Cognitive dysfunction in euthymic bipolar patients on prophylaxis of lithium monotherapy.

Sir,

Bipolar affective disorder (BPAD) is a recurrent illness with significant disability and heterogeneous outcomes.[1] The view that patients with bipolar disorder make a full recovery between episodes of illness has been widely accepted. However, investigations of patients with BPAD have demonstrated that although more than 97% of patients appear to recover clinically within 02 years, only 37% recover functionally during the same period.[2] In bipolar patients, deficits in executive functions, psychomotor skills, and memory have been reported even during the euthymic phase.[3456] Numerous factors are suspected to influence cognitive functions in BPAD; however, the impact of mood stabilizers on cognitive functions has not been examined extensively, despite its clinical relevance.[7-9] Cognitive impairment is a common complaint among patients taking lithium as a mood stabilizer for treatment of BPAD, often leading to non-compliance with lithium.[10] The various other authors such as Reus et al.,[11] Lund et al.,[12] E. Mora et al.,[13] and Murlidharan et al.[14] have all demonstrated cognitive dysfunction on lithium therapy in the domain of attention, verbal memory, and executive functions. Nevertheless, the literature on the effect of the mood stabilizer lithium on cognitive functions during the euthymic phase in BPAD patients is equivocal, and therefore, we have conducted a study that aims at determining the cognitive dysfunction in euthymic patients of BPAD patients diagnosed as per the international classification of diseases, diagnostic criteria for research, 10th revision (ICD 10 DCR)[15] from the psychiatric out-patient department (OPD) who were taking lithium monotherapy for at least 6 months on a comprehensive neuropsychological battery.

The present study was cross-sectional in design, and 30 cases were recruited in the study with informed consent after applying pre-defined inclusion and exclusion criteria. The semi-structured proforma was then applied to the patients for socio-demographic and clinical variables. In the study, the euthymic state was defined by using a score of ≤7 on the Hamilton rating scale for depression (HRSD)[16] and ≤10 on the Young Mania Rating Scale (YMRS).[17] The cognitive functions were assessed using Trail Making test part A for attention and part B for cognitive flexibility,[18] Digit Vigilance test for attention,[19] PGI-BBD memory scale to assess different domains of memory,[20] and Stroop test for executive functions of response inhibition.[19] A pilot study over ten patients was conducted to adequately train the researcher for administering the neuropsychological tests under the supervision of a clinical psychologist, and the results of the pilot study were cross-checked for inter-rater reliability (Cohen’s kappa [ĸ] = 0.64, indicating substantial agreement). The neuropsychological tests were then applied to the cases, and later, the scores of the tests were compared with the standardized normative data of respective tests. The statistical analysis of data was performed using Statistical Package for the Social Sciences (SPSS) version 23.0 (2015).

In our study, 66.7% of the cases were males, and about 76% of the cases were educated up to the 12th standard. The mean total duration of illness was 13.43 years, the mean total treatment duration was 7.97 years, and the mean mood episodes were 6.70. As depicted in Table 1, the patients over lithium were found to have severe dysfunction of attention and cognitive flexibility over Trail Making test and executive functions over Stroop test. These findings are similar to the study by Muller-oerlinghausen et al.,[21] Squire et al.,[22] E. Mora et al.,[13] and Murlidharan et al.,[14] who used similar tests and found dysfunction over long-term use of lithium. There was severe dysfunction of delayed memory, verbal retention, visual retention, and recognition. Mild-to-moderate dysfunction was found on mental balance, immediate recall, and recent and remote memory in most of the cases. These findings were similar to the studies of Reus et al.,[11] Shaw et al.,[23] Trivedi et al.,[24] Goswami et al.,[25] and Pattanayak et al.[26]

Table 1

Cognitive dysfunction in BPAD euthymic patients on monotherapy of lithium over Trail Making, Digit Vigilance, PGI BBD, and Stroop color tests

Test Trail Making Test	Degree of Cognitive Dysfunction
	Normal	Impaired
Trail A	1 (3.3%)	29 (96.7%)
Trail B	3 (10%)	27 (90%)
Digit Vigilance	7 (23.3%)	23 (76.7%)
Stroop Color Test	8 (26.7%)	22 (73.7%)
PGI BBD Memory scale	Normal function	Mild–Moderate dysfunction	Severe dysfunction
Recent memory	18 (60%)	12 (40%)	0 (0%)
Remote memory	26 (86.7%)	4 (13.3%)	0 (0%)
Mental Balance	8 (26.7%)	14 (46.7%)	8 (26.6%)
Attention and concentration	10 (33.3%)	11 (36.7%)	9 (30%)
Delayed Recall	2 (6.7%)	3 (10%)	25 (83.3%)
Immediate Recall	11 (36.7%)	19 (63.3%)	0 (0%)
Verbal retention for a similar pair	23 (76.6%)	6 (20%)	1 (3.3%)
Verbal retention for a dissimilar pair	1 (3.3%)	9 (30%)	20 (66.7%)
Visual Retention	3 (10%)	10 (33.3%)	17 (56.7%)
Recognition	4 (13.3%)	11 (36.7%)	15 (50%)

In the limited available research literature regarding BPAD patients, particularly those in euthymia and on lithium monotherapy, cognitive impairment measures by reliable methods have been associated with impaired functional status, which usually was assessed by subjective self-appraisal rather than with objective and quantitative measures. Thereby, the objective of our study was to assess the neurocognitive dysfunctions on standardized neuropsychological tests. This study has certain limitations such as cross-sectional design, OPD samples, and the lack of a control group, yet it has advantages that highlight the cognitive dysfunction over a commonly used mood stabilizer, lithium, which may increase the risk of non-compliance and can lead to substantial social and occupational deficits. An inability to cope with the demands of work or the family could cause stress and thus contribute to relapse further. Thereby, based on available evidence and our study result, there should be early recognition of these cognitive deficits, and if deficits are severe, advice on early management strategies for the same will benefit the patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.