Iain Campbell is a neuroscientist at the University of Edinburgh specializing in metabolic psychiatry. His research investigates the metabolic mechanisms and interventions associated with severe mental illness, particularly bipolar disorder and schizophrenia. His published work focuses on therapeutic ketosis, ketogenic metabolic therapies, insulin signaling, mitochondrial dysfunction, and diet-drug interactions in psychiatric care.
Systematic reviews of patient hospitalizations show that manic episodes peak around the spring equinox and autumn equinox.
"And if you look at systematic review of when mania occurs in patients by hospitalizations, it occurs at the spring equinox, at the autumn equinox." (said at 0:40:40)
Systematic reviews of psychiatric hospitalization and symptom data confirm robust seasonal patterns for bipolar disorder, with manic episodes and admissions consistently peaking in spring and summer, and to a lesser extent in autumn. However, systematic reviews report these trends across broader seasonal and monthly intervals (primarily spring/summer) rather than demonstrating isolated spikes strictly tied to the calendar equinoxes.
- context: Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality… (Journal of affective disorders 2014) · cited 252x in the literature
"Seasonal peaks for different BD mood episodes are observed worldwide and widely replicated. Manic episodes peak during spring/summer and, to a lesser extent, in autumn, depressive episodes peak in early winter and, to a lesser extent, summer, and mixed episodes peak in early spring or mid/late summer." (abstract, results, passage verified)
pubmedfull study (doi) - context: An Umbrella Systematic Review of Seasonality in Mood Disorders and Suicide Risk: The Impac… (The primary care companion for CNS disorders 2023) · cited 16x in the literature
"Admissions for mania are 7.4%-16% higher in spring and summer, while there are 1.5 times more admissions for bipolar depression in winter months." (abstract, results, passage verified)
pubmedfull study (doi)
Migratory birds in captivity exhibit 'Zugunruhe', a state of hypermetabolic activity, insomnia, and suppressed circadian rhythm around the spring and autumn equinoxes.
"there's a really interesting analogy in the natural world called Zugunruhe, which is a thing that Johann Andreas Naumann noted in animals in captivity. Many particularly migratory birds, for example, around the spring equinox become hypermetabolic. They start trying to bang their head off the side of the cage, they're staying up all night, their circadian rhythm is suppressed, they're having insomnia, they're getting this deep evolutionary impulse and drive that they can't express in the unnatural environment, and it's to migrate at the spring equinox. It happens also at the autumn equinox, this behavior." (said at 0:43:20)
The speaker accurately describes the core phenomenon of Zugunruhe (migratory restlessness), historically described in captive birds by German ornithologists such as Johann Andreas Naumann and Johann Friedrich Naumann. Captive migratory songbirds regularly exhibit intense nocturnal activity, wing-whirring, and marked sleep reduction (migratory sleeplessness) during seasonal migration periods without typical cognitive impairment. However, circadian rhythms are not 'suppressed'; rather, endogenous circadian clocks actively regulate Zugunruhe through the phase relationships of distinct circadian oscillators that switch normally diurnal birds into nocturnal activity during the migratory season.
Elevated brain glutamate is observed on brain imaging in epilepsy, bipolar disorder, and schizophrenia.
"So the the first thing that you see in brain imaging with um epilepsy, bipolar, uh some of the psychiatric conditions is elevated brain glutamate." (said at 1:05:22)
Proton magnetic resonance spectroscopy (1H-MRS) and related neuroimaging modalities frequently document glutamatergic abnormalities, including regional elevations in glutamate or glutamate plus glutamine (Glx), in psychiatric and neurological disorders such as schizophrenia, bipolar disorder, and focal epilepsy. However, these findings are not uniform across the entire brain: glutamate levels vary substantially depending on the specific anatomical region sampled (e.g., anterior cingulate cortex versus hippocampus), disease stage (e.g., early psychosis versus chronic illness), medication status, and mood state.
- supports: Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evi… (Frontiers in psychiatry 2018) · cited 165x in the literature
"Evidence indicates abnormalities of glutamatergic neurotransmission or glutamatergic dysfunction as playing an important role in the development of many major psychiatric disorders (e.g., schizophrenia, bipolar disorder, and major depressive disorder). ... In this review, we update evidence from recent human studies that directly or indirectly measured glutamatergic neurotransmission and function in major psychiatric disorders using modalities such as magnetic resonance spectroscopy, positron emission tomography/single-photon emission computed tomography" (abstract, results, passage verified)
pubmedfull study (doi) - context: The role of glutamate and GABA in cognitive dysfunction in schizophrenia and mood disorder… (Schizophrenia research 2022) · cited 125x in the literature
"We found that alterations in glutamatergic and GABAergic neurotransmission have been identified relatively consistently in both schizophrenia and mood disorders. However, because of the vast heterogeneity of published studies in terms of illness stage, medication exposure, MRS acquisition parameters and data post-processing strategies, we still do not understand the relationship between those neurotransmitters and cognitive dysfunction in mental illness" (abstract, results, passage verified)
pubmedfull study (doi)
Systematic reviews establish that elevated glutamate is a major feature of bipolar disorder and epilepsy, and glutamate reduction is a marker of treatment response.
"the um elevated glutamate in systematic reviews is a major feature of bipolar and epilepsy, and reduction of glutamate is considered a marker of response to treatment." (said at 1:06:40)
Systematic reviews and meta-analyses of proton magnetic resonance spectroscopy (1H-MRS) studies confirm that glutamatergic neurometabolites (such as Glx, a composite of glutamate and glutamine) are significantly elevated in patients with bipolar disorder compared to healthy controls, particularly in the anterior cingulate cortex and frontal regions. Similarly, in epilepsy, excessive extracellular glutamate and glutamatergic hyperexcitability are central pathophysiological mechanisms. Furthermore, several mood stabilizers (e.g., lithium, valproate, lamotrigine) and antiepileptic drugs attenuate glutamatergic transmission, and reductions in brain glutamate/Glx have been observed following successful treatment. However, proton MRS generally measures total tissue concentrations (including metabolic and glial pools, often bundled as Glx) rather than synaptic neurotransmission directly, metabolite levels vary by mood state and age, and glutamate reduction serves as an investigational research marker of treatment effect rather than a validated clinical biomarker for routine patient management.