Genetic and Genetic and Environmental Environmental

Influences Underlying Influences Underlying DepressionDepression

Maya SubbaraoMaya Subbarao

EHS 504EHS 504

3-23-20053-23-2005

What do these people have in What do these people have in common?common?

Princess Diana, Mike Wallace, Tipper Princess Diana, Mike Wallace, Tipper Gore, Winston Churchill, Barbara Gore, Winston Churchill, Barbara Bush, Sir Isaac Newton, Winona Bush, Sir Isaac Newton, Winona Ryder, Bonnie Raitt, Drew Cary, Jim Ryder, Bonnie Raitt, Drew Cary, Jim Carrey, Paul Simon, Abraham Lincoln, Carrey, Paul Simon, Abraham Lincoln, Richard Dreyfuss, Oksana Baiul, Richard Dreyfuss, Oksana Baiul, Monica Seles, Ralph Nader, Jackson Monica Seles, Ralph Nader, Jackson Pollack, Judy Collins, Larry King…Pollack, Judy Collins, Larry King…

Who has depression?Who has depression?

Presentation OverviewPresentation Overview

What is DepressionWhat is DepressionMonoamine HypothesisMonoamine HypothesisThe Role of SerotoninThe Role of SerotoninUnderlying GeneticsUnderlying GeneticsCaspi et al. (2003) and Kaufman et Caspi et al. (2003) and Kaufman et

al. (2004)al. (2004)Genetic Testing ConsiderationsGenetic Testing Considerations

What is Depression?What is Depression?

Diagnostic and Statistical Manual of Mental Diagnostic and Statistical Manual of Mental Disorders-4Disorders-4thth Edition. (American Psychiatric Edition. (American Psychiatric Association, 1994)Association, 1994)

Allows clinicians to communicate and conceptualize Allows clinicians to communicate and conceptualize a disorder with a wide array of symptomsa disorder with a wide array of symptoms

Allows for agreement on symptoms that define a Allows for agreement on symptoms that define a disorderdisorder

Educational tool and reference in conducting clinical Educational tool and reference in conducting clinical trials, prevalence studies, and outcome researchtrials, prevalence studies, and outcome research

Not used to categorize and/or label individuals—Not used to categorize and/or label individuals—Remember a person has cancer, but is not cancer Remember a person has cancer, but is not cancer themselves.themselves.

What is Depression?What is Depression?

Among the top 5 leading causes of disability and Among the top 5 leading causes of disability and disease burden throughout the world (Tang and disease burden throughout the world (Tang and Lopez, 1997)Lopez, 1997)

Stressful events involving threat, loss, humiliation Stressful events involving threat, loss, humiliation influence onset and course of condition.influence onset and course of condition.

Diagnoses can be made on Diagnoses can be made on affective, behavioral, affective, behavioral, cognitive, somaticcognitive, somatic symptoms symptoms

Affective—depressed mood, feeling of Affective—depressed mood, feeling of worthlessness, guiltworthlessness, guilt

Behavioral—social withdrawal, agitationBehavioral—social withdrawal, agitation Cognitive—difficulty in concentration or making Cognitive—difficulty in concentration or making

decisionsdecisions Somatic—insomnia, hypersomniaSomatic—insomnia, hypersomnia

What is Depression?What is Depression? Focus on Major Depressive Disorder (MDD)Focus on Major Depressive Disorder (MDD)

Melancholic FeaturesMelancholic Features: at least three of the following: loss : at least three of the following: loss in pleasure in most activities, depressed in morning and in pleasure in most activities, depressed in morning and wake up agitated, extreme feelings of guilt, substantial wake up agitated, extreme feelings of guilt, substantial weight loss, affects men and women equally but more weight loss, affects men and women equally but more prevalent among the elderly, treated with antidepressants. prevalent among the elderly, treated with antidepressants.

Atypical FeaturesAtypical Features: brightened mood when good things : brightened mood when good things happen, at least two of the following: substantial weight happen, at least two of the following: substantial weight gain, sleeping too much, sensitivity to rejection, more gain, sleeping too much, sensitivity to rejection, more commonly seen in teens, women are 2-3 times more likely commonly seen in teens, women are 2-3 times more likely to be affected.to be affected.

