Primary challenges and practical solutions in preventive psychiatry

Fusar‐Poli et al ¹ provide a scholarly and detailed overview of the state of knowledge on preventive approaches in psychiatry. Their paper should be considered an obligatory read for anyone entering or already practicing in this emerging field.

The need for preventive approaches in psychiatry is readily transparent. According to the US National Comorbidity Survey ² , a nationally representative population‐based survey of mental disorders, one in two adults in the US suffers from the symptomatic and functional challenges of one mental disorder during his/her lifetime. Almost one in three adults will suffer from two or more mental disorders. Regrettably, like much else in psychiatry, preventive approaches are lagging behind general medicine. Fusar‐Poli et al make strong arguments about several crucial challenges that critically hamper the implementation of preventive strategies. Here we elaborate on some of the key challenges mentioned in the review, and introduce a set of possible solutions to those.

The primary challenge is finding those who are at risk. Despite the longstanding history of neurobiological research, the underlying causal mechanisms of mental disorders remain mostly unknown. Symptom ratings have been widely used in psychiatry to detect individuals at risk. However, outside of specialty clinics, this strategy seems prone to failure. In a population‐based study of 18 to 21‐year‐olds ³ , the presence of symptoms, while associated with subsequent hospitalization for mental disorders, had positive predictive values ranging from 0.54% to 1.99%. In other words, for every correctly identified “case”, there would be between 50 and 200 “non‐cases” that would be incorrectly identified as “cases”. Such a high false‐positive detection rate, often found when prodrome studies are extrapolated to the general population, questions the utility of current paradigms that aim to identify at‐risk groups for large‐scale preventive efforts.

Advances in genetic research have identified some syndromic cases across multiple mental disorders, yet the overwhelming majority of individuals with these disorders, and especially those with common disorders (depression, anxiety), are idiopathic, with an unknown etiology. Target­able biomarkers are unavailable to use for early detection and/or efficient early intervention. As Fusar‐Poli et al ¹ note, only two of 162 peripheral biomarkers were reliably associated with psychosis, bipolar disorder, or depression. Collectively, our current lack of both understanding of underlying causal mechanisms and targetable biomarkers for mental disorders that can be applied at the population level substantially limit preventive strategies.

An additional challenge is that even early intervention often comes too late. Considerable evidence from genetics, epidemiology, basic neuroscience, and neuroimaging implicates early neurodevelopment as the critical period for the risk of developing most mental disorders. Almost all mental disorders are recognizable before or during the second decade of life. Yet, atypical neurobiological development surely predates the emergence of many mental disorders. For instance, evidence suggests that the first signs of cognitive abnormalities in those who will later develop schizophrenia are detectable by the age of four – decades before the disorder is usually diagnosed ⁴ . Furthermore, the brain most rapidly develops in utero, and continues to do so during early childhood. Indeed, evidence in children of patients with schizophrenia implicates aberrant early, possibly prenatal, brain development ⁵ . Therefore, these early periods are those when preventive strategies are most likely to have an impact. Fusar‐Poli et al ¹ highlight this point, but it is transparent that targeting this developmental period is particularly challenging.

A final challenge underscores how we address comorbidities ² . Comorbidity rates are high in psychiatry and conform to a 50% rule. Approximately half of all people with one psychiatric disorder meet the criteria for a second disorder concurrently; half the people with two disorders meet the criteria for a third; and so on. Evidence based on multiple studies highlights a general underlying dimension, termed the p factor, which captures the tendency to develop psychopathology. In the Dunedin Multidisciplinary Health and Development Study, conducted in an unselected longitudinal birth cohort, higher scores on the general tendency to psychopathology were associated with compromised early‐life brain function, and impairments in maturation ⁶ . Such findings foster the debate regarding categorical versus dimensional models that are relevant to research and in the clinic. In sum, since psychiatric disorders often co‐occur, the challenge to clinicians is how to target higher‐order psychopathological dimensions and the p factor without loss of specificity ⁷ .

A possible way to address these challenges is to identify those cases that will contribute disproportionally to morbidity and mortality. One source of intriguing evidence comes from another study of the Dunedin Multidisciplinary Health and Development sample, showing that 80% of the health burden is attributable to 20% of cases ⁸ . That study showed that early‐life factors (familial socioeconomic characteristics, maltreatment, IQ, and self‐control) clustered into 20% of the population, that accounted for disproportionately high levels of health care use (e.g., 78% of prescription fills and 57% of hospital nights). These findings imply that early life is a critical period for preventive measures for a select group in the population. However, there is potential to abuse this approach; population segments may suffer from stigma. Nevertheless, easing the effects of childhood disadvantage is a critical aim which, if attained in early life, may support families and children, as well as benefit all of society.

A second alternative is to implement universal psychiatric prevention. General medicine has advanced in this prevention (e.g., the efficacy of the COVID‐19 vaccines). Evidence‐based examples in psychiatry are few, but there are some, such as means restriction to prevent suicide, and physical activity to prevent incident anxiety and depression ⁹ . Selective universal prevention subtly differs by stratifying prevention to a large group in the population (e.g., nutrient use among pregnant women and the elderly). Better designed, easier to administer universal prevention strategies have the potential to reduce incident mental disorders. They may involve a significant financial investment, but also indirect benefits, including improvements in general health, unemployment, and even crime.

A third alternative is to target not the outcome but an effect modifier for intervention. While biomarkers for mental disorders are not yet available, it is well established that cognitive impairment accompanies, and most often predates by many years, the onset of the majority of mental disorders. There are also reliable ways to measure cognitive functioning and plausible intervention strategies. Implementing interventions to ameliorate cognitive impairments early in life may be a means for psychiatric prevention with substantial societal benefits beyond prevention of psychiatric outcomes (e.g., increasing the cognitive reserve in midlife may be a strategy to reduce dementia).

So, there are multiple challenges to implementing preventive strategies in psychiatry. There is, however, a clear need, and the time is ripe to make the leap towards primary and secondary prevention pathways in the critical period of early life and via cognition.