PSY 3604 Fall 2024 Introduction to Psychopathology: Etiology 1 PDF

PSY 3604 Fall 2024 Introduction to Psychopathology: Etiology 1, Genes & Environment Scott Vrieze Professor Department of Psychology 1 Causes and risk factors for psychopathology Central question: What cau...

PSY 3604 Fall 2024 Introduction to Psychopathology: Etiology 1, Genes & Environment Scott Vrieze Professor Department of Psychology 1 Causes and risk factors for psychopathology Central question: What causes psychopathology? Answering this question is enormously difficult Genes Brain structure/function Psychological 3 billion DNA base pairs 100 billion neurons Symptoms 20,000 genes 100 trillion connections >700 million genetic variants All of this happens within environmental contexts over the course of development Often only know correlates or “risk factors” rather than causes 2 Correlates and causes “Correlate” is often of limited value, and routinely misinterpreted as “cause” or “likely cause”. Especially in longitudinal data post hoc ergo propter hoc 3 Types of Causes INUS – Insufficient but Necessary parts of a collection which is itself Unnecessary but Sufficient. – Short circuit that burns a house down may be INUS Insufficient but Necessary parts of a collection which is itself Unnecessary but Sufficient Consider the collection of events: House Short circuit Proximity of flammable material Absence of firefighters Within this collection, each part is an insufficient cause. For example, the short circuit by itself would not have caused the fire. But each is necessary within this collection of events. That is, they all must be present to burn the house down. Together the collection is unnecessary but sufficient to the house burning down Why is it unnecessary? Because many other collections of events could burn the house down, such as arson. Having a house, there being a short circuit, etc., are each INUS for the occurrence of the house burning down. Alcohol affecting the developing brain may be INUS. Significant life event that causes depression may be INUS Types of Causes: Timeframe distal (far away)causal factors proximal (immediate) causal factors Diathesis-Stress Model: The Prevailing “Causal Theory” of Mental Illness Diathesis (risk): Stress: Response to more Relatively distal cause proximal events/demands that is not sufficient to that are contributory rarely cause disorder necessary, and not sufficient Diathesis-stress model: Combination of diathesis and stress causes disorder Diathesis Stress Model Fascinating but very rare scenario “additive” model “interactive” model Depression = Diathesis + Stress Depression = Diathesis + Stress + Diathesis x Stress Viewpoints for Understanding the Causes of Abnormal Behavior Biological Social Psychological Biopsychosocial  Genes and environment Genes Brain structure/function