SAD—symptoms begin in fall and end in spring, seen with SAD—symptoms begin in fall and end in spring, seen with recurrent MDDrecurrent MDD

Genetics of Depression—What Genetics of Depression—What we knowwe know

Complex mode of inheritance—multiple genes Complex mode of inheritance—multiple genes that interact with each other & environment?that interact with each other & environment?

Different susceptibility genes in different Different susceptibility genes in different familiesfamilies

Parameters of penetrance of the variant allele Parameters of penetrance of the variant allele and its frequency are unknownand its frequency are unknown

First degree relatives have 3 fold increase in First degree relatives have 3 fold increase in chance of developing MDD.chance of developing MDD.

Heritability of 40-70%Heritability of 40-70% Genetic factors may be shared with Genetic factors may be shared with

generalized anxiety disorders generalized anxiety disorders

Molecular Genetics of Molecular Genetics of DepressionDepression

Zubenko et al. (2003) found several loci Zubenko et al. (2003) found several loci that may underlie MDD—81 family studythat may underlie MDD—81 family study Concluded that “Gene products derived from…Concluded that “Gene products derived from…

genes that participate in cellular signaling genes that participate in cellular signaling pathways that converge on CREB and that allelic pathways that converge on CREB and that allelic variants of the downstream target genes of variants of the downstream target genes of CREB may affect the susceptibility of mood CREB may affect the susceptibility of mood disorders.”disorders.”

Abkevich et al. (2003) investigated 1890 Abkevich et al. (2003) investigated 1890 individuals from 110 pedigrees and discovered individuals from 110 pedigrees and discovered that 12q22-12q23.2 is a sex-specific disposition that 12q22-12q23.2 is a sex-specific disposition locus for MDD.locus for MDD.

Monoamine Hypothesis of Monoamine Hypothesis of DepressionDepression

““The underlying biological or The underlying biological or neuroanatomical basis for depression is a neuroanatomical basis for depression is a deficiency of central noradrenergic and/or deficiency of central noradrenergic and/or serotonergic systems and that targeting serotonergic systems and that targeting this neuronal lesion with an antidepressant this neuronal lesion with an antidepressant would tend to restore normal function in would tend to restore normal function in depressed patients” (Hirschfeld, 2000).depressed patients” (Hirschfeld, 2000).

Formulated over 30 years ago based on Formulated over 30 years ago based on the mechanisms of antidepressantsthe mechanisms of antidepressants

Formulation of the Monoamine Formulation of the Monoamine HypothesisHypothesis

1950’s research on lysergic acid 1950’s research on lysergic acid diethlamide (LSD) showed that this diethlamide (LSD) showed that this hallucinogen blocked peripheral hallucinogen blocked peripheral serotonin receptors.serotonin receptors.

Reserpine (antihypertensive agent) Reserpine (antihypertensive agent) depleted brain serotonin and depleted brain serotonin and increased 5-HIAA in urine, thus increased 5-HIAA in urine, thus inducing depressive symptoms in inducing depressive symptoms in individuals.individuals.

In 1951, isoniazid and iproniazid In 1951, isoniazid and iproniazid found to inhibit MAO, which found to inhibit MAO, which degrade serotonin and degrade serotonin and norepinephrine in tubecular norepinephrine in tubecular patients.patients.

By early 1960’s, use of tricyclic By early 1960’s, use of tricyclic antidepressants (TCAs) as reuptake antidepressants (TCAs) as reuptake inhibitors—drastic side-effectsinhibitors—drastic side-effects

Development of Selective Serotonin Development of Selective Serotonin Reuptake Inhibitors (SSRIs)Reuptake Inhibitors (SSRIs)

Although there are limitations to Although there are limitations to the hypothesis, it has been basis the hypothesis, it has been basis for current research on the for current research on the biological basis of depression.biological basis of depression.

Evidence of Serotonin’s Role in Evidence of Serotonin’s Role in the Monoamine Hypothesisthe Monoamine Hypothesis

Increase in density of postsynaptic 5-HTIncrease in density of postsynaptic 5-HT22 receptor receptor binding sites in frontal cortices of un-medicated binding sites in frontal cortices of un-medicated depressed patients (Stanley and Mann 1983).depressed patients (Stanley and Mann 1983).

5-HIAA levels lower than normal in CSF of 5-HIAA levels lower than normal in CSF of depressed patients (Lowther et al., 1997).depressed patients (Lowther et al., 1997).

