Mental Disorders Due to a General Medical Condition

Aberration in brain function Treatment: restore normal brain chemistry

Mood Disorder Due to a General Medical Condition

Depression AKA Secondary Mood Disorders Prominent mood alteration thought to be the direct physiological effect of a specific medical illness or agent Key feature: prominent, persistent, distressing, or functionally impairing depressed mood (anhedonia) or elevated, expansive, or irritable mood

Epidemiology
Men and women equally Major depressive disorder = women 50% of all poststroke patients depressive illness Pancreatic cancer 40% of Parkinsons disease depressed Major & minor depressive eps: Huntingtons, HIV infection, MS Secondary mania is less prevalent

Etiology
Drug Intoxication Drug Withdrawal Tumor

Trauma

Infection

Cardiac & Vascular

Physiological or Metabolic

Endocrine

Nutritional

Demyelinating

Neurodegenerative

Diagnosis and Clinical Features

Psychological
Sad mood

Somatic
fatigue

Both psychological and somatic

Diagnosis and Clinical Features

Depressive features
Major depressive-like episodes
Manic features Mixed features

Course and Prognosis

COURSE: largely depends on course of underlying medical state Extent of concurrent psychiatric intervention PROGNOSIS: best when etiological medical illnesses or medications are most susceptible to correction Formal psychiatric treatment

Treatment
Standard antidepressant medications (e.g., tricyclic drugs, selective serotonin reuptake inhibitors [SSRIs], psychostimulants, etc) Electroconvulsive therapy (ECT) to those who dont respond to medication Clinician: treat underlying medical cause as effectively as possible standard treatment approaches Psychotherapy

Psychotic Disorder Due to a General Medical Condition

Not associated with changes in the sensorium

Psychotic Disorder Due to a General Medical Condition

Epidemiology

Gen. population unknown 40% of patients with temporal lobe epilepsy selected clinical populations (such as Nursing Home residents)

Etiology Any cerebral or systemic disease that affects brain function Degenerative disorders (Alzheimers or Huntingtons) present initially with new-onset psychosis, with min evidence of cognitive impairment at the earliest stages.

Diagnosis and Clinical Features

Delusions

Hallucinations

PSYCHOTIC SYMPTOMS ASSOCIATED WITH ABNORMALITY OF SPECIFIC BRAIN REGIONS Symptoms Site Laterality First-rank symptoms: Thoughts spoken aloud Voices commenting Third-person voices arguing Made actions Made feelings Though withdrawal Though diffusion Delusional perception Complex delusions Anton syndrome Anosognosia

Temporal lobe

Dominant hemisphere

Subcortical or limbic Occipital lobe, optic tract Parietal lobe Bilateral Nondominant hemisphere

Misidentification Parietal, temporal, frontal syndromes lobes Capgras syndrome Reduplicative paramnesia Fregoli syndrome Intermetamorphosis syndrome

Nondominant hemisphere, bilateral

Course and Prognosis

COURSE: course of the underlying medical illness or substance use Psychosis caused by certain medications, such as immunodepressants, gradually may subside even when use of those medications is continued. Minimizing dosages consistent with therapeutic efficacy often facilitates resolution of psychosis.

Course and Prognosis

Certain degenerative brain disorders (Parkinsons disease) can be characterized by episodic lapses into psychosis, even as underlying medical condition advances. Substance abuse psychosis may fail to remit even during extended intervals of abstinence if the abuse persists over a long time.

Treatment
Similar to those for any secondary neuropsychiatric disorder 1. Rapid identification of the etiological agent 2. Treatment of the underlying cause Antipsychotic medication for symptomatic relief

Anxiety Disorder Due to a General Medical Condition

Definition
Anxiety experienced causes clinically significant distress or impairment in functioning Anxiety must represent a direct physiological, not emotional, consequence of a general medical condition.

Definition: Substance-induced Anxiety Disorder

Anxiety symptoms product of a prescribed medication or stem form intoxication or withdrawal from a nonprescribed substance, typically a drug of abuse

Epidemiology
Little data exist to estimate prevalence Medically ill individuals believed to generally have higher rates of anxiety disorder Rates of panic and generalized anxiety are especially high in neurological, endocrine, and cardiology patients. Approximately of hypothyroidism patients and of hyperthyroidism patients 40% of patients with Parkinsons disease Higher in women than in men

Etiology
Substance-related states intoxication with caffeine, cocaine, amphetamines, and other sympathomimetic agents; withdrawal from nicotine, sedative-hypnotics, and alcohol Endorcinopathies pheochromocytoma, hyperthyroidism, hypercortisolemic states, and hyperparathyroidism

