Acting early: the key to preventing mental health problems

This article is based on the ‘Children in Crisis’ lecture delivered at the Royal Society of Medicine on 9 January 2018

The case for prevention

Mental health problems are a spectrum of health conditions with heterogeneous clinical phenotypes and severity. Together, they are the leading contributors to Years Lived with Disability in the Global Burden of Disease. ¹ Much of the focus on addressing this burden has been on improving the lives of those who are affected by these problems, ² although the coverage of evidence-based treatments remains very low in most countries, and especially so in low- and middle-income countries. ³ Much less attention has been devoted to prevention, certainly when compared to other health conditions such as non-communicable diseases (for example, strategies to reduce tobacco consumption) and infectious diseases (for example, the development and roll-out of vaccines). In large measure, this has been due to the heterogeneity of the clinical phenotypes of mental health problems (including the blurred boundaries distinguishing one from the other) and, as a result, the challenges to identify specific aetiological risk factors which may be prevented or mitigated. However, this is a misplaced assumption for, no matter what the phenotype in adulthood may look like, we do have specific targets for prevention of a range of mental health problems. Importantly, these are clustered in the early years of life, from birth through young adulthood.

Three sets of epidemiological observations underlie the opportunity to reimagine prevention of mental health problems. The first is that regardless of the clinical phenotype of the mental health problem, childhood neglect and deprivation (which takes a range of forms, from adverse family circumstances and the effects of poverty to exposure to abuse and violence) is a strong risk factor.^4,5 For some conditions, one might even see risks as strong as those observed between smoking and certain non-communicable diseases. Indeed, childhood deprivation is also a risk factor for other non-communicable diseases, possibly through similar pathways as for mental health problems.^6,7 The second observation is that the majority of mental health problems encountered in adulthood have their origins before the age of 24 years. ⁸ Both these observations point to the critically important role of the developmental phase stretching from early childhood through young adulthood in the aetiology of mental health problems. The third observation, which neatly triangulates with these findings, is that of the growing evidence base on interventions (which I turn to later) which target the social environments and psychological capabilities of children and young people in preventing mental health problems.

Two relatively recent discoveries related to brain development, thanks largely to novel neuroimaging technologies, offer a compelling mechanistic explanation for these observations. The first is the demonstration of the plasticity of the brain in response to environmental influences, such as under-nutrition and child neglect. Structural neuroimaging studies show that deficits in the volume of grey matter is influenced by family environment and socio-economic status during early childhood.^9,10 These deficits are particularly marked in the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala and corpus callosum, which are important for cognitive functions such as memory, social-emotional processing, executive function and language, respectively.^11,12 Diffusion tensor imaging studies show deficits in structural connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during response inhibition, working memory and emotion processing.^13,14 Other neuroscientific methods are also shedding light on these mechanisms: for example, a recent study has reported an association between the history of child abuse with cell type-specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional programme. ¹⁵ Evidence from animal models suggest that deprivation accelerates the neurodevelopmental process of synaptic pruning and limits myelination, resulting in age-specific reductions in cortical thickness and white matter integrity. ¹⁶ Studies comparing animals raised in deprived environments to those reared in enriched ones have observed changes in anatomical, electrophysiological, molecular and epigenetic aspects of the brain, which contribute to behavioural and cognitive changes in individuals.^17,18

The second discovery is the result of a new generation of cognitive psychology and neuroscience studies which have transformed our understanding of brain development in adolescence. The central finding of these studies is the observation of the differential maturation of different regions of the brain, over a period extending from early adolescence up to young adulthood. The prefrontal cortex which is concerned with higher order executive functioning (such as impulse control) matures five to six years later than the limbic region which mediates the so-called ‘hot’ cognitions, which refer to thinking (and emotions) occurring in the context of high levels of arousal. ¹⁹ This is a key reason why impulsivity, thrill-seeking and risk-taking behaviours are a characteristic of adolescence. The observation that the hormone testosterone moderates risky behaviours might also explain the large sexual dimorphism observed in these behaviours. ²⁰ Psychological changes during this phase lead to an increasing importance of the opinion of peers, making adolescents more to become sensitive to social stimuli, which may be positive (social approval and acceptance) or negative (social exclusion and repeated defeat) in nature, and having an increased propensity to undertake risky behaviours.^21,22 Not surprisingly, some commentators describe adolescence as a second ‘sensitive period’ for the developing brain which may explain why there is a surge of mental and substance use disorders in this phase of life.

