Gender differences in body-sway factors of center of foot pressure in a static upright posture and under the influence of alcohol intake

This study aimed to examine gender differences in 4 body-sway factors of the center of foot pressure (CFP) during a static upright posture and the influence of alcohol intake on them. Four body-sway factors were interpreted in previous studies using factor analysis (the principal factor method and oblique solution by promax-rotation) on 220 healthy young males and females as follows; unit time sway, front-back sway, left-right sway and high frequency band power. The CFP measurement for 1 min was carried out twice with 1 min rest. The measurements of blood pressure, heart rate, whole body reaction time, standing on one leg with eyes closed, and CFP were carried out before and after the alcohol intake using 11 healthy young males and females. The measurement device used was an Anima's stabilometer G5500. The data sampling frequency was 20 Hz. Reliability of 4 body-sway factors was very high. Significant gender differences were found in the left-right sway and the high frequency band power factors, but the influence on body-sway is, as a whole, can be disregarded. These four sway factors can determine the influence of alcohol intake as efficient as 32 sway parameters.     

Examination of the factor structure of center of foot pressure movement and cross-validity

This study aimed to determine the factor structure of the center of foot pressure (CFP) movement during static upright posture, and to objectively categorize and summarize parameters to evaluate CFP movement. The subjects were 220 healthy young males and females. The measurement of CFP was carried out 3 times with 1 min rest and the mean of trials 2 and 3 was used for the analysis. The measurement device was an Anima's stabilometer G5500. The data sampling frequency was 20 Hz. Thirty-four parameters with high reliability were selected from the following 6 domains except for the center position which is a fundamental attribute: distance, distribution of amplitude, area, velocity, power spectrum, and body sway vector. Factor analysis (principal factor method and promax rotation) was applied to a correlation matrix consisting of 32 parameters. Four factors abstracted were interpreted as follows; unit time sway, front and back sway, left and right sway and high frequency band of power spectrum. The reliability coefficient (ICC=0.89-0.95) and the congruence coefficient (phi=0.80-0.97) between factors abstracted from the original and the cross-validity groups were very high. It was considered that the CFP movement consists of the above 4 factors that evaluate the amount of body sway and can be synthetically evaluated by them.     

Effect of Japanese sitting style (seiza) on the center of foot pressure after standing

Seiza is one of the most commonly used sitting postures in various enrichment lessons of Japanese origin. It is reported that Seiza with large knee flexion produces harmful effects on the cartilage of knee joints and hemodynamics of the lower legs. This study aimed at examining the influence of Seiza on tissue oxygenation kinetics of the lower limbs, plantar somatic and cutaneous sensation, and the center of foot pressure (COP) sway using 10 young adults. COP sway was measured for 1 min just after sitting on a chair for 10 min (pre-test), after 30-min Seiza (post-test 1), and 5 min after Seiza (post-test 2). To evaluate the COP sway, we used 4 body sway factors; unit time sway factor (F1), front-back sway factor (F2), left-right sway factor (F3) and high frequency band power spectrum factor (F4). Physiological parameters (i.e., tissue oxygenation kinetics in the lower legs and sensation on the sole) were measured during 30-min Seiza (continuously on tissue oxygenation, and at 1 min intervals on sensation), and for 1 min just before each COP test (pre-test, post-test 1 and 2).Oxygenated hemoglobin/myoglobin (Hb/Mb) concentration decreased markedly and deoxygenated Hb/Mb concentration increased markedly, resulting in reaching a plateau state at around 7 min. Tissue Hb/Mb index changed little during Seiza. Proprioceptive perception thresholds increased rapidly about 17 min after Starting Seiza. Means of 3 COP sway factors of F1, F2 and F4 were significantly higher in post-test 1 than in pre-test and post-test 2. In conclusion, a marked decrease in tissue oxygen concentration of the lower legs within 4-5 min, and an increase of proprioceptive perception thresholds in the sole at about 17 min are induced by Seiza. Although wiggle and quick body sway in the antero-posterior axis increases markedly in an upright posture just after maintaining Seiza for 30 min, sway recovers after sitting on a chair for 5 min.     

