PSYCH 005: Cellular and Synaptic Basis of Neural Signalling

PSYCH 013: Immune–Brain Interactions in Psychiatry

The brain does not operate in isolation from the body’s defence systems. This chapter explores the evolving understanding of how the immune system and the brain interact - not only in illness, but as part of normal regulation of mood, behaviour, and cognition. In this episode, we examine how immune signalling molecules, particularly cytokines, influence brain function. These signals can alter neurotransmission, neural plasticity, and circuit activity - effectively shifting how the brain processes information. We explore the concept of “sickness behaviour” - a coordinated response to inflammation characterised by fatigue, low mood, reduced motivation, and social withdrawal. While adaptive in acute illness, similar patterns may become maladaptive when immune activation is prolonged or dysregulated. This provides a powerful framework for understanding aspects of depression, as well as emerging links between inflammation and other psychiatric conditions. The boundary between physical and mental illness becomes increasingly blurred - revealing shared biological pathways. This chapter invites a reframing of psychiatric symptoms: not solely as disorders of the brain, but as states influenced by systemic processes - where the immune system becomes an active participant in shaping experience. Key Takeaways * The immune system and brain interact through signalling molecules such as cytokines. * Immune activation can influence neurotransmission, plasticity, and neural circuits. * “Sickness behaviour” reflects adaptive responses that can resemble depressive symptoms. * Chronic or dysregulated inflammation may contribute to psychiatric disorders. * The distinction between physical and mental illness is increasingly blurred. * Immune–brain interactions offer new perspectives on mechanisms and treatment targets. * Psychiatry must consider systemic biology, not just brain-specific processes. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit drmanaankarray.substack.com/subscribe [https://drmanaankarray.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_2]

PSYCH 012: Psychoneuroendocrinology

The mind does not exist in isolation from the body. This chapter explores psychoneuroendocrinology - the interface between brain, hormones, and behaviour - and how internal physiological states shape emotional and psychological experience. In this episode, we examine how the brain communicates with the endocrine system, particularly through the hypothalamic–pituitary–adrenal (HPA) axis. This system translates perception into physiological response, mobilising the body in the face of challenge and restoring balance afterwards. We explore how hormones such as cortisol act not only on the body, but back on the brain - influencing mood, cognition, memory, and perception. Stress is therefore not just a psychological experience, but a whole-body process with neural consequences. A central theme is regulation. Acute stress can be adaptive, sharpening attention and preparing for action. Chronic or dysregulated stress, however, can alter neural systems, impair resilience, and contribute to disorders such as depression, anxiety, and trauma-related conditions. This chapter reframes psychiatric symptoms as embodied phenomena. The boundary between mind and body dissolves - replaced by a continuous feedback loop in which each shapes the other. Key Takeaways * Psychoneuroendocrinology studies the interaction between brain, hormones, and behaviour. * The HPA axis is central to the stress response. * Hormones such as cortisol influence both body and brain function. * Stress responses can be adaptive in the short term but harmful when chronic or dysregulated. * Brain and endocrine systems operate in continuous feedback loops. * Dysregulation contributes to mood, anxiety, and trauma-related disorders. * Psychiatric symptoms are often embodied, not purely psychological. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit drmanaankarray.substack.com/subscribe [https://drmanaankarray.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_2]

