Elsevier

Journal of Affective Disorders

Volume 227, February 2018, Pages 109-116
Journal of Affective Disorders

Research paper
Cognitive functioning in first episode bipolar I disorder patients with and without history of psychosis

https://doi.org/10.1016/j.jad.2017.10.003Get rights and content

Highlights

  • Cognition in new onset BDI with (BDP+) or without (BDP-) psychosis did not differ.

  • BDP+ with (MCP) or without mood incongruent (MIC) psychosis also did not differ.

  • However, BDP+ were more impaired compared to HC than was BDP-.

  • MIC and MCP also showed different patterns of impairment compared to HC.

  • Thus, these patient subgroups may display unique cognitive deficits at illness onset.

Abstract

Background

Psychosis in bipolar I disorder (BDI) has been associated with increased cognitive dysfunction, which may relate to poorer functional outcomes. However, it is not known whether cognition differs between BDI patients with (BDP+) or without (BDP-) history of psychosis early in the disease course, or if it is impacted by the presence of mood congruent (MCP) versus incongruent (MIC) psychotic features. We compare cognition between these groups in BDI patients recently recovered from first episode of mania.

Methods

Attention, verbal learning/memory, processing speed and executive functioning were compared between: 1) all BDI patients (n = 73) and healthy controls (HC, n = 45), 2) BDP+ (n = 60) and BDP- (n = 13) patients and 3) MCP (n = 27) and MIC (n = 33) patients. Post-hoc analyses compared all patient groups with HC.

Results

While BDI patients performed worse than HC in all domains, there were no significant differences between BDP+ and BDP-, or MCP and MIC, patients. However, BDP+ and MIC groups demonstrated different patterns of impairment compared to HC then did BDP- or MCP. Executive functioning and cognitive flexibility in particular appeared to be a deficit area in BDP+ patients.

Limitations

This study may have been underpowered to detect differences in direct comparison between BDP+ and BDP- patients.

Conclusion

While replication in larger samples is required, these results suggest that subtle cognitive differences between BDP+ and BDP-, and between MIC and MCP, patients may be present shortly after disease onset. These patient subsets may therefore be of interest in examining early intensive strategies to preserve cognition.

Introduction

Cognitive dysfunction is a core feature of bipolar I disorder (BDI), with deficits in executive functioning, verbal learning and memory detectable in both acutely symptomatic and remitted patients (Martinez-Aran et al., 2004, Torres et al., 2007). These impairments are present at illness onset and may be more correlated with functional outcomes than clinical symptomatology (Daglas et al., 2015, Depp et al., 2012, Lee et al., 2014, Martinez-Aran et al., 2007, Torres et al., 2010). However, while moderate – severe cognitive deficits compared to healthy controls have been consistently replicated on the group level in BDI, there is significant heterogeneity in the degree to which individual patients display these deficits (Bora, 2015). Attempts to characterize the range of cognitive deficits in BDI have found that approximately one third of patients meet criteria for ‘impairment’ (i.e. 1–2 SD below the mean) (Gualtieri and Morgan, 2008, Iverson et al., 2011, Martino et al., 2014), while between 40–70% of patients may not display clinically significant impairment (Szmulewicz, 2015). Identifying the clinical features which characterize the cohort of patients displaying greater cognitive dysfunction early in the disease course could help target those who require the most support to achieve full functional recovery.

The presence of psychotic features is one such variable that may be related to cognitive functioning. Although the degree to which the clinical course differs between BDI patients with (BDP+) and without (BDP-) psychotic features is unclear, some studies have found an association between psychosis and more frequent mood episodes, increased symptom severity and poorer functional outcomes (Carlson et al., 2012, Coryell et al., 2001, Keck et al., 2003, Van Riel et al., 2008). The two groups may also be neuropathologically distinct, with smaller medial temporal, cingulate and lateral prefrontal volumes seen in BDP+ patients compared to BDP- (Tost et al., 2010, Velakoulis et al., 1999). Previous studies have reported that between 60–90% patients with bipolar disorder have a lifetime history of psychotic symptoms (Dunayevich and Keck, 2000); given the above clinical and neuropathological data, BDP- patients may therefore represent either a less severely affected or pathophysiologically distinct minority.

