Scenario for Analysis

Joan is a 48-y.o. white, married female in her second marriage to a very supportive, second husband who is convinced that she could be helped with her symptoms through hypno-behavioral therapy and relaxation.

Joan was diagnosed and suffering with Chronic Fatigue, Epstein Barr Virus, and Arthritis for over four years. Prior to these diagnoses, she had a minor traffic accident in which she sustained minimal neck injury. This accident seemed to send her physical system into chronic pain.

Joan was pre-morbidly a very active, overachieving, bank employee who raised her three children alone after her first husband – abusive both physically and emotionally – left her with no support. She admits to chronic worry prior to her illness, but a determination to be “strong,” keeping feelings internal while presenting a capable, competent, and happy face to the world.

After the accident, she became aware of numerous painful symptoms ultimately diagnosed as the above diseases. She had pain continuously in her extremities and back, had not been able to find a comfortable position for sitting or standing, had been restless, and had felt hopeless to find relief. She tried “every medical intervention available” including medications, cortisone injections, and physical therapy. She was facing the decision to undergo radical surgery to sever nerves when she came for therapy.

She presented with suicidal ideation to release her from her pain.

What are other important assessment questions for Joan and her family from a biological, psychological and social perspective?
What possible medical conditions or concerns would you need to rule out?


Statistic: People with chronic medical illnesses have a 41% higher rate of psychiatric disorders than do their physically healthy counterparts. (24)

Depression and/or anxiety are found to be co-morbid in many medical conditions. The presence of psychological symptoms may be:

- Secondary to the chemical issues inherent with the illness,
- Due to the impact of the illness on the patient and its meaning to him/her
- Indicative of a primary psychiatric illness that can predispose clients to medical complications.

When depression or anxiety is present, it affects the physical well-being of the individual. Psychological stressors can have a profound impact on the systems of the body, as we have detailed in the discussion on the effects of trauma. Moreover, adrenal and immune systems will be affected by continuous stress, with cellular metabolism and healing disrupted.

Depressed patients have been found to have twice the risk of developing diabetes than normal individuals. The prevalence of asthma is much greater in those with high levels of depression and anxiety. Up to 40% of patients with cancer suffer from depression and anxiety - and the presence of these mental symptoms has a negative effect on recovery. (9)

Chronic pain patients and those experiencing the effects of chemotherapy are also more likely to be at risk for developing depression. Their recovery is further complicated by the effects of depression and anxiety on their physical health due to the body’s response to stress.

This issue of co-morbidity can easily become a question of “which came first the chicken or the egg?”-- the mental/emotional or the physical illness? Regardless of the cause, often, the physical illness is the first to require treatment. Occasionally, it is the mental health professional who is first to encounter the client/patient.

Statistic: About 5% of patients with an initial diagnosis of Major Depression have been found to have a medical illness as the cause of their depression. (19)

It is necessary for the mental health professional to be aware of this close link between the mental, emotional and physical systems. As noted in earlier sections, the mental health clinician may be the first provider to listen to the client's complaints in depth, leading to increased responsibility to differentiate symptoms described as typical of psychiatric illness or to pick up on the subtle clues that may indicate the presence of a physical illness.

It is also important to note that medications used for treatment of the psychological symptoms may be affected by the physical illness and may require adjustments from normal levels. If the physician treating the client for the physical illness is not kept aware of the development of depression on the part of the patient, he or she may not be attuned to the need to adjust the medication accordingly.

Whenever there is co-morbidity, the clinician should be working closely with the primary care physician or specialist to provide the most coordinated plan of safe, effective and comprehensive treatment for the client.

