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The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.44.

There is increasing awareness of the limitations of the disease oriented approach in medical care. The primary goal of psychosomatic medicine is to correct this inadequacy by incorporation of innovative operational strategies into clinical practice. Psychosomatic practice can be recognized by 2 distinctive features: the holistic approach to patient management (encompassing psychosocial factors) and the clinical model of reasoning (which reflects a multifactorial frame of reference). A basic psychosomatic assumption is the consideration of patients as partners in managing disease. The partnership paradigm includes collaborative care (a patient-physician relationship in which physicians and patients make health decisions together) and implementation of self-management (a plan that provides patients with problem-solving skills to enhance their self-efficacy). Pointing to strategies that focus on individual needs may improve patient quality of life and final outcomes.

Background. Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression). Method. Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural responses to a face-matching paradigm, and regional grey matter (GM) volumes were studied at 3.0 T in the amygdala, hippocampus, anterior cingulated cortex (ACC) and prefrontal cortex (PFC). The severity of ACEs was assessed. Participants included 20 consecutively admitted in-patients affected by chronic undifferentiated schizophrenia, and 20 unrelated healthy volunteers from the general population. Results. Patients reported higher ACEs than controls. Worse ACEs proportionally led to decreasing responses in the amygdala and hippocampus, and to increasing responses in the PFC and ACC in all participants. Patients showed higher activations in the amygdala and hippocampus, and lower activations in the PFC and ACC. Higher ACEs were associated with higher GM volumes in the PFC and ACC, and schizophrenia was associated with GM reduction in all studied regions. Conclusions. Structural and functional brain correlates of emotional reactivity are influenced by both current chronic undifferentiated schizophrenia and the severity of past ACEs. "Background. Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression). Method. Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural responses to a face-matching paradigm, and regional grey matter (GM) volumes were studied at 3.0 T in the amygdala, hippocampus, anterior cingulated cortex (ACC) and prefrontal cortex (PFC). The severity of ACEs was assessed. Participants included 20 consecutively admitted in-patients affected by chronic undifferentiated schizophrenia, and 20 unrelated healthy volunteers from the general population. Results. Patients reported higher ACEs than controls. Worse ACEs proportionally led to decreasing responses in the amygdala and hippocampus, and to increasing responses in the PFC and ACC in all participants. Patients showed higher activations in the amygdala and hippocampus, and lower activations in the PFC and ACC. Higher ACEs were associated with higher GM volumes in the PFC and ACC, and schizophrenia was associated with GM reduction in all studied regions. Conclusions. Structural and functional brain correlates of emotional reactivity are influenced by both current chronic undifferentiated schizophrenia and the severity of past ACEs."

PURPOSE: A cross-sectional national study was initiated in order to evaluate healthcare services and survivorship from the perspective of Danish adolescents and young adults (AYAs) with cancer. The purpose of the paper was to examine (Q1) to what extend Danish AYAs experienced fears and worries about dying; (Q2) with whom, if anyone, they had shared those worries; and finally, (Q3) how fears and worries influenced their daily life. The emphasis will be on Q3.METHODS: A 151-item questionnaire (including two closed- and one open-ended questions about fears of death and dying) was distributed among all 15-29-year-old Danes registered with a cancer diagnosis from 2009 to 2013. A total study population of 822 persons participated. Data was analyzed using a mixed design of descriptive statistics and qualitative content analysis.RESULTS: Q1: Almost 80 % of AYAs with cancer expressed some worries about death; hereof, more than half of them expressed quite a bit or very much. The analysis showed significant gender differences, whereas age and duration of disease did not have any significant impact on such thoughts. Q2: One third had not talked to anybody about his or her worries. Q3: The analysis resulted in three overall categories: fear of disease and death having little or no influence (n = 100), fear influencing in various ways (n = 215), and fear of disease and death having a substantial influence (n = 75).CONCLUSIONS: The majority of AYAs had experienced fears and worries about dying, but one third of them had not talked to anybody about those thoughts. It is an important clinical point that young age does not preclude fears and worries about dying in AYAs with cancer.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment.

According to the stress-diathesis hypothesis, depression and suicidal behavior may be precipitated by psychosocial stressors in vulnerable individuals. However, risk factors for mental health are often gender-specific. In the present study, we evaluated common risk factors for female depression in association with depressive symptoms and suicidal ideation in a community sample of women. The sample was composed by 415 women evaluated for mood disorders (MDs), depressive symptoms and suicidal ideation by structured interviews and the Beck depression inventory II (BDI II). All women also filled in the Eysenck personality questionnaire to evaluate neuroticism and were interviewed for social contact frequency and stressful life events (SLEs). In the whole sample, 19% of the women satisfied criteria for MD and suicidal ideation was reported by 12% of the women. Though stressful life events, especially personal and interpersonal problems, and poor social network were associated with all the outcome variables (mood disorder, depressive symptomatology and suicidal ideation), neuroticism survived to all multivariate analyses. Social network, together with neuroticism, also showed strong association with depressive severity, independently from current depressive state. Though we were unable to compare women and men, data obtained from the present study suggest that in women neurotic traits are strongly related to depression and suicidal ideation, and potentially mediate reporting of stressful life events and impaired social network. Independently from a current diagnosis of depression, impaired social network increases depressive symptoms in the women.