Etiology
Metabolic derangement - hypoxemia, hypercalcemia, and hypoglycemia Neurological disorders (including vascular, trauma, and degenerative types) Obsessive compulsive symptoms tied to development of pathology in the basal ganglia

Diagnosis & Clinical Features

Physical complaints chest pain, palpitation, abdominal distress, diaphoresis, dizziness, tremulousness, and urinary frequency Generalized symptoms of fear and excessive worry Outright panic attacks associated with fear of dying or losing control Recurrent obsessive thoughts or ritualistic compulsive behaviors Phobia with associated avoidant behavior

Diagnosis & Clinical Features

With generalized anxiety: if excessive anxiety or worry about a number of events or activities predominates in the clinical presentation With panic attacks: if panic attacks predominate in the clinical presentation With obsessive - compulsive symptoms: if obsessions or compulsions predominate in the clinical presentation

Course & Prognosis

Usually fluctuates in direct relation to the course of the provoking factor Medical conditions responsive to treatment or cure provide concomitant relief (may lag the rate or extent of improvement) of anxiety symptoms Chronic, incurable medical conditions associated with persistent physiological insult or recurrent relapse to substance use - contribute to seeming refractoriness of associated anxiety symptoms Medication-induced anxiety dose reduction (if complete cessation is not possible) brings substantial relief

Treatment
Benzodiazepines decrease anxiety symptoms Supportive psychotherapy psychoeducational issues focusing on diagnosis and prognosis Antidepressant medications for panic attacks SSRIs for obsessive-compulsive symptoms Behavior therapy for simple phobias

Sleep Disorder Due to a General Medical Condition

Diagnosis & Clinical Features

Four ways of manifestation: 1. Hypersomnia excess of sleep 2. Insomnia deficiency of sleep 3. Parasomnia abnormal behavior or activity during sleep 4. Circadian rhythm sleep disorders disturbance in the timing of sleep

Diagnosis & Clinical Features

Specify types: 1. Insomnia type predominant sleep disturbance is insomnia 2. Hypersomnia type predominant sleep disturbance is hypersomnia 3. Parasomnia type predominant sleep disturbance is parasomnia 4. Mixed type more than one sleep disturbance is present and none predominate the comparable sexual dysfunction that was not substanceinduced

Etiology & Differential Diagnosis

MEDICAL CONDITIONS COMMONLY ASSOCIATED WITH A SECONDARY SLEEP DISORDER Condition Sleep Symptoms

Parkinsonism Dementia
Epilepsy Cerebrovascular disease Huntingtons disease Kleine-Levin syndrome Uremia

Frequent awakenings, disturbance of circadian rhythms Sundowning, frequent awakenings

Difficulty initiating sleep, frequent awakenings, parasomnias Difficulty initiating sleep, frequent awakenings Frequent awakening Hypersomnia

Restless legs, nocturnal myoclonus

Treatment
First addresses the underlying neurological or medical disease Symptomatic treatments behavior modification (e.g., improvement of sleep hygiene) Pharmacological options Benzodiazepines restless legs syndrome or nocturnal myoclonus Stimulants hypersomnia Tricyclic antidepressant medications manipulation of rapid eye movement (REM) sleep

Mental Disorders Due to A General Medical Condition Not Elsewhere Classified

Diagnoses: 1. Catatonic disorder due to a general medical condition 2. Personality change due to a general medical condition 3. Mental disorder not otherwise specified due to a general medical condition

Catatonic Due to a Medical Condition

Caused by a variety of medical or surgical conditions Characterized usually by fixed posture and waxy flexibility. Associated features: mutism, negativism, echolalia

Epidemiology
Uncommon condition Mostly seen in advanced primary mood or psychotic illnesses Among inpatients with catatonia 25-50% - related to mood disorders (e.g., major depressive episode, recurrent, with catatonic features) 10% - associated with schizophrenia

Diagnosis & Clinical Features

Most characteristic feature: peculiarities of movement, usually rigidity Hyperactivity and psychomotor agitation

Course & Prognosis

Intimately related to the cause Neoplasms, encephalitis, head trauma, diabetes, other metabolism disorders If the underlying disorder is treatable, the catatonic syndrome will resolve

Treatment
Must be directed to the underlying cause Antipsychotic medications improve postural abnormalities even though they have no effect on underlying disorder Schizophrenia must always be ruled out.

Personality Change Due to a General Medical Condition

Personality change the persons fundamental means of interacting and behaving have been altered Brain injury suspected when true personality change occurs in adulthood Almost every medical disorder can be accompanied by personality change.

