Di4PR1&2

Discussion Board 4

Jodianne Davidson, Andrew Lara, Christina Kim, Renee Miller, Samuel Schulze

1. What is a pedigree and what information can you gather from this concept?

A pedigree is a genetic representation of a family tree that diagrams the inheritance of a trait or

disease through several generations. The pedigree shows the relationships between family

members and indicates which individuals express or silently carry the trait in question.

2. Difference between autosomal dominant and recessive, X-linked diseases? Name a few

psychiatric conditions that have either of these?

A child of a person affected by an autosomal dominant condition has a 50% chance of being

affected by that condition via inheritance of a dominant allele. By contrast, an autosomal recessive

disorder requires two copies of the mutated gene (one from each parent) to cause the disorder

● Autosomal dominant psych DO: bipolar affective disorder (BD) and schizophrenia

● X-linked psych DO: schizophrenia (SCZ), major depression disorder (MDD), bipolar

disorder (BPD, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder

(ASD)

3. Difference between gene therapy and the Human Genome project?

Gene therapy is a medical treatment approach that involves manipulating a patient's genes to treat

or prevent a disease. This can involve either adding a function copy of a missing or defective gene

or disabling or removing a harmful gene. The potential for gene therapy includes the cure for

genetic disorders, improving the effectiveness of treatments including HIV and cystic fibrosis.

The Human Genome Project, is a scientific research project that aims to map and sequence the

entire human genome, which is the complete set of genes in the human body. The project was

completed in 2003 and resulted in the identification of approximately 20,000-25000 human genes.

The main goal was to provide a comprehensive understanding of human genetics, including how

genes work and interact with each.

Gene therapy is a clinical application while the human genome project was an endeavor to

discover new information on the human genome.

4. Why is genetic testing important in psychiatry?

Genetic testing is important in psychiatry because it can help identify specific genetic variations

that may increase a person's risk for developing certain mental health disorders. By identifying

these genetic risk factors, psychiatric providers can create personalized treatment and

management plans that may be more effective in treating the individual's specific symptoms

(Bousman & Potkins, 2014).

5. What is the role of neuropeptide in psychiatry?

Neuropeptides are small molecules that are involved in the transmission of signals in the brain and

nervous system. They play a critical role in regulating mood, emotion, and behavior, and have been

implicated in a number of psychiatric disorders, including depression, anxiety, and addiction

(Rufener & Bruchas, 2017). In psychiatry, neuropeptides are studied for their potential to be used

as targets for developing new medications and therapies that may be more effective in treating

these conditions (Rufener & Bruchas, 2017).

6. What is DNA Duplication?

DNA duplication is the process by which a cell makes an exact copy of its DNA. This is a critical

process that occurs before cell division, as it ensures that each new cell receives an identical copy

of the genetic material (Alberts et al., 2014). DNA duplication involves the separation of the two

strands of the DNA molecule and creation of a new complementary strand for each original strand

(Alberts et al., 2014). This process is facilitated by a number of proteins and enzymes, and errors

in DNA replication can lead to mutations and genetic disorders (Alberts et al., 2014).

7. Differentiate between transcription and translation?

Transcription - Transcription is the transfer of cell nucleus DNA code to cytoplasmic RNA code

(Hall & Hall, 2021). For Nucleic DNA to be transcribed to RNA, it must first split from a double-

stranded structure to a single-stranded structure. This single-stranded DNA provides a template

by which transcription factors can “copy” the DNA code into a single-stranded RNA form, known as

messenger RNA (or mRNA) (Hall & Hall, 2021). After the newly formed mRNA strand makes its

way to the cytoplasmic ribosome, it can be translated into bioactive proteins.

Translation - Translation is the name of the protein-synthesis process conducted by the ribosome

(Hall & Hall, 2021). When the mRNA strand comes in contact with a ribosome it travels in between

the ribosomal subunits, the ribosome “reads” the sequence of nucleotides that make up the mRNA

strand and attaches the appropriately coded protein in the correct sequence (Hall & Hall, 2021).

8. How do mutations affect DNA?

A mutation is any inherited alteration of genetic material (McCance & Huether, 2019). They affect

DNA by altering the genetically prescribed order of base pairings that drive normal biological

functions. This may be due to substitution, in which one base pair is replaced by another, or by

another similar change in base pair sequence. Changes in DNA sequence can lead to improper

protein synthesis, resulting in disease or disability (McCance & Huether, 2019).

9. What does single nucleotide polymorphism do at the DNA level?

Single nucleotide polymorphisms, or SNPs, are substitutions of a single nucleotide at a specific

position in the genome. SNPs are the most common type of human genetic variation (Ahmadian,

2000). Single nucleotide polymorphisms occur in 1/1000 base pairings (Ahmadian, 2000). SNPs in

germ-cells are passed onto offspring and may give rise to phenotypic variation (Ahmadian, 2000).

