Bipolar I Affective Disorder (BPAD-1) is a chronic, episodic, major psychiatric illness with frequent exacerbations of mania and depression. BPAD-1 has a significant negative impact on the lives of affected individuals, and more than 6% of patients die by suicide within the first two decades after diagnosis [1]. The disorder is associated with impairments in various cognitive domains such as attention, memory, and executive functioning [2,3]. These impairments often worsen with the progression of illness and are linked to an increasing number of mood episodes and hospitalizations [4,5].

Even during remission, BPAD-1 patients experience poor functioning in occupational, social, and familial contexts [6]. Characterized by recurrent episodes of mania and depression, BPAD-1 affects approximately 1% of the population, with an equal incidence in both sexes [7]. While it most commonly begins in the second decade of life, it can occur at any age. High heritability of BPAD-1 has been demonstrated through various twin and adoption studies [8].

Cognition refers to higher-level information processing. Neurocognitive functions are linked to specific brain pathways and are influenced by disease processes. Studies have shown that cognitive domains such as attention, executive functioning, speed of information processing, working memory, and declarative memory are strongly affected by genetic factors [9].

Neurocognitive impairments in BPAD-1 persist even during remission, particularly affecting sustained attention, verbal memory, and executive functions [10]. Verbal memory dysfunction, in particular, has been associated with disease progression in patients with BPAD-1 [11].

OBJECTIVE

To examine the relationship between neurocognitive functioning and clinical variables—including age of onset, duration of illness, number of episodes, and substance use in euthymic patients with Bipolar I Disorder.

Study Population

The study comprised two groups: 30 euthymic patients diagnosed with Bipolar Affective Disorder - I (BPAD-1) who were attending the Psychiatry Outpatient Department (OPD), and 30 healthy individuals from the general population who served as normal controls.

Design of the Study

This was a cross-sectional study conducted over a period of six months.

Sampling Method

A convenience sampling method was employed. BPAD-1 euthymic patients attending the Psychiatry OPD were selected based on predefined inclusion and exclusion criteria.

Inclusion Criteria

Participants included in the study were BPAD-1 euthymic patients aged between 15 and 45 years, with formal education up to at least the 8th standard, and who provided written informed consent to participate in the study.

Exclusion Criteria

For BPAD-1 patients, individuals who had experienced manic or depressive episodes within the last six months were excluded. For the normal control group, exclusion criteria included the presence of mental retardation, any past history of psychiatric illness, neurological or systemic illness impairing cognition, head injury, substance dependence, or use of benzodiazepines or any other cognition-impairing medication within the last one month.

  Tool used

Statistical Design

The statistical design was formulated based on the data collected from various neuropsychological tests, rating scales, and socio-demographic variables. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS), version 14.0. Measures of central tendency and dispersion were calculated. For comparison of categorical variables, the Chi-square test was used, while Student’s t-test was applied for continuous variables. For comparisons involving more than two numerical variables, Tukey’s post-hoc test and Analysis of Variance (ANOVA) were employed. Correlations among variables were assessed using Pearson’s correlation coefficient.

This cross - sectional study was conducted in the psychiatry out patient department in order to assess the neurocognition in 30 BPAD-1 euthymic patients (cases) and compare with the normal controls (controls). The results are described below

Table 1: Correlation Analysis between Age of Onset in Bpad- 1 Euthymic Patients And Neurocognitive Assessment

 Age of onset in bipolar affective disorder -1 euthymic patients has negative correlation with neurocognition in this study. Rey’s Auditory Verbal Learning Test – Delayed Recall; (Correlation = -0.48, p = 0.007). In this study Younger age of onset in BPAD-1 implies worsening of Verbal Working Memory – Delayed Recall in Rey’s Auditory Verbal Learning Test in BPAD -1 Patients.

Table 2: CORRELATION ANALYSIS BETWEEN DURATION OF ILLNESS AND NEUROCOGNITIVE ASSESSMENT

Duration of illness in bipolar affective disorder -1 euthymic patients has positive correlation with neurocognition in this study. Trial Making Test A (TMT-A); (correlation = 0.67, p = 0.0001), Digit Symbol Substitution Test (DSST) (correlation =0.693, p = 0.0001) and Digit Vigilance Test (DVT) time (Correlation = 0.468, p = 0.009). In this study increased duration of illness in BPAD-1 implies worsening of processing speed – Trial Making Test – A and Digit Symbol Substitution Test in BPAD-1 patients. In this study Increased duration of illness in BPAD-1 also implies worsening of sustained attention – Digit Vigilance Test Time in BPAD-1 patients.

Table 3: CORRELATION ANALYSIS BETWEEN NUMBER OF EPISODES AND NEUROCOGNITIVE ASSESSMENT

Number of episodes in bipolar affective disorder -1 euthymic patients has positive correlation with neurocognition in this study. Trial Making Test A (TMT-A); (correlation = 0.704, p = 0.0001), Digit Symbol Substitution Test (DSST) (correlation = 0.665, p = 0.0001) and Digit Vigilance Test (DVT) time (Correlation = 0.475, p = 0.001). In this study increased number of episodes in BPAD-1 implies worsening of processing speed – Trial Making Test – A and Digit Symbol Substitution Test in BPAD-1 patients. In this study Increased number of episodes in BPAD-1 also implies worsening of sustained attention – Digit Vigilance Test Time in BPAD-1 patients.

