Risk factors for mental health: translational models from behavioural neuroscience.
TL;DR: How different approaches can be used in translational neuroscience in order to facilitate the identification of vulnerability factors, novel diagnostic markers as well as pharmacological targets to be exploited by the pharmaceutical industry for the development of innovative preventive approaches and treatment strategies is given.
About: This article is published in Neuroscience & Biobehavioral Reviews.The article was published on 2009-04-01 and is currently open access. It has received 18 citations till now. The article focuses on the topics: Psychological intervention & Mental illness.
Citations
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TL;DR: It is shown that chronic and unpredictable maternal separation induces depressive-like behaviors and alters the behavioral response to aversive environments in the separated animals when adult, highlighting the negative impact of early stress on behavioral responses across generations and on the regulation of DNA methylation in the germline.
976 citations
TL;DR: A unifying view of stress vulnerability and resilience is proposed by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits.
Abstract: Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional ‘scars’ in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to early life stress resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.
128 citations
Cites background from "Risk factors for mental health: tra..."
...…maltreatment-related posttraumatic stress disorder (PTSD) (De Bellis et al., 2002; Carrion et al., 2009), major depression induced by childhood stress (Frodl et al., 2010), harsh corporal punishment (Tomoda et al., 2009) and emotional maltreatment during childhood (Van Harmelen et al., 2010)....
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...This can result in dysfunctional neuronal systems, which might trigger the emergence of mental disorders later in life (Furukawa et al., 1999; Agid et al., 2000; Van Den Bergh et al., 2006; Cirulli et al., 2009)....
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...This increase or “overproduction” of synaptic connections is followed by “pruning” of synapses, which again shows specific temporal profiles for different cortical regions....
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...…with neurostructural and neurophysiologic alterations resulting in dysfunctional brain circuits (Rakic et al., 1994; Braun and Bogerts, 2001; Cirulli et al., 2009; Bale et al., 2010; Charil et al., 2010; McEwen, 2010; Bock and Braun, 2011; Weinstock, 2011; Baram et al., 2012; Maggio et al.,…...
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...…parental separation, handling, maternal neglect) or natural variations in maternal care can be studied (for reviews see Meaney, 2001; Pryce et al., 2005; Sullivan et al., 2006; Rice et al., 2008; Cirulli et al., 2009; Oitzl et al., 2010; Bock and Braun, 2011; Schmidt, 2011; Lucassen et al., 2013)....
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TL;DR: The need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood is revealed.
97 citations
Cites background from "Risk factors for mental health: tra..."
...The central nervous system (CNS) The brain processes environmental input from emotional, sexal and physical abuse, neglect or illness differently at critical ages Cirulli et al., 2009; Furukawa et al., 1999)....
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01 Jan 2004
TL;DR: In this paper, the authors examined the relationship between illicit drug use and 10 categories of adverse childhood experiences (ACEs) and total number of ACEs (ACE score) and found that ACEs increased the likelihood for early initiation 2- to 4-fold.
Abstract: OBJECTIVE
Illicit drug use is identified in Healthy People 2010 as a leading health indicator because it is associated with multiple deleterious health outcomes, such as sexually transmitted diseases, human immunodeficiency virus, viral hepatitis, and numerous social problems among adolescents and adults. Improved understanding of the influence of stressful or traumatic childhood experiences on initiation and development of drug abuse is needed.
METHODS
We examined the relationship between illicit drug use and 10 categories of adverse childhood experiences (ACEs) and total number of ACEs (ACE score). A retrospective cohort study of 8613 adults who attended a primary care clinic in California completed a survey about childhood abuse, neglect, and household dysfunction; illicit drug use; and other health-related issues. The main outcomes measured were self-reported use of illicit drugs, including initiation during 3 age categories: or=19 years); lifetime use for each of 4 birth cohorts dating back to 1900; drug use problems; drug addiction; and parenteral drug use.
