Medical Illnes and Mental Health

The following is provided for informational purposes only. It is not to be used as a means to establish a diagnosis. The Handbook of Psychiatric Emergencies (Paperback) by Andrew E. Slaby, states that about 80% of all those who present to a hospital Emergency Room with a Psychiatric problem have an underlying medical condition accounting for their symptoms. We encourage all who seek treatment to see their Physician to rule out General Medical Conditions.

Psychiatric Presentation of Medical Illness-
Mental Disorders Secondary to General Medical Conditions
Last Updated: April 13, 2006 Rate this Article

AUTHOR INFORMATION Section 1 of 10

Author Information Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin Deficiency States Exogenous Toxins Author: Linda Chuang, MD, Clinical Instructor, Department of Psychiatry, Division of Consultation-Liaison, Bellevue Hospital, New York University
Coauthor(s): Nancy Forman, MD, Associate Director, Department of Psychiatry, Division of Consultation-Liaison Psychiatry, Bellevue Hospital Center, New York University

Linda Chuang, MD, is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Psychiatric Association, Medical Society of the State of New York, and Phi Beta Kappa

Editor(s): Alan D Schmetzer, MD, Professor and Vice-Chair for Education, Director of Residency Training, Department of Psychiatry, Indiana University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Iqbal Ahmed, MD, Program Director, General and Geriatric Psychiatry Residency Programs, Vice Chair for Education, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii; Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry, Assistant Professor, Department of Medicine, Froedtert Hospital, Medical College of Wisconsin; and Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA

INTRODUCTION Section 2 of 10

Author Information Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin Deficiency States Exogenous Toxins

Evaluation of patients who present to hospitals or physicians with altered behavior and/or mentation can be time-consuming and difficult and may lead to symptoms being quickly and prematurely dismissed as psychiatric in nature. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), the psychiatric presentation of a medical illness is classified as a "mental disorder due to a general medical condition." These disorders are characterized by the presence of mental symptoms that are the direct consequences of an underlying medical condition. Therefore, understanding common psychiatric symptoms and the medical diseases that may cause or mimic them is of utmost importance. Failure to identify these underlying causal medical conditions can be potentially dangerous because serious and frequently reversible conditions can be overlooked. Proper diagnosis of a psychiatric illness necessitates investigation of all appropriate medical causes of the symptoms.

The following features suggest a medical origin to psychiatric symptoms:

Late onset of initial presentation

Known underlying medical condition

Atypical presentation of a specific psychiatric diagnosis

Absence of personal and family history of psychiatric illnesses

Illicit substance use

Medication use

Treatment resistance or unusual response to treatment

Sudden onset of mental symptoms

Abnormal vital signs

Waxing and waning mental status
Because multiple secondary causes of mental disorders exist, as shown in the Table, this article discusses only the most common causes.

Medical Disorders That Can Induce Psychiatric Symptoms*

Medical and Toxic Effects CNS Infectious Metabolic/Endocrine Cardiopulmonary Others
Alcohol

Cocaine

Marijuana

Phencyclidine (PCP)

Lysergic acid diethylamide (LSD)

Heroin

Amphetamines

Jimson weed

gamma-hydroxybutyrate (GHB)

Benzodiazepines

Prescription drugs
Subdural hematoma

Tumor

Aneurysm

Severe hypertension

Meningitis

Encephalitis

Normal pressure hydrocephalus

Seizure disorder

Multiple sclerosis
Pneumonia

Urinary tract infection

Sepsis

Malaria

Legionnaire disease

Syphilis

Typhoid

Diphtheria

HIV

Rheumatic fever

Herpes
Thyroid disorder

Adrenal disorder

Renal disorder

Hepatic disorder

Wilson disease

Hyperglycemia

Hypoglycemia

Vitamin deficiency

Electrolyte imbalances

Porphyria
Myocardial infarction

Congestive heart failure

Hypoxia

Hypercarbia
Systemic lupus erythematosus

Anemia

Vasculitis

*(Adapted from Williams E, Shepherd S. Medical clearance of psychiatric patients. Emerg Med Clin North Am. May 2000; 18:2; 193.)

NEUROLOGIC DISORDERS Section 3 of 10

Author Information Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin Deficiency States Exogenous Toxins

Seizure disorder

Epilepsy is one of the most common chronic neurologic diseases, affecting approximately 1% of the US population. Approximately 30-50% of patients with a seizure disorder have psychiatric symptoms sometime during the course of their illness. Psychiatric symptoms can be viewed in the context of their time relationship with the seizures as preictal, ictal, postictal, and interictal. Two major categories of seizures are partial and generalized. Increased psychopathology has been associated with different features (eg, seizure phenomenology, brain pathology, antiepileptic drug use, psychosocial factors). Characteristics of the seizures and their presenting psychiatric symptoms deserve further attention.

