Psychosis is possibly the most serious and debilitating of all clinical psychiatric disorders. This is a complex, heterogeneous condition. There are still many unanswered questions, including the aetiology of psychosis, the challenge of predicting who will and who won't develop psychosis, and the best means of intervention to reduce risk. What progress has research made, over the last few years?
Causes of psychosis
We have long believed that having a first-degree relative (such as a parent or sibling) with psychosis raises an individual's risk of a similar diagnosis. However, the role of genes in triggering psychosis is presently controversial. On the one hand, complex genetic patterns that might mediate psychoses have been identified (Owen et al, 2007; DeRosse et al, 2012). On the other hand, surveys of research suggest that genetics are at best weak predictors of psychosis (Fusar-Poli et al, 2016; Catalan et al, 2021). Genetic and environmental factors may not be entirely independent, which complicates the debate. What is clear is that many with a family background of psychosis do not themselves develop the disorder, and that there are strong environmental factors shaping who does and who doesn't.
‘We have long believed that having a first-degree relative (such as a parent or sibling) with psychosis raises an individual's risk of a similar diagnosis. However, the role of genes in triggering psychosis is presently controversial.’
A major review of studies of the aetiology of psychosis (Radua et al, 2018) has explored what those environmental risk factors might be. Only a few (low birthweight, small birth size, neonatal vitamin D deficiency) of the suspect perinatal factors are associated with later psychosis, and the association is only mild. Some suspect behaviours – principally substance abuse, particularly heavy cannabis use – are associated with raised risk of psychosis. But overall, recent research shows that the major environmental contributor to later psychosis is socio-economic adversity. Individuals from groups often associated with disadvantage, (such as those of Black or Carribean ethnicity and second-generation immigrants) are at higher risk than others. The crucial factors seem to be socio-economic stress, social isolation and fragmentation, feelings of helplessness and defeat. In light of which, we might expect the events of the past 2 years (pandemic, lockdowns, and the exacerbation of consequent economic and existential problems by the war in Ukraine) to trigger a rise in psychosis in young people. Research from China (Wu et al, 2021) has already found a significant increase in psychotic-like experiences in adolescents after lockdown.
Predicting psychotic disorder
An international meta-analysis (Solmi et al, 2021) confirms that the onset of most mental disorders is in mid-adolescence. Diagnosis of psychosis is rare before the age of 12 years, but rises steadily through adolescence to peak at the age of 20 years. However, it is generally accepted that the warning signs of future psychosis are evident well before clinical diagnosis (Fusar-Poli et al, 2017; Catalan et al, 2021), and that it is important to intervene as early as possible in the disease progression. A review of the research (Millan et al, 2016) reported that once psychosis has become established, treatment prospects are limited.
‘The crucial factors seem to be socio-economic stress, social isolation and fragmentation, feelings of helplessness and defeat.’
A meta-review (Catalan et al, 2021) suggests that efforts to identify those at high risk of developing psychosis have had mixed results. These efforts focus on the CHR-P (clinical high-risk-psychosis) programme, recently revised (Fusar-Poli et al, 2017). This provides a prognostic system for identifying individuals at risk of developing psychosis and suggesting appropriate early intervention. Just as prognostic systems for cancer predict the outcome in terms of stages of symptoms, so the CHR-P suggests that there are ‘stages’ of risk for the development of psychosis. These stages are:
- Stage 0 – asymptomatic genetic risk. Catalan et al's (2021) meta-analysis finds that overall, the risk of developing psychosis here is no different from the general population over a 4-year period. The risk may be slightly higher where there are also socio-environmental risk factors (Fusar-Poli et al, 2016; Radua et al, 2018). The suggested intervention (if any) is to offer support for improved mental health where needed, and monitor for deterioration to higher-risk stages.
- Stage 1a – negative and cognitive symptoms. Individuals at this stage would have a variety of signs and symptoms, such as problems with cognition or emotional response. These are possibly signs of incipient psychosis, but could also reflect other problems, from depression and anxiety to substance abuse. Again, the risk of progression to psychosis is low (Fusar-Poli et al, 2017) but may be worth monitoring, and individuals may benefit from interventions to improve mental health – and certainly from interventions to reduce substance abuse where relevant.
- Stage 1b – attenuated psychotic symptoms (APS). Here, the individual begins to display some of the symptoms more specifically diagnostic of psychosis, such as altered perceptions and cognition, delusions and hallucinations. These are much more serious warning signs, and warrant close monitoring and psychological interventions such as cognitive behavioural therapy (CBT). Around 20% of individuals showing APS will transition to psychosis within 24 months (Fusar-Poli, 2017).
- Stage 1c – brief, limited, intermittent psychotic symptoms (BLIPS). These are individuals who briefly show limited and remitting symptoms of a full-blown psychosis. Around 40% of individuals showing BLIPS will transition to psychosis within 24 months (Fusar-Poli, 2017). Again, the advice is that such individuals should be closely monitored, and offered psychological therapies such as CBT.
- Stage 2 – Full episode of psychosis. Technically, this is no longer a risk stage as psychosis is already established. This is the group for whom more serious interventions are required, including anti-psychotic drugs and vocational rehabilitation (Fusar-Poli et al, 2017).
Intervening to head off psychotic disorder
When applied specifically to populations where there is already a suspicion of risk of psychosis the CHR-P programme can be as effective as (say) cancer staging systems, though application to a less selective population will obscure its utility (Fusar-Poli, 2017). But what it does successfully is identifying groups, specifically those with APS or BLIPS who are at high risk of psychosis (Catalan et al, 2021). What it does not do is identify which individuals within these high-risk groups will develop full-blown psychosis and which will not.
It is worth noting that the majority (80% of those with APS, and 60% of those with BLIPS) identified as CHR-P stages 1b and 1c do not go on to develop psychosis over a 2-year period. This poses practical challenges. Should we offer all with APS or BLIPS expert intervention? For all disorders, the NHS (NICE) calculates the NNT (number needed to treat) to prevent one bad outcome. It is accepted that we should treat many who will not benefit, to protect the one. NNT can be high: 250 for some disorders, 33 for others, and some experts think such NNT are too high, so that many are treated needlessly (Bogaty, 2005). Needless treatment is not without cost: for example, treating a teenager scored high risk of psychosis labels that individual in ways likely to alter how they are perceived and treated by others (and self) – which may be acceptable for the 20% APS who might be saved from full-blown psychosis, but what about for the other 80%? Labels can be damaging (Thornton, 2016).
Catalan et al's (2021) meta-analysis concluded that the evidence of effectiveness for this or that intervention in heading off psychosis is too poor to offer clear policy, even if CAMHS had the resources to intervene for all. The overall conclusion so far as intervention is concerned is: more research is needed.