The sum of these two discoveries provide compelling biological evidence on the impact of environmental factors on the morphology and functions of regions of the brain concerned with cognition, emotions and behaviour.

Pathways to mental health in early childhood

We also now have at least two plausible pathways to explain how childhood neglect, maltreatment and deprivation might lead to structural and functional changes in the brain. The first is through parenting behaviours (which will take different shapes according to the developmental phase). New neural connections are formed in the brain as children learn from, and play and conversationally interact with their parents, especially in regions of the brain which are being stimulated, for example, in the language regions during spoken interactions. ²³ Similar beneficial effects may be assumed to occur in response to affectionate interactions (and, conversely, harmful effects in response to fear or injury). Through these continuing interactions, over years, the architecture of the brain’s countless connections is built, impacting on the person’s psychological resilience and vulnerabilities. The second type of exposure relates to stressful (or threatening) experiences. Most such experiences, exemplified by separation anxiety in childhood, typically lead to acute anxiety (associated with increased heart rate and stress hormone release). Such acute stressful experiences are integral to the development of resilience, especially when they are short-lived and followed by restorative experiences (for example, the return of the parent or the provision of affection by an alternative care-giver). Stress results in a structural remodelling of neural architecture, in which excitatory amino acids and glucocorticoids play key roles, along with a growing list of mediators such as brain-derived neurotrophic factor. The result is a continually changing pattern of gene expression mediated by epigenetic mechanisms. ²⁴ Some stressful experiences, however, are more long-lasting or recurrent or accompanied by extraordinary levels of threat or not accompanied by restoration. Such stressors are believed to have damaging effects on the developing brain (and thus the term ‘toxic stress’), setting the stress response system permanently on a heightened alert mode with reduced neural connections in brain areas concerned with emotional regulation.

Importantly, both these key pathways can be influenced through interventions which modify the environments in childhood. There is evidence in support of parenting interventions which combine strategies to promote physical wellbeing (in particular, nutrition and protection from infections and toxins) and emotional attachment (in particular, through structured play interactions and promoting responsive, non-punitive and consistent parenting practices) and for policy interventions to promote early childhood development and education (for example, pre-school creches), for the detection and prevention of childhood maltreatment and neglect, and the mitigation of toxic stress in the context of catastrophic events (such as sexual abuse or severe traumas such as loss of parents, violence or conflict). The evidence base for these interventions is strong: not only do these interventions lead to better developmental outcomes in childhood but better educational outcomes and reduced mental health problems in later life, ultimately translating into better adjusted and economically productive adults, in effect confirming the causal inferences drawn from the observations of the association between childhood deprivation and mental health. ²⁵

Pathways to mental health in youth

A somewhat different mechanism explains the association between environmental adversities and poor mental health in adolescents. The unique features of neurodevelopment at this stage of life, described earlier, essentially translates into the higher probability of risk-taking and thrill-seeking behaviours as ‘hot’ cognitions and emotions are acted upon more impulsively with less consideration for their consequences. ¹⁹ While these characteristics have enormous evolutionary and developmental advantages in terms of learning the critical skill of decision-making, they also pose threats in the context of inadequate support or adverse social environments. The latter include environments characterised by violence and bullying, exposure to alcohol and drugs, lack of trust, orthodox social norms around sexuality, gender inequity and lack of access to meaningful educational opportunities. ²⁶ More recently, exposures to the digital environment have also been increasingly under the spotlight with regard to concerns of their adverse effects on child development, for example through cyber-bullying, grooming by radical groups and for sexual trafficking. It is the interaction between these social determinants and neurodevelopmental changes (and, indeed, the major social transitions) occurring during this phase of life which is the most plausible pathway to explain why risk-taking behaviours with potential adverse consequences for health, such as casual sexual encounters, self-harm, substance use and violence, are most frequently observed in adolescence and young adulthood.

