Psychiatric Disorders due to Medical Conditions

Organic Mental Disorder

Definition: Psychological or behavioral abnormalities associated with transient or permanent brain dysfunction.

Prevalence: 2nd most common (second to adjustment disorders) in general hospital consultation cases (17-27%).

Classifications:

Global Cognitive Impairment: Delirium and Dementia.
Selective Cognitive Impairment: Psychotic Symptoms (Hallucinations, Delusions) and Amnestic Syndromes.
Resembling a Primary Psychopathology: Affective and Anxiety Syndrome.
Altered Personality: Personality Syndromes and Catatonic Disorders.
ETOH/Substance Intoxication and Withdrawal Syndromes.
Sleep and Sexual Disturbances.
Cognitive and Mental Disorders Not Otherwise Specified Due to a General Medical Condition.

Clinical Evaluation - 4 levels of evaluation

Overall: patients suffering from mental disorders originating from medical etiology usually have

Normal premorbid personality: with no previous past psychiatric illness, nor family history of mental illness.

Late age of onset of mental disturbances: with coexisting deficit syndromes and atypical features

Pre-existing medical/neurological illness

First Level:

Present Episode: Onset and nature of the illness.

Past Psychiatric History: Previous illnesses in the patient and/or the patient's family, history of previous treatments.

Past Medical History: Any pre-existing medical (HTN, DM, old CVA) or neurological illness (including exposure to toxic chemicals, substances, and ETOH) in the patient and the patient's family.

Medication History

Mental Status Examination: Behavior, level of consciousness, orientation, attention/concentration, memory, higher cortical functions, speech, affect, thought process/content, perception, insight and judgment. Apply Mini-Mental-Status Exam.

Vital Signs, and general physical examination: emphasis on neurological status.

Second Level:

Complete Physical and Neurological Examination.

Routine Laboratory Tests: CBC/Differential, Chemistry-23, urine analysis and toxic screening, thyroid function tests, VDRL, vitamin B12 and folate, ECG, and CXR.

Third Level:

Specific Laboratory Tests: Lumbar puncture, blood gases, heavy metal screening, and etc.

Neuroimaging: CT Scan.

Fourth Level:

Advanced Neuroimaging: MRI, SPECT.

Common Etiologies

All can present with psychitatric symptom being the primary symptom

CNS Pathology: Trauma, Epilepsy, CVA/Stroke

Basal ganglia Disorders: Parkinson’s Þ depression/anxiety/psychosis; Huntington’s Þ psychosis (schizoaffective disorder, boderline personality disorder (GABA depletion Þ Ý dopamine), predilection toward ETOH because it slows down the motor symptoms

Demyelinating disorders (multiple sclerosis, etc): Þ depression/anxiety

Tumors Þ full spectrum of disorders (personality disorders, schizophrenia, etc.)

Infection: herpes encephalitis Þ acute psychosis, neurosyphillis

Seizures: Þ can have psychotic elements post-ictally

Normal pressure hydrocephalus: Þ balance, gait/dementia/incontinence, dependence

Endocrinopathies: Hyper/Hypo-thyroidism, Hypopituitarism, Hyper/Hypoadrenalcorticism, Hyper/Hypoparathyroidism, and Diabetes Mellitus.

Infectious Disease: Systemic (hepatitis, pneumonia, etc.), Syphilis, Influenza, HIV/AIDS, etc.

Hypoxia (secondary to): Cardiovascular Disorders, Anemia, Pulmonary Disorders, and etc.

Deficiencies: Thiamine, Niacin, Folate, and Vitamin B12.

Electrolyte Imbalance Renal: dialysis (electrolyte shift from ECF) Þ psychosis, confusion

Heavy Metals/Drugs/Toxins/ETOH: Intoxication and Withdrawal.

Medications: Antihypertensives, Corticosteroids, Hypnotics/Sedatives, Anti-cholinergic Agents, Antibiotics, Hormone Replacements, Stimulants, and etc.

Examples of Psychiatric Disorders Caused By Medical Conditions

(1) Delirium

Definition: transient, reversible disorder of cognition due to widespread dysfunction in cerebral metabolism and neurotransmitters

Prevalence: 5-10% of all hospitalized medical/surgical patients; 40% of geriatric patients

Clinical Presentation: The onset of delirium is usually rapid, with a fluctuating course. Changes in psychomotor activity, disturbances in sleep-wake cycle, incoherent speech, disorientation, memory impairment, perceptual disturbances (especially visual), disorganized thinking, and persecutory delusions.

