Depression is not one thing, and treating it as if it were may be why so many people don't get better. In this episode, Prof Brenda Penninx offers a sharper way to think about it.
Recorded ahead of her guest lecture at the British Association for Psychopharmacology (BAP) Summer Meeting, Brenda talks to André Tomlin (The Mental Elf) about \"immuno-metabolic depression\": the 20–30% of depressed patients who show low-grade inflammation and metabolic dysregulation, clustered with atypical, energy-related symptoms such as fatigue, oversleeping, increased appetite and leaden paralysis. Drawing on the large Netherlands Study of Depression and Anxiety (NESDA), she explains why these patients respond slightly less well to standard antidepressants, and why that matters.
00:00 Meet Brenda Penninx
01:03 Why Depression Varies
03:03 Defining Immunometabolic Depression
04:11 Cause or Vicious Cycle
05:56 Treatment Targets and Trials
07:41 Proof of Concept IL6 Study
10:26 Lifestyle as Medicine
13:19 From Concept to Clinic
15:11 Mind Body Care Gap
16:29 Conference Takeaways
Is the biology a cause or a consequence of depression? Neither, Brenda argues: it's a vicious cycle, with common roots in genetics, lifestyle and childhood adversity. She discusses what this means for treatment (anti-inflammatory drugs, metabolic and lifestyle interventions) and why the key is targeting the right subgroup rather than the whole depressed population. She reflects on the recent Bristol tocilizumab proof-of-concept trial (Foley & Khandaker, JAMA Psychiatry), the Wellcome-funded ASPIRE project bringing these trials together, and why running therapy should be treated as a genuine, supported intervention rather than a slogan.
Finally, the conversation turns to what still stands between concept and clinic (how to identify the right patients, which intervention to choose) and Brenda's wish to bring mental and physical healthcare back together.
About the guest: Prof Brenda Penninx is Professor of Psychiatric Epidemiology at Amsterdam UMC / Vrije Universiteit Amsterdam and lead of the Netherlands Study of Depression and Anxiety (NESDA).
Find out more about Brenda Penninx's talk at the 2026 BAP Summer Meeting: https://www.bap.org.uk/summersessiondetails.php?meetingID=19&sessionID=740
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