An exploratory magnetic resonance imaging study of suicidal ideation in individuals at clinical high-risk for psychosis
Introduction
Individuals with schizophrenia die almost 15 years earlier than individuals without schizophrenia (Hjorthoj et al., 2017). Much of this excess risk is related to suicidality (Bushe et al., 2010). Upwards of half of individuals with psychotic disorders experience suicidal ideation (SI) during their lifetimes (Fenton et al., 1997; Skodlar et al., 2008) and approximately 30% attempt suicide at some point in their lives (Barrett et al., 2011). The lifetime risk of dying by suicide in schizophrenia and related disorders has been reported to be between 5 and 10% (Carlborg et al., 2008; Kasckow et al., 2011; Palmer et al., 2005; Siris, 2001). Therefore, suicidality constitutes a significant problem among individuals with psychotic disorders.
Suicide and suicidal ideation are especially problematic in the early stages of psychosis when patients are at an even greater risk of dying by suicide (Dutta et al., 2010; Mortensen and Juel, 1993; Nordentoft et al., 2004; Palmer et al., 2005). Neurobiological work on suicide in psychosis is limited but has revealed abnormalities in white matter (Lee et al., 2016; Long et al., 2018; Rusch et al., 2008) and brain function (Minzenberg et al., 2015; Potvin et al., 2018). Some of the most consistent work has demonstrated cortical thinning or lower gray matter volumes in several regions including in temporal and insular cortices (Besteher et al., 2016; Giakoumatos et al., 2013) as well as other abnormalities (Aguilar et al., 2008; Spoletini et al., 2011). The importance of these brain regions to suicide is highlighted by a recent, comprehensive review by Schmaal and colleagues (Schmaal et al., 2020). In this review, Schmaal and colleagues provide a model of suicidal thoughts and behaviors in which an extended ventral and posterior network, including temporal and insular cortices, may be responsible for negative and blunted emotional and mood states, while a more dorsal network would be more responsible for suicidal behavior due to its role in cognitive control and flexibility (Schmaal et al., 2020).
There is substantially less work on suicidality in the pre-syndromal or clinical high-risk (CHR) period. However, the available evidence suggests that SI and suicide attempts are very common – upwards of 50% or more in some studies (Andriopoulos et al., 2011; DeVylder et al., 2012; Gill et al., 2015; Hutton et al., 2011). These data are consistent with evidence that the mere presence of positive symptoms, either frank or attenuated, is strongly associated with suicidality (Kelleher et al., 2013, 2012; Yates et al., 2019).
Despite these important findings which suggest that identifying suicidality, and biomarkers of suicidality, in the early stages of psychosis could potentially identify those who will go on to attempt suicide, there remain no studies of the neurobiology of suicide in the CHR phase of the illness.
Aleman and Denys have written that despite the prevalence of suicidality, its societal impact, and its financial burden, as well as that suicidality is preventable and treatable, not enough progress has been made towards understanding and treating suicidal behavior (Aleman and Denys, 2014). They suggest that psychiatry has neglected research on suicidality for reasons such as cultural taboo, its complicated and multi-factorial nature, and potentially diverse etiologies between fatal and non-fatal suicide attempts. To address these issues, they advise a number of solutions, including funding further research on the psychological and neurobiological roots of suicide.
Therefore, the goals of this exploratory, pilot study were to examine the neurobiology of SI, the precursor to suicidal behavior, among CHR individuals. We focused on cortical thickness given that the most robust and replicated findings on the neurobiology of suicide in psychosis suggest abnormalities in cortical thickness and gray matter volumes in schizophrenia (Girgis, 2020). In particular, while we examined the full cortical mantle, our primary areas of interest were insula and temporal cortex given that these were the primary areas found to be abnormal in two prior studies of cortical thickness and gray matter volume in individuals with schizophrenia and related psychotic disorders who had previously attempted suicide (Besteher et al., 2016; Giakoumatos et al., 2013). We hypothesized that temporal and insular cortices among CHR individuals with SI would be thinner than in CHR individuals without SI and healthy control subjects.
Section snippets
Participants
Subjects were recruited at the Center of Prevention and Evaluation (COPE), an outpatient research program for the evaluation and treatment of attenuated positive symptoms of psychosis at the New York State Psychiatric Institute (NYSPI)/Columbia University Irving Medical Center (CUIMC) in New York City. The NYSPI Institutional Review Board approved the research. All adults provided written informed consent, while minors provided written assent, with written informed consent obtained from a
Demographic and clinical variables at baseline
The CHR group with suicidal ideation was significantly younger than the healthy controls (p = 0.037). Those with suicidal ideation had a higher severity of general symptoms (GTOT) i.e. sleep, mood, motoric disturbances and impaired tolerance to stress compared to those without suicidal ideation (p = 0.009). This is expected given that suicidality would be captured in this section of the SIPS. Also as expected, their functioning (GAF) was significantly lower compared to those without suicidal
Discussion
In the current exploratory, pilot MRI study, we observed increased cortical thickness in insular and middle temporal regions in CHR individuals with SI compared to those without SI and, to a lesser degree, healthy control subjects. In addition, we observed no relationships between the intensity of SI and cortical thickness in any cortical regions.
These findings are consistent with the findings of Giakoumatos and colleagues and Besteher and colleagues who found abnormalities in cortical
Funding & disclosure/conflicts of interest
This work was supported by the National Institutes of Health R01MH093398–01.
R. Girgis acknowledges receiving research support from Otsuka, Allergan/Forest, BioAvantex, and Genentech and advances/royalties for books published by Wipf and Stock and Routledge/Taylor and Francis. G. Brucato acknowledges receiving advances/royalties for books published by Prometheus Books and Routledge/Taylor and Francis. F. Provenzano is an equity holder in and advisor for IMIJ technologies. All other authors deny
Acknowledgements
We acknowledge the individuals who participated in this study.
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These authors contributed equally.