Does Herpes Virus Cause Mood Disorders?
A fascinating link between herpes virus infection and mood disorders has been discovered. Remarkably, these findings have ramifications far beyond herpes virus infection and shed light on the incredible links between infection, inflammation, brain function and mood disorders.
Published in Frontiers in Microbiology, Dr Bhupesh Prusty and his team conducted post-mortem biopsies of the brains of people diagnosed with bipolar mood disorder (BMD), major depressive disorder (MDD), and schizophrenia. As a reference, they also included a control group of individuals with no history of psychiatric illness. They found that signs of herpes virus infection were more common in the brains of deceased MDD and BMD sufferers compared to schizophrenia and controls.
Amazingly, hospitalisation for infection during childhood increases the risk of developing schizophrenia, MDD and BMD. This applies irrespective of whether the infection was viral or bacterial, and involved the brain or not. Why should this be the case? Does herpes provide clues about the underlying microbiology? Rather than a single pathogen being responsible, this may reflect a more general effect of how early immune activation influences the manner in which the brain regulates inflammation later in life. This is a critical point.
Inflammation and Depression
There is an growing body of evidence that shows a relationship between inflammation and depression. Cytokine concentrations increase in the plasma of depressed patients. This applies to interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF). The antidepressant, fluoxetine, reduces interleukin-6 levels in the blood of depressed patients.
Selective serotonin reuptake inhibitors (SSRIs) are the most common type of antidepressant. Curiously, depressed patients who do not respond to SSRIs, continue to demonstrate raised IL-6 levels after commencement of treatment. Increased levels of IL-1, IL-6 and TNF also appear in BMD.
This illuminates at a deeper phenomenon: immune reactions arise not only to physical illness but also to mental illness. Consider this telling fact: the behaviour of depressed patients is very similar to the sickness behaviour of patients with acute infection. Both groups show alterations in sleep cycle, changes in appetite, hightened sensitivity to pain, irritability, reduced sexual activity, and reduced interest in getting out (exploratory behaviour). Even the cognitive changes, such as impaired concentration, poor short-term memory and executive dysfunction, are similar.
An interesting proposition is a biological pathway that could provide a link between inflammation and mood disorders. One such possibility may be the role of indoleamine 2,3-dioxygenase (IDO). IDO is present in immune cells, including microglia in the brain, and is ubiquitous in the organs of the body. Put simply, inflammation may shift how the brain processes tryptophan—away from serotonin production and toward metabolites that can impair mood and cognition.
IDO increases in animals with sickness behaviour. Tellingly, we can deactivate the IDO gene in mice. When we do so, those mice do not manifest sickness behaviour in the face of immunological challenge. IDO activation and inflammation could cause depression by tryptophan depletion or by kynurenine toxicity.
Looking Beyond Symptoms
Research into inflammation, infection, and brain function raises important questions about the biological factors that may contribute to symptoms such as depression, anxiety, brain fog, fatigue, and bipolar disorder. At Ormond Neuroscience we take a systems-based approach to brain health, looking beyond symptoms alone to understand how biology influences brain function as a whole. Learn more about Neuroharmonics.
Roseoloviruses include Herpes
Of course, there are multiple factors that might cause inflammation in the brain, but viral infections are one of the most common causes. Prusty et al focused on a common type of virus that infects a large percentage of the human population, the roseolovirus genus. Specifically, they investigated two forms of the human herpes virus (HHV), HHV-6A and HHV-6B. There are more than a 130 types of herpes virus, of which nine infect humans. More than 90% of people have been infected with at least one of these herpes viruses.
As is the case with viruses, a latent form remains in most people with the potential for reactivation. Roseoloviruses have a tissue tropism for immune cells, such as T cells, B cells, natural killer cells, monocytes and macrophages. Incidentally, respiratory particles transmit these viruses, not sexual behaviour.
The Cerebellum in Mood Disorders
The cerebellum is increasingly understood not just as a motor structure, but as a key regulator of prediction, timing, and emotional processing. Perinatal viral infection causes long-term anatomical changes in the cerebellum. It also results in behavioural disturbances in adult animals. Animal research has established these facts. Dr Prusty therefore chose to investigate the cerebellum.
Of relevance, cerebellar dysfunction has been associated with a number of psychiatric conditions, autism being perhaps the best-known. We know that corticocerebellar tracts are abnormal in schizophrenia, and that the cerebellum tends to be a bit smaller in patients with MDD and in BMD.
The images above (from Alalade et al.) show reduced cortico-cerebellar connectivity in depressed geriatrics, compared to healthy geriatrics. The seed region for the connectivity trace is in the cerebelum and is shown in the bottom row. Compare especially the leftmost and middle columns and notice that there is almost no frontal connectivity in the depressed group.
