Targeted treatment for depression may benefit patients with psychosis

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Patients with early onset psychosis may benefit from treatment for depression, including with anti-depressants alongside other medication, research shows. According to scientists at the University of Birmingham’s Institute for Mental Health, depression may be an intrinsic part of early phase psychotic disorders that should be treated together with other more prominent symptoms to improve patient outcomes.

Depression is often identified alongside psychotic disorders such as schizophrenia in the early stages of the disorder, but is not currently routinely treated. In the study, the researchers set out to find out more about the associations between depression and psychosis, and particularly whether there were similarities in brain structure that could help future diagnostic pathways at an early stage.

Data was gathered from 1,700 patients as part of the PRONIA study, a large-scale European study which uses machine learning to find ways to predict how people with recent onset psychosis might recover.

The team used demographic and clinical data along with detailed symptom measures and neuro-imaging information from a structural MRI scan from participants with recent onset psychosis and recent onset depression. They interrogated the data using machine learning software to try to find out whether it was possible to identify a subgroup of patients with distinct symptoms of both depression and psychosis.

Their results showed that, in fact, there was little difference in either the patients’ depressive symptoms or in the structural brain changes in patients with depression, with and without psychosis. This shows that there is no subgroup of patients with both depression and psychosis, but rather that depression may be an intrinsic part of a majority of patients’ psychosis.

The team argue their findings show that treatments focused on depression may well be an effective additional first-line treatment for psychosis, to be given alongside regular interventions.

Professsor Rachel Upthegrove, of the University of Birmingham’s Institute for Mental Health, led the study. She says: “Our results suggest that depression is absolutely inherent in early phases of schizophrenia and so may one of the most important factors that we can target with treatments.

“We know that depression in patients with schizophrenia frequently leads to poorer outcomes, and so understanding how treatment such as antidepressant might be used to improve these outcomes could be a big step forward.”

Paris Lalousis, a Priestly PhD Fellow at the University of Birmingham and the University of Melbourne, contributed to the study. He says: “Machine learning is a tool that has the potential to help solve the diagnostic and treatment conundrums that the complexity of mental health disorders present, and analyses using multi-modal data are needed to advance the field. Our results show that using a principled approach and both psycho-pathological and biological factors can shed light into the experiences of patients with depression in early psychosis.”

The team has already embarked on a clinical trial to test the approach in patients. The ADEPP trial will test people in the first stages of psychosis who take anti-depressants alongside anti-psychotic drugs. The trial will assess over a six-month period whether the anti-depressants have an effect on the patients’ ability to recover from their psychosis.

Abstract
Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit.

Authors
Rachel Upthegrove, Paris Lalousis, Pavan Mallikarjun, Katharine Chisholm, Sian Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Renate Reniers, Alexandra Stainton, Marlene Rosen, Anne Ruef, Dominic B Dwyer, Marian Surman, Theresa Haidl, Nora Penzel, Lana Kambeitz-llankovic, Alessandro Bertolino, Paolo Brambilla, Stefan Borgwardt, Joseph Kambeitz, Rebekka Lencer, Christos Pantelis, Stephan Ruhrmann, Frauke Schultze-Lutter, Raimo K R Salokangas, Eva Meisenzahl, Stephen J Wood, Nikolaos Koutsouleris, PRONIA Consortium

 

University of Birmingham material

 

Schizophrenia Bulletin abstract

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