This section of the training will:

- Explore the biochemical mechanisms of co-morbidity
- Explore psychological mechanisms of co-morbidity
- Present a list of more frequently encountered physical illnesses that are co-morbid with depression and/or anxiety

Biochemical Mechanisms of Co-morbidity

The mechanisms by which co-morbidities develop are found in the nervous, endocrine and immune systems and their components. These systems are designed to communicate and interact through their biochemical pathways. Thought processes, in response to environmental stimuli, initiate in the cerebral cortex and limbic system of the brain and activate the neuroendrocrine HPA axis (discussed earlier).
Hormonal messengers travel between the adrenals, the pituitary and the hypothalamus to stimulate responses outside of the brain. The immune system responds to signals from the HPA axis and sends signals to it as well. The protective activities of the immune system rely on neuro-chemicals to begin the processes that fight infection and respond to stress. (8)

There is a dependence on levels of hormones circulating throughout the system to serve as feedback messengers to inhibit HPA activity after a sufficient response has occurred. When the balanced regulation of the hypothalamic, pituitary and adrenal systems is disrupted there is malfunction of other systems.

Abnormal nervous system firing in the hippocampus, as seen in chronic stress/trauma and neurologic disorders, sends an alert to the adrenal and immune systems unnecessarily and vice versa. The neuro-chemical messengers in this process are norepinephrine, endorphins, cortisol, and dopamine. (8) By now you recognize these chemicals as critical in their effect on mood as well as many higher level cognitive activities.

In the disease process, the nervous, endocrine and immune systems detect the metabolic and cellular changes that eventually cause the signs and symptoms of disease. The resources of the body are initiated to stop the disease process.

This is a very automatic process that does not require cognitive directions to the body. However, there are potential effects of thoughts that are ruminative and fear/pain based with negativity, hopelessness and worry. The previous discussion on stress creating an imbalance in the hypothalmic-pituitary-adrenal (HPA) axis indicates that physical body destruction can occur with extended catecholamine depletion.

Wherever there is neurochemisty involved there is the possibility for psychiatric conditions to occur in the course of medical illnesses and in some cases actually contribute to the manifestations of the physical disease. This is the case of illness discussed in the first section such as MS, lupus, Parkinson’s and HIV. The physiology of these diseases causes the neuro-chemical imbalances that lead to psychiatric symptoms.

In the case of pain, the message is transmitted through neural pathways that carry information about touch and temperature causing specific neuro-chemical responses. Painful stimuli have been discovered on magnetic resonance imaging (MRI) and positron emission tomography (PET) to cause activation in the brain responsible for memory, emotion and personality. These stimuli activate neurotransmitters to be released at the sight causing a local inflammatory reaction while stimulating central pain receptors. (24)

Endorphins and serotonin are part of the chemical process the body uses to inhibit pain. The effects of these chemicals on mental status often go beyond pain modulation to include mood enhancement, behavior modulation and influence the development of tolerance or dependence on narcotics. (24)

Psychological Mechanisms of Co-morbidity

In all cases of medical illness it is normal for the client to respond with a grief/loss reaction to their loss of health. Hopelessness often accompanies this grief especially when the illness is life-threatening, demoralizing or without a clear diagnosis or prognosis.

Chronic illness is often characterized by loss of function and limitations in daily activities. Clients are separated from the systems that support their sense of self such as jobs, families and activities. They may be forced to comply with treatments that are uncomfortable yet seemingly ineffective. Medical patients commonly experience insomnia, fatigue, weight loss and motor retardation though not to the degree present in psychiatric illnesses. They are often unable, due to disability or medication, to perform self care or participate in rehabilitative activities.

Studies have indicated that there is a strong negative correlation between coping resources and depression. Where coping resources are solid and strong, depression is less likely. When resources are reduced or eliminated there is a higher incidence of depression. (6) In medical illness, such resources as a strong support network, tension reduction methods, problem-solving skills and confidence may be compromised leaving the client with feelings of hopelessness and helplessness.

Conversely, chronic life stress coupled with mental illness may set up a series of biologic processes that ultimately result in a physiologic or medical disorder. The effects of stress on body systems have been presented previously.

Having an optimistic attitude is one of the best treatments one can have. Healing chemicals are actually produced by the body in response to feelings of love, joy and peace; whereas, anger, fear, pain, worry, and other negative feelings send chemical messages that lead to cellular stress and breakdown.

