Brain illustration with amygdala and hippocampus glowing, cityscape background.

Unlocking the Mystery: How Brain Structure Relates to Persistent Negative Symptoms in Psychosis

Theo Raines in Health & Wellness July 2025 • 4 min read.

"New research sheds light on the link between the amygdala, hippocampus, and the challenging symptoms of psychosis, offering hope for early intervention and improved outcomes."

Negative symptoms are a significant obstacle for individuals experiencing psychosis, often leading to reduced motivation and a lack of goal-directed behavior. These symptoms, when persistent, can severely impact a person's ability to function and thrive in daily life. Understanding the underlying causes is crucial for developing effective treatments.

A recent study published in Translational Psychiatry has uncovered a fascinating connection between the structure of the brain, specifically the amygdala and hippocampus, and the presence of persistent negative symptoms (PNS) in individuals experiencing their first episode of psychosis (FEP). This research offers valuable insights into the neurobiological basis of these symptoms.

The study differentiated between those with early persistent negative symptoms (ePNS), those with secondary persistent negative symptoms (sPNS) and those without PNS to explore how volume and shape of hippocampus and amygdala play in role with age.

The Amygdala-Hippocampus Connection: What the Research Reveals

Brain illustration with amygdala and hippocampus glowing, cityscape background.

The research team, led by C Makowski and M Lepage, utilized magnetic resonance imaging (MRI) to examine the brain structures of individuals with FEP. They focused on the amygdala and hippocampus, two brain regions known to play critical roles in emotional processing, motivation, and memory. The study compared patients with early persistent negative symptoms (ePNS), patients with persistent negative symptoms due to other factors (sPNS) and those without PNS.

The findings revealed several key differences in brain structure among the groups:

Reduced Volumes: Individuals with ePNS showed significantly smaller volumes in the left amygdala and right hippocampus compared to those without PNS.
Age-Related Changes: The relationship between age and brain structure differed significantly. In individuals with ePNS, the amygdala and hippocampus showed different patterns compared to the other groups.
Surface Area Differences: Morphometric analysis revealed decreased surface area in specific regions of the amygdala in ePNS patients compared to other patient groups and controls.

These findings suggest that persistent negative symptoms in psychosis are associated with specific structural changes in the amygdala and hippocampus. Furthermore, the differing age trajectories indicate that these changes may reflect an altered developmental process in individuals with ePNS.

Implications for Early Intervention and Treatment

This research highlights the importance of early identification and intervention for individuals experiencing psychosis. Understanding the neurobiological basis of persistent negative symptoms can pave the way for more targeted and effective treatments. Further studies are needed to fully elucidate the complex interplay between brain structure, age, and symptom presentation in psychosis. By parsing apart these symptom constructs, researchers can develop more precise diagnostic tools and therapeutic strategies to improve outcomes for those affected.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1038/tp.2017.168, Alternate LINK

Title: Linking Persistent Negative Symptoms To Amygdala–Hippocampus Structure In First-Episode Psychosis

Subject: Biological Psychiatry

Journal: Translational Psychiatry

Publisher: Springer Science and Business Media LLC

Authors: C Makowski, M Bodnar, J J Shenker, A K Malla, R Joober, M M Chakravarty, M Lepage

Published: 2017-08-01

Everything You Need To Know

What are persistent negative symptoms (PNS) in psychosis, and why is it important to understand their underlying causes?

Persistent negative symptoms (PNS) in psychosis involve reduced motivation and a lack of goal-directed behavior, which significantly impairs daily functioning. The research indicates that these symptoms are associated with structural changes in the brain, specifically the amygdala and hippocampus. Understanding the connection between these symptoms and brain structure is crucial for developing effective treatments to improve the lives of those affected. Further research into the specific molecular mechanisms driving these structural and functional differences is needed to develop targeted therapies.

According to the study, what specific differences in brain structure were observed in individuals with early persistent negative symptoms (ePNS)?

The study revealed that individuals with early persistent negative symptoms (ePNS) had smaller volumes in the left amygdala and right hippocampus compared to those without PNS. Morphometric analysis also showed decreased surface area in specific regions of the amygdala in ePNS patients. Additionally, the relationship between age and the structure of these brain regions differed significantly in individuals with ePNS compared to other groups.

How does this research highlight the importance of early intervention and treatment for individuals experiencing psychosis?

This research emphasizes the significance of early identification and intervention in individuals experiencing psychosis. By understanding the neurobiological basis of persistent negative symptoms (PNS), particularly the structural changes in the amygdala and hippocampus, researchers can develop more targeted and effective treatments. This may involve therapies aimed at promoting neuroplasticity or compensating for structural deficits. However, more research is needed to determine the most effective interventions.

How did the research team, led by C Makowski and M Lepage, investigate the connection between brain structure and persistent negative symptoms (PNS) in first-episode psychosis (FEP)?

The study by C Makowski and M Lepage utilized magnetic resonance imaging (MRI) to examine the brain structures of individuals experiencing their first episode of psychosis (FEP). The researchers focused on the amygdala and hippocampus. They compared patients with early persistent negative symptoms (ePNS), patients with persistent negative symptoms due to other factors (sPNS) and those without PNS to explore how volume and shape of hippocampus and amygdala play in role with age.

What do the differing age trajectories observed in the amygdala and hippocampus suggest about the development of persistent negative symptoms (PNS) in psychosis?

The differing age trajectories observed in the amygdala and hippocampus among individuals with early persistent negative symptoms (ePNS) suggest an altered developmental process. This implies that the structural differences in these brain regions may not simply be a consequence of the illness but could reflect underlying neurodevelopmental abnormalities that predispose individuals to PNS. This could impact cognitive and emotional development of individuals. Further longitudinal studies are needed to fully understand these developmental changes.