1. Erik Messamore, MD, PhD Psychosis: Origin, Occurrence, Treatment

2. What is Psychosis? Historical Origin of the Term: -’itis’ signifies inflammation -’osis’ signifies disorder without knowledge of cause Neuritis: nervous system disease with inflammation Neurosis: nervous system illness with no obvious signs of inflammation or other cause Psychosis: illness affecting awareness (psyche) without evidence of inflammation; referred to severe change in mental status or function 19 th century concepts

3. What is Psychosis? Modern definition of Psychosis: The presence of one or more of: -Delusions (fixed false beliefs) -Hallucinations (auditory is most common, but can occur with any of the senses -Disorganized speech (sometimes to the point of incoherence) -Greatly disorganized behavior -Catatonia

4. Psychosis is relatively common Approximately 15% of the population will experience hallucinations 5% to 8% of the population will have some form of psychotic disorder 3% of the population will have some form of recurring or chronic psychosis

5. What is Psychosis? It is a symptom, not by itself a specific disease Examples of nonspecific symptoms: -Fever -Cough -Vomiting -Low Energy -Depressed mood

6. Nonspecific Symptoms: Causes and Treatments of Fever AspirinAntibioticQuinineSteroid Physostigmine BacteriaEffective No VirusEffectiveNo Parasite (e.g. malaria) EffectiveNoEffectiveNo Autoimmune disease (e.g. lupus) Partly Effective No YesNo Drug effect (atropine) No Effective For a particular cause: some drugs are effective, some are not For a particular drug: some causes respond, others don’t

7. Three Broad Categories of Cause: Psychiatric Illness ‘Medical’ Illnesses Medications/Drugs Causes of Psychosis

8. Schizophrenia Bipolar Disorder Major Depression Post-partum syndrome Severe stress or anxiety Personality disorders Causes of Psychosis: Psychiatric Illnesses

9. Autoimmune diseases (e.g. Lupus) Endocrine diseases (thyroid, insulin, steroid hormones) Infections (incl. HIV, Syphilis, CNS infections) Narcolepsy Seizure disorder Tumors (in brain, or eleswhere) CNS degenerative diseases Nutritional deficiencies Celiac disease Delirium Causes of Psychosis: Medical Illnesses

10. Stimulants (including ADHD meds) Steroids (therapeutic and anabolic) Parkinson’s disease treatments Opiate pain medications Cardiovascular medications Nonsteroidal anti-inflammatory medications (e.g, aspirin, ibuprofen) Antibiotics (ciprofloxacin) Causes of Psychosis: Medications & Drugs

11. Medications for ADHD are very much overprescribed. They are increasingly used as ‘performance-enhancing drugs.’ Rate of psychosis from therapeutic doses is difficult to estimate. Estimates range from 0.25% to 5%. Causes of Psychosis: Stimulants and Marijuana

12. Short-term paranoia/psychosis is a widely-known cannabis side effect. Some users will develop long-lasting psychosis after years of regular (and otherwise unremarkable) cannabis use. Numerous well-designed epidemiological studies point to 200 – 500% increased risk of psychosis with long-term cannabis use. Not ‘medicinal’ for vulnerable brains. “Spice” (synthetic cannabis) is a mental health disaster. Causes of Psychosis: Stimulants and Marijuana

13. Clinicians have to rely on history (of the individual patient as well as family medical and psychiatric history) – with attention to timing, nature of symptoms, co-occurrence with other symptoms, course of symptoms, age/time of onset, and many other factors. All patients with new-onset psychosis need a medical workup that excludes medical-toxic causes of psychosis A primary psychotic disorder, such as schizophrenia, is usually a diagnosis of exclusion. Psychosis: How to know the cause

14. -Celiac disease involves antibodies formed against wheat protein. -Two case reports of schizophrenia-like psychosis in otherwise normal individuals who – years later – developed clinical signs of celiac disease. -Grain+Milk-free diet accelerated rate of recovery from acute psychosis Dohan, F.C., et al. (1969). Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet. Br J Psychiatry 115, 595–596. Dohan, F.C., et al. (1969). Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet. Br J Psychiatry 115, 595–596. Psychosis: side note - gluten

15. Gluten antibodies are over-represented in schizophrenia Psychosis: side note - gluten Schizophrenia n = 1,401 Control group n = 900 Tissue transglutaminase antibodies 5.4%0.8% Anti-gliadin antibodies23.1%3.1% Cascella, N. G. et al. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population. Schizophr Bull 37, 94–100 (2011).

16. Detailed clinical history Physical and Neurological exams Blood count Comprehensive chemistry panel Urinalysis Screening tests for inflammation Thyroid studies HIV and syphilis screens Brain imaging Psychosis: Exams and Tests

17. Treatment is based on the presumed cause Psychosis: Treatment

18. Dopamine receptor blockers (‘antipsychotic’ medications) Clozapine Lithium Anti-epileptic Antidepressant Psychosis: Medications

19. Early detection and treatment is associated with better outcome. Delayed treatment (long-duration) of psychosis is associated with greater functional impairment. Average duration of untreated psychosis is 3 – 7 years. Psychosis: Awareness and Treatment are Important