Young adults at risk of psychosis show reduced brain connectivity, a deficit that cannabis use appears to worsen, a new study has found. The breakthrough paves the way for psychosis treatments targeting symptoms that current medications miss. In the first-of-its-kind study, McGill University researchers detected a marked decrease in synaptic density in individuals at risk of psychosis, compared to a healthy control group.
“Not every cannabis user will develop psychosis, but for some, the risks are high. Our research helps clarify why,” said Dr Romina Mizrahi, senior author of the study and professor in McGill’s Department of Psychiatry.
“Cannabis appears to disrupt the brain’s natural process of refining and pruning synapses, which is essential for healthy brain development.”
Hope for new treatments
Using advanced brain scanning technology, the team studied 49 participants aged 16 to 30, including individuals with recent psychotic symptoms and those considered at high risk. The results, published in JAMA Psychiatry, indicate that lower synaptic density is linked to social withdrawal and lack of motivation, symptoms the researchers say are difficult to treat.
“Current medications largely target hallucinations, but they don’t address symptoms that make it difficult to manage social relationships, work, or school,” said first author Belen Blasco, a PhD student at McGill’s Integrated Program in Neuroscience. “By focusing on synaptic density, we may eventually develop therapies that enhance social function and quality of life for those affected.”
While cannabis is a known risk factor for developing psychosis, which can progress to schizophrenia, this is the first time researchers have measured structural changes in the brains of a high-risk population in real time.
The team’s next research phase will explore whether these observed brain changes could predict psychosis development, potentially enabling earlier intervention.
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A study by researchers at the University of Helsinki and HUS Helsinki University Hospital found a significant association among adolescents between having psychotic-like experiences and depressive symptoms, as well as with self-destructive behaviours.
Psychotic-like experiences resemble symptoms of psychosis, but are milder, less frequent and much more common than psychotic disorders. While these symptoms do not constitute a disorder diagnosed as psychosis, they can still be disruptive, distressing or detrimental to functional capacity. Typical psychotic-like experiences include perceptual distortions and hallucinations, suspicious paranoid thinking, delusions and bizarre, unusual thoughts.
Psychotic-like experiences are abundant among adolescents referred to care, but are generally considered fairly neutral, with only some of the adolescents reporting them as frightening, worrisome or harmful. In the study, published in the journal Psychosis, the correlation between psychotic-like experiences and depressive symptoms turned out to be strong. This link was not explained by connections between individual psychotic-like experiences and depressive symptoms, but by factors that more broadly measure paranoia and unusual thoughts. In addition to depressive symptoms, paranoid thoughts and unusual thought content were also associated with self-destructive thinking.
Making questions about psychotic-like experiences part of care
The findings show that psychotic-like experiences should be systematically surveyed in all adolescents seeking psychiatric care. It should also be assessed how frightening, worrisome or harmful they are considered to be. Particularly in the case of responses emphasising bizarre thinking and exaggerated suspiciousness, attention should also be paid to assessing mood and self-destructive thinking, as these factors can remain hidden without further enquiry.
“Our findings provide a clear recommendation for treatment practices: psychotic-like experiences should be assessed as part of routine procedures, but it is also important to determine how they are perceived. These phenomena cannot be uncovered unless separately and systematically asked,” says the principal investigator, Docent Niklas Granö.
It should be clearly explained to adolescents and their families that these symptoms are common and often manageable. In addition, applications of cognitive psychotherapy, even brief interventions, can help adolescents understand their symptoms and alleviate the strain they cause.
New findings from McGill University researchers could help clinicians understand the course of delusions in youth and young adults that signal the need for a timely intervention to prevent a full relapse of psychosis.
Delusions – strong beliefs that don’t align with commonly accepted reality – are a defining symptom of psychosis but are not sufficiently understood.
For the first time, researchers studied whether delusion themes, such as paranoia or grandiosity, stay the same or shift between psychotic episodes in youth and young adults undergoing early intervention treatment.
The importance of timely treatment
Notably, most patients did not relapse at all following their first episode, showing the efficacy of early intervention and highlighting the need for improved access, said the researchers. An estimated 75% of children with mental disorders do not use specialised treatment services, according to Youth Mental Health Canada.
“Early intervention is essential if we want to give young people the best chance at lasting recovery,” said lead author Gil Grunfeld, a recent master’s graduate from McGill’s Department of Psychiatry and a current doctoral student at Boston University.
Detecting patterns in delusions
The study, published in JAMA Psychiatry, found that in the less likely instances of relapse, patients almost always had the same type of delusion as their first episode.
“The return of similar narratives potentially suggests the mind may be reflecting the same patterns seen in earlier episodes,” said Grunfeld.
