Schizophrenia is Brain Damage and the Hippocampus's Role in Alzheimers

Check out the latest articles here: https://nicolashubacz.substack.com

Schizophrenia is Brain Damage

Leonard Lado MD, ABPN, RPh - President & Medical Director at Lado Healing Institute, American Board of Neurology & Psychiatry

Having a family member with schizophrenia is a deeply personal journey, one that has driven me to learn more each day about this condition. It’s not just an academic interest but a heartfelt quest to understand what they’re going through—physically, emotionally, and mentally. The question of why schizophrenia is associated with brain volume loss and the destruction of neural tissue is not just scientific—it’s deeply human, tied to the experiences of those we love.

Understanding Brain Volume Loss in Schizophrenia

Schizophrenia is known to cause measurable reductions in brain volume, particularly in regions critical for memory, emotion, and reasoning, such as the prefrontal cortex, hippocampus, and temporal lobes. This loss isn’t merely a biological oddity—it’s a visible reflection of the struggles many individuals face with cognition and emotional regulation.

Neurotoxicity and Neuroplasticity

Daniel Weinberger et al. (2002) highlighted how neurotoxic processes—where brain cells are damaged or destroyed—can result in this volume loss. They also pointed to disrupted neuroplasticity, the brain’s ability to adapt and reorganize itself, especially during critical periods of adolescence. This disruption may underlie some of the cognitive and emotional difficulties seen in schizophrenia. For me, understanding this brings a certain clarity—it’s not a failure of the person but of their brain’s natural systems. [Read More](https://jamanetwork.com/journals/jamapsychiatry/article-abstract/206472)

White Matter and Connectivity: The Highways of the Brain

G. Bartzokis (2002) explored the role of white matter, the brain’s connective tissue. His research suggests that schizophrenia might be a breakdown in the lifelong process of brain maturation, where the brain’s “highways” fail to develop properly. This helps explain why someone with schizophrenia might experience fragmented thinking or difficulty processing complex tasks. [Read More](https://www.sciencedirect.com/science/article/pii/S0893133X02003640)

Developmental Roots

K. Karlsgodt and colleagues (2008) delved into how schizophrenia may begin with developmental disruptions, long before symptoms manifest. During adolescence, the brain undergoes significant synaptic pruning, a process meant to refine its connections. In schizophrenia, this pruning may become overactive, eliminating crucial neural pathways. Knowing this, I often reflect on how these unseen processes shape my loved one’s experiences in ways they can’t control. [Read More](https://www.cambridge.org/core/journals/development-and-psychopathology/article/developmental-disruptions-in-neural-connectivity-in-the-pathophysiology-of-schizophrenia/1BD1B47F068568DCB0269187033E2E64)

Inflammation: An Invisible Fire in the Brain

Researchers like P. Falkai et al. (2015) propose that neuroinflammation may worsen tissue damage in schizophrenia. Chronic inflammation might erode neural structures over time, creating a cycle of damage that compounds cognitive and emotional challenges. This concept resonates deeply—it’s like an invisible battle happening within their brain, a constant fight they might not even be aware of. [Read More](https://www.nature.com/articles/mp201535)

Changes in the Hippocampus and Beyond

FM Benes (2000) identified the hippocampus—a region essential for memory and emotion—as a key area of volume loss. It’s heart-wrenching to think about how these changes affect my family member’s ability to connect with their own past or navigate emotions. Yet, understanding these changes gives me hope that targeted therapies might someday make a difference. [Read More](https://www.sciencedirect.com/science/article/pii/S0165017399000417)

Genetics, Environment, and the Human Experience

The causes of these brain changes are multifactorial. Genetics lay the groundwork, but environmental factors like stress or prenatal complications can act as triggers. Fiala et al. (2002) studied dendritic spine loss—tiny structures on neurons that are essential for brain communication—and found that their reduction could be both a cause and a result of schizophrenia’s progression. This reminds me how deeply interconnected biology and environment are in shaping the human mind. [Read More](https://www.sciencedirect.com/science/article/pii/S0165017302001583)

A Human Story Behind the Science

For me, learning about the mechanisms behind schizophrenia’s effects is a way to bridge the gap between science and humanity. It helps me better understand my loved one’s experience and gives me hope for future treatments that might alleviate their struggles. Each study, each discovery, brings us closer to answers—not just for my family but for the millions of others navigating this condition.

The Hippocampus & Alzheimers

Nicolas Hubacz, M.S. - Business Development Manager at Magstim and Founder of NH Sponsorships

In the earliest stages of Alzheimer’s disease, the hippocampus is one of the first regions to be affected. This small, seahorse-shaped structure deep in the brain plays a critical role in forming new memories and spatial navigation—functions that are severely disrupted in Alzheimer's patients.

Here’s what happens at the cellular level:

1?? Synaptic Loss Alzheimer’s begins with synaptic dysfunction. Connections between neurons in the hippocampus weaken, making it harder to encode and retrieve new memories. This is why short-term memory loss is often the first noticeable symptom.

2?? Neurofibrillary Tangles Inside neurons, tau proteins become abnormally twisted into neurofibrillary tangles, particularly in the hippocampus. These tangles disrupt cellular transport systems, effectively starving neurons of the nutrients they need to function.

3?? Amyloid Plaques Between neurons, amyloid-beta plaques accumulate. While these plaques form throughout the brain, their presence in the hippocampus is particularly damaging. They trigger inflammatory responses and contribute to widespread neuronal death.

?? What Does This Mean for Memory?

With the hippocampus shrinking and neurons dying, patients lose the ability to form new memories. Over time, they also lose long-term memories and spatial awareness, leading to confusion, disorientation, and eventually a total disconnect from reality. Image credit goes to Von Oostveen, Imaging Techniques in Alzheimer's Disease.

A Big Thank You to Our Founding Member Subscribers: Joshua N. | Peter Michiels | Darby Kramer

Science Leaders to Follow: Owen M.