Repetitive spinal motor neuron discharges following single transcranial magnetic stimulation: relation to dexterity

Transcranial magnetic stimulation allows to study the properties of the human corticospinal tract non-invasively. After a single transcranial magnetic stimulus, spinal motor neurons (MNs) sometimes fire not just once, but repetitively. The biological significance of such repetitive MN discharges (repMNDs) is unknown. To study the relation of repMNDs to other measures of cortico-muscular excitability and to physiological measures of the skill for finely tuned precision movements, we used a previously described quadruple stimulation (QuadS) technique (Z'Graggen et al. 2005) to quantify the amount of repMNDs in abductor digiti minimi muscles (ADMs) on both sides of 20 right-handed healthy subjects. Skillfulness for finger precision movements of both hands was assessed using a finger tapping task. In 16 subjects, a follow-up examination was performed after training of either precision movements (n=8) or force (n=8) of the left ADM. The size of the QuadS response (amplitude and area ratios) was greater in the dominant right hand than in the left hand (QuadS amplitude ratio: 47.1±18.1 versus 37.7±22.0%, Wilcoxon test: P<0.05; QuadS area ratio: 49.7±16.2% versus 36.9±23.0%, Wilcoxon test: P<0.05), pointing to a greater amount of repMNDs. Moreover, the QuadS amplitude and area increased significantly after finger precision training, but not after force training. This increase of repMNDs correlated significantly with the increase in performance in the finger tapping task. Our results demonstrate that repMNDs are related to handedness and therefore probably reflect supraspinal excitability differences. The increase of repMNDs after skills training but not after force training supports the hypothesis of a supraspinal origin of repMND

Life events, depression and supportive relationships affect academic achievement in university students

Students often simultaneously deal with shifting support networks, stressful life changes and psychological distress which may affect academic achievement. Methods: 285 students completed the General Health Questionnaire (GHQ-12) to assess depression and the Computerized Life Events Assessment Record (CLEAR), to establish life events and supportive relationships. Module grades were used to measure academic achievement. A general linear model was used with student grade as the dependent variable and life events, depression and supportive relationships as independent variables. Confounding variables included age and sex. Results: A three-way interaction between life events, depression and lack of supportive relationships was found. It indicated the performance of depressed students depended on whether they had supportive relationships and that this interaction also depended on whether they had experienced a life event in the past year. Conclusions: Universities need to provide more support to students with life stress as they transition into university life

Perinatal risk factors and subclinical hypomania: A prospective community study.

BACKGROUND: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population. METHODS: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. RESULTS: Prenatal alcohol exposure (β = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (β = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (β = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (β = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history. LIMITATIONS: Familial confounding could not be fully adjusted for. Rater reports include some biases. CONCLUSIONS: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts

The moderation effect of secure attachment on the relationship between positive events and wellbeing

Positive events can reduce depression as well as enhance wellbeing. The role of secure attachment style in moderating the relationship between positive events and wellbeing is examined to further understand wellbeing models. Participants (n = 490) included two midlife groups and a student group from the UK. They completed the online Computerised Life Event Assessment Record (CLEAR), a measure of life events, the Vulnerable Attachment Style Questionnaire (VASQ) and the Warwick Emotional Wellbeing Scale (WEMWBS). Age was associated with higher rates of wellbeing and secure attachment style. A significant relationship was found between number of positive events and wellbeing, number of people close, and secure attachment score. Hierarchical multiple regression indicated a significant interaction between secure attachment style, number of positive life events and wellbeing. Simple slopes analysis demonstrated the association between positive life events and wellbeing was significant for secure attachment (B = 1.27, p = .003) but not insecure attachment (B = .04, n.s.). This suggests securely attached individuals are better able to take advantage of positive life events than insecurely attached individuals and experience a greater increase in wellbeing

Measuring life events and their association with clinical disorder: a protocol for development of an online approach

