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Hear what Dr. Henderson has to say about biological illnesses that can present with psychiatric symptoms.
“Over time, the explanation of psychiatric illnesses has shifted from afflictions by evil humors or spirits to dysfunction in neurophysiological processes. More recently, research and clinical experience has shown that infectious agents, such as viruses, can cause the neurophysiological dysfunction. Just as research proved syphilis could cause psychiatric symptoms and dementia in the 1940’s-1960’s, recent research is demonstrating that viral and certain bacterial infections can persist undetected in the brain and cause a wide array of symptoms.”
Unlike the medical diagnostic process in the rest of medicine, psychiatric diagnoses are neither objective, nor precise. For example, hypercholesterolemia is defined as a cholesterol level above certain objectively defined numerical norms. Histopathology is the primary means of diagnosing and characterizing cancer. In contrast, psychiatric diagnoses are made by following largely subjective descriptors developed by committees. Increasingly, the Diagnostic and Statistical Manual of Mental Disorders (DSM) has become a system of pigeonholes that do not provide insight into psychiatric illnesses, but instead are used by insurance companies to discriminate against patients. DSM diagnoses are not formulated based on demonstrable pathophysiological disruptions in the brain1. There are few objective findings in psychiatry to identify any single diagnosis. Moreover, diagnoses deduced by different methods often fail to agree. For example, Rettew and colleagues demonstrated that structured clinical interviews often yield a different diagnosis compared to that derived by clinical evaluation2. In addition, research has made it clear that there is more than one mechanism underlying a given psychiatric diagnosis, such as depression3,4 or ADHD5,6,7. So, it is unlikely that DSM diagnoses represent distinct neurophysiological entities. They will likely prove to represent groups of neurophysiological processes.
More importantly, growing evidence suggests that not all psychiatric symptoms, such as anxiety, fatigue, listlessness, low mood, or poor concentration, result from intrinsic flaws in the patient’s brain. Extrinsic causes, such as infections and toxins, can cause these psychiatric symptoms. The resulting cluster of symptoms might mimic anxiety, depression and other psychiatric disorders, leading to misdiagnosis and ineffective treatment. For example, lead or other heavy metal toxicity can lead to poor attention, hyperactivity, and impulsivity – mimicking ADHD8. Hypothyroidism can mimic depression in every way, but be unresponsive to antidepressant medications. Mild traumatic brain injury can lead to depression, anxiety, inattention, and loss of motivation9,10. Certain rare autoimmune disorders can lead to the formation of antibodies against specific neurotransmitter receptors11,12. Much more widespread autoimmune disorders, such as systemic lupus erythematosus, can lead to cognitive changes, anxiety, seizures, and mood disorders13,14.
It is not a surprise that infectious agents also may trigger psychiatric symptoms. Most people have experienced fatigue and mental fogginess during an acute viral infection. But there is now evidence that a number of infectious agents can induce chronic infections leading to long-standing or progressive psychiatric symptoms of a profound nature. For example, specific DNA belonging to a bacteria that spends part of its life cycle living inside human cells (chlamydiae species) was found in higher rates in patients with schizophrenia. Chlamydiae has been found in the blood of 50% of the schizophrenic population, compared to 7% of the healthy controls, by Dr. Rudolf Wank at the Institute of Immunology, University of Munich15. The association between infectious agents and schizophrenia is a long-standing one. Studies based on populations affected by the Nazi blockade of cities in Netherlands during World War II showed that mothers who were ill or under starvation conditions during the second trimester of pregnancy were at much higher risk of having a child with schizophrenia16. In 2008, a large Swedish national cohort study of 1.2 million children born between 1973 and 1985 and followed for over 20 years showed an increased incidence of schizophrenia in people who had childhood infections of the mumps virus or cytogegalovirus (CMV)17.
Recent studies have shown that the DNA of Herpes-1 virus (the cold sore virus) is located in the pathological plaques in Alzheimer’s disease18. Cultured brain cells with the genetic material of the Herpes-1 virus inserted into their DNA accumulate amyloid abnormally19. Transgenic mice containing the Herpes-1 virus genetic material develop the mouse equivalent of Alzheimer’s disease far more rapidly20. As time goes on, research may confirm that infectious elements contribute to Alzheimer’s disease and other neuropsychiatric illnesses21,22,23, including the neurodevelopmental variation seen in the genetic disorder Down Syndrome22. We have but to look. Using in situ hybridization, a research group in Japan has found the DNA of the Herpes simplex 1 virus in the cortices of patients with AD24.
