Unraveling the pathological alterations of cholinergic neurons in schizophrenia and affective psychosis

Cognitive preservation has become a primary goal in the modern treatment for psychotic disorders. While traditional antipsychotic strategies effectively manage positive symptoms, their inherent anticholinergic properties often contribute to a secondary cognitive burden that hinders long-term recovery. There is an urgent clinical need to transition toward pro-cognitive therapies.

Psychotic symptoms exist across a spectrum including schizophrenia and affective psychosis. These disorders share genetic risk factors and clinical manifestations, yet they exhibit distinct differences in etiology and clinical trajectories. Although previous studies have identified cholinergic dysfunction within the basal forebrain in patients with psychotic features, it remains unclear whether this dysfunction represents a generalized mechanism common to all psychotic manifestations, or if there is fundamental neuropathological heterogeneity in biotypes between schizophrenia and affective psychosis.

Therefore, we will investigate the neurobiology of basal forebrain cholinergic neurons in the nucleus basalis of Meynert, a primary cholinergic niche in human brain, comparing neural mechanisms in schizophrenia and affective psychosis to identify similarities and differences. We aim to find neuroprotective markers for cholinergic neurons in schizophrenia and/or affective psychosis.

In this project. you will study:

• Neuroanatomy: Exploring the human basal forebrain.
• Brain banking: Sample collection and matching protocols for human brain research.
• Laboratory techniques: Paraffin section preparation, in situ hybridization, and immunohistochemistry (we can discuss biomarkers of your specific interest).
• Advanced imaging: Image acquisition using the Zeiss system and subsequent digital analysis.
• Data science: Statistical analysis and professional data collection.
• Scientific communication: Developing graphical illustrations, figure adjustments, academic writing, and presentation skills.

We are seeking motivated MSc students with a passion for cognitive neuroscience, neurobiology, and psychiatry. To ensure a successful internship, candidates should ideally possess:

• A strong academic interest in neuroscience and neuropsychiatry.
• Prior experience in a neurobiological laboratory setting.
• A highly organized and detail-oriented working style.
• Availability for a full-time period of 5 to 10 months.

Information

For additional information please contact Lin Zhang (l.zhang@nin.knaw.nl).

Please Note: Due to the high volume of applications we receive, we will only be able to contact students selected for an interview. We appreciate your understanding and thank you for your interest in our research.

Application and deadline

Applicants are requested to submit a curriculum vitae and a motivation letter.