PSYCH 011: Intraneuronal Signalling

PSYCH 022: Animal Models in Psychiatry

Much of what we understand about brain function and psychiatric illness has been built through animal research. Yet modelling the human mind in animals is inherently complex. This chapter explores how animal models are used in psychiatry - and the limits of what they can truly represent. In this episode, we examine different types of animal models, including those based on genetic manipulation, pharmacological induction, and behavioural paradigms. These models allow us to study neural circuits, molecular mechanisms, and treatment effects in controlled environments. We explore the concept of validity - face validity, construct validity, and predictive validity - and how each determines the usefulness of a model. No model fully captures human psychiatric experience; instead, each isolates specific components of complex conditions. This raises an important tension: animal models offer precision and control, but human psychiatry involves subjective experience, meaning, and context - elements that are difficult, if not impossible, to replicate. This chapter encourages a nuanced view. Animal models are not replicas of psychiatric disorders, but tools - valuable for understanding mechanisms, yet always requiring careful interpretation when applied to human experience. Key Takeaways * Animal models are used to study mechanisms underlying psychiatric disorders. * Models may be genetic, pharmacological, or behavioural in design. * Validity is assessed through face, construct, and predictive criteria. * No model fully captures the complexity of human psychiatric conditions. * Animal research provides mechanistic insight and supports treatment development. * Translation to human psychiatry requires careful interpretation. * Models are tools for understanding components, not entire disorders. 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 021: Pharmacogenetics

Why does one patient respond well to a medication while another experiences no benefit - or significant side effects? Pharmacogenetics seeks to answer this question by examining how genetic variation influences drug metabolism, efficacy, and tolerability. In this episode, we explore how differences in genes encoding drug-metabolising enzymes, receptors, and transporters can alter how medications are processed and how they act within the brain. Variations in systems such as cytochrome P450 enzymes can determine whether a drug is broken down too quickly, too slowly, or unpredictably. We examine how these differences translate into clinical outcomes - affecting dosing, response rates, and risk of adverse effects. This introduces the possibility of more personalised prescribing, moving away from trial-and-error approaches. However, pharmacogenetics also comes with limitations. Genetic factors are only one part of the picture; environment, comorbidity, and psychological context also shape treatment response. The promise of precision must therefore be balanced with clinical judgement. This chapter reframes prescribing as an interpretive process - where biology informs decisions, but does not dictate them. It offers a glimpse of a more tailored future, while reminding us of the complexity inherent in treating the human mind. Key Takeaways * Pharmacogenetics studies how genetic variation affects drug response. * Genes influence drug metabolism, receptor sensitivity, and transport mechanisms. * Variations in enzymes (e.g. cytochrome P450) can alter drug levels and effects. * Genetic differences contribute to variability in efficacy and side effects. * Pharmacogenetics supports more personalised approaches to prescribing. * Clinical decisions must still integrate non-genetic factors. * Precision medicine enhances, but does not replace, clinical judgement. 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 020: Epigenetics in Psychiatry: The Promise for New Biomarkers and Treatments

If the genome provides the script, epigenetics determines how it is read. This chapter explores how environmental influences - from early life experiences to chronic stress - can modify gene expression without altering the underlying DNA sequence. In this episode, we examine mechanisms such as DNA methylation and histone modification, which regulate whether genes are activated or silenced. These processes act as molecular switches, shaping how genetic potential is realised across development and throughout life. Crucially, epigenetics provides a bridge between biology and experience. It offers a framework for understanding how adversity, trauma, and environment can become biologically embedded - influencing vulnerability to psychiatric disorders. We also explore the emerging potential of epigenetic markers as biomarkers for diagnosis and prognosis, as well as targets for novel treatments. However, this promise is accompanied by complexity - epigenetic changes are dynamic, context-dependent, and not easily reduced to simple clinical tools. This chapter reframes nature versus nurture as a false dichotomy. Instead, it presents a dynamic interaction where experience continuously shapes biology - and biology, in turn, shapes experience. Key Takeaways * Epigenetics involves changes in gene expression without altering DNA sequence. * Mechanisms include DNA methylation and histone modification. * Environmental factors can influence gene expression across the lifespan. * Epigenetics provides a biological link between experience and psychiatric vulnerability. * Adversity and stress can become biologically embedded through these mechanisms. * Epigenetic markers hold potential as biomarkers and treatment targets. * Gene–environment interaction is central to understanding psychiatric disorders. 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 019: Gene Mapping Investigations of Psychiatric Disorders

If multi-omics reveals layers of biological complexity, gene mapping attempts to locate patterns within that complexity. This chapter explores how researchers identify genetic contributions to psychiatric disorders - not through single genes, but through probabilistic associations across the genome. In this episode, we examine approaches such as linkage studies, candidate gene studies, and genome-wide association studies (GWAS). These methods do not identify deterministic causes, but patterns of increased risk distributed across many genetic loci. We explore the concept of polygenicity - the idea that psychiatric disorders arise from the cumulative effect of many small genetic variations rather than a single mutation. This reframes conditions such as schizophrenia, depression, and bipolar disorder as complex traits rather than discrete genetic diseases. We also examine the challenges: small effect sizes, overlapping genetic risk across disorders, and the difficulty of translating statistical associations into biological mechanisms or clinical practice. Gene mapping does not provide simple answers. Instead, it offers a map of probabilities - a way of understanding vulnerability as distributed, shared, and context-dependent. This chapter invites a shift from certainty to pattern recognition - where risk is not located in a single place, but emerges from the architecture of the genome as a whole. Key Takeaways * Gene mapping identifies associations between genetic variants and psychiatric disorders. * Methods include linkage studies, candidate gene approaches, and GWAS. * Psychiatric disorders are highly polygenic, involving many variants with small effects. * Genetic risk is probabilistic, not deterministic. * There is significant overlap in genetic risk across different psychiatric conditions. * Translating genetic findings into clinical practice remains challenging. * Understanding risk requires thinking in patterns rather than single causes. 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 018: Genome, Transcriptome, and Proteome: The Molecular Genetics, Biochemistry, and Multi-Omics Underlying the Neurobiology of Mental Disorders

If genes are the script, they are only the beginning of the story. This chapter expands the lens to multiple layers of biological information - genome, transcriptome, and proteome - revealing how psychiatric disorders emerge not from single mutations, but from complex systems of regulation and interaction. In this episode, we explore how the genome provides the foundational code, while the transcriptome reflects which genes are actively expressed, and the proteome represents the functional molecules that carry out biological processes. Together, these layers form a dynamic, multi-level system - often referred to as “multi-omics”. We examine how these systems interact across time and context, influenced by development, environment, and experience. The same genetic code can lead to different outcomes depending on how it is expressed and regulated. This framework moves psychiatry beyond simple genetic determinism. Mental disorders are not the result of isolated gene defects, but of complex networks involving gene expression, protein function, and environmental interaction. The chapter also introduces the potential of multi-omics approaches in advancing diagnosis, prediction, and personalised treatment - while highlighting the current limitations and complexity of translating these findings into clinical practice. Ultimately, this is a chapter about depth - revealing that beneath observable symptoms lies a layered biological system, intricate and still only partially understood. Key Takeaways * The genome provides genetic code, but expression occurs through transcriptome and proteome layers. * Multi-omics integrates these levels to understand biological function. * Gene expression is dynamic and influenced by environment and development. * Psychiatric disorders arise from complex interactions, not single gene defects. * Biological processes operate across multiple interconnected layers. * Multi-omics offers potential for personalised psychiatry but remains complex. * Understanding these systems shifts thinking from static genetics to dynamic regulation. 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]