Background: Severe life events are acknowledged as important aetiological factors in the development of clinical disorders, including major depression. Interview methods capable of assessing context and meaning of events have demonstrated superior validity compared to checklist questionnaire methods and arguments for interview approaches have resurfaced as choice of assessment tool has been implicated in gene-environment interactions in depression. Such approaches also have greater potential for understanding and treating clinical cases or for use in interventions. Objectives: (i) To argue that life events need sophisticated measurement not satisfactorily captured in checklist approaches. (ii) To review life events measures and key findings related to disorder, exemplifying depression. (iii) To describe an ongoing study with a new online measure, to assess its psychometric properties and the association of life events in relation to disorder and educational outcomes. Methods: The Computerised Life Events Assessment Record (CLEAR) is under development as a tool for online assessment of adult life events. Based on the Life Events and Difficulties Schedule (LEDS) interview, CLEAR seeks to assess life events to self and close others, link these to other events and difficulties and utilise calendar-based timing, to improve upon checklist approaches. The phases of the study are outlined in terms of its samples of midlife cases with depression, unaffected controls and students, testing of the psychometric properties of CLEAR, as well as proposed investigations of its association with disorder and educational outcomes. Conclusions: There is currently no sophisticated technological application of social risk factor assessment, such as life events and difficulties. CLEAR is designed to gather reliable and valid life event data whilst combatting the limitations of interviews (e.g. time consuming and costly) and life event checklists (e.g. inability to accurately measure severity and independence of life events). The advantages of using such innovative methodology for research, clinical practice and interventions are discussed

Early neurophysiological stimulus processing during a performance-monitoring task differentiates women with bipolar disorder from women with ADHD

Adults with attention-deficit/hyperactivity disorder (ADHD) or bipolar disorder (BD) may display similar cognitive impairments and clinical symptoms, which might reflect shared mechanisms. Initial evidence indicates disorder-specific and overlapping neurophysiological alterations using event-related potentials (ERPs) in individuals with BD or ADHD during attentional tasks, but it is unknown whether impairments generalize across other processes and tasks. We conduct the first comparison between women with ADHD (n = 20), women with BD (n = 20) and control women (n = 20) on ERPs from a performance-monitoring flanker task. The BD group showed a significantly attenuated frontal ERP of conflict monitoring (N2) compared to the ADHD group across both low-conflict (congruent) and high-conflict (incongruent) task conditions, and compared to controls in the high-conflict condition. However, when controlling for an earlier attentional ERP (frontal N1), which was significantly reduced in participants with BD compared to participants with ADHD and controls, N2 group differences were no longer significant. These results indicate that ERP differences in conflict monitoring may be attributable to differences in earlier attentional processes. These findings identify neural differences in early attention between BD and ADHD which precede conflict monitoring processes, potentially pointing to distinct neural mechanisms implicated in the two disorders

Characteristics of severe life events, attachment style, and depression – Using a new online approach

Objectives Severe life events are established as provoking agents for depression in combination with vulnerability factors. Identifying features of severe events improves the prediction of disorder but are rarely utilized, mainly because life event research is increasingly dominated by self‐report checklists with no capacity for inferring such characteristics. This paper investigates the association of severe life events’ features with depression and insecure attachment styles using a new online measure of life events in a clinical and control sample. Methods A total of 202 participants (75 clinical and 127 matched control participants), taken from an earlier national Depression Case Control genetic study and followed up after 12 years, completed the Computerised Life Events Assessment Record to assess characteristics of life events, the Vulnerable Attachment Style Questionnaire to measure attachment insecurity, and the General Health Questionnaire to measure depression. Results The clinical group had higher self‐reported depression, severe life events, and insecure attachment style. They also reported more loss, danger, humiliation, and trauma severe events. Intra‐respondent analysis showed individuals experiencing these types of events were more likely to report depression. Insecure attachment style and severe life events were both significantly related to recent depression and history of depressive disorder. Anxious attachment style was significantly related to relationship events and bereavements, as well as severe loss or humiliation events, whereas avoidant style was not. Conclusions Identifying salient features of severe life events improves associations with depression and insecure attachment style. Utilizing a new online approach can aid research and clinical approaches for depression at low cost. Practitioner points Salient features of severe life events (e.g., loss, humiliation) give insight into the potential impact on attachment vulnerability and depression. Clinicians and researchers can use online methods to economically gain detailed life event information needed for clinical formulation and valid data on stressors. The self‐reported scale for recent depression is only a proxy measure of clinical disorder, but the clinical group selection is a more robust criterion for depression history

Childhood maltreatment and the medical morbidity in bipolar disorder: a case-control study.