Characteristic Features of Disorders of the Upright Posture in Patients with Poststroke Hemipareses

Characteristic features of upright posture maintenance and mechanisms of postural disorders in poststroke hemiparetic patients were studied using a bilateral force platform. The following features of postural disorders were revealed in the patients tested: an increase in the velocity and amplitude of the center-of-pressure (CP) sway as compared to in healthy subjects, an absolute decrease in the half-cycles of the CP sway, asymmetry of weight bearing by both feet, and a shift of the center of pressure of an affected foot towards the toe. The disturbance of stability of the vertical posture in such patients is to a greater extent associated with weight-bearing asymmetry. It was shown that the character of the CP sway is mainly determined by a disorder of the sensory motor control, whereas damage to the efferent pathways is responsible for the postural asymmetry. Increase in the muscle tone restricts the sway amplitude. Thus, several forms of postural instability are characteristic of hemiparetic patients. Predominantly sensory, motor, or tonic disorders are responsible for these disturbances of stability.     

Sinusoidal galvanic stimulation of the labyrinths and postural responses

We studied the effect of sinusoidal stimulation of the labyrinths on postural reflexes in man, using a 0.3 Hz current of alternating polarity and +/- 1 mA intensity for stimulation. The test subjects were tested binaurally by the bipolar method (BB), with two electrodes on the mastoid processes, and binaurally by the monopolar method (BM), with electrodes localized bilaterally on the mastoid process and the hand. Stabilographic postural parameters were measured in 22 subjects in five experimental situations. Each situation lasted 60 s. Body sway, detected by astabilometer, was recorded on a Philips FM tape-recorder and then analysed off-line on a PDP-11/34 computer. On BB stimulation of the labyrinths, the variance of body sway in the left-right (LR) direction increased more than in the anteroposterior (AP) direction. In BM stimulation, only the variance of LR sway increased. Other posturographic parameters displayed a similar effect. From the aspect of body sway frequency, BB stimulation produced a peak in the course of the power spectral density of the lateral stabilogram at 0.3 Hz. In this experimental situation, a habituation effect was manifested, depending on the subject. It can be stated that binaural bipolar (BB) stimulation of the labyrinths selectively influences lateral body sway, while the increase in AP body sway in this situation is merely a concomitant phenomenon.     

Postural control during the Stroop test in dyslexic and non dyslexic teenagers

Postural control in quiet stance although simple still requires some cognitive resources; dual cognitive tasks influence further postural control. The present study examines whether or not dyslexic teenagers experience postural instability when performing a Stroop dual task for which their performances are known to be poor. Fifteen dyslexics and twelve non-dyslexics (14 to 17 years old) were recruited from the same school. They were asked to perform three tasks: (1) fixate a target, (2) perform an interference Stroop test (naming the colour or the word rather than reading the word), (3) performing flexibility Stroop task: the subject performed the interference task as in (2) except when the word was in a box, in which case he had to read the word. Postural performances were measured with a force platform. The results showed a main task effect on the variance of speed of body sway only: such variance was higher in the flexibility task than for the other two tasks. No group effect was found for any of the parameters of posture (surface, mediolateral and anteroposterior sway, variance of speed). Further wavelet analysis in the time-frequency domain revealed an increase in the spectral power of the medium frequency range believed to be related to cerebellum control; an accompanying increase in the cancellation time of the high frequency band related to reflexive loops occurred for non-dyslexics only. These effects occurred for the flexibility task and could be due to its high cognitive difficulty. Dyslexics displayed shorter cancellation time for the medium frequency band for all tasks, suggesting less efficient cerebellar control, perhaps of eye fixation and attention influencing body sway. We conclude that there is no evidence for a primary posture deficit in 15 year old teenagers who come from the general population and who were recruited in schools.     