Generalized seizures simultaneously involve both cerebral hemispheres, with classic symptoms of loss of consciousness, tonic-clonic movements or limbs, tongue biting, and incontinence. While the diagnosis is relatively straightforward, the postictal state is characterized by a gradual clearing of delirium lasting a few minutes to many hours.

Partial seizures have focal signs and symptoms resulting from electrical discharge in a limited site in one brain hemisphere. Simple partial seizures occur without any impairment of consciousness and usually stem from primary motor, sensory, or visual cortical regions. Complex partial seizures are associated with impairment of consciousness and usually originate from a focus in the temporal lobe. In such seizures, psychiatric signs abound, with memory dysfunction, affective auras, perceptual changes (eg, hallucinations), and depersonalization.

In temporal lobe epilepsy, the most common psychiatric abnormality is personality change. Hyperreligiosity, hypergraphia, and hyposexuality are reportedly more commonly associated with temporal lobe epilepsy. Development of psychosis is also described in temporal lobe epilepsy.

An estimated 4-27% (average, ~10%) of patients with complex partial epilepsy have psychotic symptoms such as paranoid ideation, thought disorder, and hallucinations. Mood disorder symptoms occur most often with foci in the temporal lobe. Statistically, 30% of patients with epilepsy have a history of suicide attempts, which attests to the importance of diagnosing depression in these patients. Fear and anxiety are the most common ictal affective states.

Parkinson disease

Parkinson disease (PD) is a disorder characterized by movement abnormalities caused by degeneration of the neurons in the substantia nigra. Currently, PD affects approximately 1% of the population older than 50 years and up to 2.5% of the population older than 70 years (Marsh, 2000). PD affects all races about equally; men are more often affected than women.

The hallmark clinical signs of the motor triad include (1) tremor, usually a rest tremor involving the hands, described as pill rolling; (2) rigidity; and (3) bradykinesia/akinesia. The classic motor signs may not be obvious early in the disease, and patients may initially present with only clinical signs of depression (Gonera, 1997). Thus, PD may be misdiagnosed as a primary depressive illness, and concomitant depression may remain undiagnosed in a patient with PD. Similarities in the symptoms common to major depression and PD include impaired memory/concentration, slowed psychomotor activity, restricted affect, and fatigue or decreased energy.

The prevalence of major depression in patients with PD is estimated to be 40%, with prevalence rates of 4-70% (Mayeux, 1992). Considerable evidence indicates that depression can precede development of motor symptoms, suggesting that the depression itself may be a neurologic sign of PD. In addition to mood disturbances, patients with PD commonly present with symptoms of anxiety, including general anxiety disorder, social phobia, and panic disorder, with a prevalence rate of 25% (Fukunishi, 1991).

The anxiety syndromes in PD are apparently related to an underlying brain disease, with evidence implicating noradrenergic dysfunction. In several studies, anxiety syndromes developed before or after the onset of motor symptoms (Stein, 1990).

Hallucinations and delusions can also occur in as many as 40% of patients with PD (Goetz, 1993). The psychosis can develop spontaneously or in association with mood disturbance but usually develops either late in the disease process (when significant cognitive impairment is also evident) or with use of dopaminergically active medication (Olanow, 1998).

Most treatments are aimed at patients' specific symptoms. PD must be considered in the differential diagnosis of an elderly person presenting with first-time depression/anxiety symptoms, especially when the patient appears depressed but denies experiencing a depressed mood. In addition, treatment of symptoms can be complicated in patients with PD because antiparkinsonian drugs may exacerbate psychiatric symptoms and vice versa. Consultation with both neurologists and psychiatrists can be helpful when treating these patients.

Brain tumors

Brain tumors and cerebrovascular disease are important causes of psychiatric symptoms and patients with these diseases can present with virtually any symptom. A complete clinical history and neurologic examination are essential in diagnosing either condition. Given the nature of the onset and presentation of a cerebrovascular event, it is rarely misdiagnosed as a mental disorder. However, up to 50% of patients with brain tumors reportedly have manifestations of a psychiatric nature (Galasko, 1988).

In general, meningiomas are likely to cause focal symptoms because they compress a limited region in the cortex, whereas gliomas can cause more diffuse symptoms. Delirium is most often secondary to a large, fast-growing, or metastatic tumor. The specific psychiatric symptoms largely depend on the location of the tumor within the brain and the structures affected by direct invasion or pressure.

Frontal lobe tumors, which are responsible for approximately 88% of the patients with psychiatric symptoms, can elicit presenting signs such as cognitive impairment, personality change, or motor and language dysfunction (Skuster, 1992). Patients also frequently have bowel or bladder incontinence.