10. What impact does psych medication have on genes?

Psychiatric medications, just as neurotransmission, other drugs and the environment, regulate processes

that can chemically modify the structure of chromatin through chemical modifications that include:

methylation, acetylation and phosphorylation among other chemical modifications (Stahl, 2021). When a

drug modifies the chemical structure of chromatin, this affects the epigenetic control over whether a gene

is expressed or whether it is silenced; therefore, psych medications have the ability to modify genes by

affecting whether some genes are expressed and or silenced (Stahl, 2021).

An example is when a drug causes histones (in DNA) to be methylated, this causes the chromatin to

become more compact, closes of f access of molecular transporter transcription factors to the promoter

regions of DNA, and the consequence is the silencing of this region of the gene, therefore, no protein from

that gene is manufactured (Stahl, 2021).

Most psychotropic drugs act on processes that control the chemical neurotransmission on the level of

neurotransmitters and the upregulation and down regulation of the enzymes and their receptors.

11. What is teratogenic? Name several teratogenic medications in psychiatry? What schedule of

Drugs are absolute contraindicated in pregnancy?

Teratogens

Teratogens are agents that cause abnormalities in the developing fetus. Some examples of teratogens

include: various drugs, exposure to X-rays, maternal infections (e.g. German measles or syphilis), and their

effects are especially dependent on the timing of the exposure during fetal development (Armstrong,

2008). During fetal development, the fetus is most susceptible to the damaging effects during the first

trimester. All currently used psychotropic agents and metabolites cross the placenta, by simple diffusion.

An example of a teratogen is the vitamin A-related substance isotretinoin, known as Accutane, indicated

for acne, produces serious birth defects and should be avoided by sexually active women (Meyer, 2023).

Teratogens may affect the fetus in several ways: structural teratogenesis (birth defects), behavioral

teratogenesis, and perinatal syndromes (Armstrong, 2008).

During pregnancy, many providers avoid prescribing psychoactive drugs during pregnancy, even

though there is morbidity associated with these disorders and increasing evidence or the risk and benefits

about their use during pregnancy. Psychiatric symptoms can affect pregnancy because of the effect on the

mother’s emotional state, functional status, and risk of engaging in dangerous behavior. Untreated

maternal mental illness after birth will also affect the infant’s development and well-being, if the mother

the mother remains untreated during her pregnancy (Armstrong, 2008).

Treatment Guidelines for Depression and Bipolar Medications During Pregnancy and Postpartum

What schedule of Drugs are absolute contraindicated in pregnancy?

The FDA classifies drugs into 5 categories: A, B, C, D & X. Category X is absolutely contraindicated for

pregnancy.

What are the names of several teratogenic medications in psychiatry?

Anxiolytics and Hypnotics (Most benzodiazepines)

• Estazolam - Pregnancy category X

• Flurazepam - Pregnancy category X

• Quazepam - Pregnancy category X

• Temazepam - Pregnancy category X

• Triazolam - Pregnancy category X

• Alprazolam - Pregnancy category D

• Chlordiazepoxide - Pregnancy category D

• Clonazepam - Pregnancy category D

• Clorazepate - Pregnancy category D

Antiepileptics and Mood Stabilizers

• Carbamazepine - Pregnancy category D

• Lithium - Pregnancy category D

• Valproic Acid - Pregnancy category D

• Lamotrigine (Lamictal) - Pregnancy category D

Antidepressants

• Paroxetine (Paxil) - Pregnancy category D

12. Differentiate between these genetic terms:

a. Chromosomes and genes

i. Chromosomes are structures in the nucleus of cells that contain genetic

information or DNA. They are made up of DNA and histone proteins and appear as

visible structures during cell division. Humans have 23 pairs of chromosomes, with

the sex chromosomes determining biological sex. Abnormalities in chromosomes

can cause genetic disorders or diseases.

ii. Genes are segments of DNA that contain instructions for making proteins or RNA

molecules, passing traits from parents to offspring. They are located on

chromosomes and can exist in different forms. Gene expression can be influenced

by the environment, lifestyle, and epigenetic modifications. Genetics has important

implications for medicine, agriculture, and biotechnology.

b. DNAs, RNAs,

i. DNA (short for deoxyribonucleic acid) is a molecule that carries the genetic

instructions used in the development, functioning, growth, and reproduction of all

living organisms. It is a double-stranded, helical structure made up of nucleotide

building blocks containing the four nitrogenous bases: adenine, thymine, cytosine,

and guanine. DNA provides the blueprint for the production of proteins and RNA

molecules that carry out various biological processes in cells and organisms.

ii. RNA (short for ribonucleic acid) is a single-stranded molecule that plays a critical

role in the production of proteins from the genetic information carried by DNA. It is

made up of nucleotide building blocks containing the four nitrogenous bases:

adenine, uracil, cytosine, and guanine. RNA can act as a messenger, transferring

genetic information from DNA to the ribosomes, where proteins are synthesized. It

can also have other functions in regulating gene expression and other cellular

processes.

c. Phenotype and genotype

i. Phenotype refers to the observable physical, biochemical, and behavioral

characteristics of an organism, resulting from the interaction between its genetic

makeup and the environment. It encompasses a wide range of traits, including

anatomical features, physiological functions, and behaviors, that can be studied and

measured. The phenotype of an organism can be influenced by genetic factors,

environmental factors, or a combination of both.

