Psychosis and schizophrenia

I recently found several articles dealing with psychopathology. First, Bronstein et al. (2025) published “Delineating Empirically Plausible Causal Pathways to Suicidality among People at Clinical High Risk for Psychosis” in Journal of Psychopathology and Clinical Science. Here are the edited abstract and impact statements:

Suicidality is common among people at clinical high risk (CHR) for psychosis. Delineating causal pathways to suicidality and identifying its determinants would inform tailored intervention efforts for these individuals. To this end, we analyzed data on CHR samples from the second and third North American Prodrome Longitudinal Studies (NAPLS-2, n = 355; NAPLS-3, n = 266). Data on correlates of suicidality—including depression and attenuated psychosis symptoms, sleep, and childhood trauma—from two initial study timepoints were submitted to the greedy relaxations of the sparsest permutation algorithm. Intervention calculus was used to estimate the (lower bound) total empirically plausible causal effects of each variable on suicidality. Across both samples, greedy relaxations of the sparsest permutation suggested that symptoms of depression—particularly hopelessness, self-deprecation, and depressed mood—were likely direct causes of suicidality among people at CHR for psychosis. Across samples and measurement time points, intervention calculus indicated that depressed mood exerted the greatest influence over suicidality of all measured variables. This study provides data-driven, testable hypotheses about the causal pathways leading to suicidality among people at CHR for psychosis and suggests promising targets for interventions on suicidality tailored to these individuals. Future experimental research should test these hypotheses by, for example, comparing the suicide risk reduction afforded by interventions aimed at each aforementioned target. 

This study suggests that specific symptoms of depression—particularly hopelessness, self-deprecation, and depressed mood—likely contribute to suicidality among youth at clinical high risk for psychosis. It further suggests that depressed mood is likely to be a particularly critical determinant of suicidality in these youth. 

The findings are not surprising but I thought it was helpful that a longitudinal study with a good size sample supported these findings. It makes sense that targeting hopelessness, self-deprecation, and, especially, depressed mood can be helpful in working with suicidality. The next study turns to personality and looks at experience after the onset of psychosis. Martin, Blank, Jonas, Liann & Kotov (2025) published “Personality in Psychosis Decades after Onset: Tests of models of the relations between psychopathology and personality” in Journal of Psychopathology and Clinical Science. The edited abstract and impact statement follows:

Models have been put forth to describe relations between psychopathology and personality. However, the relation in individuals with psychotic disorders is unclear. As a test of models of psychopathology-personality in psychosis, the current study included 239 individuals, each with one of four psychotic disorders—schizophrenia (SZ), bipolar disorder with psychotic features (BPp), major depressive disorder with psychotic features (MDDp), and substance-induced psychosis (SIP)—and compared their personality to a never-psychotic sample (NP; n = 257). In support of the complication + scar model, we found SZ, BPp, MDDp, and SIP were significantly higher on neuroticism and detachment, and most were higher on mistrust and eccentric perceptions than the NP group (average Cohen’s d = |0.83| across all personality measures). Also compared to the NP group, SZ was lower on extraversion, agreeableness, and conscientiousness; MDDp was lower on extraversion and conscientiousness; and SIP was lower on agreeableness and conscientiousness (average Cohen’s d = |0.77|). Differences were observed among the psychotic disorder groups (SZ, BPp, MDDp, SIP), with effects up to d = 1.38. In support of the complication model, the non-recovered group was significantly higher on mistrust, eccentric perceptions, and detachment but lower on extraversion and conscientiousness than the recovered group (average d = |0.57| across measures). In support of the scar model, individuals who met threshold for recovery continued to manifest personality deviations, although smaller in magnitude (average d = |0.32| across measures) compared to NP. Overall, we found support for the complication and scar models, suggesting that while symptoms are associated with personality differences, psychosis is associated with permanent personality alterations.

There are multiple, nonmutually exclusive models to explain the relation between personality and psychopathology. The current study provides evidence for two models, which together suggest that the experience of psychosis is associated with personality differences compared to healthy individuals and that these differences persist to varying degrees following symptom remission. 

Although I had to pass a stat exam in grad school, it’s been a long time since I had to use statistics. This study, like the last, involves statistical procedures I never learned. I was not surprised that the non-recovered group is higher on mistrust, eccentric perceptions, and detachment with lower extraversion and conscientiousness. I also thought it intriguing that the people persisted in the same personality characteristics but at lower levels. The final study loks at schizophrenia. Zavitsanou, Waldren, Walton & Baltramonaityte (2024) published “The Role of Loneliness and Social Isolation in Mediating the Relationship between Childhood Maltreatment and Schizophrenia: A genetically informed approach” in Journal of Psychopathology and Clinical Science. Here are edited excerpts:

Observational studies have found loneliness and social isolation to mediate the relationship between childhood maltreatment and schizophrenia. Limitations with observational studies (e.g., confounding and reverse causation), however, have meant the robustness of these relationships has thus far not been explored. To address this gap, the current study utilized genomic structural equation modeling (genomic SEM) and Mendelian randomization (MR) to perform a genetic mediation analysis between childhood maltreatment, loneliness/isolation, and schizophrenia, using summary statistics from three genome-wide association studies (sample sizes 105,318–487,647). While we observed a putative effect of both childhood maltreatment (inverse variance weighted OR = 3.44 per standard deviation increase, 95% confidence interval [CI] [1.66–7.13], p < .001) and loneliness/isolation (OR = 2.98, 95% CI [1.37–6.46], p = .006) on schizophrenia, our hypothesis that loneliness/isolation would mediate the relationship between childhood maltreatment and schizophrenia was not supported (genomic SEM indirect effect = −0.05, SE = 0.05, p = .255; MR indirect effect = 0.10, SE = 0.11, p = .369). Furthermore, reverse mediation analysis indicated that the effect may be in the opposite direction (genomic SEM indirect effect = 0.11, SE = 0.02, p < .001; MR indirect effect = 0.01, SE = 0.00, p < .001), accounting for 20.3%–28.9% of the total effect. 

This study suggests that loneliness/social isolation does not mediate the relationship between childhood maltreatment and schizophrenia. Contrary to previous research, our results indicate that targeting loneliness and social isolation in individuals with a history of childhood maltreatment is unlikely to diminish schizophrenia risk. In fact, we find evidence of mediation in the reverse direction, whereby a genetic predisposition to schizophrenia increases the risk of loneliness/social isolation, which in turn increases childhood maltreatment risk.

As such, while there may be merit in clinical interventions targeting loneliness/isolation in individuals who have experienced childhood maltreatment, the current results suggest that targeting loneliness/isolation in this group is unlikely to reduce the risk of developing schizophrenia. Greater benefits may be observed by intervening in loneliness/isolation in individuals with a genetic predisposition toward schizophrenia, as this may diminish childhood maltreatment risk. Taken together, these findings provide key novel insights into the link between childhood maltreatment and schizophrenia, with significant implications for targeted clinical interventions.

This is a huge sample and I like the fact that it circles nicely back to the Bronstein et al. study in that it is not that child maltreatment causes schizophrenia but that people with high genetic risk of developing schizophrenia more often experience childhood trauma. Together, these studies illustrate that, with more sophisticated statistical strategies, we stand a much better chance of developing appropriately targeted interventions.