Number of transporter sites reduced in platelets Number of transporter sites reduced in platelets of antidepressant-naïve depressed patients, but of antidepressant-naïve depressed patients, but no alteration of transporter sites in people with no alteration of transporter sites in people with atypical depression.atypical depression.

Gibbons and Davis (1984) show that Gibbons and Davis (1984) show that concentration of serotonin is reduced in concentration of serotonin is reduced in hypothalamus and amygdala of postmortem brain hypothalamus and amygdala of postmortem brain tissue in patients with depression.tissue in patients with depression.

Evidence for the Role of Evidence for the Role of SerotoninSerotonin

Studies conducted in which a Studies conducted in which a tryptophan-free drink was tryptophan-free drink was administered to patientsadministered to patients

67% of patients who were 67% of patients who were responding to antidepressants two responding to antidepressants two weeks prior to investigation, had weeks prior to investigation, had relapse in depressive symptoms relapse in depressive symptoms within 5-7 hours of trp depletion within 5-7 hours of trp depletion (Delgado 2000)(Delgado 2000)

Lack of depressive symptoms upon Lack of depressive symptoms upon trp depletion in un-medicated trp depletion in un-medicated depressed individuals and in depressed individuals and in healthy individuals—dysfunction healthy individuals—dysfunction not at level of neurotransmitter.not at level of neurotransmitter.

Benkelfat et al. (1994) showed that Benkelfat et al. (1994) showed that 30% of subjects who had a family 30% of subjects who had a family history demonstrated depressive history demonstrated depressive symptoms upon trp depletionsymptoms upon trp depletion..

Genetics of Depression—Genetics of Depression—Serotonin (5-HT)Serotonin (5-HT)

5-HT transport protein (5-HTT) is involved 5-HT transport protein (5-HTT) is involved in regulation of serotoninin regulation of serotonin

5-HTT expression mainly in cortical and 5-HTT expression mainly in cortical and limbic areas of brain associated with limbic areas of brain associated with behavior and emotionsbehavior and emotions

5-HTT encoded by SLC6A4 gene located on 5-HTT encoded by SLC6A4 gene located on chromosome 17q12chromosome 17q12

Serotonin and DepressionSerotonin and Depression Gene-linked polymorphic Gene-linked polymorphic

region called 5-HTTLPR, which region called 5-HTTLPR, which is located 5’ to the SLC6A4 is located 5’ to the SLC6A4 gene.gene.

5-HTTLPR site is composed of 5-HTTLPR site is composed of 16 repeat elements. The 16 repeat elements. The polymorphism results in either polymorphism results in either a 44bp insertion or deletion.a 44bp insertion or deletion.

Short (s) and long (l) Short (s) and long (l) Lesch et al. (1996) transfected Lesch et al. (1996) transfected

lymphoblastoid cells with lymphoblastoid cells with luciferase reporter and fused luciferase reporter and fused this to the 5-HTTLPR region. this to the 5-HTTLPR region.

Discovered that the l variant Discovered that the l variant had twice as much basal txn had twice as much basal txn than s variant.than s variant.

l/l were 30-40% more likely to l/l were 30-40% more likely to bind [bind [125125I]RTI-55 and 1.9-2.2 I]RTI-55 and 1.9-2.2 times more likely to take up times more likely to take up [[33H]5-HTH]5-HT

Lesch et al. (1996) Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Lesch et al. (1996) Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region. Sicen Region. Sicen

ScienceScience 274274: 1527-31.: 1527-31.

Influence of Life Stress on Influence of Life Stress on Depression: Moderation by Depression: Moderation by a Polymorphism in the 5-a Polymorphism in the 5-

HTT GeneHTT Gene

Caspi, A., Sugden, K., Moffitt, T.E., Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., Taylor, A., Craig, I.W., Harrington, H.,

McClay, J., Mill, J., Martin, J., Braithwaite, McClay, J., Mill, J., Martin, J., Braithwaite, A., and Poulton, R. A., and Poulton, R. ScienceScience (2003) (2003) 301301: :

386-89.386-89.

Caspi et al.’s Investigative Caspi et al.’s Investigative ApproachApproach

5-HTT may “moderate the serotonergic response to stress” 5-HTT may “moderate the serotonergic response to stress” even though it may not be directly associated with even though it may not be directly associated with depression.depression.

