A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Bipolar Disord

Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Bipolar Disorders (Impact Factor: 4.97). 12/2008; 10(7):806-15. DOI: 10.1111/j.1399-5618.2008.00628.x
Source: PubMed


Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects.
Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable.
With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory.
Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.

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    • "However, this was a sub-analysis on a small sample of patients and did not address issues such as duration of treatment with mood stabilizers, duration of combination treatment with antipsychotics, differences between the two medication groups in terms of illness duration and other clinical variables, and association between mood stabilizer dose and cognitive performance. Another study reported more errors on a spatial working memory task in valproate treated as compared to lithium treated BD patients, although this was not statistically significant (Holmes et al., 2008). "
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    ABSTRACT: In bipolar disorder (BD), lithium and valproate are both reportedly associated with mild cognitive deficits with impaired psychomotor speed and verbal memory ascribed to both while impairments in learning and attention are mainly attributed to valproate. However, there are few direct comparisons of the impact of lithium and valproate on cognitive function in early BD. Using data from the STOP-EM study, we compared neurocognitive functioning in BD patients, who had recently recovered from a first episode of mania, and were on treatment with lithium (n=34) or valproate (n=38), to a comparable sample of healthy controls (HC; n=40), on the domains of processing speed, attention, verbal memory, nonverbal memory, working memory and executive functions. The three groups were comparable on socio-demographic (all p>0.12) and clinical variables (all p>0.08). MANOVA revealed a significant difference between the three groups on overall cognitive functioning (Wilk's lambda=0.644; F= 3.775; p<0.001). On post hoc Tukey test, the valproate group performed poorer on working memory compared to the lithium (p=0.001) and HC groups (p<0.001). There was no significant difference between the lithium and valproate groups on other cognitive domains (all p>0.13). Treatment with valproate and not lithium may be associated with working memory deficits early in the course of BD.
    European Neuropsychopharmacology 09/2014; 25(2). DOI:10.1016/j.euroneuro.2014.09.005 · 4.37 Impact Factor
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    • "A small number of studies examining cognition in bipolar depression have included assessment of aspects of visuo-spatial memory. While some have reported deficits in patients compared to controls (Martinez-Aran et al. 2004; Rubinsztein et al. 2006) others have found no differences (Sweeney et al. 2000; Taylor Tavares et al. 2007; Holmes et al. 2008). One study by Gallagher et al. (2014) that examined a broad range of cognitive processes in bipolar depression and matched controls demonstrated significant differences on a number of visuo-spatial memory tasks, including pattern and spatial recognition (from CANTAB), and forward and reverse spatial span (a CANTAB analogue to the Corsi block-tapping test of visuo-spatial short-term/working memory), visual pattern span (Della Sala et al. 1999), and self-ordered pointing (McGonigle & Chalmers 2002). "
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    ABSTRACT: Background: Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine their relationship with broader neurocognitive performance. Method: Fifty participants (25 patients with BD in a current depressive episode and 25 matched healthy controls) completed the OLM paradigm which assessed three different aspects of visuo-spatial memory: positional memory, object-location binding, and a combined process. Secondary neurocognitive measures of visuo-spatial memory, verbal memory, attention and executive function were also administered. Results: BD patients were significantly impaired on all three OLM processes, with the largest effect in exact positional memory (d = 1.18, p < 0.0001). General deficits were also found across the secondary neurocognitive measures. Using hierarchical regression, verbal learning was found to explain significant variance on the OLM measures where object-identity was present (the object-location binding and combined processes) and accounted for the group difference. The group difference in precise positional memory remained intact. Conclusions: This study demonstrates that patients with bipolar depression manifest deficits in visuo-spatial memory, with substantial impairment in fine-grain, positional memory. The differential profile of processes underpinning the visuo-spatial memory impairment suggests a form of 'cognitive scaffolding', whereby performance on some measures can be supported by verbal memory. These results have important implications for our understanding of the functional cognitive architecture of mood disorder.
    Psychological Medicine 07/2014; 45(3):1-14. DOI:10.1017/S0033291714001676 · 5.94 Impact Factor
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    • "Several studies have used combinations of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to explore aspects of attention, executive function and visuospatial memory in bipolar depression, with mixed findings. Some studies have found very few differences between depressed BD patients and controls (Sweeney et al. 2000), especially in medication-free patients (Taylor Tavares et al. 2007; Holmes et al. 2008; Roiser et al. 2009), whereas others have reported widespread impairments, at a clinically significant level (< 5th percentile of controls) in up to 42% of the group (Rubinsztein et al. 2006). Broad deficits have also been described using the multiple subscales of the Wechsler Adult Intelligence Scale-III (WAIS-III; Schneider et al. 2008). "
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    ABSTRACT: Previous studies of neurocognitive performance in bipolar disorder (BD) have focused predominantly on euthymia. In this study we aimed to compare the neurocognitive profile of BD patients when depressed with healthy controls and explore the component structure of neurocognitive processes in these populations. Method Cognitive tests of attention and executive function, immediate memory, verbal and visuospatial learning and memory and psychomotor speed were administered to 53 patients with a SCID-verified diagnosis of BD depression and 47 healthy controls. Test performance was assessed in terms of statistical significance, effect size and percentile standing. Principal component analysis (PCA) was used to explore underlying cognitive factor structure. Multivariate analysis revealed an overall group effect, depressed BD patients performing significantly worse than controls. Patients performed significantly worse on 18/26 measures examined, with large effect sizes (d > 0.8) on tests of speed of processing, verbal learning and specific executive/working memory processes. Almost all tests produced at least one outcome measure on which ∼25-50% of the BD sample performed at more than 1 standard deviation (s.d.) below the control mean. Between 20% and 34% of patients performed at or below the fifth percentile of the control group in working memory, verbal learning and memory, and psychomotor/processing speed. PCA highlighted overall differences between groups, with fewer extracted components and less specificity in patients. Overall, neurocognitive test performance is significantly reduced in BD patients when depressed. The use of different methods of analysing cognitive performance is highlighted, along with the relationship between processes, indicating important directions for future research.
    Psychological Medicine 06/2013; 44(05):1-14. DOI:10.1017/S0033291713001487 · 5.94 Impact Factor
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