Psychological 3 billion DNA base pairs 100 billion neurons Symptoms 20,000 genes 100 trillion connections >700 million genetic variants All of this happens within environmental contexts over the course of development Genetics: Basic Concepts DNA provides instructions that build our bodies and affect our behavior Each person inherits DNA from their mother and father Genes are functional units of DNA that code for proteins (1%) Environments influence the impact of inherited genes Simple but telling example is cell differentiation Muscle Nervous Bone Etc. Human genome consists of 23 pairs of homologous chromosomes First 22 pairs are autosomes and numbered 1-22 Last pair is the sex chromosomes, X or Y Human genome consists of 23 pairs of chromosomes One inherited from mother and the other inherited from father (diploid) Only one of each pair is transmitted to offspring (haploid) Genetics: Basic Concepts DNA is made of four bases A (adenine) G (guanine) C (cytosine) T (thymine) The sequence of bases determines the genetic information Genes are sections of sequence that code for mRNA and proteins Many other kinds of functional units in the genome DNA p  Sequencing the Genome Chromosome 2 CTAAATTTTGCTCTGGGACAAATTCCAAAAAAAATTAGCTTTAATCAAATTTACTTTTACTTTATCTTTCTGAACCTTC AAGGTCCAAAAGCATTGGTTAATAATTCTGCTTCTAAACTTAACATTGCAGCACAGGGCATGTTCTGCCCCCAAGGC AAAGACCATAAGCTACTGTTGTCTGGAAAACATACAAATAGATATCTCAGCAAAAGCTACTCATATATTCTTGTTCTT TTGGGTAAATCATTGTCAGTGACTGATTTTTTTTTTATGAAAGGATAAAAACACGCCCTCTATTGGGGTCAGGTTTT GTGCTGGTATTTCTCCCACCTACTGTATCATAGGAGCTTAGATTCCCAGCTGCTTGCTCTCAGCTGCAGTTCTCTGATG GCTTGCACAGGGTGGACCAGCCCCCTTCCTCTATGTGTGTGTCTGCTGCTGACCTGTGGCTTTGCCGAGGCAGGGA AGCTACTGGTAGTGCCCATGGATGGGAGCCACTGGTTCACCATGAGGTCGGTGGTGGAGAAACTCATTCTCAGGG GGCATGAGGTGGTTGTAGTCATGCCAGAGGTGAGTTGGCAACTGGGAAGATCACTGAATTGCACAGTGAAGACTT ATTCAACTTCATATACCCTGGAGGATCTGGACCGGGAGTTCAAGGCTTTTGCCCATGCTCAATGGAAAGCACAAGT ACGAAGTATATATTCTCTATTAATGGGTTCATACAATGACATTTTTGACTTATTTTTTTCAAATTGCAGGAGTTTGTTTA AAGACAAAAAATTAGTAGAATACTTAAAGGAGAGTTCTTTTGATGCAGTGTTTCTCGATCCTTTTGATAACTGTGGC TTAATTGTTGCCAAATATTTCTCCCTCCCCTCCGTGGTCTTCGCCAGGGGAATACTTTGCCACTATCTTGAAGAAGGT GCACAGTGCCCTGCTCCTCTTTCCTATGTCCCCAGAATTCTCTTAGGGTTCTCAGATGCCATGACTTTCAAGGAGAGA GTACGGAACCACATCATGCACTTGGAGGAACATTTATTATGCCACCGTTTTTTCAAAAATGCCCTAGAAATAGCCTCT GAAATTCTCCAAACACCTGTTACGGAGTATGATCTCTACAGCCACACATCAATTTGGTTGTTGCGAACGGACTTTGT TTTGGACTATCCCAAACCCGTGATGCCCAACATGATCTTCATTGGTGGTATCAACTGCCATCAGGGAAAGCCGTTGC CTATGGTAAGTTATCTCTCCTTTAGCACCTTAAGAATACTTCACCTTTGGAAATTAAAAAAGGATTCTTTACTGAACT GTGATTTGACATTTTCATTTGTTTCATTTCAAATTTCTTTCCAGTTTAACAAATTATTTTGTGCCAATGCGTGTACTCGT CAGTAGCAAATTTTATAAAACTGCCCTTCTTGAAGATATGTATTTATAACTTATAAAATTGTGGAACATATTCAGCCTA CATTTTTAAGTACCATG  Enumerate 234,244,933 ctaaattttg ctctgggaca aattccaaaa aaaattagct ttaatcaaat 234,244,983 ttacttttac tttatctttc tgaaccttca aggtccaaaa gcattggtta 