The role of life events in depression in primary medical care versus psychiatric settings

BACKGROUND: The relationship between negative life events and depression is inconsistent. The purpose of the current study is to investigate the hypothesis that depression in the community may be related more to major life events than is depression in psychiatric settings. METHODS: This hypothesis was tested using depressed primary medical care (PC; n=70) and psychiatric patients (n=62). Nondistressed (n=109) and distressed/nondepressed PC patients (n=43) served as comparison-control groups. Life events were rated using the contextual method of Brown and Harris (Brown, G.W., Harris, T.O., 1978. Social origins of depression. Tavistock, London). RESULTS: Depressed PC patients, but not depressed psychiatric patients, were significantly more likely to have recent severe events than the comparison-control groups. Self-reported distress in the absence of depression was not associated with severe life events. LIMITATIONS: History of depression was assessed using a simple count of number of previous episodes, and the assessment of depression history may require more sophisticated assessment. The measure of endogenous depression used in this study was created post-hoc and needs replication. CONCLUSIONS: Diathesis-stress models need to accommodate a lack of universality for severe stress prior to the onset of depression. Clinical strategies may need to reflect patient treatment preferences associated with differences across settings with respect to the perceived role of stress in their depression.     

Do life events have their effect on psychosis by influencing the emotional reactivity to daily life stress?

BACKGROUND: Life events (LE) have consistently been found to influence course and outcome of psychotic disorders. However, the mechanism through which they operate is not known. The present study investigated whether LE have their effect by impacting on the emotional sensitivity for daily hassles. METHOD: Patients with clinically remitted psychotic illness (N=42) were studied with the Experience Sampling Method (a structured diary technique assessing current context and mood in daily life) to assess: (1) appraised subjective stress related to daily events and activities; and (2) emotional reactivity conceptualized as changes in both negative affect (NA) and positive affect (PA). LE were assessed with the Brown & Harris Life Event and Difficulties Schedule. RESULTS: Multilevel regression analyses showed that previous exposure to LE influenced the appraised stressfulness of neither daily events nor the activities in which the subjects were involved. However, a history of LE did modify the emotional reaction to daily life stress, both in models predicting NA and in models predicting PA. CONCLUSIONS: By their cumulative effect on emotional reactivity to daily activities and events, LE may render individuals more vulnerable to the onset or persistence of psychotic experiences.     

Provoking agents, vulnerability factors and depression in an Italian setting: a replication of Brown and Harris's model.

The aetiological model of depression proposed by Brown and Harris in 1978 was examined in a sample of 120 women in Milan, using the same method for the assessment of life stresses. The role of provoking agents (severe events and major difficulties) was found to be similar to that of the earlier study. There was some evidence that lack of an intimate relationship with a husband or a boyfriend acted as a vulnerability factor, increasing the risk of depression in the face of provoking agents. The overall results support the Brown-Harris aetiological model in a quite different cultural setting.     

The List of Threatening Experiences: a subset of 12 life event categories with considerable long-term contextual threat

In a survey of a random sample of the general population recent life events, collected and rated for long-term contextual threat according to the methods of Brown & Harris (1978), were also recorded where possible on an inventory of life event categories (Tennant & Andrews, 1977). Of the 82.5% of all events collected which were covered by the inventory, 12 of the 67 event categories accounted for 77% of life events with an aetiologicaly significant rating of marked or moderate long-term threat. Where practical and economic constraints oblige research workers to choose the inventory method, a brief list of event categories, such as the List of Threatening Experiences, is recommended in preference to much longer lists.     

Humiliation, loss and other types of life events and difficulties: a comparison of depressed subjects, healthy controls and their siblings

BACKGROUND: It has been proposed that adverse life events involving loss or humiliation are particularly potent in provoking depressive episodes. We have also previously suggested that experiencing high rates of non-severe events may play a role in the development of resilience to the impact of severe threatening events when these occur. METHOD: The Life Events and Difficulties Schedule (LEDS) (Brown & Harris, 1978) was used to record the life events experienced by 108 depressed probands and their nearest aged siblings as well as 105 healthy control subjects and their nearest aged siblings. All subjects were interviewed using the Schedule for the Clinical Assessment of Neuropsychiatry (SCAN) (Wing et al. 1990). RESULTS: Depressed probands were significantly more likely to have experienced a severe threatening event, loss event, or a humiliation event compared to the other subjects. These events also made up a greater proportion of the total number of events, in the depressed probands. Humiliation events were more frequent in depressed men than depressed women. There were no differences between the four groups for experiencing a non-severe event, although depressed probands also experienced more difficulties than the other three groups. Fifty-six healthy subjects who had not become depressed despite having experienced at least one severe and threatening event, had significantly more non-severe events, than the 116 subjects who were depressed at the time of interview. CONCLUSIONS: The findings support the hypothesis that loss and humiliation events are particularly depressogenic. Experiencing a high rate of non-severe events may be associated with resilience to becoming depressed in the face of a threatening event.     