Three lines of evidence for a GXE interaction:Three lines of evidence for a GXE interaction:1) 1) -/- and +/- mice exhibited greater-/- and +/- mice exhibited greater

fear and elevated adrenocorticotropinfear and elevated adrenocorticotropin when responding to stresswhen responding to stress

2)2) -/- and +/- in Rhesus macaques correlated-/- and +/- in Rhesus macaques correlatedwith decrease in 5-HIAA in CSF in monkeyswith decrease in 5-HIAA in CSF in monkeysraised in stressful environments compared toraised in stressful environments compared tothose raised in non-stressful environments.those raised in non-stressful environments.

3)3) s/s and s/l had greater amygdala neuronal s/s and s/l had greater amygdala neuronal activityactivity

when exposed to scary pictures (Hariri et al., when exposed to scary pictures (Hariri et al., 2002).2002).

Neuronal Amygdala Neuronal Amygdala Imaging in Response to Imaging in Response to

Fearful StimuliFearful Stimuli

Hariri et al. (2002) Serotonin Transporter Genetic Variantion and the Response of the Hariri et al. (2002) Serotonin Transporter Genetic Variantion and the Response of the Human Amygdala. Human Amygdala. ScienceScience 297297: 400-403.: 400-403.

The Fearful StimuliThe Fearful Stimuli

Hariri et al. (2002) Serotonin Transporter Genetic Variantion and the Response of the Hariri et al. (2002) Serotonin Transporter Genetic Variantion and the Response of the Human Amygdala. Human Amygdala. ScienceScience 297297: 400-403.: 400-403.

Study DesignStudy Design 847 Caucasian, no-Maori from Dunedin 847 Caucasian, no-Maori from Dunedin

Multidisciplinary Health and Development StudyMultidisciplinary Health and Development Study Used life-history calendar to assess stressful Used life-history calendar to assess stressful

events between 21events between 21stst-26-26thth birthday birthday Stressful events included: relationship stressors, Stressful events included: relationship stressors,

education, employment, housing, financeseducation, employment, housing, finances 5-HTTLPR genotype did not influence exposure to 5-HTTLPR genotype did not influence exposure to

stressful events since no significant difference in stressful events since no significant difference in number of events experienced between groupsnumber of events experienced between groups

Diagnosed using DSM-IV criteria and Diagnositc Diagnosed using DSM-IV criteria and Diagnositc Interview ScheduleInterview Schedule

““Tested association between depression and 1)5-Tested association between depression and 1)5-HTTLPR genotype 2) stressful life events 3) their HTTLPR genotype 2) stressful life events 3) their interactioninteraction””

Caspi et al.’s ResultsCaspi et al.’s Results By age 26, self-reports of By age 26, self-reports of

depression were higher depression were higher for s/s and s/l individuals for s/s and s/l individuals (p<0.02)(p<0.02)

Carrying s allele Carrying s allele predicted MDD diagnosis predicted MDD diagnosis in individuals who did in individuals who did not have prior history of not have prior history of depression (p=0.002 for depression (p=0.002 for s/s and p=0.001 for s/l)s/s and p=0.001 for s/l)

Similar findings for Similar findings for suicide ideation and self-suicide ideation and self-reports of depressionreports of depression

Caspi et al.’s Results Caspi et al.’s Results Continued…Continued…

Lack of evidence for GXG interaction Lack of evidence for GXG interaction (ie: individuals have genetic (ie: individuals have genetic susceptibility to enter stressful events)susceptibility to enter stressful events)

If stressful events represented If stressful events represented influential environmental factors, then influential environmental factors, then depression should not be predicted depression should not be predicted prior to 21prior to 21stst birthday since life-events birthday since life-events were not assessed at this point were not assessed at this point

Evidence of GXE InteractionEvidence of GXE InteractionSelf-Reports of Depression Symptoms

Predictor Variables

Inter-cept

Sex 5-HTTLPR Life Events, ages 21-26 5-HTTLPR X Life Events

b se t p b se t p b se t p b se t p

Depression Symptoms, age 26

3.32 -2.44 0.69 3.53 0.001 0.49 0.75 0.65 0.52 2.57 0.48 5.39 0.001

-0.89 0.37 2.39 0.02

Depression Symptoms, age 21

6.39 -2.69 0.76 3.53 0.001 -0.07 0.83 -0.09 0.93 2.18 0.53 4.09 0.001

-0.53 0.41 1.29 0.20

Depression Symptoms, age 18

5.56 -4.20 0.70 6.01 0.001 0.30 0.76 0.40 0.69 1.67 0.49 3.40 0.001

-0.l7 0.38 0.44 0.66

5-HTT and Childhood 5-HTT and Childhood MaltreatmentMaltreatment

Interaction Interaction between 5-HTTLPR between 5-HTTLPR and maltreatment and maltreatment predicted predicted adulthood adulthood depression only depression only among s allele among s allele carrierscarriers