Age-related changes in force and power associated with balance of women in quiet bilateral stance on a firm surface

Quantitative assessment of the fluctuations of the body centre of mass (CM) while in a stationary bilateral stance on a firm surface is an important criterion of the functional state of human motor-vestibular and sensory apparatus. From analysis of the literature we conclude that more objective characteristics of human balance in quiet standing may be the amount of energy used to maintain the CM in a constant position. Further analysis of the references showed that these characteristics have not been investigated in neurological practice.In this study, the displacement of CM in participants standing in a normal anatomical position was analysed. Forty-five healthy women in three age groups: 18–24, 45–55 and over 60 years participated in the experiments, which consisted of recording changes in partial body weight on the force platform (under one leg) in situations with opened and closed eyes. The specific power of oscillation of body sway and force of lateral swing of CM were calculated. Results indicated that the maximum specific power of oscillation and force of lateral swing were observed in the group of women older than 60 years, especially in the absence of vision. Minimum values occurred in the group of 18–24 years.We also found a considerable variability in all indices in all age groups. This indicates that the stability of the vertical posture in humans depends also on the individual biological characteristics of the central nervous and muscular systems.     

Effect of ageing and vision on limb load asymmetry during quiet stance

Although the identification and characterization of limb load asymmetries during quiet standing has not received much research attention, they may greatly extend our understanding of the upright stance stability control. It seems that the limb load asymmetry factor may serve as a veridical measure of postural stability and thus it can be used for early diagnostic of the age-related decline in balance control. The effects of ageing and of vision on limb load asymmetry (LLA) during quiet stance were studied in 43 healthy subjects (22 elderly, mean age 72.3+/-4.0 yr, and 21 young, mean age 23.9+/-4.8 yr). Postural sway and body weight distribution were recorded while the subject was standing on two adjacent force platforms during two 120 s trials: one trial was performed with the eyes open (EO), while the other trial was with the eyes closed (EC). The results indicate that LLA was greater in the old adults when compared with the young control subjects. The LLA values were correlated with the postural sway magnitudes especially in the anteroposterior direction. Eyes closure which destabilized posture resulted in a significant increase of body weight distribution asymmetry in the elderly but not in the young persons. The limb load difference between EO and EC conditions showed a significantly greater effect of vision on LLA in the elderly compared to the young subjects. The observed differences in the LLA may be attributed to the decline of postural stability control in the elderly. Ageing results in the progressive decline of postural control and usually the nervous system requires more time to complete a balance recovery action. To compensate for such a deficiency, different compensatory strategies are developed. One of them, as evidenced in our study, is preparatory limb unload strategy (a stance asymmetry strategy) which could significantly shorten reaction time in balance recovery.     

Falls in the elderly related to postural imbalance.

Two hundred and forty-three elderly people aged 60 to 96 years were questioned about their falls, and their sway was measured. For comparison sway was also measured in 63 younger subjects. Sway increased with age and was higher in women at all ages. There was no difference in sway between those with no history of falls and those who fell only because of tripping. In both sexes sway was significantly increases in people who fell because of loss of balance and in women whose falls were due to giddiness, drop attacks, turning the head, and rising from bed or a chair. This suggests that there is a physiological decline in postural control with advancing age and also a decline due to disease of the central nervous system.     

The effects of early stages of aging on postural sway: A multiple domain balance assessment using a force platform

Technical advancements in instrumentation and analytical methods have improved the ability of assessing balance control. This study investigated the effects of early stages of aging on postural sway using traditional and contemporary postural indices from different domains. Eleven healthy young adults and fourteen healthy non-faller older adults performed two postural tasks: (a) functional limits of stability and (b) unperturbed bipedal stance for 120 s. Postural indices from spatial, temporal, frequency, and structural domains were extracted from the body’s center of pressure (COP) signals and its Rambling and Trembling components. Results revealed a preservation of functional limits of upright stability in older adults accompanied by larger, faster, and shakier body sway in both anterior-posterior and medio-lateral directions; increased medio-lateral sway frequency; increased irregularity of body sway pattern in time in both directions; and increased area, variability, velocity, and jerkiness of both rambling and trembling components of the COP displacement in the anterior-posterior direction (p < 0.02). Such changes might be interpreted as compensatory adjustments to the age-related decline of sensory, neural, and motor functions. In conclusion, balance assessment using postural indices from different domains extracted from the COP displacement was able to capture subtle effects of the natural process of aging on the mechanisms of postural control. Our findings suggest the use of such indices as potential markers for postural instability and fall risk in older adults.     

