Can you remember silence? Epigenetic memory and reversibility as a site of intervention.

Just over 20 years ago, molecular biologists Leonie Ringrose and Renato Paro published an article with a provocative title, "Remembering Silence", in BioEssays. The article focused on how epigenetic elements could return to their silent state, operationally defined as their epigenetic status before their modulation by experimental or environmental factors. Though Ringrose and Paro's article was on fruit flies and factors affecting embryological growth, the article asked a question of considerable importance to rapidly expanding research in neuroepigenetics on the correlation between trauma and neuropsychiatric risk: If you experience a traumatic event and, as a result, acquire an epigenetic trait that is considered pathological, can you free yourself of that trait? Ultimately, we are interested in how a return to silence is envisioned in neuroepigenetics research, how interventions purported to bring about that silence might function, and what this might mean for people who live in the aftermath of trauma.

Homeorhesis: envisaging the logic of life trajectories in molecular research on trauma and its effects.

What sets someone on a life trajectory? This question is at the heart of studies of 21st-century neurosciences that build on scientific models developed over the last 150 years that attempt to link psychopathology risk and human development. Historically, this research has documented persistent effects of singular, negative life experiences on people's subsequent development. More recently, studies have documented neuromolecular effects of early life adversity on life trajectories, resulting in models that frame lives as disproportionately affected by early negative experiences. This view is dominant, despite little evidence of the stability of the presumably early-developed molecular traits and their potential effects on phenotypes. We argue that in the context of gaps in knowledge and the need for scientists to reason across molecular and phenotypic scales, as well as time spans that can extend beyond an individual's life, specific interpretative frameworks shape the ways in which individual scientific findings are assessed. In the process, scientific reasoning oscillates between understandings of cellular homeostasis and organisms' homeorhesis, or life trajectory. Biologist and historian François Jacob described this framework as the "attitude" that researchers bring to bear on their "objects" of study. Through an analysis of, first, historical and contemporary scientific literature and then ethnographic research with neuroscientists, we consider how early life trauma came to be associated with specific psychological and neurobiological effects grounded in understandings of life trajectories. We conclude with a consideration of the conceptual, ontological, and ethical implications of interpreting life trajectories as the result of the persistence of long-embodied biological traits, persistent life environments, or both.

Troubling Neurobiological Vulnerability: Psychiatric Risk and the Adverse Milieu in Environmental Epigenetics Research.

In post-genomic science, the development of etiological models of neurobiological vulnerability to psychiatric risk has expanded exponentially in recent decades, particularly since the neuromolecular and biosocial turns in basic research. Among this research is that of McGill Group for Suicide Studies (MGSS) whose work centers on the identification of major risk factors and epigenetic traits that help to identify a specific profile of vulnerability to psychiatric conditions (e.g., depression) and predict high-risk behaviors (e.g., suicidality). Although the MGSS has attracted attention for its environmental epigenetic models of suicide risk over the years and the translation of findings from rodent studies into human populations, its overall agenda includes multiple research axes, ranging from retrospective studies to clinical and epidemiological research. Common to these research axes is a concern with the long-term effects of adverse experiences on maladaptive trajectories and negative mental health outcomes. As these findings converge with post-genomic understandings of health and also translate into new orientations in global public health, our article queries the ways in which neurobiological vulnerability is traced, measured, and profiled in environmental epigenetics and in the MGSS research. Inspired by the philosophy of Georges Canguilhem and by literature from the social studies of risk and critical public health, we explore how the epigenetic models of neurobiological vulnerability tie into a particular way of thinking about the normal, the pathological, and the milieu in terms of risk. Through this exploration, we examine how early life adversity (ELA) and neurobiological vulnerability are localized and materialized in those emerging models while also considering their broader conceptual and translational implications in the contexts of mental health and global public health interventions. In particular, we consider how narratives of maladaptive trajectories and vulnerable selves who are at risk of harm might stand in as a "new pathological" with healthy trajectories and resilient selves being potentially equated with a "new normal" way of living in the face of adversity. By troubling neurobiological vulnerability as a universal biosocial condition, we suggest that an ecosocial perspective may help us to think differently about the dynamics of mental health and distress in the adverse milieu.

Shared Relations: Trauma and Kinship in the Afterlife of Death.

Since 2013, we have studied the logic and narratives of an environmental epigenetics research team that studies the correlations between early childhood adversity (ECA), specific biomarkers, and suicide risk. Within this research program, kin of the deceased participate in psychological autopsies, which researchers use to establish to classify the deceased within a typology of suicide with or without abuse. We focus on the words of these family respondents and their reflections on the life and death of their loved ones, and life after that death, to consider the slippery, transgressive, and relational character of trauma and its effects. Studies of the residues of past experiences provide crucial insights into the complex, unpredictable, and unsettled nature of kin relations. These relations are based in entwined biographies of the living and the dead and illustrate the holds that people have on each other and destabilize biomedical models of individualized trajectories of suicide risk. [suicide, psychological autopsies, trauma, care, kinship].