Epidemiology
No reliable epidemiological data exist Specific personality trait changes for particular brain diseases Passive and self-centered behaviors in patients with dementia of the Alzheimers type Apathy described in patients with frontal lobe lesions

Etiology
Prominent personality change in frontal lobe or subcortical structure diseases Head trauma common cause Frontal lobe tumors (meningiomas and gliomas) can grow to considerable size before coming to medical attention because they can be neurologically silent Progressive dementia syndrome (especially subcortical pattern of degeneration like acquired immune deficiency syndrome (AIDS) dementia complex, Huntingtons disease, or progressive supranuclear palsy)

Etiology
Multiple Sclerosis (MS) impinge personality, reflecting subcortical white matter degeneration Exposure to toxins with a predilection for white matter, such as irradiation produce significant personality change disproportionate to the cognitive or motor impairment.

Diagnosis & Clinical Features

Specify types predominant feature: Labile type affective lability Disinhibiated type poor impulse control as evidenced by sexual indiscretions, etc. Aggressive type aggressive behavior Apathetic type marked apathy and indifference Paranoid type suspiciousness or paranoid ideation Other type presentation is not characterized by any of the above subtypes Combined type more than one feature predominated in the clinical picture Unspecified type

Course and Prognosis

Depends on the nature of the medical or neurological insult Personality changes resulting from medical conditions likely to yield to intervention (vs. static or progressive in nature) more amenable to improvement

Treatment
First directed toward the underlying cause Lithium carbonate (Eskalith), carbamazepine (Tegretol), valproic acid (Depakote) control affective lability and impulsivity Lithium, anticonvulsant medications, or a combination of both treat aggression or explosiveness Centrally active I2-adrenergic receptor antagonists Apathy and inertia with psychostimulant agents Psychotherapy cognition and verbal skills may be preserved in patients with secondary personality changes

Specific Disorders: Epilepsy

Most common chronic neurological disease in the general population Major concerns about epilepsy: Consideration of an epileptic diagnosis in psychiatric patients Psychosocial ramifications of a diagnosis of epilepsy for a patient Psychological and cognitive effects of commonly used anticonvulsant drugs 30-50% of all persons with epilepsy have psychiatric difficulties Change in personality most common behavioral symptom of epilepsy

Definitions
Seizure transient paroxysmal pathophysiological disturbance of cerebral function caused by a spontaneous, excessive discharge of neurons. Epilepsy is present when patient has a chronic condition characterized by recurrent seizure. Ictus/ictal event seizure itself Nonictal periods categorized as preictal (aura), postictal, and interictal.

Definitions
Symptoms during an ictal event determined primarily by a. Site of origin in the brain for the seizure b. The pattern of the spread of seizure activity through the brain Interictal symptoms influences: ictal event and other neuropsychiatric and psychosocial factors, the presence of psychosocial stressors, and premorbid personality traits.

Classification
2 major categories: Partial epileptiform activity in localized brain regions Generalized entire brain

Generalized Seizures
Classic symptoms (tonic-clonic): loss of consciousness, generalized tonic-clonic movements of the limbs, tongue biting, and incontinence Postictal state slow, gradual recovery of consciousness and cognition Recovery period: few minutes to many hours

Generalized Seizures
Most common psychiatric problems: helping patients adjust to a chronic neurological disorder and assessing the cognitive or behavioral effects of anticonvulsant drugs.

Absence Seizure (Petit Mal)

Difficult type of seizure for a psychiatrist to diagnose Usually begins at childhood between 5-7 years old and ceases by puberty Characteristic motor or sensory manifestations may be absent or so slight it may not arouse suspicion

Absence Seizure (Petit Mal)

Characteristics: brief disruptions of consciousness but no true loss of consciousness and no convulsive movements during the episodes Rare case: adult-onset petit mal epilepsy sudden, recurrent psychotic episodes or deliriums that appear and disappear abruptly; symptoms accompanied by history of falling or fainting spells

Partial Seizures
Classified as: simple (without alterations in consciousness) or complex (with an alteration in consciousness) More than half of all patients with partial seizures have complex partial seizures Other terms for complex partial seizures: temporal lobe epilepsy, psychomotor seizures, limbic epilepsy

Partial Seizures
Most common form of epilepsy in adults: complex partial epilepsy (~3/1000 persons) 30% of patients have major mental illness (e.g., depression)

Symptoms

Preictal Symptoms
Autonomic sensations fullness in the stomach, blushing, changes in respiration Cognitive sensations dj vu, jamais vu, forced thinking, dreamy states Affective states fear, panic, depression, elation Automatisms lip smacking, rubbing, chewing

Ictal Symptoms
Brief, disorganized, and uninhibited behavior Cognitive symptoms amnesia for the time during seizure, period of resolving delirium after seizure Multiple normal EEGs are often obtained for a patient with complex partial epilepsy Use of long-term EEG recordings (24-72 hours) help detect seizure focus

