Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966

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Predictors of long-term change in adult cognitive performance: systematic review and data from the Northern Finland Birth Cohort 1966

Objective: Several social life events and challenges have an impact on cognitive development. Our goal was to analyze the predictors of change in cognitive performance in early midlife in a general population sample. Additionally, systematic literature review was performed. Method: The study sample was drawn from the Northern Finland Birth Cohort 1966 at the ages of 34 and 43 years. Primary school performance, sociodemographic factors and body mass index (BMI) were used to predict change in cognitive performance measured by the California Verbal Learning Test, Visual Object Learning Test, and Abstraction Inhibition and Working Memory task. Analyses were weighted by gender and education, and p-values were corrected for multiple comparisons using Benjamini–Hochberg procedure (B–H). Results: Male gender predicted decrease in episodic memory. Poor school marks of practical subjects, having no children, and increase in BMI were associated with decrease in episodic memory, though non-significantly after B–H. Better school marks, and higher occupational class were associated with preserved performance in visual object learning. Higher vocational education predicted preserved performance in visual object learning test, though non-significantly after B-H. Likewise, having children predicted decreased performance in executive functioning but non-significantly after B-H. Conclusions: Adolescent cognitive ability, change in BMI and several sociodemographic factors appear to predict cognitive changes in early midlife. The key advantage of present study is the exploration of possible predictors of change in cognitive performance among general population in the early midlife, a developmental period that has been earlier overlooked

Response to antipsychotic drugs in treatment-resistant schizophrenia : Conclusions based on systematic review

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Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.This study was supported by grants from the Brain and Behavior Research Foundation, Northern Finland Health Care Support Foundation, Sigrid Jusélius Foundation, and the Signe and Ane Gyllenberg Foundation, Finland. NFBC 1966 received financial support from the Academy of Finland (104781, 120315, 129269, 1114194, 24300796, 268336, 278286), Center of Excellence in Complex Disease Genetics and SALVE, Oulu University Hospital, Oulu, Finland, Biocenter of Oulu, Finland, University of Oulu, Finland (75617, 24002054, 2400692), Ministry of Social Affairs and Health (50459, 50691, 50842, 2749, 2465), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-(201413), EU FP7 EurHEALTHAgeing (277849), EU FP7 EurHealth Epi-Migrant (279143), European Regional Development Fund 537/2010 (24300936) and the Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.eurpsy.2015.04.00

Mobile Phone and Wearable Sensor-Based mHealth Approach for Psychiatric Disorders and Symptoms : Systematic Review and Link to the m-RESIST Project

Background: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST) is an EU Horizon 2020-funded project aimed at designing and validating an innovative therapeutic program for treatment-resistant schizophrenia. The program exploits information from mobile phones and wearable sensors for behavioral tracking to support intervention administration. Objective: To systematically review original studies on sensor-based mHealth apps aimed at uncovering associations between sensor data and symptoms of psychiatric disorders in order to support the m-RESIST approach to assess effectiveness of behavioral monitoring in therapy. Methods: A systematic review of the English-language literature, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed through Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases. Studies published between September 1, 2009, and September 30, 2018, were selected. Boolean search operators with an iterative combination of search terms were applied. Results: Studies reporting quantitative information on data collected from mobile use and/or wearable sensors, and where that information was associated with clinical outcomes, were included. A total of 35 studies were identified; most of them investigated bipolar disorders, depression, depression symptoms, stress, and symptoms of stress, while only a few studies addressed persons with schizophrenia. The data from sensors were associated with symptoms of schizophrenia, bipolar disorders, and depression. Conclusions: Although the data from sensors demonstrated an association with the symptoms of schizophrenia, bipolar disorders, and depression, their usability in clinical settings to support therapeutic intervention is not yet fully assessed and needs to be scrutinized more thoroughly.Peer reviewe

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases

Background: Variants in POLG are one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. / Methods: A multinational, retrospective study using data from 155 patients with POLG variants recruited from seven European countries. / Results: We describe the spectrum of clinical features associated with POLG variants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset—onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. / Conclusion: Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course

Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.Peer reviewe

The impact of gender, puberty, and pregnancy in patients with POLG disease

OBJECTIVE: To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. METHODS: Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. RESULTS: We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. INTERPRETATION: Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor

Phenotype-genotype correlations in Leigh syndrome : new insights from a multicentre study of 96 patients

Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. Objective We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. Methods We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. Results We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m. 8993T> G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m. 8993T> C mutation. Conclusion Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.Peer reviewe

Diagnostic value of serum biomarkers FGF21 and GDF15 compared to muscle sample in mitochondrial disease

The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme-labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy takenPeer reviewe