Child-specific and family-wide risk factors using the retrospective Childhood Experience of Care & Abuse (CECA) instrument: a life-course study of adult chronic depression - 3

BACKGROUND: An earlier paper [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022] documented an association between parental maltreatment and risk of adult chronic depression. This paper explores the contribution of other child-specific factors (e.g. conduct problems) and family-wide factors (e.g. parental discord). METHODS: Data are derived from an enquiry of 198 women largely comprising of adult sister pairs. Data was collected by semi-structured interviews covering a wide range of parental behaviour and childhood behaviour. RESULTS: Parental maltreatment emerged as channelling the effect of family-wide factors on risk of adult chronic depression, but with a child's conduct problems and shame-withdrawal partly mediating this link. A child's depression before 17, although correlated with parental maltreatment, did not appear to play a significant role in adult depression. This core model is supplemented by analyses exploring the mechanisms involved. A mother's rejection/physical abuse and her depression via her lax control, for example, account for the link of parental maltreatment with conduct problems. Also 'rebelliousness' of a child relates to the chances of her low affection moving to rejection. "Rebelliousness" also appears to play a role in why the paired sisters so often had a different experience of maltreatment. LIMITATIONS: The data is collected retrospectively - but see [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b-this issue. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument - A life-course study of adult chronic depression - 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. CONCLUSIONS: Child-specific factors play a major role in the origins of adult chronic depressive episodes. This, however, is fully consistent with an equally significant contribution from family-wide factors. The crucial point is that the link of the latter with such depression appears to be indirect and mediated very largely by parental maltreatment.     

Inferring vagal effects on the heart from changes in cardiac cycle length: implications for cycle time-dependency

Since the now classical experiments by Brown and Eccles in 1934, the effect of a stimulation of the vagus nerve on the heart has been derived from changes in the length of cardiac periods. Based on a simple model for the genesis of heartbeats, it is shown that the procedure employed by Brown and Eccles gives a distorted picture of the actual vagal effect. A corrected procedure for inferring the vagal effect from changes in heart period length is proposed. This new procedure is applied to empirical data from animal experiments with direct stimulation of the vagus nerve. It is shown that, if the vagal effect depends on time of stimulation within the cardiac cycle (cycle time-dependency), single vagal effect curves for each time of stimulation within the cycle have to be constructed. Other data reduction procedures are reviewed with respect to their appropriateness for demonstrating cycle time-dependency.     

A metacognitive model of problem drinking

Previous research has demonstrated significant relationships between metacognition and problem drinking. In this study, we aimed to investigate further these relationships by testing the fit of a metacognitive model of problem drinking in a sample of 174 problem drinkers from a university student population. In the model presented, it is proposed that positive metacognitive beliefs about alcohol use and negative affect lead to alcohol use as a means of affect regulation. Positive metacognitive beliefs about alcohol use are also associated with a reduction in metacognitive monitoring which further contributes to alcohol use. Once alcohol use is initiated it brings a disruption in metacognitive monitoring leading to a continuation in drinking. Following a drinking episode, alcohol use is appraised as both uncontrollable and dangerous, which in turn strengthens negative metacognitive beliefs about alcohol use. These beliefs are associated with an escalation of negative affect, which acts as a trigger for further drinking. The specified relationships among these variables were examined by testing the fit of a path model. Results of this analysis indicated a good model fit consistent with predictions. The conceptual and clinical implications of these data are discussed. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message: ? A cognitive‐attentional model that may aid assessment, conceptualization and treatment for moderate or at risk problem drinkers.     

Toward a common language for biobanking

To encourage the process of harmonization, the biobank community should support and use a common terminology. Relevant terms may be found in general thesauri for medicine, legal instruments or specific glossaries for biobanking. A comparison of the use of these sources has so far not been conducted and would be a useful instrument to further promote harmonization and data sharing. Thus, the purpose of the present study was to investigate the preference of definitions important for sharing biological samples and data. Definitions for 10 terms –[human] biobank, sample/specimen, sample collection, study, aliquot, coded, identifying information, anonymised, personal data and informed consent–were collected from several sources. A web-based questionnaire was sent to 560 European individuals working with biobanks asking to select their preferred definition for the terms. A total of 123 people participated in the survey, giving a response rate of 23%. The result was evaluated from four aspects: scope of definitions, potential regional differences, differences in semantics and definitions in the context of ontologies, guided by comments from responders. Indicative from the survey is the risk of focusing only on the research aspect of biobanking in definitions. Hence, it is recommended that important terms should be formulated in such a way that all areas of biobanking are covered to improve the bridges between research and clinical application. Since several of the terms investigated here within can also be found in a legal context, which may differ between countries, establishing what is a proper definition on how it adheres to law is also crucial.     