P=0.05P=0.05

Limitations of StudyLimitations of Study

Unable to test endophenotypes since Unable to test endophenotypes since it is difficult to take CSF it is difficult to take CSF

Environmental exposures hard to Environmental exposures hard to control and gene effects may be control and gene effects may be conditional on these exposuresconditional on these exposures

Further studies needed to confirm Further studies needed to confirm resultsresults

Social Supports and Social Supports and Serotonin Transporter Serotonin Transporter

Gene Moderate Gene Moderate Depression in Maltreated Depression in Maltreated

ChildrenChildrenKaufman, J., Yang, B.Z., Douglas-Palumberi, H., Kaufman, J., Yang, B.Z., Douglas-Palumberi, H.,

Houshyar, S., Lipschitz, D., Krystal, J.H., Gelernter, J.Houshyar, S., Lipschitz, D., Krystal, J.H., Gelernter, J.PNASPNAS 2004 2004 101101: 17316-17321: 17316-17321

Depression one of the most common sequelae Depression one of the most common sequelae reported in maltreated children.reported in maltreated children.

Caspi et al. (2003) focus only on adults with current Caspi et al. (2003) focus only on adults with current life-stressorslife-stressors

Studies have shown that non-human primates raised Studies have shown that non-human primates raised in stressful situations (peer-reared) with s allele show in stressful situations (peer-reared) with s allele show increased emotional distress, elevated HPA response increased emotional distress, elevated HPA response to stress, and basal serotonergic function (Barr et al., to stress, and basal serotonergic function (Barr et al., 2003).2003).

Purpose: Identify if the provision of social supports Purpose: Identify if the provision of social supports modifies the development of depression in modifies the development of depression in maltreated children.maltreated children.

ResultsResults

Maltreated children had significantly higher Maltreated children had significantly higher depression scores compared to CC’s.depression scores compared to CC’s.

l/s and l/l maltreated children only had l/s and l/l maltreated children only had slightly higher depression scores than CC’s slightly higher depression scores than CC’s of the same genotype. of the same genotype.

s/s maltreated children had depression s/s maltreated children had depression scores twice as high as both CC’s and scores twice as high as both CC’s and other maltreated children.other maltreated children.

s/s maltreated children with low social s/s maltreated children with low social supports had depression scores twice as supports had depression scores twice as high as CC’s of same genotype and social high as CC’s of same genotype and social situation.situation.

Contact with Primary SupportContact with Primary Support

Who the child talks to problems about, Who the child talks to problems about, buys items of need, spends time with/has buys items of need, spends time with/has funfun

20% maltreated children report seeing 20% maltreated children report seeing primary support less than a few times per primary support less than a few times per yearyear

Maltreated children with at least one s Maltreated children with at least one s allele and with minimal contact with the allele and with minimal contact with the primary support showed a 33% increase in primary support showed a 33% increase in depression scoredepression score

Is depression gendered?Is depression gendered? Caspi et al.’s (2003) study is hard to replicate Caspi et al.’s (2003) study is hard to replicate

because different populations are exposed to because different populations are exposed to different stressors at varying frequencies.different stressors at varying frequencies.

Women are twice as likely to suffer form an MDD Women are twice as likely to suffer form an MDD episode than men. (Kessler et al., 1994)episode than men. (Kessler et al., 1994)

Eley et al. (2004) showed that there is an Eley et al. (2004) showed that there is an increased risk for depression in adolescent increased risk for depression in adolescent females with the s/s genotype and exposed to females with the s/s genotype and exposed to high environmental risk, but not for males.high environmental risk, but not for males.