Herpes, the Cerebellum and Mood Disorders
(A quick technical point: “late proteins” primarily refer to viral proteins encoded by late genes that are expressed after viral genome replication has occurred. The terminology refers to the position of these proteins in the chronological cascade of the viral replication cycle. Late, as opposed to early proteins that are synthesized immediately after the virus infects the host.)
In other words, late proteins form after replication of a virus and are therefore a marker of active infection. Prusty et al looked for late proteins. They were able to detect signs of active HHV-6A and HHV-6B infection in the Purkinje cells of the cerebellum in MDD and BMD cadavers.
Compared to controls, statistical significance was greatest in the MDD group, slightly less in the BMD group, and absent in the schizophrenia group. Additionally, there was occasional staining of GABAergic interneurons of the molecular layer, and astrocytes and microglia in the vicinity of positively stained Purkinje cells. These results provide compelling evidence for a strong and specific effect of herpes virus, HHV-6 in particular, on Purkinje nerve fibres.
So, does herpes cause MDD and BMD? No, not directly at least, but via the effects of inflammation on brain function, herpes may contribute to a biological environment that increases vulnerability to depression. It would seem that perinatal HHV-6 infection is the first step. In adulthood, reactivation of latent HHV-6 sets in motion inflammation that may lead to MDD and BMD. Whether this requires an emotional trigger or not requires clarification. In my clinical experience, some patients are unable to identify an obvious emotional cause of their depression and perhaps their illness is entirely biological and without a psychological cause.
From Infection to Regulation: A Different Way of Thinking About Treatment
If these findings are correct, they point to something important. Mood disorders may not simply be “chemical imbalances” or purely psychological conditions. They may reflect disruptions in how the brain regulates itself in the face of inflammation, stress, and internal bodily signals.
In this context, the question is not only what caused the problem, but how the brain is currently functioning.
Inflammation, viral reactivation, and immune signalling all influence key regulatory systems in the brain, including those involved in mood, energy, sleep, and cognition. These systems do not operate in isolation. They are part of a broader network that integrates bodily state with emotional and cognitive experience.
This is where treatment approaches such as vagus nerve stimulation (VNS) become relevant. The vagus nerve is a major communication pathway between the body and the brain, particularly in relation to immune function and inflammation. By modulating vagal activity, it is possible to influence inflammatory signalling, autonomic balance, and the brain’s overall regulatory state.
Rather than targeting a single neurotransmitter or symptom, as is common when treating depression, this represents a shift toward improving how the brain regulates itself.
Within a broader framework such as our Neuroharmonics model, the goal is not simply symptom suppression, but restoring more adaptive patterns of brain function—where the system is better able to respond to internal and external demands.
From this perspective, factors such as viral exposure, inflammation, and stress are not isolated causes, but contributors to a complex system that has become dysregulated. Treatment, therefore, is not about removing a single cause, but about restoring balance within that system.
To function optimally, the brain and body must operate in a state of dynamic neural harmony, where biological, emotional, cognitive, and social systems remain well regulated and able to adapt to changing circumstances.
If this discussion has piqued your curiosity, you can learn more about Neuroharmonics and vagus nerve stimulation at Ormond Neuroscience. Thanks for your time and interest.
Selected References & Further Reading
Alalade, E., Denny, K., Potter, G., Steffens, D., Wang, L., & Taylor, W. D. (2011). Altered cerebellar-cerebral functional connectivity in geriatric depression. Journal of Affective Disorders, 131(1–3), 299–306.
Journal of Affective Disorders
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., & Maes, M. (2013). So depression is an inflammatory disease, but where does the inflammation come from? BMC Medicine, 11, 200.
Christmas, D. M., & Potokar, J. (2011). A biological pathway linking inflammation and depression: Activation of indoleamine 2,3-dioxygenase. Neuropsychiatric Disease and Treatment, 7, 431–439.
Neuropsychiatric Disease and Treatment
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446–457.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-6, and IL-1: A meta-analysis. Psychosomatic Medicine, 71(2), 171–186.
Khandaker, G. M., Zimbron, J., Dalman, C., Lewis, G., & Jones, P. B. (2012). Childhood infection and adult schizophrenia: A meta-analysis of population-based studies. Schizophrenia Research, 139(1–3), 161–168.
Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65(9), 732–741.
Phillips, J. R., Hewedi, D. H., Eissa, A. M., & Moustafa, A. A. (2015). The cerebellum and psychiatric disorders. Frontiers in Public Health, 3, Article 66.
Prusty, B. K., Gulve, N., Govind, S., Krueger, G. R. F., Feichtinger, J., Larcombe, L., Aspinall, R., Ablashi, D. V., & Toro, C. T. (2018). Active HHV-6 infection of cerebellar Purkinje cells in mood disorders. Frontiers in Microbiology, 9, 1955.