Relationship between Spectral Characteristics of Spontaneous Postural Sway and Motion Sickness Susceptibility

Motion sickness (MS) usually occurs for a narrow band of frequencies of the imposed oscillation. It happens that this frequency band is close to that which are spontaneously produced by postural sway during natural stance. This study examined the relationship between reported susceptibility to motion sickness and postural control. The hypothesis is that the level of MS can be inferred from the shape of the Power Spectral Density (PSD) profile of spontaneous sway, as measured by the displacement of the center of mass during stationary, upright stance. In Experiment 1, postural fluctuations while standing quietly were related to MS history for inertial motion. In Experiment 2, postural stability measures registered before the onset of a visual roll movement were related to MS symptoms following the visual stimulation. Study of spectral characteristics in postural control showed differences in the distribution of energy along the power spectrum of the antero-posterior sway signal. Participants with MS history provoked by exposure to inertial motion showed a stronger contribution of the high frequency components of the sway signal. When MS was visually triggered, sick participants showed more postural sway in the low frequency range. The results suggest that subject-specific PSD details may be a predictor of the MS level. Furthermore, the analysis of the sway frequency spectrum provided insight into the intersubject differences in the use of postural control subsystems. The relationship observed between MS susceptibility and spontaneous posture is discussed in terms of postural sensory weighting and in relation to the nature of the provocative stimulus.     

The Influence of Diabetic Peripheral Neuropathy on Local Postural Muscle and Central Sensory Feedback Balance Control

Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m²) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m²) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-control_slope = 1.23±1.06×10^-2 cm²/sec, P<0.01), which suggests a compromised local-control balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-control_slope-Log = 0.39±0.23, P<0.02), which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (r _Pearson = 0.65-085, P<0.05) and the history of diabetes (r _Pearson = 0.58-071, P<0.05). Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation mechanism using sensory feedback depends on the level of neuropathy and the history of diabetes.     

Spherical Lenses and Prisms Lead to Postural Instability in Both Dyslexic and Non Dyslexic Adolescents

There is controversy as to whether dyslexic children present systematic postural deficiency. Clinicians use a combination of ophthalmic prisms and proprioceptive soles to improve postural performances. This study examines the effects of convergent prisms and spherical lenses on posture. Fourteen dyslexics (13–17 years-old) and 11 non dyslexics (13–16 years-old) participated in the study. Quiet stance posturography was performed with the TechnoConcept device while subjects fixated a target at eye-level from a distance of 1_m. Four conditions were run: normal viewing; viewing the target with spherical lenses of −1 diopter (ACCOM1) over each eye; viewing with −3 diopters over each eye (ACCOM3); viewing with a convergent prism of 8 diopters per eye. Relative to normal viewing, the −1 lenses increased the surface of body sway significantly whereas the −3 diopter lenses only resulted in a significant increase of antero-posterior body sway. Thus, adolescents would appear to cope more effectively with stronger conflicts rather than subtle ones. The prism condition resulted in a significant increase in both the surface and the antero-posterior body sway. Importantly, all of these effects were similar for the two groups. Wavelet analysis (time frequency domain) revealed high spectral power of antero-posterior sway for the prism condition in both groups. In the ACCOM3 condition, the spectral power of antero-posterior sway decreased for non dyslexics but increased for dyslexics suggesting that dyslexics encounter more difficulty with accommodation. The cancelling time for medium range frequency (believed to be controlled by the cerebellum), was shorter in dyslexics, suggesting fewer instances of optimal control. We conclude that dyslexics achieve similar postural performances albeit less efficiently. Prisms and lenses destabilize posture for all teenagers. Thus, contrary to adults, adolescents do not seem to use efferent, proprioceptive ocular motor signals to improve their posture, at least not immediately when confronted to convergence accommodation conflict.     