Patients who are depressed have a higher probability of dying after heart attack or stroke compared to those who are not suffering with depression. (10) There is some evidence that depression can actually lead to cardiovascular disease. (16)

Among other disease states, studies show depression or anxiety adversely affects the recovery rate from cancer, response to cancer therapy and the death rate of cancer patients. Asthma is much more prevalent in clients with high levels of depression and anxiety. Depressed patients are twice as likely to develop diabetes that normal individuals. (9)

Frequently Encountered Physical Illnesses that are Co-morbid with Depression and/or Anxiety

Depressive symptoms, often with anxiety, are part of the primary manifestations in endocrine disorders, metabolic imbalances, viral infections, inflammatory disorders, malignancies (cancers), hormonal imbalance, and cardiopulmonary (heart/lung) conditions. (8)

Endocrine disorders are such diseases as:

- Hypothyroidism and Hyperthyroidism -- too little and too much thyroid hormone. With too little thyroid hormone there may be dullness of facial expression, forgetfulness, intellectual impairment and gradual personality changes including psychosis. Where there is too much of this hormone, a client will frequently present with nervousness and increased activity, sweating, sensitivity to heat, rapid heart rate, insomnia and weakness. (22)
- Cushing’s Syndrome – over-functioning of the pituitary or adrenal glands and is also known as hyper-adrenalism. This disease is the result of a chronic excess of cortisol, the major adrenocortical steroid. This steroid may be familiar to you in the generic drug Prednisone. This leads to facial puffiness, weight gain, hypertension, glucose intolerance and psychiatric disturbances. (22)
- Addison’s Disease – hypo-adrenalism due to under-functioning. This disorder presents as weakness, fatigue, dizziness on standing up quickly (orthostatic hypotension) and skin changes. Weight loss and dehydration with small heart size are later in the illness and may be fatal if untreated. (22)

Of these three disorders, the mental health clinician will most likely encounter thyroid related problems. Hypothyroidism is surprisingly common. Whenever a client appears with depression, it is advisable to verify that the client has had a complete physical that included a thyroid profile. Moreover, if the client has had a history of cancer and cancer treatment, it has been noted that there may be thyroid related problems even if the thyroid levels show up as normal in the client's blood work.

Because hypothyroidism slows the client's overall metabolism, weight gain may accompany lowered levels of thyroid hormones. There may also be increased metabolic sensitivities, such as changes in response to sugar intake. If the thyroid problems occur suddenly, these changes may be apparent to the client. If the thyroid function deteriorates slowly, the symptoms identifying the potential of thyroid problems may be more difficult to discern.

Endocrinologists may be the best referral resources for client with weight and energy issues when you suspect thyroid problems

Metabolic imbalances include such changes as:

- Serum sodium and potassium reductions as found in bulimia or dehydration
- Vitamin B12, Niacin, Vitamin C deficiencies or Iron deficiency (anemia) where, without necessary nutrients, the cell are unable to function normally in all parts of the body including the neurotransmitters
- Metal intoxication from mercury or thallium that acts as a poison, impairing the function of cells and ultimately destroying them
- Uremia which is the insufficiency of kidneys to excrete and regulate fluids and is the last stage of chronic renal (kidney) failure which is the ultimate poisoning of the system as the kidneys are no longer able to excrete toxins (22)

Viral/bacterial infections are such diseases as:

- Infectious Hepatitis – liver infection sending toxins and cellular changes throughout the body
- Encephalitis – inflammatory disease of the brain leading to impaired cellular functioning or eventual ischemia with resultant mental symptoms depending on the area affected
- Tuberculosis – an acute or chronic infection caused by mycobacterium tuberculosis that can affect the lungs and other areas of the body including the central nervous system which likewise includes the brain and spinal cord (22)
- AIDS – with the most common initial signs and symptoms of AIDS Dementia - Complex being changes in mentation (thinking) and personality, followed by organic mood disorder and organic delusional disorder with Major Depression and uncomplicated bereavement following soon after diagnosis (8)
- Epstein Barr, Fibromyalgia and Chronic Fatigue Syndrome all present with fatigue, pain, depressive symptoms - likely the result of their biochemical impact on the nervous system.