PSYCH 011: Intraneuronal Signalling

While synapses transmit signals between neurons, the real transformation happens within. This chapter explores intraneuronal signalling - the complex cascade of intracellular processes that determine how a neuron responds to incoming information. In this episode, we move inside the neuron to examine how signals are not simply received, but interpreted. Neurotransmitters bind to receptors, triggering intracellular pathways involving second messengers, protein kinases, and gene transcription. These cascades shape everything from immediate responses to long-term changes in structure and function. We explore how the same external signal can produce different outcomes depending on the internal state of the neuron. Context matters - receptor subtype, intracellular environment, and prior activity all influence how a signal is processed. This is where short-term communication becomes long-term adaptation. Intraneuronal signalling underpins plasticity, learning, and memory, but also vulnerability. Dysregulation at this level can alter how information is processed, contributing to psychiatric conditions in ways that are not visible at the level of synapses alone. This chapter reveals a deeper layer of complexity: the brain is not just a network of connections, but a system of interpretive units, each transforming signals into meaning. Key Takeaways * Intraneuronal signalling involves intracellular cascades triggered by receptor activation. * Second messengers and protein kinases play key roles in signal transduction. * Neurons interpret signals rather than simply transmitting them. * The same neurotransmitter can produce different effects depending on intracellular context. * These processes link short-term signalling to long-term changes such as gene expression and plasticity. * Dysregulation can alter how signals are processed, contributing to psychiatric disorders. * Understanding intracellular pathways is key to deeper mechanistic insight in psychiatry. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit drmanaankarray.substack.com/subscribe [https://drmanaankarray.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_2]

PSYCH 010: Neurotrophic Factors

Not all neural processes are about signalling in the moment. Some operate on a different axis entirely - governing growth, survival, and long-term adaptation. This chapter explores neurotrophic factors, the molecules that support the development, maintenance, and plasticity of neural systems. In this episode, we examine key neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and their role in promoting neuronal survival, guiding synaptic formation, and enabling plastic change. These systems act less like messengers and more like nurturers - sustaining the health and adaptability of neural circuits. We explore how neurotrophic activity is influenced by experience, stress, and environment. Enriched environments and learning can enhance these pathways, while chronic stress may suppress them - linking biology directly to lived experience. This has profound implications for psychiatry. Conditions such as depression are increasingly understood not only as chemical imbalances, but as states of reduced plasticity and impaired neural resilience. Treatments - from antidepressants to psychotherapy - may, in part, work by restoring these growth-promoting systems. This chapter reframes the brain as something that must be maintained, not just activated - a system that requires support to remain flexible, adaptive, and capable of change. Key Takeaways * Neurotrophic factors support neuronal survival, growth, and plasticity. * BDNF is a key molecule involved in synaptic formation and adaptation. * These systems influence learning, memory, and long-term neural change. * Experience and environment can enhance or suppress neurotrophic activity. * Chronic stress may impair these pathways, reducing neural resilience. * Psychiatric disorders may involve reduced plasticity rather than simple chemical imbalance. * Treatments may work by restoring growth and adaptability in neural systems. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit drmanaankarray.substack.com/subscribe [https://drmanaankarray.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_2]

PSYCH 009: Novel Neurotransmitters

For decades, psychiatry has centred on a core set of neurotransmitters - dopamine, serotonin, noradrenaline. Yet the brain’s chemical language is far richer than once imagined. This chapter explores emerging and “novel” neurotransmitters that challenge traditional models and open new pathways for understanding and treatment. In this episode, we examine systems such as glutamatergic modulation beyond classical pathways, endocannabinoids, nitric oxide, and other unconventional signalling molecules. These do not always conform to the standard rules of neurotransmission - some act retrogradely, some diffuse freely, and others influence entire systems without clear synaptic boundaries. We explore how these systems contribute to plasticity, perception, mood regulation, and stress response. Their roles are often subtle but profound - shaping how signals are filtered, integrated, and prioritised. Importantly, these discoveries are reshaping psychiatric treatment. The emergence of agents targeting glutamate systems, for example, has transformed approaches to conditions such as depression, moving beyond traditional monoamine frameworks. This chapter represents a frontier - a reminder that our current models are incomplete, and that the biology of the mind is still being uncovered. Key Takeaways * Novel neurotransmitters expand beyond classical monoamine and amino acid systems. * These include endocannabinoids, nitric oxide, and advanced glutamatergic mechanisms. * Some act in unconventional ways (e.g. retrograde signalling, diffusion-based transmission). * They play roles in plasticity, mood regulation, perception, and stress response. * These systems challenge traditional models of neurotransmission. * Emerging treatments increasingly target these pathways (e.g. glutamate modulation). * Psychiatry is evolving as new biological mechanisms are discovered. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit drmanaankarray.substack.com/subscribe [https://drmanaankarray.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_2]