RESULTS
Each ACE increased the likelihood for early initiation 2- to 4-fold. The ACE score had a strong graded relationship to initiation of drug use in all 3 age categories as well as to drug use problems, drug addiction, and parenteral drug use. Compared with people with 0 ACEs, people with >or=5 ACEs were 7- to 10-fold more likely to report illicit drug use problems, addiction to illicit drugs, and parenteral drug use. The attributable risk fractions as a result of ACEs for each of these illicit drug use problems were 56%, 64%, and 67%, respectively. For each of the 4 birth cohorts examined, the ACE score also had a strong graded relationship to lifetime drug use.
CONCLUSIONS
The ACE score had a strong graded relationship to the risk of drug initiation from early adolescence into adulthood and to problems with drug use, drug addiction, and parenteral use. The persistent graded relationship between the ACE score and initiation of drug use for 4 successive birth cohorts dating back to 1900 suggests that the effects of adverse childhood experiences transcend secular changes such as increased availability of drugs, social attitudes toward drugs, and recent massive expenditures and public information campaigns to prevent drug use. Because ACEs seem to account for one half to two third of serious problems with drug use, progress in meeting the national goals for reducing drug use will necessitate serious attention to these types of common, stressful, and disturbing childhood experiences by pediatric practice.
94 citations
TL;DR: It is pointed out that mechanisms involved in structuring and optimizing neural circuits during brain development might also be used in moulding personality and behaviour during psychotherapy in the adult brain.
Abstract: The maturation of prefronto-limbic neuronal pathways that mediate essential affective and social regulatory functions is experience dependent. Immediately after birth the infant’s affective experiences, especially those embedded in the relationship with the primary caregiver, trigger the reorganization and adaptive fine-tuning of synaptic circuits. Research in humans and in animal models supports the hypothesis that socio-emotional deprivation and emotional trauma during early childhood may leave ‘scars’ in prefronto-limbic function, brain regions that are essential for emotional behaviour, learning, and memory. The focus of this review is to point out that mechanisms involved in structuring and optimizing neural circuits during brain development might also be used in moulding personality and behaviour during psychotherapy in the adult brain.
51 citations
Cites background or result from "Risk factors for mental health: tra..."
...Thereby neuronal synaptic circuitries can adapt to an adverse environment, socio-emotional neglect, and traumatic experiences, which may underlie the aetiology of mental disorders.(5,7,9,14) Is there evidence that the human brain undergoes synaptic reorganization, similar to findings in animals? Phases of synaptic proliferation and pruning have been described during human brain development, where different cortical regions display differential time courses of synaptic development,(30) which, analogous to the findings in experimental animal studies, may be modulated by emotional experiences....
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...Evidence from research in animal models as well as from clinical work indicates that perinatal environmental influences affect the behavioural development of the offspring.(5,6) There is also reasonable evidence that neonatal emotional neglect, socio-emotional deprivation, and trauma are risk factors for developing behavioural dysfuncions, which in humans may result in a variety of behavioural and mental disorders....
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References
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TL;DR: These projections represent a set of three visions of the future for population health, based on certain explicit assumptions, which enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends.
Abstract: Background Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results. Methods and Findings Relatively simple models were used to project future health trends under three scenarios—baseline, optimistic, and pessimistic—based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015. Conclusions These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries.
10,090 citations
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
Abstract: Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
4,503 citations
TL;DR: It is suggested that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.
Abstract: Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r 9s > −0.6). These findings suggest that maternal behavior serves to “program” hypothalamic-pituitary-adrenal responses to stress in the offspring.
3,020 citations
TL;DR: Mental health affects progress towards the achievement of several Millennium Development Goals, such as promotion of gender equality and empowerment of women, reduction of child mortality, improvement of maternal health, and reversal of the spread of HIV/AIDS.
2,943 citations
"Risk factors for mental health: tra..." refers background in this paper
...The Global Burden of Disease report has revealed that neuropsychiatric conditions account for a quarter of all disability-adjusted life years (Prince et al., 2007)....
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TL;DR: Preclinical studies suggest that early life stress induces long-lived hyper(re)activity of corticotropin-releasing factor (CRF) systems as well as alterations in other neurotransmitter systems, resulting in increased stress responsiveness.
2,561 citations