Interictal Symptoms

Personality Disturbances: Personality disorders most frequent psychiatric abnormalities in epileptic patients; most likely to occur in temporal lobe epilepsy Most common features: a. Religiosity b. Heightened experience of emotions (called viscosity of personality; most noticeable in patients conversation)
Hypergraphia speech tendencies often mirrored in the patients writing; considered virtually pathognomonic for complex partial epilepsy

c. Changes in sexual behavior hypersexuality; deviations in sexual interest; hyposexuality (most common)

Interictal: Psychotic Symptoms

More common than ictal psychoses Risk factors: female gender, left-handedness, onset of seizures during puberty, left-sided lesion Most characteristic symptoms: hallucinations and paranoid delusions Usually remain warm and appropriate in affect Most common thought disorder symptoms : involving conceptualization and circumstantiality

Violence
Problem of temporal and frontal lobe origin epilepsy Extreme rarity of violence as an ictal phenomenon

Mood Disorder Symptoms

Depression and mania seen less often Tend to be episodic and appear most often when the foci affect the temporal lobe of the nondominant cerebral hemisphere Importance: attested to by the increased incidence of attempted suicide in epileptics

Diagnosis
Psychiatrists must maintain high level of suspicion during evaluation and must consider the possibility of an apileptic disorder. Differential diagnosis: pseudoseizure patient has some conscious control over mimicking the symptoms of a seizure

DIFFERENTIATING FEATURES OF PSEUDOSEIZURES AND EPILEPTIC SEIZURES

Feature Clinical Features Nocturnal Seizure Stereotyped aura Cyanotic skin changes during seizures Self-injury Common Usually Common Common Uncommon None None Rare Epileptic Seizure Pseudoseizure

Incontinence Postictal confusion

Body movements Affected by suggestion EEG features Spike and waveforms Postictal slowing Interictal abnormalities

Common Present
Tonic or clonic or both No

Rare None Nonstereotyped and asynchronous

Yes

Present Present Variable

Absent Absent Variable

 Patients with previous epilepsy diagnosis: appearance of new psychiatric symptoms should be considered as possibly representing an evolution in their epileptic symptoms; compliance with anticonvulsant drug regimen evaluated; 1-2 EEG examinations Patients who no previous epilepsy diagnosis: 4 characteristics clinician is suspicious on the possibility 1. Abrupt onset of psychosis in person previously regarded as psychologically healthy 2. Abrupt onset of delirium without a recognized cause 3. History of similar episodes with abrupt onset and spontaneous recovery 4. History of previous unexplained falling or fainting spells

Treatment

Generalized tonic-clonic seizures: valproate and phenytoin (Dilantin) Partial seizures: carbamazepine, oxcarbazepine (Trileptal), and phenytoin Absence (petit mal) seizures: ethosuximide (Zarontin) and valproate Carbamazepine, valproic acid, and typical antipsychotic drugs control symptoms of irritability and outbursts of aggression Psychotherapy, family counseling, group therapy Many antiepileptic drugs cause mild to moderate cognitive impairment. Adjustment of dosage is needed.

Brain Tumor

Definition
Cerebrovascular diseases by nature of onset and symptom pattern, are rarely misdiagnosed as mental disorders Tumors associated with fewer psychopathological signs and symptoms

Definition
Two key approaches to diagnosis of brain tumors and CVD: comprehensive clinical history, complete neurological examination Usually the final diagnostic procedure: performance of the appropriate brain imaging technique (imaging should confirm clinical diagnosis)

Clinical Features, Course, and Prognosis

Mental symptoms experienced by 50% of patients during the course of illness 80% with mental symptoms tumors found in frontal or limbic brain regions Meningiomas cause focal symptoms by compressing a limited region of the cortex

Clinical Features, Course, and Prognosis

Gliomas cause diffuse symptoms Delirium most often a component of rapidly growing, large, or metastatic tumors Bowel or bladder incontinence = frontal lobe tumor Abnormalities in memory and speech = temporal lobe tumor

 Cognition: impaired intellectual functioning Language Skills: disorders may be severe, if tumor growth is rapid; defects often obscure all other mental symptoms Memory: loss of memory is frequent symptom; exhibit Korsakoffs syndrome and retain no memory of events since the illness began; lost memories of immediate past events (including painful ones); retain old memories and are unaware of loss of recent memory

 Perception: associated with behavioral disorders (patient must integrate tactile, auditory, visual perceptions to function normally) Awareness: alterations of consciousness are common late symptoms of increased intracranial pressure Akineticmutism, or vigilant coma unique symptom caused by tumors in the upper part of the brainstem; patient is immobile and mute, yet alert

Colloid cysts
Not brain tumors Located in third ventricle Can exert physical pressure on structures within the diencephalon and produce mental symptoms (depression, emotional lability, psychotic symptoms, personality changes) Position-dependent intermittent headaches classic associated neurological symptoms