Certain bacteria may contribute to at least some cases of Alzheimer’s disease. In 2011, a meta-analysis of several different studies estimated that the bacterium Borrelia burgdorferi was found in the brains of 25.3% of patients with Alzheimer’s disease. That is 13 times more than in the brains of people not affected by Alzheimer’s Disease25.
Over the years, numerous studies have demonstrated a link between chronic viral infections and a number of conditions that alter brain function. For example, research has shown a number of chronic viral infections can be found in patients with Chronic Fatigue Syndrome (CFS). Viruses such as Epstein-Barr virus (EBV), CMV, and several herpes viruses (e.g., Herpes 1, 6, 7 – HSV-1, HHV-6, HHV-7) cause or contribute to the symptoms of a large percentage of patient with CFS. These infections are generally not acute, but represent intracellular reactivation of an old infection; hence, an elevation of IgM antibodies is typically not seen with active infections of EBV, CMV, or HHV-6. Careful studies have shown 70% of patients with CFS had active HHV-6 infection through the use of primary cell cultures and confirmation using assays of monoclonal antibodies specific for HHV-6 proteins and by PCR. Moreover, a higher proportion of CFS patients have multiple simultaneous infections26, such as HHV-6 and HHV-7.
Research also has revealed chronic occult bacterial infections in patients with CFS. This, in part, reflects a compromised immune system. Indeed Nicolson and colleagues found that 52% of CFS patients had active mycoplasma infection, 30.5% had active HHV-6 infection, and 7.5% had Chlamydia pneumonia infections vs. only 6%, 9% and 1% of controls, respectively. These authors concluded, “The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients27.
CFS can often be confused with depression. Patients have low energy, loss of interest in activities, increased sleeping, low mood and therefore have many symptoms that would meet the diagnostic requirements for depression. As a result, patients can be diagnosed with depression and treated with antidepressants. These are often ineffective for CFS, as one might expect. A significant proportion of patients with “treatment-resistant depression” may in fact have CFS or a chronic viral infection.
A study by Lerner found that treating CFS patients with 6 months of antivirals resulted in a significant improvement in symptoms28,29. Similarly, Montoya and his colleagues at Stanford University treated CFS patients with a potent antiviral for 6 months30, if they had elevated IgG tests for HHV-6 and EBV and had at least 4 of the following symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression. Nine of the twelve treated patients (75%) “experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activities.” In the nine patients with a symptomatic response to treatment, EBV IgG and HHV-6 IgG titers significantly dropped30. Others have found that antivirals are effective for the treatment of CFS, especially in patients with 1) flu-like symptoms or symptoms starting with a flu-like illness; 2) elevated IgG or EA against EBV, CMV, and/or HHV-6; 3) low natural killer cell activity; 4) high RNAse-L activity; high ACE (> 35); coagulation activation; 5) high tumor necrosis factor (TNF); and/or 6) elevated or decreased total IgA, IgM or IgG levels. A number of studies have also shown dramatic improvement in patients with interferon treatments, especially those with low natural killer cell function.
In my practice, I have found that antiviral therapy in cases of CFS or myalgic encephalomyelitis is often a chronic treatment. Remember, that herpes viruses are not killed by antivirals. They are merely prevented from replicating. The virus remains ensconced in the neurons. Only a small portion of my patients have been successful at discontinuing antivirals without relapsing symptoms. I will relate one case (an amalgam of several cases) as an example. An adolescent presented with “treatment-resistant” depression. She complained of symptoms of fatigue, “brain fog”, low motivation, and seemingly mild depression. Her history was consistent with a chronic viral encephalitis with a history of acute onset following a viral illness. She responded readily to a treatment of antiviral medication with complete resolution of all symptoms. At about 6 months into treatment, her family went to Disney World. They forgot her medication, but felt that she would do fine. After all, it had been 6 months. Within a matter of a few days, her fatigue, sleepiness, and “brain fog” had recurred. She spent her Disney World vacation in bed at the hotel. Upon return, they restarted her antiviral and within a week, her symptoms were again completely resolved. In summary, cases of CFS or myalgic encephalomyelitis are difficult and challenging. Substantial evidence supports the role of viruses in these illnesses.
