2. By: Dr. M. M. O. Okonji FRCPsych. (UK) Consultant Psychiatrist

3. Evolution of a Psychiatrist – Personal Experience 1. Why the medical school 2. Why psychiatry of all the disciplines 3. Diagnosis and Treatment with time a) Classification b) Mental health service delivery Institutions Community Primary healthcare Mental healthcare financing Evolution of a psychiatrist – personal experience 2

4. Development of Drugs in General Medicine Identification of molecular pathology leads to intervention methods. Evolution of a psychiatrist – personal experience 3

5. Schematic of HIV/CD4 Cell Interaction Evolution of a psychiatrist – personal experience 4

6. Development of Drugs in General Medicine (Cont.) The treatment regime comprises a combination of ARV medication which fall into four major classes – NRTIS (Nucleotide Reverse Transcriptase Inhibitors) NNRTIS – Non Nucleotide Reverse Transcriptase Inhibitors PI – Protease inhibitors Entry inhibitors Each medication within its respective class acts to inhibit the replication process of HIV at distinct point in its viral life cycle Evolution of a psychiatrist – personal experience 5

7. DEVELOPMENT OF DRUGS IN PSYCHIATRY Serendipitous discovery of the first neuroleptic ushered in the modern era of psychiatry. 1950 Chlorpromazine was synthesised originally as antihistamine / antihelmenthic was found to be sedative and antipsychotic. Dopamine hypothesis was inferred and believed to play an important action of antipsychotic drugs Antipsychotic increase turnover of brain dopamine Evolution of a psychiatrist – personal experience 6

8. Development of Drugs in Psychiatry (Cont.) The greater the DA receptor binding affinity of antipsychotic, the greater the clinical potency. The drugs developed following this hypothesis are called Typical Antipsychotics. More than 30 compounds between 1950-1970. Between 30-40% of patients are not responsive More important, they are ineffective against negative symptoms and neurocognitive deficits. Evolution of a psychiatrist – personal experience 7

9. Development of Drugs in Psychiatry (Cont.) The challenge of dopamine hypothesis comes from primary two lines of evidence: Dopamine hypothesis does not account for negative symptoms Dopamine hypothesis does not account for nonrecognitive deficits. Evolution of a psychiatrist – personal experience 8

10. Development of Drugs in Psychiatry (Cont.) In 1970’s: atypical antipsychotics developed on the basis of reduced extrapyramidal side effects in animal models (Thioridazine and Sulpiride). 1980’s: Clozapine rediscovered with recognition of broader efficacy compared with other antisychotics 1990’s: New generation atypical antipsychotics act through multiple neurotransmitter systems in addition to dopamine. Evolution of a psychiatrist – personal experience 9

11. 10 Limitations of Efficacy of Antidepressant Drugs Severity C B A Time Comparison of efficacy of two active drugs (A, B) and a placebo with time

12. Limitations of Efficacy of Antidepressant Drugs Side effects are a problem No accurate prediction of response Two or more weeks before beginning of effective response 15-20% of patients fail to respond to any treatment Tendency for active drugs to be equipotent in any investigations 11

13. Future of psychiatry – which direction? The future of psychiatry will most likely depend on developments in molecular neuroscience. Evolution of a psychiatrist – personal experience 12

14. The Genome Project The human genome project involved the sequencing of DNA in human. The human genome consists of 3 billion genes with three million gene variations or polymorphisms. There are coding and non-coding genes. Humans have only 23,000 genes. Evolution of a psychiatrist – personal experience 13

15. MOLECULAR BASIS OF GENE- ENVIRONMENT INTERACTION Evolution of a psychiatrist – personal experience 14

16. HOW ENVIRONMENT INFLUENCE GENE EXPRESSION IN THE BRAIN Evolution of a psychiatrist – personal experience 15

17. Schematic illustration of gene-environment interactions Evolution of a psychiatrist – personal experience 16 ENVIRONMENTAL INPUTS Sensory inputs Psychotropic drugs Psychological stressors Learning (including psychotherapy) Toxins Viruses PROTEINS Neurotransmitter metabolism Receptors Ion channels Intracellular regulatory systems Transcription factors PHENOTYPE (functional properties)

18. Thank You !!