Patients with dominant temporal lesions can present with memory and speech abnormalities. Nondominant tumors can cause auditory agnosia. Bilateral lesions can lead to Korsakoff amnesia. Occipital lesions can cause visual hallucinations, agnosia, and Anton syndrome (denial of blindness). The visual pathways all cross in the temporal, parietal, and occipital lobes; therefore, visual hallucinations can occur with lesions in any of these locations. Auditory hallucinations can also occur with temporal lesions but are apparently less common.

Limbic and hypothalamic tumors can cause affective symptoms such as rage, mania, emotional lability, and altered sexual behavior (Cummings, 1985). They can also produce delusions involving complicated plots.

Hallucinations, which are often considered the hallmarks of psychiatric illness, can be caused by focal neurologic pathology.

The diagnostic procedure of choice is brain imaging with contrast head CT scan or an MRI. In many clinical cases, when a CNS tumor is considered likely, initial CT scan findings may be normal, and MRI may be required to confirm the diagnosis.

Multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disorder characterized by multiple episodes of symptoms of a neuropsychiatric nature related to multifocal lesions in the white matter of the CNS. Prevalence is estimated to be approximately 50 cases per 100,000 people. MS is more frequent in colder and temperate climates than in tropical locales, which may suggest a viral etiology. MS is more common in women than in men and usually manifests in persons aged 20-40 years. This disorder is a highly variable illness, with differences among patients and changes within a patient over time.

Symptoms can be categorized as cognitive and psychiatric. Recent reviews of neuropsychological performance in patients with MS indicate that 30-50% have cognitive deficits (Fennell, 1990). Of the cognitive deficits, memory loss is the most common and affects approximately 40-60% of patients (Grafman, 1990). Abstract reasoning, planning, and organizational skills are some of the functions also affected by MS. Dementia may eventually ensue.

Behavioral symptoms in MS include personality changes and feelings of euphoria and/or depression. Approximately 25% of patients experience euphoria that is different from hypomania and is characterized by an unusually cheerful mood. One study showed a 2-fold increase in the lifetime risk of bipolar disease in MS patients (Mahler, 1992). Major depression is very common in individuals with MS; indeed, 25-50% of patients experience major depression after the onset of MS. Suicide attempts are common in patients with MS who are depressed. Personality changes and emotional dyscontrol can also occur. Patients sometimes laugh without cause or weep suddenly. Such emotional lability can be disturbing for patients and their families and can make assessment of psychiatric symptoms more difficult in patients with

MS. INFECTIOUS DISEASES Section 4 of 10

Author Information Introduction Neurologic Disorders Infectious Diseases Endocrine Disorders Rheumatologic Disorder Metabolic Disorders Vitamin Deficiency States Exogenous Toxins

Neurosyphilis

Neurosyphilis, once a common cause of admission to mental institutions, has become rare as a result of the invention of penicillin. However, AIDS has reintroduced the infection in certain urban settings. The infection is caused by the organism Treponema pallidum, which invades the parenchyma of the brain.

Neurosyphilis is usually clinically apparent as a part of tertiary syphilis, which includes two other types: late benign (gummatous) syphilis and cardiovascular syphilis. Neurosyphilis is now the predominant form of tertiary syphilis and occurs only after a latent period of 10-20 years after the primary infection, although infection with HIV negates this general rule (Gliatto and Caroff, 2001). Neurosyphilis primarily affects the frontal lobes, which can result in personality changes, irritability, decreased self-care, mania, and progressive dementia. Delusions of grandeur occur in 10-20% of patients. Early evidence of neurosyphilis includes tremors, dysarthria, and Argyll Robertson pupils.

The diagnosis is confirmed using serologic tests. Cerebrospinal fluid (CSF) analysis always shows abnormal results and reveals primary lymphocytosis and increased protein level. Always consider neurosyphilis in patients who may have an underlying immunodeficiency disease and present with mental status changes and a progressive dementia incongruent with advanced age.

Meningitis

Acute bacterial, fungal, and viral meningitis can be associated with a psychiatric presentation with or without abnormal vital signs. Patients who are immunocompromised (eg, those with AIDS, individuals in oncology units) are particularly susceptible. Those with indwelling ventriculoperitoneal shunts are also at high risk for developing the infection. Patients usually present with acute confusion, headaches, memory impairments, and fever with possible neck stiffness. Because bacterial meningitis is a life-threatening emergency, persons at high risk who have a sudden onset of mental status changes should always undergo a workup that includes a diagnostic lumbar puncture.

More recently, the Haemophilus influenzae type b and the pneumococcal conjugate vaccines have greatly reduced cases of meningitis caused by these agents (Whitney, 2003). Penicillin resistance has emerged in Streptococcus pneumoniae infections.