Grabe et al. (2005) Study of Health in Pomerania Grabe et al. (2005) Study of Health in Pomerania (SHIP) showed that s-allele increased depression (SHIP) showed that s-allele increased depression scores for females, but not males, who had low scores for females, but not males, who had low social support and were facing unemployment social support and were facing unemployment (with genotype—22.8% variation in BL-38 score, (with genotype—22.8% variation in BL-38 score, without genotype—20.9%)without genotype—20.9%)

Overarching ConclusionsOverarching Conclusions

s-allele confers a vulnerability to s-allele confers a vulnerability to depression in individuals with life history depression in individuals with life history of stressof stress

Under non-stressful conditions, s allele Under non-stressful conditions, s allele does not increase/decrease risk for does not increase/decrease risk for depressiondepression

Negative sequelae associated with stress Negative sequelae associated with stress during early developmentduring early development

Social support may be used to promote Social support may be used to promote resiliency.resiliency.

Drug Therapies for Drug Therapies for DepressionDepression

Selective Serotonin Reuptake Inhibitors:Selective Serotonin Reuptake Inhibitors:

-Fluoxetine (Prozac)-Fluoxetine (Prozac)

-Paroxetine (Aropax)-Paroxetine (Aropax)

-Citalopram (Cipramil)-Citalopram (Cipramil)

-Fluvoxamine Sertraline (Zoloft)-Fluvoxamine Sertraline (Zoloft) Prevents reuptake of 5-HT at the nerve Prevents reuptake of 5-HT at the nerve

synapsessynapses Takes 2-6 weeks to see anti-depressant Takes 2-6 weeks to see anti-depressant

effects—which is a reason for non-effects—which is a reason for non-compliance.compliance.

SSRI’s and DepressionSSRI’s and Depression

If the s-allele of 5-HTTLPR reduces If the s-allele of 5-HTTLPR reduces txn of the transporter, how can txn of the transporter, how can SSRI’s have a therapeutic effect?SSRI’s have a therapeutic effect?

Smeraldi et al. (1998) showed that l/l Smeraldi et al. (1998) showed that l/l and l/s individuals had better and l/s individuals had better response to fluvoxamine alone than response to fluvoxamine alone than s/s individualss/s individuals

Fluvoxamine and pindolol improved Fluvoxamine and pindolol improved outcomes for all genotypesoutcomes for all genotypes

Why is that?Why is that? Hypothesize that SSRI’s Hypothesize that SSRI’s

stimulate increase in 5-HT at the stimulate increase in 5-HT at the raphe nuclei—activates raphe nuclei—activates somatodendritic 5-HTsomatodendritic 5-HT1A1A autoreceptors—negative autoreceptors—negative feedback.feedback.

5-HTT mRNA abundant in dorsal 5-HTT mRNA abundant in dorsal raphe nucleus, the initial site of raphe nucleus, the initial site of the negative feedback “as its 5-the negative feedback “as its 5-HT neurons project into the HT neurons project into the frontal cortex and are very frontal cortex and are very sensitive to self inhibition by 5-sensitive to self inhibition by 5-HTHT1A1A autoreceptors” autoreceptors”

In s/s individuals the same SSRI In s/s individuals the same SSRI dose leads to hyper negative dose leads to hyper negative feedback.feedback.

Pindolol is 5-HTPindolol is 5-HT1A 1A antagonist and antagonist and prevents negative feedbackprevents negative feedback

Genetic Screening for Genetic Screening for susceptibility to depression: can susceptibility to depression: can

we and should we?we and should we?

Morley, Hall, Carter (2004) Morley, Hall, Carter (2004) Australian and Australian and New Zealand Journal of PsychiatryNew Zealand Journal of Psychiatry 3838: 73-80.: 73-80.

DSM-IV broad definitions mean that people DSM-IV broad definitions mean that people can develop the disorder through different can develop the disorder through different “pathological pathways with different genetic “pathological pathways with different genetic contributions.”contributions.”

Problems of genetic heterogeneity, gene-Problems of genetic heterogeneity, gene-gene interaction, cultural differences in gene interaction, cultural differences in expressionexpression

Genetic Testing?Genetic Testing? We do not have We do not have

preventative preventative pharmacological pharmacological treatments—problems treatments—problems of cross-talkof cross-talk

Genetic testing can Genetic testing can disrupt family disrupt family dynamics, particularly dynamics, particularly for minors. Parents for minors. Parents may lower their may lower their expectations for their expectations for their child and alter how child and alter how they relate to the child they relate to the child (Cohen 1998). (Cohen 1998). Stigmatization and Stigmatization and discrimination?discrimination?

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