Paracetamol,pregnancy and public health

The big news this month is the meta-analysis showing that the ingestion of paracetamol (also called acetaminophen) during pregnancy is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring. Paracetamol is widely used and generally regarded as safe, but it does cross the placenta and so has the potential to affect brain development. Gou et al. (this issue) include a total of 244,940 participants in their meta-analysis and show that mothers who take paracetamol during pregnancy have a 1.25 times higher risk of having a child with ADHD. The risk is higher still if paracetamol is taken during the third trimester and for longer periods of time. The authors of this study carefully review possible confounds, including the limitations of self-reported paracetamol use, gender effects (ADHD is more common in boys), and variations in diagnostic criteria for ADHD.

Other studies have found that maternal paracetamol use is associated with higher rates of asthma, autism and neurodevelopmental disorders in the offspring. These findings are very concerning, as Gou et al. report that at least 50% of women in the United States and Europe take paracetamol during pregnancy. Research into the incidence of schizophrenia, also conceptualised as a neurodevelopmental disorder, has suggested that birth during late winter and early spring, especially after an influenza pandemic, can be associated with a higher rate of the disorder. Rather than reflecting exposure of the developing brain to viruses, this could perhaps be a result of the over-the-counter remedies taken by pregnant women suffering symptoms of winter illnesses.

The impact of earlier influences on later cognition and outcomes is also explored by Mills et al. (this issue). Using data from a Queensland birth cohort study, they show that childhood maltreatment is associated with poorer cognitive function, lower rates of high school completion and unemployment at age of 21 years. Childhood abuse and neglect was confirmed from the records of the state child protection agency. Marmot (2018) has described in detail the impact of childhood adversity on later smoking, binge drinking, cannabis and heroin use, violence victimisation and perpetration, unintended pregnancy, and incarceration. In terms of public health interventions, closer attention to maternal health during pregnancy and providing better conditions for children as they grow up are two obvious areas for intervention.

Levy (this issue) also examines the effects of early childhood experiences, blending psychoanalytic and neurobiological perspectives. She explores theoretical links between early traumatic memories and later anxious/depressive ruminations using the concept of l’apres-coup, or ‘afterwardsness’, to describe the later belated understanding or retroactive attribution of sexual or traumatic meaning to earlier events. She proposes that the earlier events are somehow retained; then, as cognitive function matures, these early experiences influence later development and behaviours.

Moving back to a public health perspective, ‘evidence’ usually refers to the effectiveness of an intervention in achieving an outcome that creates lasting changes in the health of the population. The Better Access scheme was introduced in 2006, to enable more Australians with mental disorders to access psychological treatments. The scheme was rolled out nationally, ahead of any evaluation. Gold standard appraisal using randomised controlled trial (RCT) methods was not possible. Coverage extended to the whole country so regions with and without Better Access could not be compared.

By 2013, more than 3 million people had accessed psychological services through Better Access. More than 20 million services had been provided, with the cost of these services estimated at close to $3 billion dollars (Littlefield, 2017). But has all this treatment been helpful? A previous assessment by Pirkis et al. (2011), reporting patient data before and after treatment, was positive. However, Jorm (2018) examined changes in two measures of population mental health, the K10 and annual suicide rates from 2006 to 2015, and concluded that there has been no measurable change.

Not surprisingly, there are several papers in this month’s ANZJP responding to Jorm’s analysis. Whiteford observes that the proportion of the Australian population with a mental disorder receiving treatment has increased from 37% in 2006–2007 to 46% in 2009–2010, and he estimates that coverage is now most likely greater than 50%. Therefore, it seems reasonable to expect the provision of treatment to this proportion of the psychologically distressed population to translate into population-level changes in the K10.

Lee and Frost (this issue) argue that in fact the K10 data have improved and that suicide rates are not a good measure of the impact of Better Access because many people who kill themselves do not have a diagnosable mental disorder. In addition, they consider that the permitted maximum of 10 rebateable sessions is insufficient for effective treatment. Regarding adequacy of treatment, it is noteworthy that Whiteford reports that in 2014–2015, 20% of those attending Better Access services attended only one session.