Herpes simplex encephalitis

Herpes simplex virus (HSV) is one of the most common and devastating causes of sporadic and severe focal encephalitis. Infection with HSV can occur in any person—age, sex, and demographic region are irrelevant. HSV reaches the brain from the bloodstream or peripheral nerves by cell-to-cell spread along the branches in the trigeminal nerve, which then innervates the meninges or the anterior and middle fossae. Thus, infection is characteristically localized to the temporal and frontal lobes.

Patients with HSV encephalitis commonly present with bizarre, inconsistent behavior and a waxing and waning mental status. Symptoms often include seizures, anosmia, olfactory and gustatory hallucinations, personality changes, and psychosis. Consider this diagnosis when the patient has a prodrome of 1-7 days of upper respiratory tract infection with headache, fever, and subsequent bizarre psychiatric symptoms.

Lumbar puncture, serology studies, neuroimaging, and EEG are helpful in confirming the diagnosis.

Treatment consists of intravenous acyclovir, but if the condition is not diagnosed and treated quickly, long-term psychiatric and neurologic sequelae are likely.

HIV encephalopathy

An estimated 42 million people were estimated to be living with HIV worldwide (CDC, 2001). The number of infected people continues to increase, especially among poor and socially disadvantaged persons in the United States, although the rate of increase has declined over the years. Thus, recognition and proper treatment of AIDS-related complications involving the CNS and its behavioral and neurologic manifestations is one of the most common challenges faced by physicians.

While patients with AIDS have psychiatric and neurologic symptoms from lesions (eg, primary CNS lymphoma) or opportunistic infections, HIV itself can cause a subacute encephalitis and dementing complex. Clinically, HIV encephalopathy manifests as a progressive subcortical dementia with nonspecific CSF abnormalities and cerebral atrophy with ventricular dilation. In the early stages, signs of encephalopathy include difficulty concentrating, subtle mood changes, disorientation, withdrawal, or lethargy. Motor signs, such as psychomotor slowing, hyperreflexia, and spastic or ataxic gait, may also be present. Later, psychiatric episodes may become clinically apparent as delirium, mania, or psychosis (Pajeau, 1992). Although HIV encephalopathy has become one of the leading causes of dementia in persons younger than 60 years (McArthur, 1993), it has become less frequent since the introduction of highly active antiretroviral therapy (HAART).

Consider the possibility of HIV encephalopathy in the evaluation of any patient with a psychiatric disorder who has HIV. Carefully investigate with lumbar puncture and brain imaging to exclude other causes (eg, meningitis, malignancy). Conversely, any patient presenting with first-time psychiatric symptoms and without a positive psychiatric history should undergo HIV testing. In addition, being aware of the neuropsychiatric effects of medications used frequently in HIV infection is helpful.

Early therapy with antiretrovirals, particularly azidothymidine (AZT), is recommended because retrovirals may have a protective effect in delaying or reversing some of the psychiatric and neurologic manifestations of HIV infection (Pajeau, 1992). Otherwise, symptomatic treatment with psychopharmacologic medications is an important aspect in the treatment of these patients. Because patients with HIV can be more susceptible to the adverse effects of psychotropic drugs, and because many of these medications may lower seizure thresholds, use care when prescribing them. In addition, lower doses of the drugs are recommended (at least for initial treatment), and the maxim “start low and go slow” should be followed.

ENDOCRINE DISORDERS Section 5 of 10

Parathyroid disorder

Dysfunction of the parathyroid glands results in abnormalities in the regulation of electrolytes, especially calcium. Excessive excretion of parathyroid hormone results in a state of hypercalcemia. Such hyperparathyroidism usually occurs in the third to fifth decade of life and is more common in women than in men. Annual incidence is in the 0.1% range and affects up to 0.2% of the population older than 60 years (Cryer, 1996).

Hyperparathyroidism is frequently associated with significant psychiatric symptoms, which are caused by the resultant hypercalcemia and can precede other somatic manifestations of the illness. Patients can experience delirium, sudden dementia, depression, anxiety, psychosis, apathy, stupor, and coma.

Hypomagnesemia also occurs in association with hyperparathyroidism, usually after surgical removal of a parathyroid adenoma. Delirium with psychosis is a common presentation of patients with severe hypomagnesemia. Visual hallucinations and paranoid delusional psychosis are also observed in those with a magnesium deficiency.

In hypoparathyroidism, expect to find low serum levels of calcium and magnesium. Patients most commonly experience delirium but may also experience psychosis, depression, or anxiety. Because imbalances of calcium and magnesium can cause psychiatric symptoms, serum levels of both electrolytes must be ascertained for diagnostic evaluation of any psychiatric presentation. While patients with hypercalcemia should have parathyroid hormone levels checked, they should also be evaluated for other causes of hypercalcemia.