Head Trauma

Definition
Lead to diagnosis of dementia due to head trauma or to mental disorder not otherwise specified due to a general medical condition (e.g., postconcussional disorder) Postconcussive syndrome focuses on wide range of psychiatric symptoms, some serious, that can follow what seems to be minor head trauma

Pathophysiology
Common clinical situation Most commonly occurs in people 15-25 years old 3:1 male-to-female predominance Virtually all patients with serious head trauma more than half with moderate head trauma 10% with mild head trauma have ongoing neuropsychiatric sequelae

Pathophysiology
Divisions (gross): Penetrating head trauma (e.g., produced by a bullet) brain injury localized to the areas directly affected Blunt trauma no physical penetration of the skull; far more common; motor vehicle incidents account for more than half of the blunt CNS trauma Actual head trauma = brain hits repeatedly against skull skull mismatched in rapid deceleration and acceleration focal contusions Stretching of brain parenchyma diffuse axonal injury Edema and hemorrhaging further damage the brain

Symptoms
Two major clusters of symptoms: cognitive impairment and behavioral sequelae Posttraumatic amnesia 6-12 months recovery remaining symptoms are likely to be permanent Most common cognitive problems: decreased speed in information processing, decreased attention, increased distractibility, deficits in problem-solving and ability to sustain effort, problems with memory and learning new information

Symptoms
Major behavioral symptoms: depression, increased impulsivity, increased aggression, and changes in personality Alcohol further exacerbates symptoms

Treatment
Particularly susceptible to the side effects associated with psychotropic drugs. Treatment should begin with lower dosages than usual, titrated upward more slowly than usual. Standard antidepressants vs. depression Anticonvulsants or antipsychotics vs. aggression and impulsivity

Treatment
Lithium, calcium channel blockers, I2adrengeric receptor antagonists Individual or group psychotherapy. Couples and family therapy. Help involved parties to adjust to any changes in patients personality and mental abilities.

Demyelinating Disorders
Multiple Sclerosis (MS) Amyotrophic Lateral Sclerosis (ALS)

Multiple Sclerosis (MS)

Major demyelinating disorder Characterized by multiple episodes of symptoms, pathophysiologically related to multifocal lesions in the white matter of the CNS Unknown cause Much more frequent in cold and temperate climates More common in women Predominantly a disease of young adults (age onset: 20-40 years old)

Multiple Sclerosis (MS)

Cognitive Symptoms:
30-50% have mild cognitive impairment 20-30% (of the 30-50%) have serious cognitive impairments

Memory most commonly affected cognitive function

Multiple Sclerosis (MS)

Behavioral Symptoms: Euphoria, depression, and personality changes Psychosis rare complication 25% exhibit euphoric mood that is not hypomaniac (more cheerful than the situation requires and not necessarily same as disposition before the onset) 10% have sustained and elevated mood, still not truly hypomaniac Depression common; 25-50%; results in higher rate of suicide; affects male (age: before 30) with relative recent diagnosis of MS Personality changes common; 20-40%; increased irritability or apathy

Amyotrophic Lateral Sclerosis (ALS)

Progressive, noninherited disease of asymmetrical muscle atrophy Begins in adult life and progresses over months or years to involve all the striated muscles EXCEPT:
Cardiac muscle Ocular muscles

Amyotrophic Lateral Sclerosis (ALS)

Pyramidal tract involvement Rare Progresses rapidly Death generally occurs within 4 years of onset

Infectious Disease
Herpes Simplex Encephalitis Rabies Encephalitis Neurosyphilis Chronic Meningitis Subacute Sclerosing Panencephalitis Lyme Disease Prion Disease

Herpes Simplex Encephalitis

Most common type of focal encephalitis Most commonly affects the frontal and temporal lobes Symptoms: anosmia, olfactory and gustatory hallucinations, personality changes, can involve bizarre or psychotic behaviors Complex partial epilepsy may also develop Mortality rate has decreased but many still display personality changes, symptoms of memory loss, and psychotic problems.

Rabies Encephalitis
Incubation period: 10 days to 1 year Symptoms: restlessness, overactivity, agitation Hydrophobia up to 50% of patients Intense fear of drinking water Develops from severe laryngeal and diaphragmatic spasms experienced when drinking water Once it develops, it is fatal within days or weeks.

