A neuroimaging investigation of bipolar disorder and the neurocognitive effects of 5-HT7 antagonists

Student thesis: Doctoral ThesisDoctor of Philosophy


Bipolar disorder is a psychiatric disorder characterised by pathological mood states, but there is growing recognition of the role of cognitive impairment and dysfunction of emotional processes, which has a profound impact on quality of life. Many people with bipolar disorders exhibit brain volume impairment associated with cognitive dysfunction and an increased risk of dementia.

In this thesis, I conducted a systematic review to understand the relationships between mood disorders and the 5-HT7 receptor. The 5-HT7 receptor is related to depression and anxiety, but the relationship between 5-HT7 and mania remains unclear; in addition, sleep and memory were also related to the 5-HT7 receptor. Followed by these findings, in the next two chapters, I examined the effects of 5-HT7 antagonists, using JNJ-18038683, on emotional and cognitive functioning, as well as their neural substrates. I then reported on neuroimaging investigations examining the effects of 5-HT7 antagonists on emotional processing and cognitive function in healthy volunteers to gain insight into their potential mode of action and utility for bipolar disorder. In fMRI analyses, the drug acted on 5-HT7 receptors potentially improving cognitive performance by modulating the function of the Cognitive Control Network in healthy controls.
In the above-mentioned chapters, I gained a better understanding of the 5-HT7 antagonist, JNJ-18038683, and the putative promising effects for pharmacological treatments. However, the approach taken has some limitations, including a small sample size, potential participant bias, and a lack of systematic control of medication dose and duration of administration.

In addition, in Chapter 5, I explored the brain basis of bipolar disorder and its links to cognitive and emotional dysfunction using a new ‘brain age’ approach. Individuals with bipolar disorder were found to have increased brain age compared to healthy controls.

I hope that these findings can be applied to pharmacological treatment for individuals with bipolar disorder, ultimately allowing patients to benefit from the drug in the future.
Date of Award1 Jan 2024
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorAllan Young (Supervisor), Mitul Mehta (Supervisor) & Owen O'Daly (Supervisor)

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