A new study published in the Journal of Affective Disorders has found that a specific brain connection may help explain anhedonia, the inability to experience pleasure, particularly in males with psychiatric symptoms. Researchers identified that stronger connectivity between the paraventricular nucleus of the thalamus (PVT) and the nucleus accumbens (NAc)—two brain regions important for reward processing—was linked to more severe symptoms of anhedonia in these individuals. This finding could be a step forward in understanding the brain’s role in pleasure and motivation and may lead to improved treatments for anhedonia.
Mental illness is a widespread issue, with over 20% of U.S. adults reporting a mental health condition in 2021. Many psychiatric symptoms do not fit neatly into specific diagnoses, which has led researchers to focus on “transdiagnostic” symptoms—those that cut across various mental health disorders.
Anhedonia is one such symptom, affecting people with different psychiatric conditions like depression and anxiety. It is also linked to increased risk of suicide, substance abuse, and poorer treatment outcomes. Understanding the brain mechanisms that contribute to anhedonia is therefore crucial for improving mental health treatments.
“Mental health research is of utmost importance right now and the way we understand it is changing,” explained study author Bianca T. Leonard, a MD/PhD candidate at University of California, Irvine. “There are symptoms of mental health that go beyond the boundaries of traditional diagnoses. Anhedonia, or the inability to experience pleasure, is one of those symptoms. Anhedonia is a serious and life-threatening transdiagnostic symptom because it leads to poorer outcomes, and the brain biology that contributes to it has become critical for neuroscientists to understand in the quest to innovate new treatments in psychiatry.”
The research team recruited 75 participants from the community, but due to incomplete data or poor scan quality, the final sample consisted of 63 participants, including 48 women and 15 men. The participants underwent neuropsychiatric evaluations to assess symptoms of depression, anxiety, and other mental health conditions, as well as anhedonia. The group was divided into those with psychiatric symptoms (47 participants) and those without (16 participants).
Participants also underwent brain scans using resting-state functional magnetic resonance imaging (fMRI), a technique that allows researchers to measure how different regions of the brain communicate with each other when the brain is not actively engaged in a task. The researchers focused on the functional connectivity between the PVT and the NAc. To assess anhedonia, they used a factor score based on a subset of items from the Beck Depression Inventory, which included symptoms like loss of interest and lack of pleasure.
The study found that the overall strength of the PVT-NAc connection was not significantly related to anhedonia across the entire sample. However, when the researchers looked specifically at participants with psychiatric symptoms, a different pattern emerged. In this group, there was a trend suggesting that stronger connectivity between the PVT and NAc was linked to more severe anhedonia. This was not observed in participants without psychiatric symptoms.
Moreover, when the researchers analyzed the data by sex, they found that the relationship between PVT-NAc connectivity and anhedonia was stronger in males than in females. In males with psychiatric symptoms, the connection between these brain regions was significantly related to their anhedonia scores, while in females, this relationship was weaker and not statistically significant. This suggests that brain connectivity between the PVT and NAc may play a more prominent role in anhedonia for males experiencing psychiatric symptoms.
“Neuroscientists are learning more about which parts of the brain contribute to anhedonia so that we can develop better treatments for it,” Leonard told PsyPost. “It was known in the field that the nucleus accumbens (NAc) contributes to reward processing in the brain and is affected in anhedonia. However, this study introduced a new brain region, the paraventricular nucleus of the thalamus (PVT), to the understood neurocircuitry of human anhedonia. We showed that communication between the PVT-NAc is important in anhedonia, particularly for males experiencing psychiatric symptoms.”
“These findings are very well supported by rodent literature, and there is a growing body of research on the dopaminergic neurons in the nucleus accumbens that may underlie these findings. But it was surprising to detect an effect between these small regions of the brain in a modest-sized cohort.”
The researchers did not find any significant relationships between anhedonia and connectivity involving other parts of the thalamus, which suggests that the link between the PVT and NAc is particularly important in this context. These findings align with previous studies in animals that have shown the PVT’s involvement in regulating motivation and reward-seeking behaviors.
While the study provides new insights into the brain mechanisms involved in anhedonia, it also has some limitations. One such limitation is the relatively small sample size, particularly when analyzing sex differences. With only 15 males in the final sample, it is difficult to draw firm conclusions about whether the observed differences between males and females are meaningful.
“The sex-dependent effect should not be interpreted too strongly because our numbers are low, and we did not ask specific enough questions about sex and gender identities,” Leonard noted.
The researchers suggest that future work could explore how these brain circuits contribute to decision-making in people with anhedonia, particularly in situations involving reward or motivation.
“Next, we will be studying the role of the PVT in motivational conflict resolution in people experiencing anhedonia,” Leonard explained. “We want to understand how anhedonia affects decision-making and which parts of the brain, including the PVT and NAc are involved in this process. Our larger goal is to develop better therapeutics and diagnostics for anhedonia that are upheld by neurobiology and cognitive neuroscience.”
The study, “Anhedonia is associated with higher functional connectivity between the nucleus accumbens and paraventricular nucleus of thalamus,” was authored by Bianca T. Leonard, Sarah M. Kark, Steven J. Granger, Joren G. Adams, Liv McMillan, and Michael A. Yassa.
