Greater risk of schizophrenia among people with HIV – especially those who inject drugs

While the risk of being diagnosed with schizophrenia was higher among all people with HIV in a large Danish cohort, those who acquired HIV through injecting drug use were at a much higher risk. This research also highlights the complex familial factors that may play a role in being diagnosed with schizophrenia.

Background

HIV and substance use are both associated with increased mental health challenges. In Denmark, around 10% of people with HIV acquired it through injecting drug use.

There are very few studies on diagnoses of schizophrenia spectrum disorder among people with HIV. Schizophrenia spectrum disorders include schizophrenia, delusional disorders, schizoaffective disorders and other related conditions. A diagnosis is more likely during the late teen years and early adulthood period.

Dr Cecilie Vollmond from Copenhagen University Hospital and colleagues undertook a large population-based cohort study to investigate the risk of being diagnosed with schizophrenia spectrum disorder among people with HIV. Their findings were published in AIDS.

This study is unique in that it tracked diagnoses in both people with HIV and their siblings. This is because schizophrenia is highly ‘heritable’ – it runs in families. For instance, a person’s identical twin has a 1 in 2 chance of developing schizophrenia if they have it. Additionally, rates were compared to matched individuals in the population and their siblings. Researchers aimed to identify multiple potential causes or predisposing factors associated with the development of schizophrenia spectrum disorders. This approach helps disentangle genetic causes and the family environment from HIV-related factors that may contribute to developing schizophrenia.

The study

All Danish residents receive medical care free of charge and are assigned a unique ten-digit personal identification number. HIV care is provided at ten specialised centres throughout the country. Using surveillance data from various national systems including the Danish HIV Cohort Study, researchers were able to identify people with HIV who later went on to be diagnosed with schizophrenia spectrum disorder, along with data on their siblings.

People with HIV were compared to members of the general population, while their siblings were compared to the comparators’ siblings. Researchers also considered HIV transmission category – injecting drug use, men who have sex with men, heterosexual contact, and ‘other’. The primary outcome of interest was a diagnosis of schizophrenia spectrum disorder. Additional outcomes were visits to a psychiatric hospital due to schizophrenia and receiving antipsychotic medication.

Researchers included 5191 people of Danish origin diagnosed with HIV between 1995 and 2021, aged 16 and older. The median age was 40 and most were men (86%). For each person with HIV, there were seven age and gender matched individuals from the general population without HIV, resulting in a comparison cohort of 36,337 people.

There were 7042 siblings of people with HIV included in the analyses – two-thirds of these were full siblings, sharing both biological parents – and 46,453 siblings of the comparison cohort included, with 78% of these being full siblings.

HIV linked to schizophrenia, but the picture is complex

Overall, people with HIV had an over four-fold increased risk of being diagnosed with schizophrenia spectrum disorder than people from the general population (Hazard Ratio 4.6, 95% Confidence Interval 3.8-5.6). Of this group, those who had acquired HIV through injecting drug use were at a much higher risk of being diagnosed with schizophrenic disorder (HR 11.3, 95% CI 7.7-16.4). The 20-year risk of developing schizophrenia spectrum disorder was 3.7% among all people with HIV, and 9.5% among those with injecting drug use as the transmission route. Additionally, people under 40 and women were more likely to be diagnosed with schizophrenia spectrum disorder. This general pattern was similar even when people with pre-existing mental health disorders and substance use were excluded.

There was also an increased risk of schizophrenia spectrum disorder among the siblings of people with HIV when compared to the comparison cohort’s siblings (HR 1.5, 95% CI 1.2-1.9). This pattern held more strongly for full siblings than for half siblings. Another fascinating finding was that this pattern held even more strongly for siblings of people with HIV from injecting drug use – they were nearly three times more likely to develop schizophrenia spectrum disorder than the comparison siblings (HR 2.9, 95% CI 1.9-4.5). This was not the case for people who had acquired HIV via other transmission routes.

While researchers could not collect information on the substance use habits of the siblings, these findings indicate that HIV is not the only risk factor associated with a later diagnosis of schizophrenia. Genetic and environmental exposure factors shared by siblings may predispose them to both engaging in substance use and later developing schizophrenia.

The researchers also highlighted the potential for reverse causality in the case of people who acquire HIV from injecting drug use – while the substance use may lead to mental health challenges, it may also be the case that substances are used to cope with existing mental health issues, possibly as a form of self-medicating.

More people with HIV had psychiatric hospital visits or received antipsychotic medications, compared to those in the general population. Interestingly, the finding related to medication was especially true in the year of HIV diagnosis – indicating the impact being diagnosed with HIV can have on one’s mental health, especially among those already predisposed to mental health illness.

Conclusion

The authors note that there are multiple potential explanations for their findings, including people with HIV having regular contact with health services, and therefore being more likely to be diagnosed with schizophrenia and other comorbidities, and HIV having neuro-invasive properties – potentially explaining a direct link between HIV and the development of schizophrenia.

They acknowledge that they were unable to measure certain risk factors – such as cannabis use – that also have established links to the development of schizophrenia.

Practically, the authors say that clinicians caring for people with HIV, especially people who acquired HIV through injecting drug use, should be aware of the increased risk of schizophrenia spectrum disorder.