Down training of the elderly soleus H reflex with the use of a spinally induced balance perturbation.

The purpose of this study was to determine the ability of the elderly central nervous system to modulate spinal reflex output to functionally decrease a spinally induced balance perturbation. In this case, the soleus H reflex was used as the source of perturbation. Therefore, decreasing (down training) of the soleus H reflex was necessary to counteract this perturbation and to better maintain postural control. In addition to assessing the effect of this perturbation on the H reflex, static postural stability was measured to evaluate possible functional effects. Ten healthy young subjects (age: 27.0 +/- 4.6 yr) and 10 healthy elderly subjects (age: 71.4 +/- 5.1 yr) participated in this study. Subjects underwent balance perturbation on 2 consecutive days. On day 1 of perturbation, significant down training of the soleus H reflex was demonstrated in both young (-20.4%) and elderly (-18.7%) subjects. On day 2 of perturbation, significant down training of the soleus H reflex was again demonstrated in both young (-24.6%) and elderly (-21.0%) subjects. Analysis of static stability after the 2 days of balance perturbation revealed a significant 10.1% decrease in the area of sway in elderly subjects. In conclusion, this study demonstrated that healthy, elderly subjects compared with young subjects were equally capable of down training the soleus H reflex in response to a balance perturbation. Furthermore, the improvement in static stability through balance training may provide further evidence that balance can be retrained and rehabilitated in subjects with decreased reflex function.     

The Influence of Very Low Illumination on the Postural Sway of Young and Elderly Adults

The purpose of the present study was to evaluate the influence of very low ambient illumination and complete darkness on the postural sway of young and elderly adults. Eighteen healthy young participants aged 23.8±1.5 years and 26 community-dwelling elderly aged 69.8±5.6 years were studied. Each participant performed four tests while standing on a force platform in the following conditions: in normal light (215 lx) with open eyes and with closed eyes, in very low illumination (0.25 lx) with open eyes, and in complete darkness with open eyes. The sequences of the tests in the altered visual conditions were determined by random blocs. Postural sway was assessed by means of the force platform measurements. The centre of pressure variables: the medio-lateral and antero-posterior path lengths, mean velocities, sway areas, and fractal dimensions were analysed. Very low illumination resulted in a statistically significant increase in postural sway in both the young and elderly groups compared to normal light, although the increase was significantly smaller than those observed in the eyes closed and complete darkness condition, and no significant effects of illumination on fractal dimensions were detected. The gains of the sways in the very low or no illumination conditions relative to the normal light condition were significantly larger in the group of young participants than in the group of elderly participants (up to 50% and 25%, respectively). However, the response patterns to changes in illumination were similar in the young and elderly participants, with the exception of the short-range fractal dimension of the medio-lateral sway. In conclusion, very low illumination resulted in increased postural sway compared to normal illumination; however, in the closed eye and complete darkness conditions, postural sway was significantly higher than in the very low illumination condition regardless of the age of the participants.     

Gap junctions provide new links in left-right patterning

Gap junctions are increasingly recognized as key regulators of embryonic development, nervous system function, and neoplasia. Chuang et al. (2007) now show that developing neural circuits use communication through gap junctions to establish left-right asymmetry in the central nervous system of the worm Caenorhabditis elegans, revealing that nematodes share a mechanism for left-right asymmetry in common with vertebrates.     