Table 4: CORRELATION ANALYSIS BETWEEN SUBSTANCE USE AND NEUROCOGNITIVE ASSESSMENT

Impairment in neurocognitive abilities has been previously well studied in patients with bipolar affective disorder [12]. In our study, the mean age of the study group population showed statistical significance using one-way ANOVA (p = 0.0001). However, no statistically significant differences were observed between the control group and first-degree relatives. Only individuals with formal education beyond the 8th standard were included.

In our study, a younger age of onset of bipolar affective disorder was associated with worsening of verbal working memory, as evidenced by delayed recall performance on the Rey’s Auditory Verbal Learning Test. A study by Frangou et al. also observed that early-onset BPAD is linked with impairments across several neurocognitive domains [13]. However, in our findings, only verbal working memory showed a significant correlation with age of onset. The negative correlation observed in this study implies that an earlier onset of illness results in more severe neurocognitive impairment in BPAD-1 euthymic patients, aligning with existing literature [14].

An increased duration of illness in our study was associated with neurocognitive impairments, particularly in processing speed as measured by the Trail Making Test - A (TMT-A) and the Digit Symbol Substitution Test (DSST), as well as in sustained attention, measured by the Digit Vigilance Test (DVT). These findings are consistent with prior studies, such as those by Martino et al. and Serafini et al., which reported greater cognitive impairment with longer illness duration in BPAD-1 euthymic patients [15,16]. The results reinforce the notion that cognitive decline in BPAD is progressive and closely tied to illness chronicity [17].

Our study found that a greater number of episodes was associated with impaired processing speed (TMT-A and DSST) and sustained attention (DVT). These findings were in line with studies by Valerio et al. and Sánchez et al., which demonstrated that repeated mood episodes are linked with cumulative neurocognitive deficits in BPAD-1 patients [18, 19]. The current findings suggest that recurrent mood episodes contribute to the worsening of cognitive performance, consistent with earlier longitudinal and cross-sectional observations [20].

No significant correlation was found between alcohol dependence and neurocognition in our study, possibly due to the small number of participants (3 out of 30) meeting the criteria for alcohol dependence. However, prior studies by Sánchez-Moreno et al. and Li et al. have shown that substance use, including alcohol and cocaine, exacerbates cognitive deficits in BPAD-1 euthymic patients [21,22]. The inability to replicate these findings may be attributed to the limited representation of substance use in our sample.

Limitations

This study had several limitations. Firstly, the sample size was relatively small, which may limit the generalizability of the findings. Larger sample sizes are necessary to validate and replicate the results. Secondly, the study followed a cross-sectional design, which restricts the ability to draw conclusions about changes in neurocognitive functioning over time. Longitudinal follow-up studies are recommended for a more accurate understanding of the progression of cognitive impairment in BPAD-1 patients. Additionally, the intelligence quotient (IQ) of the participants was not measured, which could have provided more insights into the baseline cognitive abilities of the subjects. The use of psychotropic medications, which might independently contribute to neurocognitive deficits, was not controlled for in this study. Lastly, individuals using tobacco were not excluded, which may have also influenced the cognitive performance of participants.

This study demonstrates that neurocognitive impairments are evident across multiple domains in euthymic individuals with Bipolar Affective Disorder - I (BPAD-1). A younger age at onset of illness was associated with more severe cognitive deficits, particularly in verbal working memory. Similarly, an increased number of mood episodes correlated with impairments in sustained attention and processing speed. Furthermore, a longer duration of illness was linked to worsening performance in these same cognitive domains. These findings suggest that neurocognitive deficits persist even during remission and are influenced by various clinical variables.

Future Directions

Future research should focus on longitudinal studies with regular follow-up assessments to monitor changes in neurocognitive functioning over time in BPAD-1 patients. There is also a need to implement and evaluate the effectiveness of cognitive remediation exercises aimed at improving cognitive outcomes in this population. Studies with larger sample sizes and improved methodological designs are essential for generating more robust evidence. Additionally, routine neurocognitive assessments should be integrated into the clinical management of BPAD-1 euthymic patients to enable early intervention and improve overall cognitive functioning and quality of life.

DECLARATION OF CONFLICTING INTERESTS

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

ETHICAL APPROVAL AND INFORMED CONSENT

The study received ethical clearance from the Institutional Ethics Committee at the Medical College. Written informed consent was obtained after the participants had thoroughly described the study in their vernacular language. All data was kept confidential, and privacy was ensured.

All relevant information was shared with the treating doctor with the patient’s consent.

FUNDING

The authors received no financial support for the research, authorship, and/or publication of this article.

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