Inflammatory disorders include:

- Arthritic and Rheumatoid Arthritis conditions - where the inflammatory process leads to pain with its specific biologic response that affects neurotransmitters, specifically, endorphins and serotonin (8) -- more than 50% of patients with Rheumatoid Arthritis experience depressive symptoms and anxiety. (16)
- Lyme Disease, also known as Lyme Arthritis, which can lead to very serious neurologic changes, as well as precipitating the biochemical effects of pain (16) (22). Lyme Disease is contracted from bacteria passed from one infected host to another through the bite of a deer tick. Named for Old Lyme, Connecticut, where it was first noted, it is a disorder that must be considered if a person has spent time in the outdoors - particularly in temperate forested regions of Northeastern, North Central and Pacific coastal parts of the US - during the spring, summer and fall hiking and camping seasons. The telltale sign of a Lyme Disease infected deer tick bite is a circular, target shaped red mark around the bite site. (37)
- Prostatitis, which is inflammation of the prostate, causing pain with its biochemical changes, as well as sexual impotence with mood alterations the result of chemical changes and loss of sexual functioning.

Malignancies present with depressive syndromes in up to 50% of the cases and the biologic relationships may exist such that depression may be the first sign of undetected cancers such as: (8)

- Abdominal carcinoma (cancer), especially pancreatic
- Brain tumors (temporal lobe)
- Breast cancer
- Gastrointestinal cancer (stomach/intestines)
- Lung cancer
- Prostate cancer
- Metastasis (change in location of disease from one organ or part to another)

The likelihood of depression is influenced by advanced phases of the disease, uncontrolled pain, disability or disfigurement, medication or chemotherapy agents, social isolation and socioeconomic pressures. (10)

Hormonal imbalances speak to the menstrual changes of the life span. Peak prevalence of depression in women is between ages 18-44 with the average in the mid-20’s. There is indication that progesterone and estrogen influence the metabolism of the neurotransmitters, such as serotonin and norepinephrine, and how they are utilized and excreted by the body. (16) Depression is twice as prevalent in women as opposed to men, possibly due to such female life-cycle events as:

- Premenstrual Depressive Disorder (PMDD) affecting 4% of women, and manifesting itself differently from a minor depressive disorder due to its cyclic nature in conjunction with the changes in the menstrual cycle (16)
- Pre- and post-menopausal symptoms that can include such emotional changes as depression, insomnia, sexual changes and fatigue
- Pregnancy, with its hormonal swings and resultant emotional effects
- Postpartum Depression (PPD), which presents with minor transient symptoms in 50-80% of women, but with 10% of these patients developing a major depression (16) as the body is reorganizing its hormonal balances once the baby is born

Cardiopulmonary diseases deserve special attention because they are associated with depressive syndromes in 20-50% of patients and anxiety disorders in 80%. The presence of depression in heart patients affects physical healing, as well as the level of compliance with cardiac rehabilitation. Treatment of the depression is effective in the majority of cases. (8)

- Acute Myocardial Infarction – malfunction of the heart muscle from necrosis (tissue death) due to reduced blood flow (22) -- More than 70% of patients remain depressed for up to a year after the attack. (8) This depression has a neurochemical basis, as the trauma to the body increases the baseline level of cortisol. However, because there may be lifestyle changes and other psychosocial losses associated with heart attacks, the neurochemical effects may also be compounded by the normal depressive response to these life changes and losses.
- Post-cardiac arrest – due to absent or inadequate heart contraction with resultant poor oxygenation of all body cells - including those functioning in neurotransmission
- Post-coronary artery bypass – incidence of depression is lower, at only 6-15% (8)
- Post –heart transplant – incidence of depression is 54 % and may be due in part to the medications used to prevent rejection of the new heart (8)
- Cardiomyopathy – a variety of non-inflammatory lesions of the myocardium (heart muscle) sometimes caused by viral infections, anemia, hypo- or hyperthyroidism, alcoholism, nutritional disorders, toxins, radiation, bacterial infections, ischemia, aging and many others (22)

Because most present day cardiologists are attuned to the potential for neurochemically-based depression in their heart patients, the mental health clinician may not have been the first professional to address depression in these patients. However, it is always important to be aware and to address the emotional components of these medical conditions in clients. The research is clear in this area. It is helpful to examine with one's clients how attuned their cardiologist may be to following their emotional well being long term.