Thyroid disorders

Hyperthyroidism is a common clinical condition caused by excess thyroid hormone. Because this disorder is so common, a high index of clinical awareness for thyroid disease and its complications is needed in any patient who presents with psychiatric symptoms. Always include evaluations of thyroid-stimulating hormone (TSH [thyrotropin]) and free thyroxine (T4) levels in the medical workup of patients presenting with psychiatric symptoms for the first time. Graves disease is the most common cause in the population. Some evidence indicates that stress can precipitate Graves disease and aggravate treated disease (Fukao, 2003). Toxic nodular goiter is most prevalent in the elderly population.

Patients can present in various ways but commonly present with symptoms of anxiety, confusion, and agitated depression. Patients can also present with hypomania and frank psychosis. When hyperthyroidism is suggested, standard clinical symptoms may be present, including heat intolerance, diaphoresis, weight loss despite increased appetite, palpitations, tachycardia, exophthalmos, and hyperactive tendon reflexes (Hutto, 1998).

In most patients who present with depression or anxiety associated with hyperthyroidism without other psychiatric history, psychiatric symptoms usually resolve with treatment of the hyperthyroidism.

Unless hypothyroidism stems from a primary pituitary disorder, it is usually caused by a lack of T4, which results in an elevated TSH level.

Similar to patients with hyperthyroidism, those with hypothyroidism often present with depression and anxiety. The usual clinical features include apathy, psychomotor retardation, depression, and poor memory. However, when hypothyroidism develops rapidly, the psychiatric features are usually delirium and psychosis, which has also been termed myxedema madness. Physical signs and symptoms, including cold intolerance, weight gain, thin and dry hair, facial puffiness, constipation, menorrhagia, muscle cramps, and slowed and decreased deep tendon reflexes, suggest this diagnosis.

Subclinical hypothyroidism can have either mild or no symptoms of thyroid hormone deficiency. It is fairly common and affects 5-10% of the population, mainly women, and occurs in 15-20% of women older than 45 years.

T4 replacement in these patients usually reverses the psychiatric symptoms, although it may not necessarily reverse the cognitive deficits that occur because of changes in metabolic activity in the CNS.

Adrenal disorders

Adrenal disorders cause changes in the normal secretion of hormones from the adrenal cortex and may produce significant psychiatric symptoms. Few studies have been performed on psychiatric symptoms of patients with Addison disease or adrenocortical insufficiency. This condition may result from fungal or, more commonly, tuberculous infection of the adrenals. Patients with this condition can exhibit symptoms such as apathy, fatigue, depression, and irritability. Psychosis and confusion can also develop. Steroid hormone replacement is used to treat patients with this condition; however, cortisol is psychogenic in nature and may produce mania and psychosis.

The existence of moderate-to-severe depression in up to 50% of patients with Cushing syndrome is well documented, with symptoms sometimes severe enough to lead to suicide. Decreased concentration and memory deficits may also be present. Some patients present with psychotic or schizophreniclike symptoms. Maintain a high index of clinical awareness for this disorder in patients who have additional clinical signs such as central obesity, hypertension, striae, easy bruising, buffalo hump, diabetes, and osteoporosis. In patients with depression believed to be etiologically related to hypercortisolemia, initiate antidepressant treatment while awaiting surgical or medical therapy for Cushing syndrome. Psychiatric symptoms usually resolve when the cortisol excess is controlled.

Pancreatic disorders

The most common pancreatic disorders that can have psychiatric presentations include diabetes mellitus with resulting glycemic dysregulation and pancreatic tumors. Either excessive exogenous insulin administration or endogenous production of insulin can cause hypoglycemia. However, hypoglycemic-induced mental status changes usually occur in persons with diabetes who are insulin dependent. Persons who engage in factitious use of hypoglycemic agents are an exception. Initial symptoms of the hypoglycemic state usually include nausea, sweating, tachycardia, hunger, and apprehension. With progression, patients may become disoriented and confused and may hallucinate. Eventually, stupor and coma ensue. Persistent cognitive impairment can be a serious sequela to frequently occurring hypoglycemic states.

Severe hyperglycemia begins with weakness, fatigability, polyuria, and polydipsia. Symptoms of clinical worsening include hyperventilation, headache, nausea, and vomiting. With ketoacidosis, disorientation and confusion can occur, and this state can be fatal if not properly identified and urgently treated.

Pancreatic tumors, although uncommon, can manifest solely in depression. Despite a broad differential diagnosis, seriously consider this diagnosis in elderly patients with new-onset depression in the setting of back pain.

RHEUMATOLOGIC DISORDER Section 6 of 10

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease of sterile inflammation involving multiple organs and multiple autoantibodies. Approximately 90% of cases are in women, usually of childbearing age. The incidence is 2.4 cases per 100,000 across genders and race, 92 cases per 100,000 for black women, and 3.5 cases per 100,000 for white women. Asians are also more often more affected than whites. The diagnosis of SLE requires that patients have at least 4 of 11 criteria set by the American Rheumatism Association. Remember that the diagnosis usually cannot be confirmed in a single encounter. The myriad of symptoms and serologic abnormalities often occur over time; therefore, diagnosis involves compiling a thorough history. Organ involvement of the synovium and skin usually prompts rheumatologists and dermatologists to consider the diagnosis. However, the neuropsychiatric manifestations of lupus can occur any time during the disease, and most appear in the first few years or before diagnosis of theillness. Thus, patients with undiagnosed lupus may initially present in psychiatric clinics, neurologic clinics, or inpatient wards.