Neurosyphilis
Also known as general paresis Appears 10-15 years after primary Treponema infection Since advent of penicillin, it became a rare disorder. AIDS associated with reintroducing it into medical practice in some urban settings. Generally affects frontal lobes Symptoms: personality changes, development of poor judgment, irritability, decreased care for self

Neurosyphilis
Delusions of grandeur 10-20% of affected patients Progression: development of dementia and tremor paresis Neurological symptoms: Argyll-Robertson pupils (small, irregular, unequal, and have light-near reflex dissociation), tremor, dysarthria, hyperreflexia CSF examination shows lymphocytosis, increased protein, positive result on a Venereal Disease Research Laboratory (VDRL) test

Chronic Meningitis
Now seen more often because of immunocompromised condition of people with AIDS Usual causative agents: Mycobacterium tuberculosis, Cryptococcus, and Coccidioides Usual symptoms: headache, memory impairment, confusion, fever

Subacute Sclerosing Panencephalitis

Disease of childhood and early adolescence 3:1 male-to-female ratio Onset follows either an infection with measles or a vaccination for measles Initial symptoms: behavioral change, temper tantrums, sleepiness, hallucinations Classic symptoms: myoclonus, ataxia, seizures, intellectual deterioration Progresses relentlessly to coma and death in 1-2 years

Lyme Disease
Caused by infection with the spirochete Borrelia burgdorferi transmitted through the bite of the deer tick (Ixodes scapularis), which feeds on infected deer and mice Characteristics: bulls-eye rash at the site of tick bite, flu-like symptoms shortly after, impaired cognitive functioning and mood changes (presenting complaint; memory lapses, difficulty concentrating, irritability, depression) No clear-cut diagnostic test available

Lyme Disease
50% become seropositive to B. burgdorferi Treatment: 14-21-day course of doxycycline (Vibramycin), which results in 90% cure rate Specific psychotropic drugs can treat sign or symptom (e.g., diazepam [Valium] for anxiety) Left untreated, 60% develop a chronic condition. May be given erroneous diagnosis of a primary depression Support groups provide emotional support

 Group of related disorders caused by a transmissible infectious protein known as prion Collectively known as subacute spongiform encephalopathy Shared neuropathological changes: a. Spongiform vacuolization b. Neuronal loss c. Astrocyte proliferation in the cerebral cortex

Prion Disease

Etiology
Prions transmissible agents; lack nucleic acid; mutated proteins generated from the human prion protein gene (PrP), which is located on the short arm of chromosome 20 PrP mutates into disease-related isoform PrPSuper-C (PrPSC) that can replicate and is infectious. Neuropathological changes caused by direct neurotoxic effects of PrPSC

Creutzfeldt-Jakob Disease (1920)

Invariably fatal, rapidly progressive disorder Occurs mainly in middle-aged or older adults Manifests initially with fatigue, flu-like symptoms, and cognitive impairment (disease progresses) focal neurological findings aphasia and apraxia Psychiatric manifestations protean; include emotional lability, anxiety, euphoria, depression, delusions, hallucinations, or marked personality changes Progresses over months, leading to dementia, akineticmutism, coma, death

Creutzfeldt-Jakob Disease
Rates: 1-2 cases/1M persons a year, worldwide Infectious agent self-replicates and can be transmitted to humans by inoculation with infected tissue and sometimes by ingestion of contaminated food Iatrogenic transmission transplantation of contaminated cornea or dura mater or to children via contaminated supplies of human growth hormone derived from infected persons Diagnosis: pathological examination of the cortex classic triad of spongiform vacuolation, loss of neurons, and astrocyte cell proliferation

Creutzfeldt-Jakob Disease
Most affected: cortex and basal ganglia EEG abnormalities; Computed tomography (CT) and MRI reveal cortical atrophy later in the course of disease; single photon emission computed tomography (SPECT) and positron emission tomography (PET) reveal heterogeneously decreased uptake throughout the cortex No known treatment. Death usually occurs within 6 months after diagnosis.

Variant CJD
Appeared in UK in 1995 Affected patients all died. All young (under age of 40), and none had risk factors of CJD Transmission of bovine spongiform encephalopathy (BSE) between cattle and from cattle to humans in the 1980s BSE originated from sheep scrapie-contaminated feed given to cattle Scrapie spongiform encephalopathy found in sheep and goats that has not been to cause human disease but transmittable to other animal species Mean age of onset: 29 years old

Variant CJD
Symptoms: behavioral and psychiatric abnormalities in association with cerebellar signs (ataxia or myoclonus) Most patients have reported depression, withdrawal, anxiety, and sleep disturbances. Paranoid delusions, too. Presence of amyloid plaques vCJD can be diagnosed antemortem by examining the tonsils with Western blot immunostains to detect the PrPSC in lymphoid tissue

Variant CJD
diagnosis relies on development of progressive neurodegenerative features No cure exists. Death usually occurs within 2-3 years after diagnosis Prevention: careful monitoring of cattle for disease and feeding them grain instead of meat by-products