234,245,033 ataattctgc ttctaaactt aacattgcag cacagggcat gttctgcccc 234,245,083 caaggcaaag accataagct actgttgtct ggaaaacata caaatagata 234,245,133 tctcagcaaa agctactcat atattcttgt tcttttgggt aaatcattgt 234,245,183 cagtgactga tttttttttt atgaaaggat aaaaacacgc cctctattgg 234,245,233 ggtcaggttt tgtgctggta tttctcccac ctactgtatc ataggagctt 234,245,283 agattcccag ctgcttgctc tcagctgcag ttctctgATG GCTTGCACAG 234,245,333 GGTGGACCAG CCCCCTTCCT CTATGTGTGT GTCTGCTGCT GACCTGTGGC 234,245,383 TTTGCCGAGG CAGGGAAGCT ACTGGTAGTG CCCATGGATG GGAGCCACTG 234,245,433 GTTCACCATG AGGTCGGTGG TGGAGAAACT CATTCTCAGG GGGCATGAGG 234,245,483 TGGTTGTAGT CATGCCAGAG GTGAGTTGGC AACTGGGAAG ATCACTGAAT 234,245,533 TGCACAGTGA AGACTTATTC AACTTCATAT ACCCTGGAGG ATCTGGACCG 234,245,583 GGAGTTCAAG GCTTTTGCCC ATGCTCAATG GAAAGCACAA GTACGAAGTA 234,245,633 TATATTCTCT ATTAATGGGT TCATACAATG ACATTTTTGA CTTATTTTTT 234,245,683 TCAAATTGCA GGAGTTTGTT TAAAGACAAA AAATTAGTAG AATACTTAAA 234,245,733 GGAGAGTTCT TTTGATGCAG TGTTTCTCGA TCCTTTTGAT AACTGTGGCT 234,245,783 TAATTGTTGC CAAATATTTC TCCCTCCCCT CCGTGGTCTT CGCCAGGGGA 234,245,833 ATACTTTGCC ACTATCTTGA AGAAGGTGCA CAGTGCCCTG CTCCTCTTTC 234,245,883 CTATGTCCCC AGAATTCTCT TAGGGTTCTC AGATGCCATG ACTTTCAAGG 234,245,933 AGAGAGTACG GAACCACATC ATGCACTTGG AGGAACATTT ATTATGCCAC 234,245,983 CGTTTTTTCA AAAATGCCCT AGAAATAGCC TCTGAAATTC TCCAAACACC 234,246,033 TGTTACGGAG TATGATCTCT ACAGCCACAC ATCAATTTGG TTGTTGCGAA 234,246,083 CGGACTTTGT TTTGGACTAT CCCAAACCCG TGATGCCCAA CATGATCTTC 234,246,133 ATTGGTGGTA TCAACTGCCA TCAGGGAAAG CCGTTGCCTA TGGTAAGTTA 234,246,183 TCTCTCCTTT AGCACCTTAA GAATACTTCA CCTTTGGAAA TTAAAAAAGG 234,246,233 ATTCTTTACT GAACTGTGAT TTGACATTTT CATTTGTTTC ATTTCAAATT 234,246,283 TCTTTCCAGT TTAACAAATT ATTTTGTGCC AATGCGTGTA CTCGTCAGTA 234,246,333 GCAAATTTTA TAAAACTGCC CTTCTTGAAG ATATGTATTT ATAACTTATA 234,246,383 AAATTGTGGA ACATATTCAG CCTACATTTT TAAGTACCAT GTTTAGAAAA  Identify Gene Boundaries 234,244,933 ctaaattttg ctctgggaca aattccaaaa aaaattagct ttaatcaaat 234,244,983 ttacttttac tttatctttc tgaaccttca aggtccaaaa gcattggtta 234,245,033 ataattctgc ttctaaactt aacattgcag cacagggcat gttctgcccc 234,245,083 caaggcaaag accataagct actgttgtct ggaaaacata caaatagata 234,245,133 tctcagcaaa agctactcat atattcttgt tcttttgggt aaatcattgt 234,245,183 cagtgactga tttttttttt atgaaaggat aaaaacacgc cctctattgg 234,245,233 ggtcaggttt tgtgctggta tttctcccac ctactgtatc ataggagctt 234,245,283 agattcccag ctgcttgctc tcagctgcag ttctctgATG GCTTGCACAG Exon 1 - start of gene 234,245,333 GGTGGACCAG CCCCCTTCCT CTATGTGTGT GTCTGCTGCT GACCTGTGGC 234,245,383 TTTGCCGAGG CAGGGAAGCT ACTGGTAGTG CCCATGGATG GGAGCCACTG 234,245,433 GTTCACCATG AGGTCGGTGG TGGAGAAACT CATTCTCAGG GGGCATGAGG 234,245,483 TGGTTGTAGT CATGCCAGAG GTGAGTTGGC AACTGGGAAG ATCACTGAAT 234,245,533 TGCACAGTGA AGACTTATTC AACTTCATAT ACCCTGGAGG ATCTGGACCG 234,245,583 GGAGTTCAAG GCTTTTGCCC ATGCTCAATG GAAAGCACAA