Drosophila melanogaster as a Model Organism of Brain Diseases

Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches

Reduced head steadiness in whiplash compared with non-traumatic neck pain

Objective: While sensorimotor alterations have been observed in patients with neck pain, it is uncertain whether such changes distinguish whiplash-associated disorders from chronic neck pain without trauma. The aim of this study was to investigate head steadiness during isometric neck flexion in subjects with chronic whiplash-associated disorders (WAD), those with chronic non-traumatic neck pain and healthy subjects. Associations with fatigue and effects of pain and dizziness were also investigated. Methods: Head steadiness in terms of head motion velocity was compared in subjects with whiplash (n=59), non-traumatic neck pain (n=57) and healthy controls (n=57) during 2 40-s isometric neck flexion tests; a high load test and a low load test. Increased velocity was expected to reflect decreased head steadiness. Results: The whiplash group showed significantly decreased head steadiness in the low load task compared with the other 2 groups. The difference was explained largely by severe levels of neck pain and dizziness. No group differences in head steadiness were found in the high load task. Conclusion: Reduced head steadiness during an isometric holding test was observed in a group of patients with whiplash-associated disorders. Decreased head steadiness was related to severe pain and dizziness

Health care contact following a new incident neck or low back pain episode in the general population; the HUNT study

Low back and neck pain are commonly reported in the general population and represent frequent causes for health care consultations. The main aim of this study was to describe the determinants of health care contact during a 1-year period in a general population with recent onset spinal pain. Methods: From 9056 participants in a general health survey in Norway we identified 219 persons reporting a recent onset (<1 month) of low back or neck pain. Questionnaires were given at 1 (baseline), 2, 3, 6 and 12 months after pain debut. The main outcome was self-reported health care contact due to spinal pain. Associations between health care contact and pain-related factors, other somatic and mental health factors, pain-related work limitations, physical activity and sociodemographic factors were explored. Results: Conventional health care was sought by 93 persons (43 %) at least once throughout the year following the onset of pain. 18 persons (8 %) sought alternative health care only and 108 persons (49 %) sought no kind of health care. Baseline reports of coexisting low back and neck pain of equal intensity, poor self-reported health, symptoms of anxiety or depression, obesity and smoking were all associated with an increased tendency to seek conventional health care. Pain intensity and pain-related work limitations at each occasion were strongly associated with concurrent health care contact throughout the year. Higher education was associated with a reduced tendency to contact health care and no association was found for physical activity. Conclusion: The main finding in this study was that people from the general population who seek health-care for a new incident of neck or low back pain report more symptoms of mental distress, poorer self-reported health and more intense pain with stronger work limitations compared to those who do not. The findings suggest that identification of complementary symptoms is highly relevant in the examination of spinal pain patients, even for those with recent onset of symptoms

The role of stress in absenteeism: Cortisol responsiveness among patients on long-term sick leave.

Objective: This study aimed to (1) See whether increased or decreased variation relate to subjective reports of common somatic and psychological symptoms for a population on long-term sick leave; and (2) See if this pattern in variation is correlated with autonomic activation and psychological appraisal. Methods: Our participants (n = 87) were referred to a 3.5-week return-to-work rehabilitation program, and had been on paid sick leave >8 weeks due to musculoskeletal pain, fatigue and/or common mental disorders. An extensive survey was completed, addressing socio-demographics, somatic and psychological complaints. In addition, a physician and a psychologist examined the participants, determining baseline heart rate, medication use and SCID-I diagnoses. During the 3.5-week program, the participants completed the Trier Social Stress Test for Groups. Participants wore heart rate monitors and filled out Visual Analogue Scales during the TSST-G. Results: Our participants presented a low cortisol variation, with mixed model analyses showing a maximal increase in free saliva cortisol of 26% (95% CI, 0.21–0.32). Simultaneously, the increase in heart rate and Visual Analogue Scales was substantial, indicating autonomic and psychological activation consistent with intense stress from the Trier Social Stress Test for Groups. Conclusions: The current findings are the first description of a blunted cortisol response in a heterogeneous group of patients on long-term sick leave. The results suggest lack of cortisol reactivity as a possible biological link involved in the pathway between stress, sustained activation and long-term sick leave