Kuru
Epidemic prion disease found in New Guinea Caused by cannibalistic funeral rituals in which the brains of the deceased are eaten More affected: women (presumably because they participate in the ceremony at a greater extent) Death: usually occurs within 2 years

Kuru
Neuropsychiatric signs and symptoms: ataxia, chorea, strabismus, delirium, dementia Pathological changes: neuronal loss, spongiform lesions, astrocytic proliferation Most affected: cerebellum Iatrogenic transmission: cadaveric material (dura mater and cornea) transplanted into normal recipients

Gerstmann-StrausslerScheinker Disease
Neurodegenerative syndrome characterized by ataxia, chorea, and cognitive decline leading to dementia Caused by a mutation in the PrP gene that is fully penertrant and autosomal dominant. Disease is inherited Genetic testing confirm presence of abnormal genes before onset

Gerstmann-StrausslerScheinker Disease (1928)

Pathological changes: spongiform lesions, neuronal loss, astrocyte proliferation Amyloid plaques found in the cerebellum Onset: 30-40 years old. No treatment currently exists

Fatal Familial Insomnia

Inherited prion disease that primarily affects the thalamus Syndrome of insomnia and autonomic nervous system dysfunction consisting of fever, sweating, labile blood pressure, and tachycardia Onset: middle adulthood Death usually occurs in 1 year. No treatment.

Immune Disorders
AIDS major immune d/o in contemporary society

Systemic Lupus Erythematosus (SLE)

Autoimmune disease Inflammation of multiple organ systems Officially accepted diagnosis: 4/11 criteria officially defined by ARA Between 5-50% - mental symptoms @ initial presentation ~50% eventually show neuropsychiatric manifestations

Systemic Lupus Erythematosus (SLE)

Major symptoms: depression, insomnia, emotional lability, nervousness, confusion Treatment: STEROIDS commonly induces further psychiatric complications, including mania and psychosis

Endocrine Disorders
Thyroid Parathyroid Adrenal Pituitary

Thyroid Disorders
Hyperthyroidism
Characterized by confusion, anxiety, and an agitated, depressive syndrome Serious psychiatric symptoms: impairments in memory, orientation, and judgment; manic excitement; delusions; hallucinations

Thyroid Disorders
Myxedema madness
Irvin Asher, 1949 In most severe form of hypothyroidism paranoia, depression, hallucinations, hypomania Physical symptoms: weight gain, deep voice, thin & dry hair, loss of lat. Eyebrows, facial puffiness, etc ~10% of px w/ residual neuropsychiatric symptoms after hormone replacement therapy

Parathyroid Disorders
Hypercalcemia
Excessive secretion of PTH Result in delirium, personality changes, apathy (50-60%), cognitive impairments (~25%) neuromuscular excitability depends on proper Ca2+ ion concentration) Ms weakness

Parathyroid Disorders
Hypocalcemia
Occur w/ hypoparathyroid disorders Result in neuropsychiatric symptoms of delirium & personality changes Symptoms: cataract formation, seizures, extrapyramidal symptoms, intracranial pressure

Adrenal Disorders
Addisons Disease
Chronic adrenocortical insufficiency Most frequently the result of adrenocortical atrophy or granulomatous invasion caused by TB or fungal infection Mild mental symptoms: apathy, easy fatigability, irritability, depresssion Tx: Cortisone or one of its synthetic derivatives

Adrenal Disorders
Cushings Syndrome
Excessive quantities of cortisol adrenocortical tumor or hyperplasia (endogenously) lead to secondary mood disorder, a syndrome of agitated depression, and often suicide doses of exogenous corticosteroids secondary mood disorder similar to mania

Pituitary Disorders
Sheehans Syndrome
Postpartum women who have hemorrhaged into the pituitary Exhibit psychiatric symptoms Combination of symptoms = (esp) thyroid + adrenal disorders Can show virtually any psychiatric symptom

Hepatic Encephalopathy Uremic Encephalopathy Hypoglycemic Encephalopathy Diabetic Ketoacidosis Acute Intermittent Porphyria

Metabolic Disorders

Metabolic Disorders
Produce alterations in mental process, behavior, neurological functions Earliest signals: impairment of memory (recent memory), & impairment of orientation As it progresses, confusion or delirium - responsivenes, stupor, and eventually, death

Hepatic Encephalopathy
From severe hepatic failure Characterized by asterixis, hyperventilation, EEG abnormalities, alterations in consciousness from apathy to drowsiness to coma Associated psychiatric symptoms: changes in memory, general intellectual skills, personality

Uremic Encephalopathy
Renal failure = alterations in memory, orientation, consciousness Assoc symptoms: restlessness, crawling sensations on the limbs, ms twitching, persistent hiccups Young people, brief eps of uremia = reversible neuropsychiatric symptoms Old people, longer eps = irreversible