Infectious disease mortality in two Outer Hebridean islands: 1. measles,pertussis and influenza

OBJECTIVES: The purpose of the study was to examine changes in mortality from measles, pertussis (whooping cough) and influenza (all epidemic diseases) in Harris and Barra, two Outer Hebridean islands, from 1855 to 1990, and to compare the findings with those from Scotland as a whole over the same period. It was also intended to relate changes in mortality to those in social and economic factors. MATERIALS AND METHODS: Ages and causes of death in Harris and Barra were ascertained from copies of death certificates held at the General Register Office, Edinburgh, and for Scotland as a whole from the Annual Reports of the Registrars General for Scotland. Data were standardized by calculating the Proportionate Mortality Ratio (PMR), the proportion of deaths due to a particular cause to all deaths over a given period. Spectral analysis was employed to examine the durations of epidemic cycles. RESULTS: Ages at death increased slightly over the period of the study. For measles and pertussis, other than for the former in Harris, there were significant relationships between numbers of deaths per decade, and numbers of new susceptibles, estimated as the numbers of births. Epidemics of measles and pertussis in the islands occurred at intervals, usually separated by years of no mortality. The highest PMRs were generally during the later decades of the 19th and first decade of the 20th centuries; this may have been related to the economic problems of agriculture and fishing, and to increasing population density. Influenza epidemics were more frequent than those of the other two diseases. For all three diseases in both islands, there were significant negative power relationships between epidemic size and frequency of occurrence; those in Harris were the stronger. The relationships between length and frequency were significant only in Harris. Generally, epidemic lengths seemed less variable than sizes, possibly because of the rather 'coarse' units of length (quarters) employed. Spectral analysis of the 'detrended' data for the period before the introduction of specific immunoprophylaxis revealed that for measles the main epidemic cycle in all three populations was between 7.3 and 7.8 years' duration. Barra and Scotland had additional 2.5- and 2-year cycles, respectively. For pertussis, Harris and Barra had main cycles of 7.4 years. Harris had an additional cycle of 3.2 years. Scotland had cycles of 4 and 2 years. For influenza, Harris had a main cycle length of 7.4 years, and a less-defined one of about 2.6 years. Barra had a main cycle of 6.9 years, and a subsidiary one of 2 years. Scotland has a single cycle of 8 years. Cubic regressions of the spectral densities on cycle frequencies showed large coefficients for Harris and Barra, but small ones for Scotland. Measles coefficients were closely similar in the two islands, but not those for pertussis. CONCLUSIONS: The findings demonstrate the episodic occurrence of epidemics of these three diseases in the two islands, as against their continual presence in the much larger population of Scotland. They reveal also the decreasing importance of these causes of death in all three populations. The data from Harris and Barra suggest that measles is a more epidemiologically 'stable' disease than pertussis. Both islands appear to obey Hamer's law of 'mass action'. The relatively long intervals between epidemics in the islands may be due partly to their isolation, and partly to the slow accumulation of sufficient numbers of susceptibles to enable an epidemic to occur.     

Do-it-yourself Healthcare: The current landscape,prospects and consequences

The wider availability and increasing use of mHealth tools – covering health applications, smartphone plug-ins and gadgets is significant for healthcare. This trend epitomises broader trajectories in access to and delivery of healthcare, with greater consumer involvement and decentralisation. This shift may be conceptualised as ‘do-it-yourself Healthcare’ – allowing consumers to monitor and manage their health, and guide their healthcare consumption. Technology that enables data collection by patients informs them about vital health metrics, giving them more control over experiences of health or illness. The information can be used alone as empowered consumers or together with healthcare professionals in an environment of patient-centred care. Current evidence suggests a large scope for do-it-yourself Healthcare, given the availability of technologies, whilst mHealth tools enhance diagnostics, improve treatment, increase access to services and lower costs. There are, however, limitations to do-it-yourself Healthcare. Notably, its evidence base is less well developed than the availability of technologies to facilitate it. A more complex model and understanding is needed to explain motivations for and consequences of engaging in do-it-yourself Healthcare. That said, its introduction alongside existing medicine may improve quality and reduce costs – potentially improving health system sustainability whilst future generations – tomorrow's middle-aged and the elderly, will become more conducive to its spread.     

