Cognitive functioning and mental health in children with a primary mitochondrial disease.

BACKGROUND: Studies regarding cognitive and mental health functioning in children with mitochondrial disease (MD) are scarce, while both are important issues given their impact on QoL. Knowledge on these aspects of functioning and its relationship with disease parameters is essential to gather more insight in working mechanisms and provide recommendations for future research and patientcare. The aim of this study was to map the cognitive functioning and mental health in children with MD in relation to disease specific factors. METHODS: Pediatric patients (< 18 year) with a genetically confirmed MD were included. Demographic and disease specific factors (International Paediatric Mitochondrial Disease Scale) were assessed, as well as cognitive functioning (intelligence, attention, working memory (WM)), and mental health (psychological functioning and quality of life). Individual patient data was described. RESULTS: Thirty-three children with MD were included. Intellectual functioning ranged from a clinically low IQ (36% of the patients, N = 12/33) to an average or above average IQ (39%, N = 13/33). A higher verbal versus performance IQ was observed (36% N = 5/14), a lower processing speed (43%, N = 6/14), attentional problems (50%, N = 7/14), and verbal WM problems (11%, N = 2/18). Regarding mental health, general behavioral problems were reported (45%, N = 10/22), and on subscale level, attention problems (45%, N = 10), withdrawn/depressed (36%, N = 8/22) and anxious/depressed behavior (14%, N = 3/22). Furthermore, QoL impairments were reported (42%, N = 5/12). The specific intelligence profiles, cognitive impairments, behavioral problems and QoL impairments occurred in every intelligence subgroup. Children with an average or above general intellectual functioning had a generally lower and less variability in IPMDS scores, less frequently epilepsy, vision and hearing problems, and a relatively later age of onset, as compared to patients with a clinically low intellectual functioning. CONCLUSIONS: Despite considerable heterogeneity, overall results showed a high rate of impairments in both cognitive and mental health functioning. Also in children with an average or above level of intellectual functioning, specific cognitive impairments were observed. Children with a clinically low intellectual functioning more often had disease related impairments compared to children with a higher intellectual functioning. The importance of structural assessment of cognitive functioning and mental health is warranted, also in children with mild disease related symptoms.

A conceptual disease model for quality of life in mitochondrial disease.

BACKGROUND: Previous studies in patients with a mitochondrial disease (MD) highlight the high prevalence of cognitive impairments, fatigue, depression, and a lower quality of life (QoL). The relationship with biological and physiological factors remains complex. The aim of this study is to investigate the status of and interrelationships between biological and physiological functioning, cognitive functioning as well as fatigue, depression, societal participation, health perceptions, and QoL, by using the Wilson and Cleary conceptual disease model, adapted to MD. METHODS: Patients with a genetically confirmed MD were included. The following health concepts in MD were investigated according to the conceptual model: (1) Biological and physiological: disease manifestation (Newcastle Mitochondrial Disease Adult Scale), (2) Symptom status: cognitive functioning, patient reported fatigue and depressive symptoms, (3) Functional health: societal participation, (4) Patient reported health perceptions, and (5) Overall QoL. Data were compared to healthy normative data and/or data from other patient groups. Correlations as well as a hierarchical regression analysis were performed to assess the relations between the different levels of health concepts in the conceptual model. RESULTS: Of the 95 included patients, 42% had a severe disease manifestation. Comparable or worse than normative data and other patient groups, 35% reported cognitive impairments, 80% severe fatigue, and 27% depressive symptoms. Patients experienced impairments in societal participation and QoL. Disease manifestation was significantly correlated with cognitive functioning, societal participation, physical functioning and overall QoL, but not with fatigue or depressive symptoms. Almost all outcome measures regarding functional health, health perceptions and QoL were correlated with symptom status variables. Overall QoL was significantly predicted by fatigue and physical functioning. CONCLUSIONS: Symptom status is related to the functional health, health perceptions and QoL in patients with MD. Moreover, fatigue and physical functioning are important contributors to the overall QoL of MD patients. In order to provide adequate patient care it is important to have a broad view on patients' functioning, not only by providing a proper clinical assessment, but also to screen for symptom status; cognitive functioning, fatigue and depression.

Cognitive functioning and mental health in mitochondrial disease: A systematic scoping review.

