Cognitive functioning in severe mental disorders

Cognitive functioning is a term referring to multiple mental abilities including general intellectual functioning, attention, psychomotor speed, learning, memory and executive function. Executive function is an umbrella term covering several higher-order cognitive functions that are used in goal directed tasks (working memory, planning, fluency and set-shifting) and in suppression of contextual and emotional distractors (inhibition and interference control). In the literature on severe mental disorders the term neurocognitive functioning is often used for the same purpose, indicating that these are tasks linked to specific regions of the central nervous system. Throughout this thesis the

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term cognitive functioning will be used, with a focus on cognitive functions that are impaired in severe mental disorders.

Schizophrenia was initially conceptualized as “dementia praecox”, indicating deterioration in cognitive abilities in young adults. Today, a large body of literature demonstrates marked impairments in multiple cognitive domains in schizophrenia. Attention, memory and executive functions are among the most severely impaired domains (Gur, 2011; Heinrichs, 2005; Heinrichs &

Zakzanis, 1998; Menkes, Armstrong, Blackford, Heckers, & Woodward, 2019). Also in bipolar disorder cognitive impairments are widely reported, particularly in many of the same cognitive domains as in schizophrenia; i.e. attention, processing speed, verbal memory, and executive functioning (Menkes et al., 2019; Samamé, Martino, & Strejilevich, 2014). The heterogeneity in cognitive impairment is, however, considerable, both between and within diagnostic categories (Lewandowski, 2018). However, the current consensus in the field is that overall cognitive

functioning is more impaired in schizophrenia than in bipolar disorder, also in the early stages of the illness (Menkes et al., 2019).

Cognitive impairments are present both during acute psychotic and affective episodes, and during stable, inter-episode periods, implying that they are trait- rather than state specific. Indeed, cognitive impairment has been viewed as a core feature of schizophrenia for a long time, and more recently also of bipolar disorder (Barch, 2009).

Importantly, cognitive impairment is shown to be a strong predictor of poor functional outcome (Green, Kern, Braff, & Mintz, 2000) and a major contributor to inadequate everyday functioning commonly seen in severe mental disorders, particularly poor occupational functioning (Christensen, 2007; Lystad et al., 2016). To date, no specific therapeutic agent has been found to enhance cognitive functioning. Mild to moderate positive effects have been reported for some antipsychotics. These effects are, however, not sufficient to be considered clinically meaningful and could be secondary to symptomatic improvements (Vreeker, van Bergen, & Kahn, 2015). Cognitive remediation therapy has,

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nevertheless, demonstrated promising treatment results. In combination with psychosocial interventions, cognitive remediation therapy is shown to improve everyday functioning (Harvey &

Bowie, 2012; Wykes, Huddy, Cellard, McGurk, & Czobor, 2011). Cognitive remediation therapy may be considered refined behavioral treatments for cognitive impairments, and emphasizes that the cognitive improvement that follows treatment should be manifested in everyday life and/or quality of life to be considered successful (Harvey & Bowie, 2012; Wykes et al., 2011).

1.3.1 Sleep and cognitive processes

Theories holding that there is a functional link between sleep and cognition, particularly learning and memory, are based on the extensive overlap between sleep mechanisms and the neurophysiology of these cognitive processes (Poe, Walsh, & Bjorness, 2010). During a cognitive process such as e.g.

attention or working memory, neural oscillations and synchronization among different brain regions occur and form a dynamic cognitive network that temporally synchronize these brain regions into a functional unit. The synchronization of these brain regions occurs at all stages (wakefulness through the different stages of sleep). Each stage of sleep is associated with various degrees, frequencies and extent of brain areas involved that aid facilitation of important learning and memory processes (Poe et al., 2010). Indeed, a wide range of studies have documented that compromised sleep leads to impaired cognition in both persons with insomnia and otherwise healthy persons (Chee & Chuah, 2008; Horne, 1993; Van Dongen, Maislin, Mullington, & Dinges, 2003). Sleep disturbances are frequent in severe mental disorders, as are impairment in cognitive processes that are dependent on sleep. Consequently, sleep disturbances may contribute to cognitive impairments in severe mental disorders, although this is an area with limited research.

Sleep disturbances and cognitive impairment in severe mental disorders

The majority of studies investigating sleep disturbances and cognitive impairments in schizophrenia have measured sleep objectively, primarily by use of polysomnography, electroencephalography or actigraphy. Together these studies suggest a link between sleep microarchitecture and cognitive impairment. More specifically, a systematic review of studies in early psychosis (Davies et al., 2017)

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points to a possible relationship between sleep architecture and performance on attention tasks, but without a consensus across studies. More clear results are found for memory, with a specific link between sleep spindle abnormalities and overnight memory consolidation in chronic schizophrenia (Baandrup, Christensen, Fagerlund, & Jennum, 2018; Ferrarelli & Tononi, 2017; Manoach et al., 2010;

Pocivavsek & Rowland, 2018; Wamsley et al., 2012).

In the bipolar disorder field, studies of sleep disturbance and cognitive impairment is based on a mix of subjective and objective measures of sleep. Studies applying subjective measurement have found disrupted sleep to predict social cognition and working memory (Russo et al., 2015), and greater total sleep time variability to predict poorer performance on tasks measuring working memory and verbal learning (Kanady, Soehner, Klein, & Harvey, 2017). Objective studies using actigraphy link sleep disturbances to attention and processing speed (Bradley et al., 2018) and verbal memory (Robillard et al., 2016). Taken together, there are indications that sleep disturbance in severe mental disorders may contribute to cognitive impairments. However, most studies are small in sample size and larger studies are needed.

1.3.3 Factors that may influence sleep and cognition

Some of the factors influencing risk of sleep disturbances, including age, gender, diagnostic group (schizophrenia or bipolar disorder), recent use of alcohol or drugs, a history of alcohol or drug dependency, the use of medication with sedative effects, and BMI, as well as current positive, negative, depressive and manic symptoms, are also of relevance to cognitive functioning.

Associations between sleep disturbances and cognitive impairment could thus be mediated or confounded by these factors.

1.3.4 Unanswered questions regarding sleep and cognition

In general, sleep disturbances have been overlooked as a potential contributor to cognitive

impairment in severe mental disorders. Previous studies suggest an association, but few studies have investigated the subjective experience of the most prevalent sleep disturbances, and there is little consensus across studies as to what cognitive domains are impaired. Thus, knowledge about how

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different types of sleep disturbance are related to cognition is limited, as is the knowledge of whether this relationship is different between schizophrenia, bipolar disorder or healthy controls.

The sample sizes of previous studies have been too small to investigate the influence of potential confounding factors. Therefore, in search of more efficient treatment options, large-scale studies investigating the relationship between sleep disturbance and cognitive functioning across severe mental disorders are required.