Cultivating mindfulness: effects on well-being

There has been great interest in determining if mindfulness can be cultivated and if this cultivation leads to well-being. The current study offers preliminary evidence that at least one aspect of mindfulness, measured by the Mindful Attention and Awareness Scale (MAAS; K. W. Brown & R. M. Ryan, 2003), can be cultivated and does mediate positive outcomes. Further, adherence to the practices taught during the meditation-based interventions predicted positive outcomes. College undergraduates were randomly allocated between training in two distinct meditation-based interventions, Mindfulness Based Stress Reduction (MBSR; J. Kabat-Zinn, 1990; n=15) and E. Easwaran's (1978/1991) Eight Point Program (EPP; n=14), or a waitlist control (n=15). Pretest, posttest, and 8-week follow-up data were gathered on self-report outcome measures. Compared to controls, participants in both treatment groups (n=29) demonstrated increases in mindfulness at 8-week follow-up. Further, increases in mindfulness mediated reductions in perceived stress and rumination. These results suggest that distinct meditation-based practices can increase mindfulness as measured by the MAAS, which may partly mediate benefits. Implications and future directions are discussed.     

Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument -- A life-course study of adult chronic depression - 2

BACKGROUND: A previous paper, using data collected retrospectively from sister pairs, reported substantial associations of adult depressive episodes lasting at least 12 months with childhood maltreatment [Brown, G.W., Craig, T.K.J., Harris, T.O. Handley, R.V. & Harvey, A.L. 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022]. Risk was far less when depressive episodes of any duration were considered. This paper considers how much scientific weight can be placed on these findings in the light of doubt often expressed about retrospective collection of childhood and adult data. METHODS: The retrospectively gathered material was obtained from adult sister pairs within 5 years of age, comprising a high-risk series (n = 118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series (n = 80) where she was selected at random. Current age ranged between early 20s and 50s. Data was collected by semi-structured interviews, using investigator-based ratings covering a wide range of parental behaviour and childhood behaviour. RESULTS: A series of analyses failed to reveal evidence of significant bias in the collection of material about adult depression or parental maltreatment. There was, however, some evidence of under reporting. LIMITATIONS: Conclusions from such analyses can only be judged in terms of degree of plausibility. CONCLUSIONS: Nothing emerged to suggest the presence of significant bias in the aetiological findings of our earlier paper. There is evidence of some underreporting of both early adverse experience and adult depressive episodes, but this is unlikely to threaten the conclusions drawn about the link of parental maltreatment with adult chronic depressive episodes.     

Unknown Mechanisms Regulating the GPCR Signal Cascade in Vertebrate Photoreceptors

The process of phototransduction – the conversion of a light signal into an electrical response occurring in vertebrate photoreceptors – is the best studied and characterized example of a GPCR signal cascade. The literature contains the view that the basic mechanisms of phototransduction are already known and that data obtained from photoreceptors can be applied to other GPCR signaling systems. In this review, we compare the contemporary model of phototransduction with data from studies of other GPCR signal cascades with the aim of identifying similarities and differences between them. Working mainly from physiological and biophysical data, we show that the current scheme of phototransduction lacks important regulatory mechanisms, whose biochemical substrates remain unknown. This provides, for example, rapid control of the lifetime of the active state of G-protein (transducin) during light adaptation. There are also slow (several minutes) processes modifying components of the signal cascade which regulate the rate of deactivation of activated receptor (rhodopsin) and transducin. By analogy with other GPCR signal cascades, the existence of several other signaling pathways from light-activated rhodopsin can be suggested; these may use different second messengers (not only cGMP but also, for example, cAMP). We also show that rhodopsin oligomerization may occur in photoreceptors and that this process may provide physiological control of amplification in the signal cascade. The missing mechanisms are by no means unimportant and may support regulation of photoreceptor sensitivity over a range from one to two orders of magnitude.     

Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement.