The effect of insomnia on neuropsychological function in patients with comorbid symptoms of pain, fatigue and mood disorders

Objectives: To examine if elevated symptoms of insomnia affects neuropsychological functioning in patients with concurrent symptoms of pain, fatigue, and mood disorders. Methods and results: A total of seventy-six subjects participated in this (cross-sectional) study. Based on the cut-off score guidelines from The Insomnia Severity Index subjects were assigned to either a clinical insomnia group (N = 35) or a comparison group (N = 41). Factors such as age, general cognitive functioning, and symptoms of pain, fatigue, depression, and anxiety did not differ between the groups. Both groups completed a questionnaire which assessed subjective memory functioning. In addition they completed a set of neuropsychological tests measuring general cognitive functioning, spatial and verbal working memory, and inhibitory control. Although the subjects with clinical insomnia did not report more memory problems than the comparison group, they presented significant deficiencies on the tests assessing spatial and verbal working memory. There was no difference between the groups in inhibitory control. Conclusions: This study shows that as the symptom severity of insomnia increases and become clinically significant, it has substantial effect on both spatial and verbal-numeric working memory functioning. By differentiating and testing different domains of working memory, this study provides a more detailed and nuanced characterization of working memory deficiencies than the previous studies within this field. The results need to be transferred to clinical practice so that neuropsychologists include assessments of sleep as part of their routine screenings

Development and course of chronic pain over 4 years in the general population: The HUNT pain study

Background: Epidemiological studies of chronic pain frequently report high prevalence estimates. However, there is little information about the development and natural course of chronic pain. Methods: We followed a random sample of participants from a population‐based study (HUNT 3) with annual measures over 4 years. Results: Among those without chronic pain at baseline, the probability of developing moderate to severe chronic pain (cumulative incidence) during the first year was 5%, a pain status that was maintained among 38% at the second follow‐up. The probability of developing chronic pain diminished substantially for those who maintained a status of no chronic pain over several years. Subjects with moderate to severe chronic pain at baseline had an 8% probability of recovery into no chronic pain, a status that was maintained for 52% on the second follow‐up. The probability of recovery diminished substantially as a status of chronic pain was prolonged for several years. Pain severity, widespread pain, pain catastrophizing, depression and sleep were significant predictors of future moderate to severe chronic pain, both among subjects with and without chronic pain at baseline. Conclusion: These findings suggest that the prognosis is fairly good after a new onset of chronic pain. When the pain has lasted for several years, the prognosis becomes poor. The same social and psychological factors predict new onset and the prognosis of chronic pain. Significance: The development and recovery of chronic pain is highly dependent on previous pain. The prognosis of chronic pain may be predicted well when considering its duration in combination with other clinical, social and psychological factors. Targeting modifiable prognostic factors may be particularly important for newly developed chronic pain

The effect of insomnia on neuropsychological function in patients with comorbid symptoms of pain, fatigue and mood disorders

Objectives To examine if elevated symptoms of insomnia affects neuropsychological functioning in patients with concurrent symptoms of pain, fatigue, and mood disorders. Methods and results A total of seventy-six subjects participated in this (cross-sectional) study. Based on the cut-off score guidelines from The Insomnia Severity Index subjects were assigned to either a clinical insomnia group (N = 35) or a comparison group (N = 41). Factors such as age, general cognitive functioning, and symptoms of pain, fatigue, depression, and anxiety did not differ between the groups. Both groups completed a questionnaire which assessed subjective memory functioning. In addition they completed a set of neuropsychological tests measuring general cognitive functioning, spatial and verbal working memory, and inhibitory control. Although the subjects with clinical insomnia did not report more memory problems than the comparison group, they presented significant deficiencies on the tests assessing spatial and verbal working memory. There was no difference between the groups in inhibitory control. Conclusions This study shows that as the symptom severity of insomnia increases and become clinically significant, it has substantial effect on both spatial and verbal-numeric working memory functioning. By differentiating and testing different domains of working memory, this study provides a more detailed and nuanced characterization of working memory deficiencies than the previous studies within this field. The results need to be transferred to clinical practice so that neuropsychologists include assessments of sleep as part of their routine screenings