“Recognizing this pattern of delusions in those who go on to relapse could help clinicians understand the experience of their patients and adjust the care they provide,” said Dr Jai Shah, an Associate Professor in McGill’s Department of Psychiatry and a researcher at the Douglas Hospital Research Centre.
Delusions often persisted even as other symptoms improved, suggesting delusions may require different treatment strategies, he added.
“Delusions are often highly distressing and difficult to define, which makes closing the gap in research all the more crucial. There is a great deal of future work to be done,” said Grunfeld.
The researchers followed about 600 patients ages 14 to 35 for up to two years. All were receiving treatment at an early-intervention service for psychosis in Montreal.
The illicit use of amphetamines (aka ‘speed’) is linked to a 5-fold heightened risk of psychosis, according to the results of a decade-long study published in the journal Evidence-Based Mental Health.
This increased risk was seen across all age groups, but was especially noticeable among women and those who had been arrested several times for possession of the drug, the findings show.
The estimated global prevalence of amphetamine use is less than 1%, but around 1 in 10 users become addicted.
The drug affects neurotransmitter signalling in the brain and often causes psychosis, the symptoms of which mimic those of schizophrenia, with paranoia, voices, and hallucinations. Though these psychotic episodes usually subside after a few days, in up to 15% of users they may last for years.
While the link between amphetamine misuse and psychosis has been known for many decades, it’s not clear exactly what the magnitude is of this risk or how effective rehab is at successfully weaning users off the drug.
To try and find out, the researchers drew on information supplied to the Taiwan Illicit Drug Issue Database (TIDID) and the National Health Insurance Research Database (NHIRD) between 2007 and 2016.
The TDID contains anonymised data on date of birth, sex, arrest records and deferred prosecution for rehabilitation treatment for illicit drug users, while the NHIRD contains anonymised data on mental and physical health issues for the population of Taiwan.
The researchers identified 74 601 illicit amphetamine users and 298 404 age- and sex-matched comparisons. Their average age was 33 and most (84%) were men.
Compared with those who weren’t using, illicit amphetamine users had poorer health: depression (2% vs 0.4%); anxiety (0.9% vs 0.3%); ischaemic heart disease (1.3% vs 0.8%); cardiovascular disease (0.8% vs 0.45%); and stroke (1.3% vs 0.7%).
By the end of the 10 year monitoring period, amphetamine users were more than 5 times as likely to experience psychosis than those who weren’t using after accounting for age, sex, and coexisting health issues. The annual cumulative incidence rates for psychosis among the comparison group and amphetamine users were 77 and 468 per 100 000 people, respectively.
The number of new cases of psychosis was similar across all age brackets, but was more common in the amphetamine users among those aged 45 and above.
While psychosis risk increased with comorbidities, overall, it was higher among illicit amphetamine users without coexisting conditions, suggesting a direct impact of amphetamine on inducing psychotic symptoms, the researchers said. Psychosis risk rose in tandem with the number of arrests, and fell when patients received psychotherapy for their addiction (rehab).
Those who had been arrested 5 or more times were more than 6 times as likely to experience psychosis, while users who went to rehab during deferred prosecution were 26% less likely to experience psychosis than those who didn’t. This suggests that rehab may help to stave off the risk of subsequent psychosis, say the researchers.
In common with previous research, illicit amphetamine use was linked to greater levels of anxiety and depressive symptoms as well as cardiovascular complications.
“Because persistent psychotic symptoms could represent a risk for cognitive decline in amphetamine users, identifying [those] with psychosis and providing treatment early might prevent subsequent damage of cognitive functions,” write the researchers. But rehab is voluntary, and only offered to around 1 in 10 users, they point out.
By way of an explanation for the gender discrepancy observed, the researchers suggest that the detrimental impact of amphetamines on behaviour might be enhanced by the presence of oestrogen.
“Another possibility is that women arrested for illicit amphetamine use were particularly disadvantaged in comparison with men, with higher levels of trauma, lack of psychosocial support and stigma,” they noted.
As an observational study, it cannot establish cause, and addiction could not be quantified. Illicit amphetamine use could also precipitate and aggravate schizophrenic symptoms, so it’s possible that amphetamine induces rather than causes the psychotic symptoms seen in amphetamine users.
The researchers concluded: “The relation of an induced paranoid psychosis with amphetamine abuse has been known for many decades. None the less, our findings are from a detailed and comparative analysis using a comprehensive and large population dataset.
“Furthermore, it would be worthwhile to investigate the health benefits and cost effectiveness of deferred prosecution for drug crime offenders by providing appropriate therapy for drug addiction.”
