse (p<0.0001), with an additive effect for these two substances (p=0.005). Higher BIS-10 total scores were also associated with rapid cycling (p=0.006) and history of mixed episodes (p=0.002), with an additive effect of these two variables (p=0.0006). LIMITATIONS: We used only one clinical measurement of impulsiveness and did not carry out cognitive assessment. CONCLUSION: This study demonstrates that trait-impulsiveness may be considered as a dimensional feature associated with BD and with a more severe clinical expression of the disease, characterized by a history of substance misuse, rapid cycling and mixed episodes. We found no association between impulsiveness and SA characteristics in bipolar patients, confirming some previous negative results.

Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior.

BACKGROUND: The clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised. METHODS: In a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables. RESULTS: Of the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal behaviour in bipolar patients, whereas impulsivity and affective lability/intensity were not associated with suicidal behaviour. LIMITATIONS: This study had a retrospective design with no replication sample. CONCLUSIONS: Bipolar patients with earlier onset, mood instability (large number of depressive episodes, rapid cycling) and/or particular addictive and anxiety comorbid disorders might be at high risk of suicidal behaviour. In addition, hostility dimensions (indirect hostility and irritability), may be trait components associated with suicidal behaviour in euthymic bipolar patients.