Neurocognitive functioning in the premorbid stage and in the first episode of bipolar disorder: A systematic review

Highlights

• There is a paucity of studies that explored the neurocognitive functioning in the premorbid stage and in the first episode.

• There is evidence that IQ is not impaired in the premorbid stage.

• Impairments in verbal memory, attention, and executive functions tend to be present during and after the first episode.

• Some impairment in specific cognitive domains might precede the onset of illness.

Abstract

It is well known that patients with bipolar disorder (BD) have cognitive impairments even during periods of euthymia. However, to date it remains unclear the moment when these deficits onset. Therefore, the aim of this study was to review the evidence focusing on the cognitive status of patients with BD in their premorbid stage and in their first episode. An extensive search was conducted through the online databases Pubmed/PsychInfo, covering the period between 1980 and 2014. A total of 23 studies were selected for the review (nine studies explored premorbid stage of people who lately develop BD and 14 examined first-episodes in bipolar patients). There is evidence that general intelligence is not impaired in the premorbid stage. Impairments in verbal memory, attention, and executive functions tend to be present during and after the first episode. Preliminary evidence suggests that these deficits in specific cognitive domains might precede the onset of illness.

Introduction

Over the last two decades, a growing body of evidence has suggested that euthymic patients with bipolar disorder (BD) have impairments in verbal memory, attention, and executive functions compared with healthy controls, with medium–large effect sizes in most studies (Robinson et al., 2006, Torres et al., 2007, Bora et al., 2009, Mann-Wrobel et al., 2011) and somewhat less in other (Bourne et al., 2013). Cognitive deficits in BD are present in different subtypes of the disorder (Martino et al., 2011a, Bora et al., 2011) and may extend beyond traditional neurocognitive domains (Martino et al., 2011b, Samamé et al., 2012). Likewise, the association between cognitive deficits and functional outcome has been consistently reported both in cross-sectional (Zubieta et al., 2001, Dickerson et al., 2004, Martinez-Arán et al., 2004) and longitudinal (Jaeger et al., 2007, Tabarés-Seisdedos et al., 2008, Martino et al., 2009) studies.

Despite the advance in the field of neurocognition, to date it is not clear when the cognitive impairments onset in patients with BD. Some recent reviews have suggested that patients with BD show relatively intact cognitive status in the premorbid stage, throughout childhood and adolescence, and that it is just when symptoms of illness arise that neurocognitive functioning deteriorates (Kumar and Frangou, 2010, Lewandowski et al., 2011, Trotta et al., 2015). This perspective is in accordance, regarding the neurocognitive performance in the premorbid stage, with the notion of illness progression and staging introduced in BD (Berk, 2009, Kapczinski et al., 2009, Post et al., 2012, Kapczinski et al., 2014). The model of staging proposes a progression from latent (at-risk) to more severe and refractory presentations associated with the cumulative effects of illness episodes, drugs abuse, life stress, and inherited vulnerability (Kapczinski et al., 2009). Specifically from a neurocognitive point of view, staging models suggest no cognitive impairments in the premorbid stage or even in patients with well-defined periods of euthymia without overt psychiatric symptoms, to progressive cognitive impairments in further stages (Kapczinski et al., 2009).

Data about intact premorbid cognitive functioning in patients with BD contrast, however, with findings from neurocognitive studies in healthy first-degree relatives of affected subjects. Arts et al. (2008) conducted a meta-analysis and reported that, compared with 692 healthy controls, the 336 first-degree relatives of probands with BD had impairments in executive functions and verbal memory with small effect sizes. In this study, the performance of first-degree relatives was intermediate between the ones of healthy controls and patients with BD (Arts et al., 2008). Similarly, Bora et al. (2009) in another meta-analysis found that 443 first-degree relatives of patients with BD had impairments in response inhibition, set shifting, executive function, verbal memory, and sustained attention with small to medium effect sizes. Therefore, the fact that patients with BD have a preserved premorbid cognitive functioning as suggested, while healthy first-degree relatives of bipolar subjects do not, is somewhat contradictory. It has been recently pointed out that this contradiction could be due to sample selection bias, medication, drug use, cognitive decline prior to the first episode, or other confounding factors (Arango et al., 2014).

These controversial results warrant further research in this field. Clarification of the onset of neurocognitive deficits is relevant to a better clinical description of the disorder, to identifying similarities and differences with other neuropsychiatric disorders, and to contribute to understanding pathophysiological processes underlying this illness. Accordingly, the aim of this study was to review the evidence gathered in recent years focusing on the cognitive status of patients with BD in their premorbid stage and in their first episode, in order to gain some insight into the onset of neurocognitive impairments in BD.