The implications for interventions are similar to those related to the first critical developmental phase: modifying the social environment to enhance protective factors can prevent mental health problems. Given the widening social worlds (compared with children) of adolescents, it is not surprising that the social determinants, and thus the interventions, which influence mental health are more complex and span several ecological levels. ²⁷ At the level of the individual, building skills for emotional regulation and inter-personal communication, typically through classroom-based life skills curricula, and providing guided self-help for distress, enjoy the strongest support. At home, strong evidence supports the use of parenting interventions for behavioural and emotional problems; authoritative parenting styles which provide developmentally graduated guidance and support, eschew violence and respect the growing autonomy of the adolescent are conducive to promoting mental health. In schools, whole-school interventions to promote trust, agency and participation of young people, prohibit bullying and promote quality education, help retain adolescents in school and promote mental health. In the neighbourhood, interventions (in particular, those led by youth) which address violence, build social networks and stop the availability of drugs and harmful substances are effective. In the healthcare system, access to brief, empirically supported, psychological therapies delivered in school or primary care settings, by competent counsellors (who may include non-specialised providers such as teachers or peer counsellors), is key for secondary prevention. In the rare instances where the mechanisms of psychological therapies have been studied, these have been associated with structural changes in parts of the social brain network such as anterior cingulate cortex, medial prefrontal cortex and amygdala. ²⁸

Conclusions

The critical requirements for scaling up interventions for the prevention of health problems is the availability of four types of knowledge: the observation of a causal association between a risk factor and the health problem; the observation, or at the very least a highly plausible inference, of a mechanism; the controlled trial evidence of interventions which target the risk factor and/or pathways to the health problem and the evidence of scalability of these interventions. Acting early in the life course, from birth (and some would argue, from the fetal stage) through to young adulthood, to modify social environments, is likely to be the most promising investment to prevent mental health problems (and realise many other goals, including better educational outcomes, better physical health and lesser social dysfunctions) in the population.

The major challenge in implementing this knowledge is the fragmented approach to the life course with a multitude of disciplines specialising in different stages viewed through diverse disciplinary prisms, so that the unique longitudinal trajectory of development for each individual is lost from sight. Another result of this fragmentation is the preference, driven by clinical specialists, to view the behavioural phenotypes which emerge in adolescence as being distinct from each other. Thus, for example, early child development practitioners focus on cognitive development in the first few years of life, child mental health practitioners focus on emotional and behavioural problems in children and adolescents and adolescent health practitioners focus on social determinants and risk behaviours in adolescence (notably sexual risk behaviours in the context of HIV). Yet, as the evidence emphatically shows, the phenotypes (both those describing diverse mental health conditions and those reflecting a range of risk behaviours) share similar determinants, and that it is the cumulative experiences of adversity and protection across the early life course which provides the best prediction of adult well-being. In practice, the translation of this evidence will require convergence at the level of every platform of the response to young people’s well-being, from policy development to delivery at the coal-face. And, at the heart of this process, must be the voices of young people themselves.

In conclusion, the brain is a work in progress, particularly from early childhood into young adulthood, and environments profoundly influence the developing architecture of the brain. I would like to propose four ways to think about joining up for the wellbeing of the generations of young people today who will be the adults of tomorrow. First, we must think of each individual life story as an unbroken continuum from birth into young adulthood and offer universal interventions seamlessly from a population perspective. Second, we must embed within this universal framework, targeted interventions for secondary prevention to high-risk groups, such as children living in poverty or in crises (for example, affected by conflict), those who have experienced severe adversities (for example, those who have been sexually abused) and those who have developed frank mental health problems. Third, we need coordinated planning of delivery across three primary platforms, viz. the home, the school and the neighbourhood, in which the vast majority of children will live most of their lives. Fourth, we must actively promote the engagement of young people not only as beneficiaries but as critical stakeholders who will be involved in the design and delivery of interventions and, most importantly, holding programmes accountable.