ii. Genotype refers to the genetic makeup of an organism, including the specific

combination of alleles, or alternative forms of a gene, that determine its traits and

characteristics. It is the set of instructions encoded in an organism's DNA that

dictate its physical and functional traits. The genotype of an organism can influence

its phenotype, although the relationship between genotype and phenotype can be

complex and influenced by environmental factors.

d. Messenger RNA, ribosomal RNA, and transport RNA,

i. Messenger RNA (mRNA) is a type of RNA molecule that carries genetic information

from the DNA in the nucleus to the ribosomes in the cytoplasm of a cell. It serves as

a template for protein synthesis by providing the sequence of amino acids that

make up a protein. mRNA is produced by a process called transcription, during

which a portion of DNA is copied into a complementary RNA sequence. The mRNA

then serves as a template for translation, during which the ribosomes use the

mRNA sequence to synthesize proteins.

ii. Ribosomal RNA (rRNA) is a type of RNA molecule that is a component of the

ribosomes, the cellular organelles responsible for protein synthesis. It plays a

crucial role in the structure and function of ribosomes by providing a framework

for the assembly of the ribosomal subunits and participating in the catalytic activity

of the ribosome. rRNA is transcribed from DNA and processed to form mature

rRNA molecules, which are then combined with proteins to form the two subunits

of the ribosome.

iii. Transport RNA (tRNA) is a type of RNA molecule that delivers amino acids to the

ribosome during protein synthesis. It has a specific three-dimensional structure

that allows it to recognize and bind to a particular amino acid at one end and to the

corresponding codon on the messenger RNA (mRNA) at the other end. tRNA

molecules carry amino acids to the ribosome in a specific order, determined by the

sequence of codons on the mRNA. This process allows the ribosome to synthesize

proteins with the correct sequence of amino acids.

e. Polygenic, multifactorial, and monogenic

i. Polygenic refers to a trait or characteristic that is controlled by the combined

effects of multiple genes, rather than a single gene. Polygenic traits are influenced

by the interaction of multiple genetic and environmental factors, which can make

their inheritance and expression more complex than traits that are controlled by a

single gene. Examples of polygenic traits include height, skin color, and intelligence,

which can vary widely due to the combined effects of multiple genes and

environmental factors.

ii. Multifactorial refers to a trait or condition that is caused by a complex interplay of

multiple genetic and environmental factors. It typically involves the interaction of

multiple genes, each contributing a small effect, as well as environmental factors

such as nutrition, exposure to toxins, and lifestyle. Multifactorial traits and

conditions can be difficult to study and understand due to their complex nature and

the large number of variables involved. Examples of multifactorial conditions

include heart disease, diabetes, and some types of cancer.

iii. Monogenic refers to a trait or condition that is determined by a single gene. In

monogenic inheritance, a specific gene variant or mutation is responsible for the

trait or condition, which is typically inherited according to well-defined patterns,

such as autosomal dominant, autosomal recessive, or X-linked inheritance.

Examples of monogenic conditions include sickle cell anemia, cystic fibrosis, and

Huntington's disease.

References

References

Ahmadian, A. et. al. (2000). Single-nucleotide polymorphism analysis by pyrosequencing. Department of

Biotechnology, The Royal Institute of Technology. Stockholm, Sweden.

Alberts, B., Johnson, A., Lewis, J., Morgan, D., Raff, M., Roberts, K., & Walter, P. (2014). DNA replication,

repair, and recombination. In Molecular biology of the cell (6th ed., pp. 1091-1148). Garland

Science.

Armstrong, C. (2008, September 15). ACOG guidelines on psychiatric medication use during pregnancy and lactation. American Family Physician. Retrieved March 12, 2023, from https://www.aafp.org/pubs/afp/issues/2008/0915/p772.html

Bousman, C. A., & Potkin, S. G. (2014). The role of genetics in the diagnosis and treatment of mood

disorders. Current Psychiatry Reports, 16(11), 1-11. doi: 10.1007/s11920-014-0505-6

Hall, J. E., & Hall, M. E. (2021). Guyton and Hall textbook of medical physiology (14th ed.). Philadelphia, PA:

Elsevier.

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults

and children (Eight ed.). St. Louis, MO: Elsevier.

Rufener, K. S., & Bruchas, M. R. (2017). Neuropeptide regulation of emotional state.

Neuropsychopharmacology, 42(1), 216-241. doi: 10.1038/npp.2016.116

Single-Nucleotide Polymorphism Analysis by Pyrosequencing Afshin Ahmadian, Baback Gharizadeh, Anna

C. Gustafsson, Fredrik Sterky, Pål Nyre´n, Mathias Uhle´n, and Joakim Lundeberg1 Department of

Biotechnology, The Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden

Stahl, S. M. (2021). Stahl's essential psychopharmacology: Prescriber's guide (5th ed.). Cambridge

University Press.