Judd and Davis (this issue) observe that rates of mental disorder depend on both the occurrence of new cases and change in prevalence of established cases. A focus entirely on treatment does not address risk factors such as adverse childhood experiences and other social determinants of health. Mihalopoulos (this issue) adds that there may be population-level confounds (such as the rise of social media) and outcomes such as the use of other healthcare services and productivity that were not measured.

Jorm has replied to these commentaries in this month’s issue of the journal. He includes more recent K10 data on the prevalence of high or very-high psychological distress, showing that there was no decline between 2006 and 2017–2018. Concluding that increasing the uptake of psychological treatments has not reduced the prevalence of psychological distress or suicide, he proposes that any further reforms should be introduced gradually, with pilot trials and evaluation to determine if benefits are present under real world conditions.

Continuing the theme of evaluation, but on a smaller scale, Harris et al. (this issue) examine the effectiveness of Community Treatment Orders (CTOs). While the element of legal compulsion may seem unattractive, lack of insight, poor medication adherence, and risks of violence to self and others mean that sometimes compulsory treatment is needed. The hope is that with regular treatment, insight will develop and a cooperative relationship with clinicians can be established. Using a case-control method, Harris et al. found that people on CTOs had fewer admissions and more days of community care, compared to matched controls.

There are several papers in this month’s ANZJP proposing new avenues of treatment. Inserra (this issue) worries that Australia is missing out on researching the use of psychedelic drugs to treat psychiatric disorders. Interestingly, this academic debate is occurring in the context of increasing community concern about illicit drug use and controversy about pill testing at music festivals. Cannabis also gets a mention, with a letter (Makiol and Kluge, this issue) describing remission of treatment-resistant schizophrenia when cannabidiol was added to clozapine. Sher (this issue) speculates that endocannabinoids may be involved in the pathophysiology of suicide. Moving on to treatment-resistant depression, Bassett et al. (this issue) provide a useful summary of augmenting agents, ranked according to levels of evidence – and perhaps Inserra will be somewhat encouraged by the inclusion of psilocybin, albeit with only Level 5 Evidence (emerging clinical observations and/or open trials).

Treatments generally follow on from diagnosis, and this month’s ANZJP tackles some interesting diagnostic controversies. For instance, Thomas et al. (this issue) present evidence of a continuity between schizotypal symptoms and schizophrenia, a view that is consistent with Guloksuz and Van Os’ (2018) concept of a proneness–persistence–impairment model of psychotic disorder. These authors suggest that the diagnostic category of ‘schizophrenia’ is hampering progress and should be replaced by ‘psychosis spectrum disorder’. This revisionist tone is continued by Malhi et al. (this issue), who propose the excision of hypomania and in turn the removal of the bipolar II disorder category. Instead, they ‘highlight’ the importance of specifying the duration of mania, illustrated by a mania chronometer, which is a colourful cross between a speedometer and a watch (perhaps worn on the wrist, like a Fitbit for mood).

Finally, we come to neurophysiological changes associated with psychiatric disorders. This issue of the journal has two papers reporting imaging research from Chinese and Korean Universities. The prevalence of substance use is much less in these populations, so the researchers can exclude participants with cannabis, alcohol and amphetamine use, and this is valuable because these comorbidities are a major confound for Australian researchers working with young people. Kwak et al. (this issue), from Seoul, South Korea, used magnetic resonance imaging (MRI) scans to demonstrate significant frontoparietal cortical thinning in young people at clinical risk for psychosis (most of whom will not convert to a psychotic disorder). Chen et al. (this issue), from Shanghai, China, used functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy to show correlations between right thalamic glutamate levels and functional connectivity in the right dorsal anterior cingulate cortex and middle occipital gyrus in obsessive compulsive disorder (OCD).

This month’s ANZJP has a strong public health theme, using population-level data to detect antenatal and childhood risk factors for mental disorders, and to evaluate widely available treatments. Perhaps, the next steps for psychiatry will be to further influence the social determinants of mental health and to undertake rigorous research to ensure the services provided to our patients are effective, well targeted and good value for money.