Differences between these two groups may also extend to neuropsychological functioning. A meta-analysis of studies comparing neurocognitive performance in acutely ill and remitted BDP- and BDP+ patients found significant impairment in the latter group, particularly in the domains of processing speed, verbal memory, verbal learning, working memory and planning (Bora et al., 2010). These impairments have been found in euthymic patients, and previous studies have found the neuropsychological profiles of BDP+ patients to be more similar to patients with primary psychotic disorders than they are to BDP- (Bora et al., 2007, Martinez-Aran et al., 2008, Simonsen et al., 2011). However, most of these studies have only examined patients with long duration of illness, raising the possibility that detected differences may be confounded by the more severe clinical course and long term medication effects of BDP+ patients (Palsson et al., 2013). A recent study which examined BDI patients within 12 months of initiating treatment, one third of whom had experienced previous untreated manic episodes, found no correlation between history of previous psychotic episodes and current neuropsychological functioning (Demmo et al., 2016). This would suggest that BDP+ patients do not display significant early cognitive dysfunction, but such results require replication in other first episode BDP+ populations.

Furthermore, effect sizes for neuropsychological differences between BDP+ and BDP- have been modest (Bora et al., 2010). It has been suggested that certain subsets of BDP+ patients, such as those with family history of primary psychotic disorder, display more severe deficits, and pooling all BDP+ patients into a single group may obscure these more pronounced impairments (Bora, 2015, Iverson et al., 2011). The nature of psychotic content in BDP+, such as the presence of mood incongruent (MIC) vs. mood congruent (MCP) features, may also help delineate such phenotypically distinct subtypes. Although the clinical relevance of this distinction remains unclear, evidence suggests that MIC is associated with incomplete interepisode recovery, decreased medication responsiveness and higher rates of suicide compared to MCP BDP+ (Association, 2013, Gaudiano et al., 2007, Marneros et al., 2009, Miklowitz, 1992, Strakowski et al., 2000). There is also evidence of partial overlap in susceptibility genes between schizophrenia and MIC, and MIC BDP+ has been associated with more prominent volumetric changes in medial temporal, dorsolateral/ventrolateral prefrontal and cingulate cortices compared to healthy subjects and other BDI patients (Goes et al., 2008, Goes et al., 2007, Tost et al., 2010). Investigation of the potential neuropsychological differences between these two groups, however, has been limited. To our knowledge there has been only one comparison of cognition in MIC vs. MCP patients, conducted as a secondary analysis, which found no significant differences (Bora et al., 2007).

To investigate differences in cognitive functioning between bipolar I disorder (BDI) patients with (BDP+) and without (BDP-) history of psychosis, and to control for clinical variables such as illness severity, duration and long term medication effects, we compare the neuropsychological profiles of BDP+ and BDP- patients who have recently recovered from their first episode of mania. To our knowledge this is the first neuropsychological analysis of exclusively first episode BDP+ and BDP- patients, and will help clarify whether there are indeed differential early impairments between the two groups. We also compare performance between BDP+ patients with mood congruent (MCP) and mood incongruent (MIC) psychotic features, to determine whether the two sub-groups have distinct neurocognitive signatures at disease onset.

Section snippets

Participants

The data for this analysis comes from the Systematic Treatment Optimization Program for Early Mania [STOP-EM] Program which enrolled patients meeting DSM-IV TR criteria for BDI within 3 months of their first manic episode (Association, 2000). Patients were recruited from UBC Hospital (UBCH) and affiliated sites, as well as community referrals from physicians. The University of British Columbia (UBC) Clinical Research Ethics Board approved all study procedures, and written informed consent was

Demographic comparison

All groups were matched in terms of age, years of education, gender distribution and premorbid IQ. Amongst the patient groups, there was no significant difference in YMRS and HDRS scores, number of previous depressive episodes, and duration of illness. Patient groups also did not differ in the use of mood stabilizer or antipsychotic medications (Table 1). A significantly higher percentage of BDP+ patients had a lifetime history of THC use compared to BDP-.

Planned contrasts

There was a statistically significant

Discussion

Cognitive functioning in bipolar I disorder, independent of traditionally defined symptomatology, impacts patients’ ability to regain their full premorbid functional capacity (Martinez-Aran et al., 2007). Previous studies have found cognitive deficits to be already present in first episode BDI patients (Lee et al., 2014), and we here examined subsets of newly diagnosed BDI patients defined by the presence (BDP+) or absence (BDP-) of psychosis in their first manic episode, and by the mood

Acknowledgements

None.

Role of the funding source

This research was supported by an unrestricted grant from AstraZeneca Canada.

Declaration of interest

Dr. Yatham has been a member of advisory board, received research grants, and been a speaker for Astrazeneca, Janssen, Lilly, GSK, Bristol Myers Squibb, Novartis, Servier, and Pfizer. Ivan J. Torres has served as a consultant for Lundbek Canada. Golnoush Alamian, Jan-Marie Kozicky and Trisha Chakrabarty report no disclaimers.

Contributors

Trisha Chakrabarty conducted data analysis and was the main manuscript author. Golnoush Alamian

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