Neuropsychiatric manifestations of patients with lupus have a prevalence of up to 75-90% (Ainiala, 2001). Major psychiatric symptoms include depression, emotional lability, delirium, and psychosis. The presence of severe depression or psychosis is associated with anti-P antibodies in the serum, which suggests an autoimmune mechanism for inducing mental symptoms.

Treatment is with high-dose steroids, which can precipitate or exacerbate psychiatric symptoms. However, most instances of psychosis in patients with lupus who are on steroid therapy are secondary to lupus cerebritis, and many improve with an increase in dosage. When patients are on steroid therapy, remembering to exclude infectious causes of possible brain dysfunction is always important because steroids may mask fever, resulting in an atypical presentation of infection.

Because of the multiple organ systems involved and the complexities of this illness, it behooves the clinician to consult rheumatologists, neurologists, and psychiatrists as appropriate.

METABOLIC DISORDERS Section 7 of 10

Sodium imbalance

Hyponatremia occurs in various conditions. This condition is usually observed in postoperative patients and in patients with severe vomiting and diarrhea, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), extensive burns, cirrhosis, or endocrine abnormalities (eg, myxedema, Addison disease). Consider hyponatremic disorders in patients experiencing acute mental status changes. Classic symptoms of hyponatremia include nausea, anorexia, and muscle weakness. As the serum sodium level continues to drop, patients may become irritable, confused, depressed, and intensely anxious (Lishman, 1998). Delusions and hallucinations can also occur at this stage. Without proper treatment, seizures, stupor, and coma ultimately ensue. Treatment consists of correcting the serum sodium level at a slow but adequate rate. Overly rapid correction of hyponatremia can lead to central pontine myelinolysis.

Hypernatremia usually results from inadequate ingestion of water or from the inability of the kidneys to conserve water. The elderly population is particularly sensitive to dehydration, and elderly persons can have acute mental status changes. As with hyponatremia, the rate of correction of hypernatremia is important. Overly rapid correction can lead to cerebral edema. Always consider cerebral edema if the patient has worsened mental status when hypernatremia has been corrected.

Hepatic failure and encephalopathy

Hepatic encephalopathy is a complex neuropsychiatric syndrome that complicates advanced liver disease. In acute hepatic encephalopathy, fulminant hepatic failure is usually present. Cerebral edema plays an important etiologic role in this setting. Chronic hepatic encephalopathy usually occurs in patients with chronic liver disease, and it manifests as subtle neuropsychiatric disturbances. The clinical picture of this form of encephalopathy varies and is characterized by acute exacerbations and remissions accompanied by neurologic abnormalities. The clinical manifestations of stages of hepatic encephalopathy are listed below (Andreoli, 1993).

Stage I

Apathy

Restlessness

Impaired cognition

Impaired handwriting

Reversal of sleep rhythm

Stage II

Lethargy

Drowsiness

Disorientation

Asterixis

Beginning of mood swings

Beginning of behavioral disinhibition

Stage III

Arousable stupor

Hyperactive reflexes

Short episodes of psychiatric symptoms

Stage IV - Coma (responsive only to pain)
In acute exacerbations, impairment of consciousness is prominent. Rapid changes in consciousness can be accompanied by hallucinations, mainly visual. Hypersomnia also occurs early in the course of illness. Prior to the development of coma, patients can also experience abrupt mood swings and behavioral disinhibition. Patients may also experience short episodes of depression, hypomania, anxiety, and obsessive-compulsive symptoms. At this stage, patients usually have neurologic signs, which may include asterixis, myoclonus, constructional apraxia, and/or hyperreflexia.

The etiology of such changes is unclear; however, the pathogenesis of hepatic encephalopathy is believed to involve inadequate hepatic removal of mostly nitrogenous compounds or other toxins formed in the GI tract. Inadequate removal of these toxins results from both impaired hepatocyte function and shunting of portal blood into the systemic circulation. Treatment involves identification of precipitating factors, dietary protein restrictions, and removal of ammonia from the bowel.

Uremic encephalopathy

Uremia results from impairment in kidney functioning. Initially, patients feel nonspecifically and generally unwell and often describe a sense of fatigue. They may have difficulty with concentration and may experience some memory impairment. As uremia progresses, memory worsens. Depression, apathy, and social withdrawal become clinically apparent. In advanced uremia, patients may experience impaired mentation, lethargy, myoclonus, asterixis, and other neuropsychiatric symptoms similar to those in hepatic encephalopathy. Psychosis can also occur.

