Summary: A new study has discovered a biological link between inflammation and motivational deficits in people with schizophrenia, suggesting a promising therapeutic target for symptoms that are not resolved by current medications. Elevated levels of the inflammatory marker C-reactive protein were associated with reduced activity in brain regions involved in reward and motivation, such as the ventral striatum and ventromedial prefrontal cortex.
These brain changes were specifically associated with negative symptoms, such as difficulty initiating tasks or maintaining social relationships, rather than delusions or hallucinations. These findings provide the basis for studies of health-related drugs targeting inflammation in this subgroup of patients.
Important facts:
- The link between inflammation and motivation: Elevated levels of C-reactive protein are associated with motivational deficits.
- Affected brain circuit: Inflammation alters reward-related activity in the ventral striatum and prefrontal cortex.
- Targeted therapy trials: Infliximab is being tested in patients with high levels of inflammation and negative symptoms.
Source: Emory University
A new study from Emory University reveals a biological link between inflammation and motivational deficits in people with schizophrenia, offering new hope for treating symptoms that have long been resistant to current treatments.
The study, published in Neuropsychopharmacology, the official journal of the American College of Neuropsychopharmacology, found that high levels of C-reactive protein (a blood biomarker of inflammation produced by the liver) are associated with reduced activity in brain circuits associated with reward and motivation.
These brain changes, in turn, were linked to the negative symptoms of schizophrenia, particularly motivational deficits, such as difficulty finding work, relationships or studying. Inflammation was not associated with other symptoms of schizophrenia, such as delusions, hallucinations or depression.
The findings are important because current antipsychotics do not address these motivational deficits and in some cases may even exacerbate them. These symptoms are also strongly associated with poor functional functioning in patients with schizophrenia.
The researchers focused on a key brain circuit that spans the ventral striatum and ventromedial prefrontal cortex. These are areas that have previously been shown to be sensitive to inflammation in depression studies.
Dr. David Goldsmith, an associate professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, emphasized the significance of a recent breakthrough in schizophrenia research. He noted that this is the first study to establish a direct link between inflammation and alterations in the brain’s reward circuitry, which plays a crucial role in regulating motivation. These findings mark an important step forward in understanding the biological underpinnings of specific motivational symptoms often seen in individuals with schizophrenia—symptoms that have long been challenging to treat effectively. The study’s results shed new light on how inflammation may be disrupting neural pathways involved in the processing of rewards, ultimately contributing to the lack of drive or interest that many patients experience.
According to Dr. Goldsmith, this deeper understanding of the biological mechanisms behind motivational deficits opens the door to more precise, targeted treatments for schizophrenia. By identifying inflammation as a contributing factor to changes in the brain’s reward system, researchers can now begin exploring therapies that directly address this pathway, rather than relying solely on traditional antipsychotic medications, which often fall short in treating motivational impairments. This advancement brings renewed hope for developing interventions that not only manage the broader symptoms of schizophrenia but also provide meaningful relief from the specific and often debilitating lack of motivation that affects patients’ quality of life.
The study supports a precision medicine approach by suggesting that treatments that target inflammation may only benefit a specific group of patients: those with inflammatory markers and significant motivational issues.
For example, previous studies of anti-inflammatory drugs in schizophrenia patients have largely failed because it was not possible to determine which patients would benefit from this approach.
This work formed the basis of an ongoing experimental drug trial at Emory, testing the anti-inflammatory drug infliximab. Infliximab is commonly used to treat rheumatoid arthritis and inflammatory bowel disease (IBD), in schizophrenia patients who experience high levels of inflammation and motivational deficits.
This is the first study of infliximab in this patient population and is designed to examine whether the effects of inflammation on this circuit and these symptoms may be causal.
Goldsmith said there is an urgent need to develop new strategies for treating the negative symptoms of schizophrenia, which is one of the greatest needs in the area.
We hope this research will change that. If we want to support recovery from schizophrenia, we need to be able to treat these symptoms.
Funding: This research was funded by the National Institute of Mental Health through a K23 Career Development Grant (K23MH114037) totaling $957,420 over five years, and grants KL2TR002381 and UL1TR002378. The project supervisors were Andrew Miller, MD (primary mentor), Michael Treadway, PhD, and Elaine Walker, PhD.
About this inflammation and schizophrenia research news
Author: Jennifer Johnson McEwen
Source: Emory University
Contact: Jennifer Johnson McEwen – Emory University
Image: The image is credited to StackZone Neuro
Original Research: Closed access.
“Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia” by David Goldsmith et al. Neuropsychopharmacology
Abstract
Inflammation is associated with avolition and decreased resting functional connectivity in the corticostriatal reward circuit in patients with schizophrenia.
Low-grade inflammation in patients with schizophrenia is associated with negative symptoms. One of these symptoms is a lack of motivation and pleasure, especially in the context of a will, which is particularly disabling.
The effects of inflammation on motivational deficits in patients with depression are linked to changes in the corticostriatal reward circuit involving the ventral inferior striatum (iVS) and ventromedial prefrontal cortex (vmPFC).
Therefore, we investigated the relationships between inflammation, negative symptoms, and the corticostriatal reward circuit in patients with schizophrenia.
Negative symptoms and high-sensitivity C-reactive protein (hs-CRP) were measured in 57 individuals with schizophrenia. Resting-state functional connectivity (rFC) was measured in a subset of 43 of these individuals.
Associations between hSCRP and the Brief Negative Symptom Scale (BNSS) arousal and pleasure dimensions (MAP) and expressiveness (EXP), as well as LVEF and vmPFC, were examined. Covariates in all statistical models included age, sex, race, smoking status, body mass index (BMI), depression, and chlorpromazine equivalents.
hsCRP was significantly associated with BNSS MAP (β = 0.34, pcorr = 0.022), especially in the avolition and associativity domains (p < 0.05), but not with BNSS EXP (β = −0.17, pcorr = 0.57) or blunted affect or both > alogia. hsCRP was also significantly associated with reduced rsFC from the right iVS to the vmPFC (β = −0.37, pcorr = 0.029), which in turn was associated with greater aversion in individuals with higher (hsCRP > 2 mg/L) but not lower inflammation (β = −14.01, p = 0.77, p = 0.77, respectively).
HSCRP was associated with reduced arousal and corticostriatal RSFC, as well as increased inflammation, in patients with schizophrenia. This emphasizes the need for further research to replicate these associations with changes in brain connectivity in this subgroup of individuals with schizophrenia.
