中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Measuring Health: A Guide to Rating Scales and Questionnaires

Evolutionary-biological reasoning suggests that individuals should be differentially susceptible to environmental influences, with some people being not just more vulnerable than others to the negative effects of adversity, as the prevailing diathesis-stress view of psychopathology (and of many environmental influences) maintains, but also disproportionately susceptible to the beneficial effects of supportive and enriching experiences (or just the absence of adversity). Evidence consistent with the proposition that individuals differ in plasticity is reviewed. The authors document multiple instances in which (a) phenotypic temperamental characteristics, (b) endophenotypic attributes, and (c) specific genes function less like “vulnerability factors” and more like “plasticity factors,” thereby rendering some individuals more malleable or susceptible than others to both negative and positive environmental influences. Discussion focuses upon limits of the evidence, statistical criteria for distinguishing differential susceptibility from diathesis stress, potential mechanisms of influence, and unknowns in the differentialsusceptibility equation.

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Beyond Diathesis Stress: Differential Susceptibility to Environmental Influences.

Background: Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes. Methods and Findings: A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR)=1.54; 95% CI 1.16–2.04], emotional abuse [OR=3.06; 95% CI 2.43–3.85], and neglect [OR=2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR=1.92; 95% CI 1.67–2.20], emotional abuse [OR=1.41; 95% CI 1.11–1.79], and neglect [OR=1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR=3.40; 95% CI 2.17–5.32], emotional abuse [OR=3.37; 95% CI 2.44–4.67], and neglect [OR=1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR=1.78; 95% CI 1.50–2.10], emotional abuse [OR=1.75; 95% CI 1.49– 2.04], and neglect [OR=1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships. Conclusions: This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence. Please see later in the article for the Editors’ Summary.

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The Long-Term Health Consequences of Child Physical Abuse, Emotional Abuse, and Neglect: A Systematic Review and Meta-Analysis

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/30529/0000161.pdf

Sex and depression in the National Comorbidity Survey I: Lifetime prevalence, chronicity and recurrence

Survey Non-response in the Netherlands: Effects on Prevalence Estimates and Associations

Social Adversity, the Serotonin Transporter (5-HTTLPR) Polymorphism and Major Depressive Disorder

This study tested the hypothesis that a personality disposition defined by a strong sense of coherence is associated with a reduced risk of mortality. The authors prospectively examined, for < or =6 years, the relation between a strong sense of coherence and mortality due to all causes, cardiovascular disease, and cancer among 20,579 participants aged 41-80 years from the European Prospective Investigation into Cancer (EPIC)-Norfolk Study in the United Kingdom. Data were collected in 1996-2002. Participants were recruited by post from general practice age-sex registers and subsequently completed a postal assessment of their sense of coherence. During follow-up, 1,024 deaths were recorded. A strong sense of coherence was associated with a 30% reduction in mortality from all causes (rate ratio=0.69, p<0.0001), cardiovascular disease (rate ratio=0.70, p=0.001), and cancer (rate ratio=0.74, p=0.003), independent of age, sex, and prevalent chronic disease. These associations were consistent by sex, except that no association was observed for cancer mortality in women. The association for all-cause mortality remained after adjustment for cigarette smoking history, social class, body mass index, systolic blood pressure, cholesterol, hostility, and neuroticism (rate ratio=0.76, p=0.002). Results suggest that a strong sense of coherence may confer some resilience to the risk of chronic disease.

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Sense of Coherence and Mortality in Men and Women in the EPIC-Norfolk United Kingdom Prospective Cohort Study

This paper reports the course with respect to remission and relapse of a cohort of predominantly in-patient RDC major depressive subjects, who were followed at 3-monthly intervals to remission and for up to 15 months thereafter. Remission was comparatively rapid with 70% of subjects remitting within 6 months. Only 6% failed to do so by 15 months. However, 40% relapsed over the subsequent 15 months, with all the relapses occurring in the first 10 months. Greater severity of the depression and longer duration of the illness predicted a longer time to remission. Greater initial severity of depression also predicted relapse. Subjects with a worse outcome had not received less adequate treatment than the remainder. Our results confirm the comparatively poor outcome subsequent to remission that has been reported in recent literature, in spite of the availability of modern methods of treatment. The clustering of relapses in the first 10 months gives some support to the distinction between relapse and later recurrence.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033291700033134

Paul G. Surtees

Papers

Survey Non-response in the Netherlands: Effects on Prevalence Estimates and Associations

Social Adversity, the Serotonin Transporter (5-HTTLPR) Polymorphism and Major Depressive Disorder

Sense of Coherence and Mortality in Men and Women in the EPIC-Norfolk United Kingdom Prospective Cohort Study

Remission and relapse in major depression: a two-year prospective follow-up study

The serotonin transporter length polymorphism, neuroticism, and depression: a comprehensive assessment of association.