Synopsis:Microbial Dance: How infections swing the mood

Mood swing is the cardinal clinical feature of bipolar disorder of the present or manic depression of the past. Clinically bipolar disorder or manic depression, is characterized by mood swings at different rates and severity, and on that basis is classified to classical or type I, with long cycles of severe elevation and depression of mood, of at least a few months each. Milder form of the disorder or mood swings has been classified as type II, with less severe depressive and high mood (called “hypomania”). Shorter cycles of these mood swings, form days to weeks are classified as rapid cycling and within day, as ultra cycling bipolar disorder or mood swings. The high mood state that could manifest as elation or agitation and aggression, is accompanied with elation in many mood and cortical functions, such as thought racing, pressured speech, self-esteem elevation, high physical and mental energy, shopping spree, risk taking behavior, hypersexuality, less need for sleep, etc. The depressive cycle is similar to unipolar or usual depression with an inversion of almost all the mood and mental states to the low side. It seems that the higher the mood elevation, the more severe the downfall of depression would be, such as the higher risk of suicide in bipolar depression than the unipolar or major depression (26-6% vs. 17.8% suicide attempts) (6).    

The story of microbes of different kinds causing insanity or mental illness, including mood swings, manic depression or bipolar disorder is not something new, but perhaps under-recognized. Julius Wagner-Jauregg (1857-1940), an Austrian physician who won the noble prize in medicine for his discovery of malaria inoculation for the treatment of dementia paralytica or general paresis of insane caused by neurosyphlilis, was one of the first who believed in such association. In modern time, perhaps influenza virus has been the first suspicious microbe to be reported causing the symptoms of confusional state and manic psychosis. Early observations like this challenged the concept of manic depression, before later on being labeled as bipolar disorder to have a “functional” etiology, but organic. That is why Krauthammer & Klerman in 1978 in a review in the prominent journal of Archives of General Psychiatry, warned clinicians that many seemingly primary manias could in fact be secondary to other medical causes including infections: “mania occurs secondary to drugs, infection, neoplasm, epilepsy, and metabolic disturbances. These cases are best considered secondary manias. They suggest that mania–like, for example, hypertension–is a syndrome with multiple causes and that with further research many manic syndromes currently considered primary will be shifted into the secondary category.

 Borna virus has been the next microbe after influenza to be suspicious in the etiology of bipolar disorder due to its neurotropic features. Some researchers have found high Borna virus-specific antibodies in the sera of such patients. Several other infections, such as Lyme disease, Epstein-Barr virus, skin and nail infections, maternal influenza in the first and second-trimester, West Nile Virus, dengue infection, adeno-associated virus 2 and parvovirus B19, toxoplasma gondii, cytomegalovirus and inflammatory bowel inflammations and infections have also been reported in link with bipolar disorder. On the other side, while the above infecting agents could be causal in bipolar disorder, some infections, e.g. HIV and hepatitis-B &-C could cause secondary mania, precipitating mania or carry higher risks of these infections in Bipolar patients.

 The infectious agents could directly invade and infect the brain and stall its development in the fetuses of infected pregnant mothers or and could cause a cascade of immune reactions in the human subjects, leading to a central nervous functional disorder such as bipolar disorder. These microbial immune activation, as I have detailed on this site in the case of other neurodevelopmental disorders such as schizophrenia and autistic spectrum disorders, seem to only harm the vulnerable developing brain of the fetus and not the developed adult brains, e.g. the maternal brains. The footsteps of such disturbed immune system of the off springs have led many experts to interpret the neuro-developmental disorders as autoimmune conditions. For example, some researchers have found seroactive markers for inflammatory bowel disease in reaction to food derived proteins such as wheat gluten and bovine milk caseins in adult bipolar disorder subjects. Genome-wide association studies have also reported the maternal and fetal infections causing gene mutations by creating schizophrenia and bipolar-associated SNPs (single nucleotide polymorphism) in the HLA (Human Leukocyte Antigens) regions of chromosomes. This fact has even been proven on animal infection models, by causing infections to the maternal mouse models to detect the inflammatory consequences in the off springs.

 Moreover it seems that the impact of a remote infection in the mothers of inflicted off springs, is not only limited to causing neurodevelopmental disorders such as bipolar disorder, and life-long sufferings. But the enduring even low grade inflammation in the immune system of the individuals seem to cause premature cell senescence and aging by shortening the telomeres of immune cells, e.g. T-lymphocytes. The proinflammatory biomarkers such as cytokines, e.g. TNF(Tumor Necrosis Factor)-alpha seem to be specifically related to the manic or hypomanic (elevated mood states) than the depressive mood states in bipolar disorder, making this disorder closer to a neurodevelopmental and infectious origin compared to unipolar depression that could be otherwise. Interestingly the therapeutic effect of Lithium as perhaps the most effective mood stabilizer in bipolar disorder has been shown to be related to its anti-inflammatory and potential anti-oxidative properties.

 While mood stabilizers such as Lithium and anti-psychotics could have anti-inflammatory and anti-oxidant effects, first of all as it is well known, they cannot be preventive and curative, meaning that they cannot reverse the pathological process in bipolar disorder. The other interesting fact is that antibiotics not only have no efficacy in this disorder, but could have triggering effects! One wonders the reason if infection is considered in the pathophysiological mechanism of disease causation. As explained in the articles on schizophrenia and Autism, first of all the infecting machinery, acts long earlier on the fetus through gestational infestations, leaving only their impact and damages on the off springs years after, hence causing a neurodevelopmental disorder, interrupting the normal brain development, as in case of schizophrenia and Autism spectrum disorders.


Mania or hypomania which is the elevation of mood in a pathological manner, so steering away the individual out of touch with reality, even in the absence of psychosis, into an ecstatic state of mind, seems to have been initiated by the microbial world long before the person has even been born. The inflicted patient may be happy about such mood elevation and its consequences, thought racing, pressured speech, high energy, inflated self-esteem, acting flamboyantly, risk taking, substance abuse and hyper-sexuality. But such individuals are not aware that such fast and abnormal mood elevation, will result in a consequential mood downfall of severe depression that suicide could be eminent. It may take a long effort of the clinicians and the family of such individuals to help him or her to recognize that these mood swings are actually pathological, so the person finally after years of swaying around by the wind of incontrollable emotions, be convinced of having a disorder and stick to the treatment. But the available treatment is far from stabilizing these mood swings, lest curing the condition. The reason is perhaps in the lack of our full knowledge and appreciation of the pathophysiology of the bipolar disorder and other neurodevelopmental conditions, caused long time before the onset of these disorders by microbial invasions. In fact the world should know that these are the microbes, seemingly of different kinds, behind the curtain, make the inflicted persons to dance like puppets!


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