Time, trauma, and the brain: How suicide came to have no significant precipitating event.

In this article, we trace shifting narratives of trauma within psychiatric, neuroscience, and environmental epigenetics research. We argue that two contemporary narratives of trauma - each of which concerns questions of time and psychopathology, of the past invading the present - had to be stabilized in order for environmental epigenetics models of suicide risk to be posited. Through an examination of these narratives, we consider how early trauma came to be understood as playing an etiologically significant role in the development of suicide risk. Suicide, in these models, has come to be seen as a behavior that has no significant precipitating event, but rather an exceptional precipitating neurochemical state, whose origins are identified in experiences of early traumatic events. We suggest that this is a part of a broader move within contemporary neurosciences and biopsychiatry to see life as post: seeing life as specific form of post-traumatic subjectivity.

The role of population inertia in predicting the outcome of stage-structured biological invasions.

Deterministic dynamic models for coupled resident and invader populations are considered with the purpose of finding quantities that are effective at predicting when the invasive population will become established asymptotically. A key feature of the models considered is the stage-structure, meaning that the populations are described by vectors of discrete developmental stage- or age-classes. The vector structure permits exotic transient behaviour-phenomena not encountered in scalar models. Analysis using a linear Lyapunov function demonstrates that for the class of population models considered, a large so-called population inertia is indicative of successful invasion. Population inertia is an indicator of transient growth or decline. Furthermore, for the class of models considered, we find that the so-called invasion exponent, an existing index used in models for invasion, is not always a reliable comparative indicator of successful invasion. We highlight these findings through numerical examples and a biological interpretation of why this might be the case is discussed.

The effect of response scale, administration mode, and format on responses to the CAHPS Clinician and Group survey.

OBJECTIVE: To examine how different response scales, methods of survey administration, and survey format affect responses to the CAHPS (Consumer Assessment of Healthcare Providers and Systems) Clinician and Group (CG-CAHPS) survey. STUDY DESIGN: A total of 6,500 patients from a university health center were randomly assigned to receive the following: standard 12-page mail surveys using 4-category or 6-category response scales (on CG-CAHPS composite items), telephone surveys using 4-category or 6-category response scales, or four-page mail surveys. PRINCIPAL FINDINGS: A total of 3,538 patients completed surveys. Composite score means and provider-level reliabilities did not differ between respondents receiving 4-category or 6-category response scale surveys or between 12-page and four-page mail surveys. Telephone respondents gave more positive responses than mail respondents. CONCLUSIONS: We recommend using 4-category response scales and the four-page mail CG-CAHPS survey.

Pursuit of a 'normal life': mood, anxiety, and their disordering.

Throughout the process of being treated for mood and anxiety disorders, people dream of the "normal life" that awaits them. However, post-therapy, the distinctiveness of clinical normality (i.e., reduced symptomatology) and social normativity become more apparent. In this article we suggest that for people who have long felt socially excluded because of their psychiatric symptoms, being "normally shy" or "normally awkward" is not enough. Instead they aspire to an ideal life. This confusion between means and ends, between a nonsymptomatic self, a normative self, and an ideal self, leads these individuals to long-term self-doubt and confusion about how to reach their elusive goals. Yet, their never-ending pursuit of normative ideals applies to "normal" and "abnormal" people alike. An analysis of narratives of exclusion allows us to reflect the life-long search for social inclusion via a normal life.

DISCUSSION: PRACTICE-BASED EVALUATION AS A RESPONSE TO ADRESS INTERVENTION COMPLEXITY.

The aim of this special issue of the Canadian Journal of Program Evaluation was to present an overview of current practices in the field of evaluation of complex interventions. Seasoned evaluators described their approaches to these types of evaluation in the healthcare context. Building upon their contributions, this synthesis offers a cross-sectional reading of their experiences, highlighting the common and divergent features of their approaches as well as their most pressing concerns and interests.

Morals, medicine and change: morality brokers, social phobias, and French psychiatry.

This paper will examine how French neurotics are being transformed into 'social phobics' and how the appearance of this group may be tied to new personal and social ideals. There are many people and factors that contribute to this changing definition of mental illness. Amongst these, I will focus on the role of three groups who are most vocally acting as morality brokers in the creation of these new subjects: psychiatrists, patients' groups and pharmaceutical companies.

Genetic susceptibility for Alzheimer's disease: why did adult offspring seek testing?

This study explored why adult offspring of individuals with Alzheimer's disease (AD) sought genetic susceptibility testing for AD. Participants (N = 60) were a subset of subjects from the first randomized controlled clinical trial to offer such testing. Qualitative analysis revealed two central constructs: altruism and learning. Planning for the future, hoping to prevent AD, and need to know were concepts that explained the value of learning. These results add important contextual information into why people might seek information on their genetic risk for a severe neurodegenerative disease for which there are, as yet, no preventative treatments. As genetic susceptibility testing for numerous other diseases enters clinical medicine, these findings can enhance the knowledge and sensitivity of researchers and clinicians when they are asked by participants or patients whether they should be tested.