Hypoglycemic Encephalopathy
2 possible causes:
1. 2. Excessive endogenous production of insulin Excessive exogenous insulin administration

Premonitory symptoms (dont occur in every patient): nausea, sweating, tachycardia, feelings of hunger, apprehension, restlessnes Progression: disorientation, confusion, hallucinations, other neurological & medical symptoms Stupor, coma, residual & persistent dementia serious neuropsychiatric sequela

Diabetic Ketoacidosis
Begins with feelings of weakness, easy fatigability, listlessness, polyuria & polydipsia Headache, sometimes nausea & vomiting w/ diabetes mellitus - likelihood of chronic dementia w/ general atherosclerosis

Acute Intermittent Porphyria

Porphyrias d/o of heme biosynthesis that result in excessive accumulation of porphyrins Triad of symptoms:
1. 2. 3. Acute, colicky abdominal pain Motor polyneuropathy Psychosis

Acute Intermittent Porphyria

Autosomal dominant Affects more women than men Onset: between ages 20 and 50 Psychiatric symptoms: anxiety, insomnia, lability of mood, depression, psychosis Contraindication: BARBITURATES
Aggravates the attacks Prohibited in patients & persons who have relatives with the disease

Nutritional Disorders
Niacin Deficiency Thiamine Deficiency Cobalamin Deficiency

Global occurring nutritional deficiency disease seen in association with alcohol abuse, vegetarian diets, and extreme poverty and starvation

Niacin Deficiency Pellagra

Symptoms
NEUROPSYCHIATRIC

apathy irritability insomnia depression delirium

MEDICAL dermatitis peripheral neuropathies diarrhea

Course and Treatment

NICOTINIC ACID
Response is rapid Dementia from prolonged illness may improve only slowly and incompletely

Thiamine Deficiency

Beriberi
Cardiovascular and neurological changes Occurs primarily in Asia and in areas of famine and poverty

Wernicke-Korsakoff Syndrome
Most often associated with chronic alcohol abuse

Thiamine Deficiency
PSYCHIATRIC SYMPTOMS:
1. 2. 3. 4. 5. Apathy Depression Irritability Nervousness Poor concentration

Severe memory disorders can develop with prolonged deficiencies.

Cobalamin (Vit. B12) Deficiency

Failure of gastric mucosal cells to secrete a specific substance, required for normal absorption in the ileum Development of a chronic macrocytic megaloblastic anemia (pernicious anemia) Neurological manifestations resulting from degenerative changes in peripheral nerves, the spinal cord, and brain seen in 80%

Cobalamin (Vit. B12) Deficiency

Mental changes = apathy, depression, irritability, moodiness Megaloblastic madness = prominent paranoid features
TREATMENT: early and continued administration of parenteral vitamin therapy

Toxins
Mercury Lead Manganese Arsenic

Inorganic MERCURY Poisoning

Mad-Hatter Syndrome
previously seen in workers in the hat industry who softened felt by putting it in their mouths

Depression Irritability Psychosis Associated neurological symptoms: headache, tremor, weakness

Organic MERCURY Poisoning

Caused by contaminated fish or grain Result in depression, irritability, & cognitive impairment Associated symptoms: sensory neuropathies, cerebellar ataxia, dysarthria, parethesias, and visual field defects

Mercury Poisoning
In pregnant women = abnormal fetal development
TREATMENT: None specific available For acute poisoning: chelation therapy with dimercaprol

Lead Poisoning
When the amount of lead ingested exceeds the bodys ability to eliminate it Takes several months for toxic symptoms to appear Ssx depend on the level of lead in blood TREATMENT: should be instituted as rapidly as possible, even without lab confirmation Facilitate lead excretion: intravenous admin of calcium disodium edatate (versenate) daily for 5 days

>200 mg/L

Symptoms of severe lead encephalopathy Excited delirium

Convulsions, lethargy, coma

Manganese
Manganese Madness early
Affected: persons working in refining ores, brick workers, those making steel casings Symptoms: headache, irritability, joint pains, somnolence lesions in basal ganglia & pyramidal system = gait impairment, rigidity, monotonous or whispering speech, tremors of the extremities & tongue, etc Psychological effects tend to clear 3-4 months after removal from site of exposure Tx: removal from source of poisoning

Arsenic
Chronic arsenic poisoning prolonged exposure to herbicides or drinking water containing arsenic Arsenic used in manufacture of silicon-based computer chips Early signs of toxicity: skin pigmentation, GI complaints, renal & hepatic dysfunction, hair loss, characteristic garlic odor to the breath

Arsenic
Treatment: chelation therapy with dimercaprol