Hallmark : "clouding of consciousness" with ß awareness or attention/concentration.

EEG: global slowing

(2) Dementia

Definition: loss of intellectual abilities of sufficient severity to impair patient's occupational and/or social functioning.

Prevalence: 5% of people age > 65, 20% of people over age > 80. 60% of dementia: Alzheimer's type, multi-infarct type or ETOH related. Other 40%: secondary to metabolic disturbances, hydrocephalus, neoplasm, etc.

Clinical Presentation: Memory loss (hallmark), with 1 OR MORE of the following cognitive disturbances: aphasia (speech), apraxia (ability to perform learned tasks), agnosia (recognition), and/or impaired executive functioning.

"Soft" neurological signs are associated with dementia: snout reflex, grasping reflex, palmo-mental reflex, etc.

(3) Amnestic Syndrome

Definition: essential feature is impairment in BOTH short-term memory (anterograde) and long-term memory (retrograde) without any evidence of altered consciousness or loss of intellectual abilities. Confabulation is common.

Classical example: ETOH-related Wernicke-Korsakoff Syndrome.

(4) Psychoses

Hallucinosis

Definition: persistent or recurrent hallucinations (visual, gustatory, olfactory, auditory) occurring in a state of normal awareness

Delusions

Clinical presentation: Presence of delusions (fixed, false, beliefs that cannot be corrected by reasoning), symptoms found in schizophrenic disorders.

Classifications: persecutory type, jealousy type, grandiose type, erotomanic type and somatic type.

Common Causes: neurosyphilis, temporal lobe seizures, viral encephalitis, basal ganglia disease, multiple sclerosis, pernicious anemia. ETOH-induced, and stimulants.

(5) Affective Syndrome

Definition: A disturbance of mood which resembles either a manic or a major depressive disorder, but it is judged to be due to a specific medical condition.

Clinical features associated with mania: decreased need for sleep, increased activity, pressured speech, distractibility, flight of ideas, grandiosity, irritability, elevated mood, and impaired judgement.

Clinical features associated with depression: sleep disturbances, fatigue, changes in appetite and weight, diminished concentration, psychomotor retardation/agitation, anhedonia, excessive guilt feelings and sense of worthlessness, depressed mood and hopelessness, and suicidality.

(6) Anxiety Syndrome

Definition:Prominent, recurrent panic attacks or generalized anxiety attributable to a clearly defined medical condition

Causes: neurologic (25%), endocrinologic (25%), circulatory (12%), collagen vascular (12%), infectious (12%), and other (14%). Psychoactive substance abuse and withdrawal are one of the frequent causes.

(7) Personality Syndrome

Clinical Presentation: marked and persistent alteration in personality that represents a change from the individual's previous personality, secondary to a medical condition.

Relevant personality change: emotional lability or apathy, increased or reduced intensity and expression of instinctual drives, defective control of impulses, paranoia and suspiciousness, and impaired social judgement.

Classical personality syndromes:

Frontal Lobe Damage: lack of reliability and foresight, euphoria, disinhibition, facile or childish behavior

Temporal Lobe Epilepsy: a general "viscosity" of personality, associated with religiosity, a hyperethical sense, philosophical interest, obsessionalism, circumstantiality, impulsivity, anger and hyposexuality

(8) Catatonic Syndrome

Clinical Presentation: catatonia as manifested by motor immobility, extreme negativism and mutism, or excessive purposeless motor activity, peculiarity of voluntary movements, echolalia and echopraxia.

Neurophysiological Changes in Medical Conditions

Relevant Anatomy

nigro-striatal pathway: associated with initiation of movement; also sensory perception and cognition

meso-limbic and meso-cortical paths: involved with emotion, cognition, motivation; related to psychosis

midbrain nuclei (ventral tegmental area, locus coeruleus, raphae) connect to limbic regions (nucleus accumbens, septum, amygdala, hippocampus, olfactory tubercles, hypothalamus) and cortex (frontal, cingulate, pyriform)

cortical-subcortical connections: connect cortex with many lower areas (limbic nuclei, striatum, brainstem)

involve glutamate - the primary excitatory neurotransmitter in the brain

Neurotransmitters

Biogenic Amines: involved in emotion, reward, cognition, movement

norepinephrine (NE): found in locus coeruleus

dopamine (DA): in substatia nigra, ventral tegmental area, hypothalamus

serotonin (5-HT): midbrain raphae

Acetylcholine: involved in movement, cognition (decreased in Alzheimer’s)

local circuits (basal ganglia); projection to pedunclopontine, tegmental nuclei, etc

Amino Acids: anxiety, mood

excitatory: glutamate (cortical projections); can be a neurotoxin at high doses

inhibitory: GABA (interneurons and long tracts of cerebellum, hippocampus, basal ganglia, raphae, dienceph.)