Hydroxyapatite (HA) calcium phosphate cements (CPCs) are attractive materials for orthopedic applications because they can be molded into shape during implantation. However their low strength and brittle nature limits their potential applications to principally non-load-bearing applications. Little if any use has been made of the HA cement systems as manufacturing routes for preset HA bone grafts, which although not moldable pastes, are resorbable, unlike HA sintered ceramic. It is known that the strength of cements can be increased beyond that attainable from slurry systems by compaction, and this study investigates whether compaction significantly alters the specific surface area and pore-size distribution of CPC prepared according to the method of Brown and Chow. Compaction pressures of between 18 and 106 MPa were used to decrease the porosity from 50 to 31%, which resulted in an increase in the wet compressive strength from 4 to 37 MPa. The Weibull modulus was found to increase as porosity decreased; in addition the amount of porosity larger than the reactant particle size increased as porosity decreased. It is proposed that this was caused by a combination of voids created by the aqueous solvent used in fabrication and shrinkage that occurs on reaction. The specific surface area was unchanged by compaction.     

Characterization of the Immunogenicity and Allergenicity of Two Cow's Milk Hydrolysates – A Study in Brown Norway Rats

Hypoallergenic infant formulas based on hydrolysed milk proteins are used in the diet for cow's milk allergic infants. For a preclinical evaluation of the immunogenicity and allergenicity of new protein ingredients for such hypoallergenic infant formulas as well as for the investigation of which characteristics of hydrolysates that contribute to allergenicity, in vivo models are valuable tools. In this study, we examine the immunogenicity and allergenicity of two hydrolysates in a Brown Norway (BN) rat model, using i.p. dosing, which allows for the use of small quantities. Intact BLG, hydrolysed BLG and a hydrolysed whey product suitable for use in extensively hydrolysed formulas were thoroughly characterized for protein chemical features and administered to BN rats by i.p. immunization with or without adjuvant. Sera were analysed for specific IgG and IgE for evaluation of sensitizing capacity, immunogenicity and antibody‐binding capacity. For evaluation of eliciting capacity a skin test was performed. The study showed that the hydrolysates had no residual allergenicity, lacking the capacity to sensitize and elicit reactions in the BN rats. Dosing with or without adjuvant induced a large difference in immunogenicity. Only antibodies from rats sensitized to intact BLG with adjuvant were able to bind the hydrolysates, and the whey‐based hydrolysate only showed immunogenicity when dosed with adjuvant. This study showed that hydrolysates can be evaluated by an i.p. animal model, but that the choice of in vitro tests used for evaluation of antibody responses may greatly influence the result as well as may the use of adjuvant.     

TAKE THIS JOB AND LOVE IT: A MODEL OF SUPPORT,JOB SATISFACTION,AND AFFECTIVE COMMITMENT AMONG MANAGERS OF VOLUNTEERS

Several job‐related and organizational features make the work of community‐based paid managers of volunteers distinctly different from conventional management practice. Based on self‐verification (Swann & Brown, 1990) and exchange (Blau, 1964) theories, we tested a multidimensional measurement model of support specific to these managers. The dimensions include support gained from their coworkers, volunteers, and supervisors, and from the prosocial, value‐expressive nature of the work. This model of support predicted the managers’ job satisfaction, which mediated the relationship between support and affective commitment, with value‐expressive work being the strongest predictor. Both the measurement model of support and the structural predictive model were found to be invariant across managers with greater and less than 10 years of work experience. The findings spotlight the importance of sources of workplace support that shore up employees’ valued identities.     

Some methods for blindfolded record linkage

Background  

The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors.     

Characterization of indentation response and stiffness reduction of bone using a continuum damage model

Indentation tests can be used to characterize the mechanical properties of bone at small load/length scales offering the possibility of utilizing very small test specimens, which can be excised using minimally-invasive procedures. In addition, the need for mechanical property data from bone may be a requirement for fundamental multi-scale experiments, changes in nano- and micro-mechanical properties (e.g., as affected by changes in bone mineral density) due to drug therapies, and/or the development of computational models. Load vs. indentation depth data, however, is more complex than those obtained from typical macro-scale experiments, primarily due to the mixed state of stress, and thus interpretation of the data and extraction of mechanical properties is more challenging. Previous studies have shown that cortical bone exhibits a visco-elastic response combined with permanent deformation during indentation tests, and that the load vs. indentation depth response can be simulated using a visco-elastic/plastic material model. The model successfully captures the loading and creep displacement behavior, however, it does not adequately reproduce the unloading response near the end of the unloading cycle, where a pronounced decrease in contact stiffness is observed. It is proposed that the stiffness reduction observed in bone results from an increase in damage; therefore, a plastic-damage model was investigated and shown capable of simulating a typical bone indentation response through an axisymmetric finite element simulation. The plastic-damage model was able to reproduce the full indentation response, especially the reduced stiffness behavior exhibited during the latter stages of unloading. The results suggest that the plastic-damage model is suitable for describing the complex indentation response of bone and may provide further insight into the relationship between model parameters and mechanical/physical properties.