Affective symptoms and apathy in myotonic dystrophy type 1 a systematic review and meta-analysis

Highlights

• Myotonic dystrophy type 1 (DM1) is a chronic multisystem hereditary disease.

• DM1 patients may show features of depression (18%), anxiety (16%) and/or apathy (55%).

• Apathy is a characteristic feature but literature is relatively scarse.

• Depression, anxiety may represent reactive adjustments to chronic disease.

• Heterogeity between studies is high; most include a limited number of patients.

Abstract

Background

To gain insight into the prevalence of apathy, depression and anxiety symptoms in myotonic dystrophy type 1 (DM1) patients on the basis of a systematic review with a meta-analysis.

Methods

One author systematically searched and selected studies from Embase, Medline, PsychInfo and Web of Science (index periods up to August 2018). Data extraction and bias assessment were performed independently by two authors. We calculated (1) a weighted pooled prevalence and (2) weighted pooled standardized mean difference (Hedges’ g) from studies comparing DM1 patients to healthy and/or neuromuscular disease controls separately for symptoms of depression, anxiety and apathy.

Results

The pooled prevalences of depression (26 studies, n = 1267 DM1 patients), anxiety (19 studies, n = 896) and apathy (5 studies, n = 428), were 18% (95%CI: 12–25), 16 (95%CI: 13–18) and 55% (95%CI: 50–60), respectively. Effect sizes (Hedges’ g) for depression, anxiety and apathy in DM1 patients compared to healthy controls were 1.04 (95%-CI: 0.71 to 1.37), 0.87 (95%-CI: 0.51 to 1.24) and 1.13 (95%-CI:0.54–1.71). Effect sizes for symptoms of depression, anxiety and apathy were 0.29 (95% CI: -0.12 to 0.70), 0.45 (95%-CI: –0.31 to 1.22) and 1.12 (95%-CI: 0.32–1.93) for DM1 patients versus neuromuscular disease controls. In most analyses, statistical heterogeneity was high.

Conclusions

Estimated pooled prevalences of clinically significant levels of symptoms of depression, anxiety and apathy in DM1 are 19, 17 and 55% respectively. Symptoms of depression and anxiety in DM1 may reflect reactive adjustment to progressive impairment and restricted participation similar to other chronic neuromuscular disease. The literature on the prevalence and severity of apathy, although a clinically relevant and characteristic symptom of DM1, is relatively scarce.

Introduction

Myotonic dystrophy type 1 (DM1) is a hereditary multisystem disorder caused by a CTG repeat expansion in the dystrophia myotonica protein kinase (DMPK) gene on chromosome 19q13.3 (Brook et al., 1992, Fu et al., 1992). In addition to neuromuscular involvement, DM1 is characterized by heterogeneous involvement of the brain. DM1 patients may have cognitive deficits, behavioural and personality disorders, excessive daytime sleepiness, and affective disorders (anxiety, depression) (Meola and Sansone, 2007, Minier et al., 2018).

In the current study, we focused on affective symptoms (i.e. anxiety, depression) and apathy and aimed to systematically assess their prevalence. Previously, we encountered a significant amount of data on affective disorders during the conduct of two systematic reviews on brain involvement in DM1 (Okkersen et al., 2017a, 2017b). In addition, a previous study in our centre demonstrated affective disorders to be the most frequently occurring psychiatric disorders in DM1 (Kalkman et al., 2007). However, the exact prevalence of affective disorders in DM1 remains unknown. These affective disorders could be a core feature of DM1-related brain involvement. Alternatively, they could be a result of living with a progressively debilitating disease, as in other chronic diseases (Kalkman et al., 2007). Consequently, studies that compared the occurrence of affective disorders in DM1 with other neuromuscular disorders, were of interest to the current study.

Besides affective disorders, we focused on apathy, a widely recognised symptom of CNS involvement in DM1 (Gallais et al., 2015). We decided to focus on apathy as this is a very characteristic feature in clinical practice that may increase the care burden for informal caregivers (Cup et al., 2011). We expected apathy to be a well studied construct for which results from various studies would be easily aggregated. Apathy as a primary syndrome is defined as a lack of motivation that is not attributable to a decreased level of consciousness, emotional distress or cognitive impairment (Marin, 1991). Clinically, apathy is characterised by the simultaneous presence of behavioural (lack of initiative), cognitive (lack of ideas) and emotional (lack of normal emotional modulation) features. If apathy can be attributed to decreased level of consciousness, emotional distress or cognitive impairment, it may be referred to as a symptom (Marin, 1991). Therefore, in the study of affective disorders, apathy is of interest, as the symptomatology of apathy may overlap with that of depression and both depressive symptoms and apathy could potentially co-exist in DM1 patients. Their interrelation could be dynamic (variable in time), in that increasing apathy may lead to decrease in affective disorders due to affective flattening.

The exact prevalence of affective disorders and apathy in DM1 is unknown, although a recent more broadly scoped systematic narrative review thoroughly summarized the literature (Minier et al., 2018). In this systematic review with meta-analysis, we aimed to aggregate studies to provide point estimates of symptoms of depression, anxiety and apathy and to compare scores on clinical scales in DM1 patients with scores from healthy and neuromuscular controls. A systematic evaluation amalgamates the evidence provided by multiple, often smaller studies and potentially identifies gaps in clinical knowledge. The comparison of prevalence of affective disorders and apathy with other neuromuscular diseases may provide an answer to the question whether these disorders are specific to DM1 and from a therapeutic point of view, the prevalence is relevant to know. Although we recognize many other neuropsychiatric disturbances may occur in DM1 patients (Gourdon and Meola, 2017), we pragmatically opted for affective orders based on previous experience with the literature and for reasons of feasibility, as data on other neuropsychiatric features may be less easily aggregated.