By: Dr. M. M. O. OkonjiFRCPsych. (UK)

Consultant Psychiatrist

Evolution of a Psychiatrist – Personal Experience

1. Why the medical school2. Why psychiatry of all the disciplines3. Diagnosis and Treatment with time

a) Classificationb) Mental health service delivery

Institutions Community Primary healthcare Mental healthcare financing

Evolution of a psychiatrist – personal experience 2

Development of Drugs in General Medicine

Identification of molecular pathology leads to intervention methods.

Evolution of a psychiatrist – personal experience 3

Schematic of HIV/CD4 Cell Interaction

Evolution of a psychiatrist – personal experience 4

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

DEVELOPMENT OF DRUGS IN PSYCHIATRYSerendipitous 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

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

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.

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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.

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Limitations of Efficacy of Antidepressant Drugs

Severity C

BA

TimeComparison of efficacy of two active drugs (A, B) and a placebo with

time

Limitations of Efficacy of Antidepressant Drugs

Side effects are a problemNo accurate prediction of responseTwo or more weeks before

beginning of effective response15-20% of patients fail to respond to

any treatmentTendency for active drugs to be

equipotent in any investigations

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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

The Genome ProjectThe 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.

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MOLECULAR BASIS OF GENE-ENVIRONMENT INTERACTION

Evolution of a psychiatrist – personal experience 14

HOW ENVIRONMENT INFLUENCE GENE EXPRESSION IN THE BRAIN

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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)

Thank You !!