GTACGAAGTA 234,245,633 TATATTCTCT ATTAATGGGT TCATACAATG ACATTTTTGA CTTATTTTTT 234,245,683 TCAAATTGCA GGAGTTTGTT TAAAGACAAA AAATTAGTAG AATACTTAAA 234,245,733 GGAGAGTTCT TTTGATGCAG TGTTTCTCGA TCCTTTTGAT AACTGTGGCT 234,245,783 TAATTGTTGC CAAATATTTC TCCCTCCCCT CCGTGGTCTT CGCCAGGGGA 234,245,833 ATACTTTGCC ACTATCTTGA AGAAGGTGCA CAGTGCCCTG CTCCTCTTTC 234,245,883 CTATGTCCCC AGAATTCTCT TAGGGTTCTC AGATGCCATG ACTTTCAAGG 234,245,933 AGAGAGTACG GAACCACATC ATGCACTTGG AGGAACATTT ATTATGCCAC 234,245,983 CGTTTTTTCA AAAATGCCCT AGAAATAGCC TCTGAAATTC TCCAAACACC 234,246,033 TGTTACGGAG TATGATCTCT ACAGCCACAC ATCAATTTGG TTTTTGCGAA 234,246,083 CGGACTTTGT TTTGGACTAT CCCAAACCCG TGATGCCCAA CATGATCTTC 234,246,133 ATTGGTGGTA TCAACTGCCA TCAGGGAAAG CCGTTGCCTA TGGTAAGTTA Intron 1 – end of Exon 1 234,246,183 TCTCTCCTTT AGCACCTTAA GAATACTTCA CCTTTGGAAA TTAAAAAAGG 234,246,233 ATTCTTTACT GAACTGTGAT TTGACATTTT CATTTGTTTC ATTTCAAATT 234,246,283 TCTTTCCAGT TTAACAAATT ATTTTGTGCC AATGCGTGTA CTCGTCAGTA 234,246,333 GCAAATTTTA TAAAACTGCC CTTCTTGAAG ATATGTATTT ATAACTTATA 234,246,383 AAATTGTGGA ACATATTCAG CCTACATTTT TAAGTACCAT GTTTAGAAAA Central Dogma of Molecular Biology Some terminology Phenotype – observable characteristic of an organism (other than genotype) Yellow versus green pea pods Measure of mood Number of copies of some RNA transcript inside the cell Gene – Unit that codes for proteins Allele – alternative forms of DNA sequence (e.g., Y and G for yellow/green pea pod color, or A1 and A2 for a generic allele 1 and allele 2) Locus – some region of the genome that harbors alleles Genotype – for humans, the two alleles one inherits at a locus Homozygotes (here either GG or YY; A1A1 or A2A2) Heterozygotes (GY or equivalently YG; A1A2) (for wheat, for example, 6 alleles [hexaploid])  Genetic Variation Locus where there is variation in alleles, giving rise to different genotypes in different people. Genetic Sources of Individual Differences 1) Generally termed “variants” 2) Single Nucleotide Polymorphism (SNP) 3) Repeats 4) Insertions/Deletions 5) Inversions 6) Large copy number variants 7) Variable number tandem repeats 8) Etc. Autosomal dominant, Monogenic A single copy of the “deviant” gene (i.e., allele) is sufficient to produce the disorder: Genotype A1A1 A1A2 A2A2 Phenotype Unaffected Affected Affected  Autosomal dominant Illustration using Punnett square A1 A2 A1A1 A1A2 A1 Unaffected Affected A2A1 A2A2 A2 Affected Affected Distinct familial pattern of familial transmission.  Penetrance Huntington’s Disease is considered a completely penetrant disorder because: Genotype A1A1 A1A2 A2A2 Disease Risk 0% 100% 100% (Penetrance)  Penetrance HD is considered a completely penetrant disorder because: Genotype A1A1 A1A2 A2A2 Disease Risk 0% 100% 100% (Penetrance) Disorder characterized by incomplete penetrance: Genotype A1A1 A1A2 A2A2 Disease Risk 0%