Are prior mood disorders more important than positive symptoms for predicting psychosis?

Predicting which individuals will develop a psychotic disorder or transition from high risk of psychosis to symptoms is important for early intervention and offers potential to improve outcomes. Research into the association between prior mood disorders and the development of psychosis was presented at SIRS 2022.

Diagnostic categories for high risk of psychosis mainly specify the detection of positive symptoms, but this may not be the best way to screen for emerging psychotic illness in the community. "A large majority of incident psychotic disorders may not be attributable to prior positive psychotic experiences", reported Dr Umut Kirli, Ege University Institute on Drug Abuse, Toxicology and Pharmaceutical Science, Izmir, Turkey. 


Predicting psychosis in the community setting

Nearly 40% of individuals with psychotic experiences had prior mood symptoms

A representative general population-based study in Turkey, enrolling more than 4000 households, showed a relationship between prior mood episodes and future psychotic experiences at a 6-year follow up (n=2185). Just over 39% of individuals with psychotic experiences in this community setting had prior mood symptoms. Furthermore, more than 50% of individuals with psychotic experiences did not demonstrate any prior positive symptoms at all.1,2

Psychotic disorders often develop outside the exacerbation of positive symptoms


Predicting psychosis in ultra-high-risk individuals

Affective symptoms are one of the primary reasons why individuals at ultra-high risk (UHR) for psychosis seek help at early intervention services. However, predicting which of these individuals will transition to psychosis remains difficult and is an area under active investigation.

Dr Frederike Schirmbeck, University of Amsterdam, Netherlands presented data demonstrating the importance of past depression in predicting the transition to and the course of decreased psychotic symptoms (DPS).

Past depression is a risk factor for decreased psychotic symptoms in ultra-high risk individuals.

In a study of 331 individuals at UHR for psychosis, a past diagnosis of depression was associated with a statistically significant two-fold increase (hazard ratio: 2.1, P=0.012) in the risk of transition to DPS in individuals at UHR of psychosis. In addition, diagnosis of a past depressive episode negatively influenced the course of DPS.3


The affective pathway to psychosis

The affective pathway to psychosis theorises that recent life events lead to psychotic symptoms via an experience of emotional distress. Meta-analysis has shown that recent life events are not directly linked to positive and/or negative symptoms, but instead proceed through the general psychopathology of depression.4

"More focus on subgroups with a diagnosis of depressive symptoms and the use of targeted interventions may be useful in patients at UHR of psychosis", said Dr Schirmbeck.

SIRS : Schizophrenia International Research Society
UHR : ultra-high risk
DPS : decreased psychotic symptoms 

BE-NOTPR-0166, approval date : 06.2022


Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Kırlı U, et al. Psychotic experiences and mood episodes predict each other bidirectionally: a 6-year follow-up study in a community-based population. Soc Psychiatry Psychiatr Epidemiol 2019;54:331─341. 
  2. "Are prior mood disorders more important than positive symptoms for predicting psychosis?"
    Oral Session: Early Psychosis and Markers of Psychosis SIRS 2022 screenshots
  3. Schirmbeck F, et al. Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis. Schizophr Bull 2022;48:100─110. 
  4. Betz LT, et al. General psychopathology links burden of recent life events and psychotic symptoms in a network approach. NPJ Schizophr 2020;6:40.
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