In order to broaden the understanding of the biochemical co-morbid aspects of a person with pain, the authors present Joan’s case. Joan is a 48 y.o. white married female in her second marriage to a very supportive second husband who is convinced that she could be helped with her symptoms through hypno-behavioral therapy and relaxation.

Joan has been suffering with Chronic Fatigue, Epstein Barr Virus, and Arthritis for over four years. She has had pain continuously in her extremities and back, has not been able to find a comfortable position for sitting or standing, has been restless and has felt hopeless to find relief. She reports suicidal ideation to release her from her pain.

Joan was pre-morbidly a very active, overachieving, bank employee who raised her three children alone after her first husband – abusive both physically and emotionally – left her with no support. She admits to chronic worry prior to her illness, but a determination to be “strong,” keeping feelings internal while presenting a capable, competent and happy face to the world.

Without going into more detail, it should be apparent that her physical body was holding continuous stress without relief. Her body’s autonomic nervous system was registering constant “fight or flight” messages without any fighting or fleeing on her part to release these chemicals and to regain balance. Finally after a minor traffic accident in which she sustained minimal injury to her back, her physical system seemed to break down.

Chronic pain often takes the form of such syndromes, and can lead to the types of disorders present in Joan’s case. Nervous tissue injury often leads to neuropathic (any disease of the nerves) pain that the patient describes as aching, burning, or even cutting pain. Joan's pre-morbid lifestyle of exposing her body to the continuous effects of norepinephrine through elevated levels of stress served to inhibit the HPA axis. This led to cellular destruction, and left her system vulnerable to the slightest external impact – the accident -- sending her entire system into crisis.

Suddenly she became aware of numerous painful symptoms ultimately diagnosed as the above diseases. With poor coping resources pre-morbidly to deal with stressors, she became overly focused on her pain. She has tried every medical intervention available including medications, cortisone injections and physical therapy. She was facing the decision to undergo radical surgery to sever nerves when she came for therapy.

As in many cases of chronic pain, her neuropathic pain has led to an increased sensation of pain (hyperalgia), lower pain threshold (allodynia) and increased receptor sensitivity (hyperesthesia). In effect, her body’s attention to painful stimuli went on hyper-alert status. Additionally, her constant cognitive focus on hurting, seeking relief and feeling hopeless about ever having relief resulted in a deepening – and interactive - physical and psychological crisis.

In many cases, there are permanent changes in the central pain interpretation function of the body’s physiologic, biochemical, cellular and molecular responses. The body can begin to misinterpret non-painful sensations as painful, an event called plasticity. (24) This is likely present in Joan’s situation. Pain is her life -- focusing on it and worrying about it every waking moment. This obsessional focus continuously stimulates her stress response - preventing healing, and not allowing for any relief of her painful sensations.

Many patients with chronic pain respond better to the use of physical and psychological modulation techniques as well as medications or physical therapy rather than to medications or physical therapy alone. (24) For this reason, the treatment plan for Joan includes such interventions as relaxation training, guided imagery, learning the importance and practice of a positive emotional states, positive self-talk and deeper hypno-behavioral therapy to help her to release deep unexpressed feelings.


The biochemical contributors to mental illness that are found in medical patients are the same as those causing symptoms in patients with primary psychiatric disorders – catecholamine depletion, neurotransmitter production and disorders of metabolism.

Mental illness in medically ill people is potentially lethal - and vice versa.

In a person with a primary mental illness, symptoms may be considered psychosomatic and go untreated until it is too late. Furthermore, the normal cognitive functioning that is necessary for compliance with the treatment plan may not be available in mentally ill clients and may be impaired in medically ill patients by the vegetative symptoms of their co-morbid depression. (24)

Affective functioning - the emotional state of the individual - has been shown to affect the physical recovery of the individual. There is a high incidence of depression in severe medical illness. This depression lowers the potential outcome for recovery and increases mortality. (5)

Some of the more common medical illnesses with strong psychological components are such conditions as cancer, heart disease, endocrine disorders, hormone imbalances and viral infections. There may be a tendency to confuse depression with normal feelings that arise from specific life situations. The depression, therefore, often goes undiagnosed.

