What neuroscience has already done for us

: Commentary on… Why hasn’t neuroscience delivered for psychiatry?

Lindsey Isla Sinclair 1

Correspondence

Lindsey Sinclair

(Lindsey.sinclair@bristol.ac.uk) 2

date

2020-06

Abstract

Each of the components of the biopsychosocial model of mental illness is important for understanding mental illness. Biological and genetic abnormalities have been demonstrated in major mental illnesses. These are leading to changes in our understanding of these conditions, as well as our understanding of the link between life events and mental illness.

As readers will be well aware, the biopsychosocial model has underpinned psychiatry for several decades.1 Each component of this model is important for our understanding of mental illness. Professor Kingdon is therefore correct to say in his interesting editorial that neuroscience is unlikely to hold all of the answers to why people develop mental disorders and when they occur in their lifetime.2 I challenge, however, his assertion that ‘biological changes have yet to be shown to be relevant to the major mental disorders’.

Brain imaging and schizophrenia

Taking schizophrenia as an example, there are clearly demonstrable differences in the brains of individuals with schizophrenia compared with those of controls. It was first shown in the 1970s that people with schizophrenia had enlarged cerebral ventricles.3 Since then abnormalities in both grey and white matter have been convincingly demonstrated in the disorder.4 More sophisticated brain-imaging techniques have allowed the discovery in recent years that differences in brain volume are present even in medication-naive individuals with first-episode psychosis.5 It seems increasingly likely that there are differences in volume even before the at-risk mental state, although this remains difficult to prove definitively.6–8

Recently developed scientific techniques such as the use of induced pluripotent stem cells to create a ‘cortex in a dish’ (aka brain organoids) have allowed tantalising insights into why these imaging abnormalities may emerge. Using cells from individuals with schizophrenia (some with a range of predisposing genetic abnormalities) multiple studies have shown abnormalities such as impaired cellular differentiation and synapse formation.9–11

These studies add to the emerging hypothesis that the brain of someone at risk of schizophrenia differs from controls at an early stage and that these differences increase as psychosis emerges. These neuroscientific findings are a good fit with the long-standing findings from more psychosocially focused research that differences can be seen in childhood behaviour in those who later develop schizophrenia.12–15 They also suggest that, to develop better treatments for schizophrenia, we need to look beyond compounds targeting dopamine receptors.

Genetics in intellectual disability and depression

I would also challenge Professor Kingdon’s assertion that no genetic findings of use to the practising psychiatrist have been found for the major mental illnesses. Genetic testing for copy number variants is starting to form part of practice in intellectual disability services.16,17 Using his example of depression he is correct to say that the much vaunted candidate genes studied in the 1990s and 2000s have not been replicated in later, large studies.18 However, more recent, vastly better powered studies have produced findings of greater potential use. The most recent genome-wide association study on depression found 87 independent loci that were associated with depression, with a startling lack of genes involved in the 5-HT system.19 This may suggest that, although drugs acting on the 5-HT system are effective in treating depression for many people, disturbances in 5-HT are not the cause of depression. Findings such as these are likely to be of great benefit in developing new treatments.

Epigenetics and treatment targetting

Neuroscience can also help us to explain the link between life events, which are frequently assessed in psychosocial research, and mental health outcomes. For example, epigenetic studies have shown that maternal behaviour influences the expression of genes, including those involved in the glucocorticoid stress response.20,21 Because this work was done in rats it was possible to demonstrate that this effect was not genetic as it was abolished by cross-fostering with more affectionate mothers.21 Childhood maltreatment such as physical abuse has long been recognised as a risk factor for mental illness. Recent genetic and epigenetic studies are helping us to understand why some people are more resilient to the effects of this abuse than others.22,23 It has been suggested by some authors that this information could be used to better target childhood interventions, such as providing more intensive interventions to those likely to be least resilient to the effects of childhood maltreatment.

Conclusions

Our understanding of mental health problems has started to change radically in the past few decades. It is only 50 years since it was widely believed that parents could be responsible for their offspring developing schizophrenia.24 Within the past 50 years patients with intractable epilepsy were cared for in psychiatric hospitals, something that would now be unthinkable, and the parent–child relationship was seriously considered as a cause of epilepsy.25,26

This improvement in understanding has the potential to reduce stigma, to ultimately lead to new treatments and to provide patients with a better understanding of what is happening to them and why. It is critical that mental health researchers work together, rather than in methods-based silos, to further improve our understanding of why and how patients develop mental health problems.

L.I.S. has received research funding from BRACE, Dementias Platform UK, the British Neuropathological Society and the David Telling Charitable Trust.

Lindsey Isla Sinclair, MBBS, MSc, PhD, MRCPsych, is a Clinical Research Fellow in psychiatry in the Department of Population Health Sciences at the University of Bristol, UK. Her research is neuroscience based and she is a Gatsby/RCPsych travelling fellowship awardee 2019.

1

Declaration of interest: None.

2

See this issue.

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