老年帕金森病患者睡眠障碍的危险因素及其对认知功能、心理状态和衰弱的影响

摘要 目的：探讨老年帕金森病（PD）患者睡眠障碍的危险因素,并观察睡眠障碍对认知功能、心理状态和衰弱的影响。方法：选取2018年3月~2021年9月期间中国人民解放军海军青岛特勤疗养中心收治的91例老年PD患者作为研究对象,根据是否存在睡眠障碍将入选的91例患者分为睡眠障碍组（n=56）及非睡眠障碍组（n=35）。采用蒙特利尔认知评估量表（MoCA）评估所有患者的认知功能状况。采用汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）评价患者焦虑、抑郁情况。采用Tilburg衰弱评估量表评估所有患者的衰弱情况。采用多因素Logistic回归分析探讨老年PD患者睡眠障碍的危险因素,并观察睡眠障碍对认知功能、心理状态和衰弱的影响。结果：睡眠障碍组的视空间与执行功能、语言、命名、延迟回忆、注意、抽象、定向评分及总分均低于非睡眠障碍组（P<0.05）。睡眠障碍组的HAMA、HAMD评分均高于非睡眠障碍组（P<0.05）。睡眠障碍组的心理衰弱、躯体衰弱、社会衰弱评分及总分均高于非睡眠障碍组（P<0.05）。多因素Losgistic回归分析结果显示：HAMA评分偏高、多巴丝肼片等效剂量偏高、HAMD评分偏高、Hcy偏高是老年PD患者睡眠障碍的危险因素（P<0.05）。结论：HAMA评分偏高、Hcy偏高、多巴丝肼片等效剂量偏高、HAMD评分偏高是老年PD患者睡眠障碍的危险因素。同时,睡眠障碍可加重老年PD患者的认知功能障碍和衰弱程度,增加抑郁焦虑情绪。     

Eye movements of goldfish depending on the relationship between acceleration vector and otolith organ.

Prior experiments demonstrated that the acceleration deviating 15 degrees to the right (left) from the longitudinal body axis could not produce vertical eye movement in left (right) eye of the goldfish. From these results, we expected that vertical eye movement of goldfish for the acceleration perpendicular to the longitudinal body axis might different between right and left eye. However, in this experiments, there were no clear difference in magnitude of vertical eye movements for the acceleration shifted 15 degrees around the left-right body axis. On the other hand, the response of right eye was larger than that of left eye for the acceleration applied from left to right of the body. These results suggest that stimulation from medial to lateral and lateral to medial of the otolith organ has different effect on vertical eye movement in each eye of goldfish.     

Sleep disorders in elderly, the sleep apnea syndrome in particular: are they a cause of insomnia? A review of literature

In this publication a review is presented based on the findings resulting from sleep-wake investigations searching for sleep disorders associated with insomnia in relatively healthy elderly. 44 Relevant journal articles published between 1980-1998 were found. The four most important sleep disorders which can be accompanied by sleeplessness in relatively healthy elderly people are periodic leg movements disorder (PLM), restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) and sleep apnea syndrome (SAS). Of these disorders, sleep apnea and periodic leg movements occur most frequently, in a quarter of the elderly. The latter, however, seldom complain about sleeplessness. Within the category of older people disorders characterized by movements during sleep increase significantly with age, nightly respiration disorders do not. SAS, PLM and RBD appear most frequently in men and RLS in women. The disorders characterized by movements during sleep (especially RLS and RBD) are often accompanied by sleeplessness. SAS, however, is more closely associated with day-time sleepiness than with sleeplessness. No combination of demographic variables and symptoms allows a reliable prediction of these sleep disorders. Fortunately, these disorders are not a major threat to the health of older people.     

The role of pharmacogenetics in treating central nervous system disorders

Symptoms of central nervous system (CNS) disorders include abnormalities in both physical and psychological domains. Many drugs indicated for the treatment of CNS disorders are fraught with side effects and/or poor efficacy which impact patients' quality of life and drives non-compliance. Moreover, for many CNS drugs such as antidepressants and antipsychotics, it takes time to determine whether a particular drug is efficacious in an individual patient. To optimize drug treatment for each patient, prescribing physicians often need to raise or lower doses, switch drug classes, or prescribe additional drugs to mitigate side effects, often in a "trial and error" fashion. Pharmacogenetic (PGx) testing, particularly in the realm of CNS therapy, can reduce the unpredictability of this process. By determining a patient's genetic profile, individual therapy parameters may be predicted pre-treatment for drug efficacy, optimal drug dose, and the risk of adverse drug reactions (ADRs). The intent of this review is to highlight the power of PGx testing to predict the likelihood of ADRs and efficacy during the treatment of the following CNS disorders: epilepsy, bipolar disorder, schizophrenia and depression.