Furthermore, drugs used to treat chronic disease may induce mental illness. Those used to treat mental illness may lead to symptoms of physical disease. If suspected, the drug should be withdrawn and an effective alternative selected or the dosage should be reduced until the symptoms are resolved.

Detection and diagnosis of any secondary mental illness in patients with a medical illness is critical. Both the physiologic and pharmacologic (medications) factors that may be contributing to the mental symptoms must be identified before effective treatment is begun.

Summary Page

Depression/Anxiety Accompanying Medical illness: Co-morbid


Endocrine disorders:

- Hypo- and hyperthyroidism
- Cushing’s syndrome (hyper-adrenalism)
- Addison’s disease (hypo-adrenalism)

Metabolic imbalances:

- Reduced sodium and potassium as in bulimia or dehydration,
- Vitamin deficiencies
- Metal intoxication (mercury or thallium)
- Uremia where kidneys fail to eliminate toxins

Viral/bacterial infections:

- Infectious hepatitis
- Encephalitis
- Tuberculosis
- Epstein Barr
- Fibromyalgia
- Chronic Fatigue

Inflammatory disorders:

- Arthritic and rheumatoid arthritis conditions
- Lyme disease
- Prostatitis


- Abdominal carcinoma (cancer), especially pancreatic
- Brain tumors (temporal lobe)
- Breast cancer
- Gastrointestinal cancer (stomach/intestines)
- Lung cancer
- Prostate cancer
- Metastasis (change in location of disease from one organ or part to another)

Hormonal imbalance:

- Premenstrual depressive disorder (PMDD)
- Pre and post menopausal symptoms
- Pregnancy hormonal swings and resultant emotional effects
- Post-partum depression with occasional psychosis

Cardiopulmonary diseases:

- Acute Myocardial Infarction
- Post-cardiac arrest
- Post-coronary artery bypass
- Post –heart transplant
- Cardiomyopathy – a variety of non-inflammatory lesions of the myocardium (heart muscle)


Biochemical Mechanisms

The communication system within the body between its physical and psychological components operates on interconnected, similar and sometimes same pathways. These are found in the nervous, endocrine and immune systems. Thought processes originating in the cerebral cortex in response to environmental stimuli activate the HPA axis.

Hormonal messengers travel to the adrenals, the pituitary and hypothalmus to stimulate responses outside the brain. The immune system responds, signaling its protective activities through neuro-chemicals that fight infection and respond to stress.

A delicate neuro-chemical balance keeps all of these systems functioning optimally. With disease there is disruption of this process. Wherever neuro-chemistry is involved, there is the possibility for psychiatric conditions to manifest.

Psychological Mechanisms

The aspects of medical illnesses that are related to grief/loss, changes in life style and activity level all impact the patient’s sense of well being. They may be separated from job, families and activities that had previously supported their sense of self. The disease challenges their ability to cope and to adapt as well as the body’s ability to heal.

Individuals who lack pre-morbid coping skills such as a strong support network, tension reduction methods, problem solving abilities and confidence are at greater risk for psychological complications.


Factors to consider in diagnosing depression in medical patients include:

- One or more specific medical illnesses
- Family psychiatric history
- Past psychiatric history of the patient
- Definitive criteria of one of the depressive syndromes
- Response to treatment for any previous depressive episode
- Sex of patient
- Age at onset of depression
- Biologic markers for depression
- Duration of depressive illness
- Psychosocial pre-morbid events or functioning
- Relative frequency of the diagnosis in particular populations of patient

The cognitive/affective symptoms of depression that can differentiate it from medical illness include: feelings of failure, low self-esteem, guilt feelings, loss of interest in people, feelings of being punished, difficulty with decisions and crying. It is important to remember that decreased appetite, sleep disturbances and loss of energy are common symptoms in medical illness as well as depression. (24)


Untreated medical illnesses can lead to continuous cellular destruction, more and more involvement of other body systems, temporary or permanent impairment of mental and physical functioning, and ultimate death. Depression increases risk of death after heart attack and stroke, hinders the body’s healing mechanisms, and can lead to cardiovascular disease. Untreated mental/medical disorders can result in suicidal deaths.