The differential diagnosis of psychiatric symptoms in persons with chronic renal failure is quite broad and should include hypercalcemia, hypophosphatemia, hypernatremia/hyponatremia, hyperglycemia/hypoglycemia, hypertensive encephalopathy, and cerebrovascular disease, among many others. Adequate dialysis can reverse some of the psychiatric and mental abnormalities, but some subtle deficits in mentation may remain.

Dialysis dementia is a specific syndrome characterized by encephalopathy, dysarthria, dysphasia, poor memory, depression, paranoia, myoclonic jerking, and seizures (Lishman,1998). Worsening of dialysis dementia can lead to death within a year of diagnosis. High aluminum levels were found during autopsy in the brain tissue of patients who died with this clinical syndrome. The etiology was believed to be the aluminum content of the water used in making the dialysate. In the United States, the incidence of dialysis dementia has diminished because of proper water treatments.

Psychopharmacologic treatment of uremic encephalopathy should target the individual symptoms but with a lower starting dosage of medication and with small, cautious dosage adjustments.

Acute intermittent porphyria

Porphyria is a disorder of heme biosynthesis that leads to buildup of excessive porphyrins. In the classic form, patients have a triad of symptoms, including colicky abdominal pain, motor polyneuropathy, and psychosis. Acute intermittent porphyria is an autosomal dominant disorder, and onset usually occurs in persons aged 20-50 years. Some studies have shown that 0.2-0.5% of psychiatric patients have undiagnosed porphyrias. Barbiturates precipitate attacks of acute porphyria and are therefore absolutely contraindicated.

VITAMIN DEFICIENCY STATES Section 8 of 10

Vitamin B-1

When discussing the appropriate differential diagnosis of new-onset psychiatric symptoms, consideration of vitamin deficiencies is necessary, especially deficiencies of the B vitamins. Chronic and severe deficiency of vitamin B-1 (thiamine) leads to pellagra, with neuropsychiatric symptoms of asthenia, fatigue, weakness, and depressed mood. Much more commonly today, thiamine deficiency manifests as Wernicke encephalopathy, often, but not exclusively, in individuals with heavy and prolonged alcohol use. The classic triad of gait ataxia, global confusion, and ophthalmoplegia, most often involving the sixth cranial nerve, leads to the inability to abduct the eyes.

Immediate treatment with parenteral thiamine reveals that this syndrome is at least partly reversible because the ocular palsy often resolves within hours. As the confusion improves, impaired cognitive functioning (amnesia) consistent with Korsakoff syndrome often becomes evident. Long-term treatment with thiamine may result in ongoing improvement over a period of months.

Although this is a clinical diagnosis, brain pathology is evident on imaging studies and at autopsy. Symmetric lesions of the mamillary bodies, the third and fourth ventricles, and the periaqueductal areas are present.

Vitamin B-12

Deficiency of vitamin B-12 (cobalamin) is the cause of pernicious anemia. When a patient presents with megaloblastic anemia and neurologic symptoms from subacute combined spinal cord degeneration, and a low serum vitamin B-12 level is found on evaluation, the diagnosis is relatively straightforward.

Although the direct cause and effect of concomitant psychiatric symptoms is not always clear, depression, fatigue, psychosis, and progressive cognitive impairment can accompany neurologic symptoms (Hutto, 1997).

These psychiatric symptoms can predate the neurologic symptoms by months to years and may be present in the absence of anemia or macrocytosis. When suggested, even if screening vitamin B-12 levels are not revealing, measurements of serum methylmalonic acid and total homocysteine may be more helpful diagnostically (Lindenbaum, 1988).

Folate

As with vitamin B-12 deficiency, interest has been shown in the relationship between folate deficiency and psychiatric symptoms. Causality is not always clear, but evidence suggests that folate deficiency states are observed in patients with depressive syndromes and with dementing syndromes; it appears that folate deficiency is not rare and can cause or exacerbate psychiatric symptoms (Botez, 1977).

Since replacing folate in patients with B-12 deficiency can aggravate the progression of neurologic symptoms, it is important to search for and correct vitamin B-12 deficiency either prior to or concurrent with folate replacement.

EXOGENOUS TOXINS Section 9 of 10

The role of exogenous toxins is a very broad subject; however, because of the limited space and scope of this article, only a brief overview is presented. Toxins can include medications, drugs of abuse, solvents, pesticides, and heavy metals. Some of the most common medications associated with induction of a psychoactive state are listed below (Rundell, 1999).