Mitochondrial diseases (MDs) are rare, heterogeneous, hereditary and progressive in nature. In addition to the serious somatic symptoms, patients with MD also experience problems regarding their cognitive functioning and mental health. We provide an overview of all published studies reporting on any aspect of cognitive functioning and/or mental health in patients with MD and their relatives. A total of 58 research articles and 45 case studies were included and critically reviewed. Cognitive impairments in multiple domains were reported. Mental disorders were frequently reported, especially depression and anxiety. Furthermore, most studies showed impairments in self-reported psychological functioning and high prevalence of mental health problems in (matrilineal) relatives. The included studies showed heterogeneity regarding patient samples, measurement instruments and reference groups, making comparisons cautious. Results highlight a high prevalence of cognitive impairments and mental disorders in patients with MD. Recommendations for further research as well as tailored patientcare with standardized follow-up are provided. Key gaps in the literature are identified, of which studies on natural history are of highest importance.

Psychological functioning in children suspected for mitochondrial disease: the need for care.

BACKGROUND: Mitochondrial diseases (MD) are generally serious and progressive, inherited metabolic diseases. There is a high comorbidity of anxiety and depression and limitations in daily functioning. The complexity and duration of the diagnostic process and lack of knowledge about prognosis leads to uncertainty. In this study, we investigated the psychological well-being of children who are suspected for MD and their parents. METHODS: In total 122 children suspected for MD and their parents, received questionnaires as part of standard clinical investigation. RESULTS: Parent proxy report revealed a lower quality of life (QoL) compared to norms and even more physical problems compared to chronically ill patients. They also reported more behavioral problems in general and more internalizing problems compared to the norms. Most frequent reported somatic complaints were tiredness and pain. Parents did not report enhanced levels of stress regarding parenting and experienced sufficient social support. At the end of the diagnostic process, 5.7% of the children received the genetically confirmed diagnosis of MD, 26% showed non-conclusive abnormalities in the muscle biopsy, 54% did not receive any diagnosis, and the remaining received other diagnoses. Strikingly, children without a diagnosis showed equally QoL and behavioral problems as children with a diagnosis, and even more internalizing problems. CONCLUSIONS: This study highlights the psychological concerns of children with a suspicion of MD. It is important to realize that as well as children with a confirmed diagnosis, children without a diagnosis are vulnerable since explanation for their complaints is still lacking.

Depression and anxiety during pregnancy: The influence of maternal characteristics.

BACKGROUND: Depression and anxiety during pregnancy are associated with adverse health outcomes for both mother and child. This study aims to investigate the occurrence of symptoms of depression and anxiety in early and late pregnancy, the longitudinal changes from early to late pregnancy, and factors associated with symptoms of depression and anxiety in pregnant women in the Netherlands. METHODS: We studied 2897 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study. To assess symptoms of depression and anxiety, web-based questionnaires including the Hospital Anxiety and Depression Scale (HADS) and multiple questions on maternal characteristics were completed in early and late pregnancy. Cross-sectional and longitudinal multivariable linear regression analyses were conducted. RESULTS: The depressive symptoms in our population increased, with a prevalence of probable depression from 5.4% in early pregnancy to 10.0% in late pregnancy (P < .001), whereas the anxiety symptoms decreased, with a prevalence of probable anxiety from 17.9% to 14.2% (P < .001). Characteristics associated with depressive or anxiety symptoms included low level of education, multiparity, a history of depression, severe nausea, extreme fatigue, lack of physical exercise, and negative life events. Being non-Dutch, not living with a partner, and having an unplanned pregnancy or a long time to pregnancy were associated with the depressive and/or anxiety symptoms in early pregnancy only. DISCUSSION: Symptoms of depression and anxiety are common in both early and late pregnancy. Screening for risk factors in early pregnancy is important, since prenatal depression and anxiety may be related to adverse maternal and child health outcomes.

Prenatal maternal psychological stress and childhood asthma and wheezing: a meta-analysis.

The aim of this study was to systematically review and meta-analyse observational studies on prenatal maternal psychological stress and the subsequent development of asthma and wheezing in early childhood.All available published literature from 1960 until November 2013 was systematically searched through electronic databases (PubMed, Embase, PsycInfo and Web of Science). All observational studies assessing associations between any form of prenatal maternal psychological stress and respiratory morbidity in the child were included. Data extraction, quality assessment and meta-analyses were performed.The overall meta-analysis included 10 studies and showed that the prevalence of wheezing, asthma and other respiratory symptoms is higher in children of mothers who were exposed to or experienced some form of psychological stress during pregnancy than in mothers who did not (pooled OR 1.56 (95% CI 1.36-1.80)). Comparable results were observed in subgroup analyses of stress exposure, perceived stress, asthma and wheezing.This study demonstrates that prenatal maternal psychological stress is associated with respiratory morbidity, including asthma and wheezing in the child. Future studies examining the early origins of asthma and wheezing need to account for the impact of prenatal maternal stress.