BACKGROUND: Childhood maltreatment (abuse and neglect) can have long-term deleterious consequences, including increased risk for medical and psychiatric illnesses, such as bipolar disorder in adulthood. Emerging evidence suggests that a history of childhood maltreatment is linked to the comorbidity between medical illnesses and mood disorders. However, existing studies on bipolar disorder have not yet explored the specific influence of child neglect and have not included comparisons with individuals without mood disorders (controls). This study aimed to extend the existing literature by examining the differential influence of child abuse and child neglect on medical morbidity in a sample of bipolar cases and controls. METHODS: The study included 72 participants with bipolar disorder and 354 psychiatrically healthy controls (average age of both groups was 48 years), who completed the Childhood Trauma Questionnaire, and were interviewed regarding various medical disorders. RESULTS: A history of any type of childhood maltreatment was significantly associated with a diagnosis of any medical illness (adjusted OR = 6.28, 95% confidence intervals 1.70-23.12, p = 0.006) and an increased number of medical illnesses (adjusted OR = 3.77, 95% confidence intervals 1.34-10.57, p = 0.012) among adults with bipolar disorder. Exposure to child abuse was more strongly associated with medical disorders than child neglect. No association between childhood maltreatment and medical morbidity was detected among controls. CONCLUSIONS: To summarise, individuals with bipolar disorder who reported experiencing maltreatment during childhood, especially abuse, were at increased risk of suffering from medical illnesses and warrant greater clinical attention.The bipolar case–control genetic association study was funded by an unrestricted grant from GlaxoSmithKline Research and Development. Funding for the depression case–control study was provided by the UK Medical Research Council (MRC; G0701420). The BADGE study was supported by an Interdisciplinary Ph.D. studentship from the UK Economic Social Research Council (ESRC) and MRC to Dr. Hosang. Prof. Uher is supported by the Canada Research Chairs program (http://www.chairs-chaires.gc.ca/him) and Dr. Fisher is supported by an MQ Fellows Award (MQ14F40). The sources of funding had no involvement in the study design, data collection or decision to submit for publication

Web-based measure of life events using computerized life events and assessment record (CLEAR): preliminary cross-sectional study of reliability, validity, and association with depression

Background: Given the criticisms of life event checklists and the costs associated with interviews, life event research requires a sophisticated but easy-to-use measure for research and clinical practice. Therefore, the Computerised Life Events and Assessment Record (CLEAR), based on the Life Events and Difficulties Schedule (LEDS), was developed. Objectives: To test CLEAR’s reliability, validity, and association with depression. Methods: CLEAR, the General Health Questionnaire, and the List of Threatening Experiences Questionnaire (LTE-Q) were completed by 328 participants (126 students; 202 matched midlife sample: 127 unaffected controls, 75 recurrent depression cases). Test-retest reliability over 3-4 weeks was examined, and validity determined by comparing CLEAR with LEDS and LTE-Q. Both CLEAR and LTE-Q were examined in relation to depression. Results: CLEAR demonstrated good test-retest reliability for overall number of life events (.89) and severe life events (.60). Long-term problems showed similar findings. In terms of validity, CLEAR severe life events had moderate sensitivity (59.1%) and specificity (65.4%) when compared to LEDS. CLEAR demonstrated moderate sensitivity (43.1%) and specificity (78.6%) when compared to LTE-Q. CLEAR severe life events and long term problems were significantly associated with depression (OR = 3.50, 95% CI: 2.10-5.85, P < .001; OR = 3.38, 95% CI: 2.02-5.67, P < .001, respectively) whereas LTE-Q events were not (OR=1.06, 95% CI: .43-2.60, P =.90). Conclusions: CLEAR has acceptable reliability and validity and predicts depression. It therefore has great potential for effective use in research and clinical practice identifying stress-related factors for the onset and maintenance of depression and related disorders