Is There Such A Thing As Chronic Infections
Some may argue that there is no evidence for chronic infections in CFS and other “psychiatric” syndromes. While numerous studies have demonstrated a high incidence of chronic infections in CFS26,27, schizophrenia31, Alzheimer’s disease18,21-23, temporal lobe seizure disorders32,33, and even Autism34, medicine has dismissed these findings as circumstantial. Intracellular bacteria, such as Borrelia burgdorferi, which is responsible for Lyme’s disease, also can develop into chronic hidden infections35. Physicians, including infectious disease specialists, do not appreciate the impact created by the dysfunction of the immune system associated with these illnesses. Normally, with an acute infection, the body will start producing IgM antibodies against an infection and then start producing IgG antibodies within a few weeks. As a result, an elevation of both IgG and IgM antibodies occurs in an acute infection. However, in a chronic reactivating infection, there is no IgM response, because it is not a new infection. Often, due to immune system compromise, an elevation of IgG antibodies does not occur, so these antibody titers cannot be used as an effective means of detecting chronic infections in these patients. So, in patients with a compromised immune system, the body does not mount a IgM antibody response, nor does it maintain an IgG antibody response, despite the presence of an active infection. This has also been demonstrated to be true with AIDS patients who have a severe compromise of the immune system, as demonstrated in a study published in the New England Journal of Medicine36.
In CFS and other illnesses wherein the immune system is compromised, elevated IgG antibody titers will be interpreted by most physicians as evidence of an old infection or previous exposure. Unfortunately, in chronic infections, the immune system even if not compromised, cannot maintain an antibody response, so there is no evidence of an “active infection”. This standard way of detecting active infections therefore misses the overwhelming majority of patients with active intracellular viral infections. Polymerase chain reaction (PCR) testing has proven much more sensitive for detecting the presence of chronic viral infections. Yet, this can be challenging in the clinical setting, if the blood is allowed to sit for more than a few hours, the infectious organism’s DNA degrades and can go undetected. In addition, PCR of blood may miss the viral DNA because these infections are not concentrated in the blood, but rather in nerve cell bodies, the brain, and the white blood cells. Physicians must have a high incidence of suspicion and look for elevated IgG or early antigen (EA) antibodies along with other signs of chronic infections including low natural killer cell counts or activity, high RNAse-L activity, high ACE, high tumor necrosis factor (TNF), high interleukin-6 (IL-6), and other markers.
At the beginning of 2014, Dr. Henderson published two key papers on this topic. The first was published in Autism Open Access focuses on the plight of a single young boy who presented with treatment-resistant Bipolar Disorder, ADHD, and Autism Spectrum Disorder37. After treatment with an antiviral medication, all of the patient’s autistic features resolved and his mood disorder became much easier to treat with psychotropic medications. This case is presented in great detail to illustrate the fundamental shift in this patient’s function and quality of life after the viral infection was controlled. The second paper by Dr. Henderson38 is a case series of children and adolescents who were referred to Dr. Henderson with the diagnosis of “treatment-resistant depression”. He demonstrated that antiviral therapy reduced or reversed the symptoms of depression( insert link http://www.ncbi.nlm.nih.gov/pubmed/24445302 ), as well as reducing excessive sleep, fatigue, and low motivation. All were experiencing cognitive impairment or “brain fog”. Indeed, the majority of these adolescents had failing grades or had quit school. After treatment, all were able to return to school and perform academically. With improved energy, restful sleep, and mental clarity, the symptoms of depression and anxiety often melted away. Many of these young patients were able to stop taking psychotropic medications altogether. Dr. Henderson’s work sheds some light on possible candidate viruses responsible for the symptoms of fatigue, low motivation, academic failure, excessive sleep, emotional dysregulation, and anxiety which are often labeled as depression, but are in fact symptoms of a virally-induced Chronic Fatigue Syndrome.
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