Antihypertensives

Reserpine

Methyldopa

Beta-blockers

Oral contraceptives

Steroids

Histamine 2 blockers

Cancer chemotherapy agents

Vinca alkaloids

Procarbazine

L-asparaginase

Amphotericin

Interferon

Psychoactive substances

Alcohol

Opioids

Amphetamines (withdrawal)

Cocaine (withdrawal)

Benzodiazepines

Barbiturates
Idiopathic major depression is very common, as is the use of medication, alcohol, and/or illicit drugs. Separating causal factors is not always easy. A high index of clinical awareness is helpful in considering underlying causes of conditions that can appear as primary idiopathic psychiatric illness. Knowledge of the time course can also be helpful, ie, comparing the onset of symptoms to the initiation of or change in dosage of the putative offending agent.

Alcohol

Although volumes have been written concerning the pathologic changes in patients who use alcohol for short and long periods, a brief review is appropriate because patients in alcohol withdrawal can present with numerous psychiatric symptoms that can be fatal if not identified and treated quickly.

Withdrawal symptoms can emerge, particularly in the absence of a measurable blood alcohol level. Florid delirium tremens (DT) is the most serious and potentially fatal alcohol withdrawal syndrome. The clinical picture includes hallucinations (most commonly auditory and/or visual), gross confusion and disorientation, and autonomic hyperactivity (eg, tachycardia, fever, sweating, hypertension). These patients are often agitated and paranoid and may not readily allow physical examination. The temptation to view an agitated, paranoid, overtly hallucinating patient as in need of nothing further than admission to a psychiatric unit may be a grave mistake because untreated DT is potentially fatal.

Patients may also present with hallucinations in a clear sensorium (differentiating it from DT), usually in the setting of recent cessation of or significant decrease in the amount of alcohol used. Known as alcoholic hallucinosis, the hallucinations (most frequently auditory) may be relatively brief, usually resolving within approximately 30 days, but they may persist. Recurrences are likely with continued alcohol use.

Differentiating this syndrome from schizophrenia can be difficult. The hallucinations are frequently threatening and persecutory in nature, and patients may act in response to these, leading to a potentially dangerous situation that may require involuntary psychiatric hospitalization (Cassem, 1997).

Alcohol is a CNS depressant, and chronic abuse can be associated with significant depression that may, by symptoms alone, be indistinguishable from idiopathic major depression. However, of patients with depressive disorder from alcohol dependence who are monitored for 2-4 weeks without alcohol, more than 50% have full remission of symptoms without additional intervention for the depressive symptoms (O'Sullivan, 1984). A minority of patients, usually those with more severe symptoms, have a continued depressive syndrome despite sobriety and require additional treatment.

Cocaine and amphetamines

Cocaine is a powerful stimulant initially causing euphoria and increased alertness and energy. As the high wears off, the user may develop symptoms of anxiety and depression, often with drug craving. With continued regular use, symptoms of psychosis develop with hallucinations and frank paranoid delusions. The psychiatric presentation can appear similar to that observed in patients with chronic amphetamine abuse.

Amphetamines are also CNS stimulants and initially cause feelings of increased well-being, energy, and concentration. However, amphetamine abuse can cause development of psychotic symptoms.

Laboratory testing with toxicologic screening of blood and urine can assist with or confirm the diagnosis. Knowing exactly what drugs are screened for at any individual facility is important because different routine screens include different drugs. Depending on the clinical presentation, testing for additional individual drugs may need to be specified. For example, patients with phencyclidine (PCP) intoxication may present with psychosis and with particularly agitated and violent behavior; however, most routine drug screens do not test for PCP, which can nevertheless be measured when specified.

Hallucinogens

A brief mention must be made of lysergic acid diethylamide (LSD), a potent hallucinogen that causes intense and vivid hallucinations in a clear sensorium. LSD-elicited hallucinations are usually of relatively short duration, but flashbacks of varying intensity may occur in a small number of users. Hallucinogenic mushrooms containing psilocybin and psilocin can have similar effects.

Ecstasy

Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]), a designer drug synthetically derived from amphetamine, is often used in the context of large and energetic parties (raves) and at nightclubs. Initially, it causes mild euphoria, increased energy, and increased libido. Tolerance develops rapidly. Depression, anxiety, and psychosis have also been described with regular use, and some of the symptoms persist for months after cessation of use (Morgan, 2000).

Solvents

Solvent abuse or huffing involves the inhalation of organic solvents for their euphoriant effects. Inhaled solvents include glues, paints, cleaning fluids, nail-polish removers, lighter fluids, aerosol propellants, and gasolines. Long-term and heavy use can lead to hallucinations, cognitive impairment, personality change, and neurologic impairment, particularly cerebellar findings.

Heavy metals

Lead, mercury, manganese, arsenic, organophosphorous compounds, and others can cause psychiatric symptoms. Exposure is usually industrial or environmental and should be considered in the appropriate settings. Often, CNS or peripheral nervous system signs and symptoms are present.

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