Neuropeptides: cognition, emotion, control of neuroendocrine functioning

at least 60 are identified; located in hypothalamus and control neuroendocrine function and limbic system, basal ganglia, cortex, cerebellum, brainstem

Effects of Neurotransmitters

Mood: norepi, serotonin, dopamine (evidence: antidepressants affect these NT)

Psychosis: dopamine, serotonin, norepinephrine are all increased in psychosis; glutamate is decreased

evidence: neuroleptics are dopamine and serotonin antagonists; norepinephrine metabolites are increased in psychosis; PCP is a glutamate NMDA antagoinist and induces psychosis

Anxiety: GABA (benzodiazapines are GABA agonists), norepinephrine (NE at high levels can produce anxiety)

Reward: dopamine (primary action of many abused drugs), norepinephrine (also increased in abused drugs), opiates

Food Intake: serotonin inhibits food intake (clozapine Þ Ý weight), norepinephrine (low Þ stimulate intake; high Þ inhibits intake)

Movement: dopamine (in nigro-striatal pathway), acetylcholine: in basal ganglia, related to dopamine (Ý DA Þ ß ACh)

Learning/Memory: ACh (decreased in Alzheimer’s), Glutamate (critical in long-term memory), norepinephrine

Neuroendocrine control: dopamine (inhibit prolactin), serotonin, neuropeptides

Neurodegeneration: glutamate is associated with Alzheimer’s and Huntington’s Þ double edged sword, because also needed for learning and memory (you can stop the degeneration in Alzheimer’s by blocking glu, but then you kill the memory and learning functions of glu at the same time)

dopamine can produce oxidative stress

Examples of Neurotransmitter Alterations in Medical Conditions

Alzheimer’s, Huntington’s, Parkinson’s: all are associated with depression (due to ß NE, dopamine, serotonin)

Parkinson’s leads to decreased dopamine and increased ACh - opposite of schizophrenia; treatment with L-dopa works for a while, then the therapeutic window narrows, and you can easily overdose to produce psychosis

why? Þ could be that dopamine receptors get sensitized after an extended period of low dopamine

advanced Parkinson’s involves dementia due to ß ACh in the nucleus basalis

typical antipsychotics can induce Parkinsonism and tardive dyskinesia (EPS) due to blocking dopamine Þ MUST use atypicals with Parkinson’s patients

Huntington’s: striatal cells which produce GABA are lost; the basal ganglia get extensive inputs from the cortex via glutamate; Ý glutamate in HD to try to compensate for loss of striatal cells Þ neurodegeneration

Korsakov’s Psychosis: result of decreased ACh in the cortex and hippocampus

Cushing’s Disease: often associated with depression; Ý glucocorticoids Þ ß serotonin Þ depression

Stimulant Drugs: Ý dopamine, norepinephrine Þ hyperactivity and psychosis

Oxidative Stress

free radicals are normally produced at high levels in the mitochondria (from ox. phos.), and at moderate levels elsewhere

dopamine: can be metabolized to yield *OH via cytochrome P450 or auto-oxidation to a semi-quinone

glutamate: leads to Ý Ca which can increase free radical production

hypoxia, cell damage: leads to release of excitatory neurotransmitter which can lead to increased free radicals

superoxide dismutase, glutathione, and catalase serve to scavenge and neutralize free radicals

BUT superoxide dismutase turns superoxide into hydrogen peroxide which can undergo the Fenton Reaction

Fenton Reaction: H₂O₂ Þ *OH via an Fe mechanism

other antioxidants: vitamin E (lipid soluble); vitamin C (water soluble)

effects of free radicals: lipid peroxidation (Þ membrane damage and disruption of ion channel flow); protein cross-linking; direct DNA damage

brain is more susceptible to oxidative stress:

high concentration of unsaturated lipids (good substrate for peroxidation)

high amount of O₂ is supplied to the brain

protective mechanisms have a lower capacity in brain than in other places like liver

high concentration of Fe (for Fenton reaction), esp. in dopaminergic neuronsÞ Parkinson’s