GENETIC BASIS OF DEPRESSION

Introduction:
	Depression is a mood disorder that is characterized by 
significant impairments in life due to a variety of symptoms. These 
symptoms include disrupted sleeping, diminished libido, weight gain or 
loss, excessive or inappropriate guilt, and anhedonia (Barlow & Durand, 
1999). Major Depressive disorder may begin at any age but it typically 
has initial onset in the mid-twenties. It may be an isolated episode or 
it may be recurrent. These episodes may end completely (about two-
thirds of cases) or may partially remit (about one-third of cases) (DSM 
4 T-R, 2000). Major depressive disorder is associated with high 
mortality. Up to 15% of individuals with severe major depressive 
disorder die by suicide.  There is a familial pattern associated with 
depression that will be discussed during the first portion of the 
paper. There is also unaccounted for variance in depression that can be 
explained with environmental factors. The debate of polygenetic versus 
monogenetic influences will be discussed. Research designs will be 
discussed at length as well as the advantages and disadvantages of 
research designs to measure and describe depression.

Theoretical arguments concerning genes involvement in human behavior: 
Nature or Nurture and Depression.
By Jennifer Benzle

There is no use in questioning whether depression is due solely 
to genetic factors or solely to environmental ones. The investigation 
now lies in how many factors from each source contribute and 
interrelate to result in clinical depression and if there are genes or 
a gene specifically (that is universally) responsible for depression. 
The most useful data in illuminating the nature/nurture debate and 
depression has come from familial studies, including mono and dizygotic 
twin analyses. Kalat writes that both depression and bipolar disorder 
run in families. Approximately 10 to 20 percent of the parents, 
brothers and sisters of depressed and bipolar patients suffer from 
these disorders themselves. An interesting point brought out by Kalat, 
and one that is a theme in the literature, is that while certain genes 
may exist that predispose people to become depressed, other genes act 
in a way that could lead to any several psychological disorders. In 
other words, there may be genes that are specifically responsible for 
depression, or there may be genes that are responsible for behavior or 
other phenotypes that could lead to depression, such as alcoholism or 
other substance abuse (1995).
There are myriad factors that indicate a genetic basis for 
depression. There are abnormalities of hemispheric dominance. During 
depression, the rate of glucose metabolism (a good indicator of overall 
brain activity) is lower than normal, especially in the left frontal 
lobe and parts of the temporal and parietal lobes (Kalat, 1995). This 
brain biology strongly indicates genetic causes. Another factor that 
indicates a genetic basis is heritability. There are many studies that 
have described the correlation between relatives and incidence of 
depression. Carlson (1999, p.526) summarized some findings.  "Rosenthal 
(1971) found that close relatives of people who suffer from affective 
psychoses are ten times more likely to develop these disorders than 
people without afflicted relatives. Gershon et al. (1976) found that if 
one member of a set of monozygotic twins was afflicted with an 
affective disorder, the likelihood that the other twin was similarly 
afflicted was 69 percent. In contrast, the concordance rate for 
dizygotic twins was only 13 percent. Furthermore, the concordance rate 
for monozygotic twins appears to be the same whether the twins were 
raised together or apart." 
While the genetic bases are pretty clear, they do not account for 
the significant variability in depression. Using the statistics 
mentioned by Kalat, 31 percent of monozygotic twins escaped an 
affective disorder (1995). Therefore there must be other factors than 
heredity since the genetic make-up of the twins is 100 percent 
concordant. Another statistic specifically for depression is that if 
one identical twin has a serious depression, the other twin has a 65 
percent chance of experiencing depression (Mental Health Net, 2001). 
This approximate 35 percent then begs the question, what factors were 
involved that prevented this disorder? Your general level of depression 
is partly inherited, but not your level of happiness. Conscious efforts 
can influence ones level of happiness regardless of the genetic 
messages (Mental Health Net, 2001).
Some environmental correlations with sub-clinical depression are 
poor health, a reduced ability to deal with ones own private troubles, 
and structural poverty. Social experiences that are governed by 
people's own socially-situated choices and by the social constraints by 
which they live their lives were measured and described in a study of 
urban deprivation. What the scientist found was that there were several 
constraints on the population's well-being. These constraints were 
"poor health, living alone, financial penury, unsatisfactory social and 
emotional ties, private troubles, and so on." (Tulle_Winton, p. 168, 
1997). These constraining factors operated at three different levels.  
At the individual level, Tulle_Winton writes that these environmental 
factors affected the resident's ability to cope with a range of 
personal problems or private troubles. At a community level, they put 
residents at greater risk of experiencing a range of problems, and at a 
societal level these constraints confirmed the impact of the 
socioeconomic characteristics of the Glasgow conurbation on the well 
being of particular population groups. These factors are all predictors 
for at risk individuals for sub clinical depression (1997). 
In another study, the question of to what extent genetic 
influences, shared environmental influences, or unique environmental 
influences accounted for the variability in depressive symptoms was 
asked. The results were that shared rearing environment played a 
significant role indicating that early experiences shared by family 
members shape individual differences in depressive symptoms later in 
life. The author noted that the statistically most important influence 
on self reported depressive symptoms was nonshared experiences, the 
sorts of life events that happen uniquely to each person in the course 
of living. In this study only 16 percent of the variance in depressive 
symptoms was attributable to genetic differences. Influences not shared 
by family members accounted for most of the variance but there was also 
a high contribution of shared family influences. Another interesting 
finding was that there was a curvilinear relationship for age and 
depression. The highest depression scores were found in the youngest 
and oldest cohorts (Gatz, Pedersen, Plomin, Nesselroade, McClearn, 
1992). 
A third study measuring monozygotic male twins observed that all 
of the environmental variance, not explained by genetic influences, was 
due to nonshared environmental influences (Swan, Hayes, wolf, Reed, 
Miller, 2000). The unique life events that are experienced seem to have 
tremendous impact and to account for some of the variance in 
depression.
While clinical depression is most certainly partly due to genetic 
factors, location of a particular gene or genes responsible for the 
disorder has not yet been discovered. Heritability, brain biology and 
drug effects have all been substantial indicators for a genetic basis 
for depression. But it is also clear through the variation in 
monozygotic twin's concordance of depressive symptoms, that there must 
be more to depression than genetics. Some environmental influences that 
may predict that variation are, unique life experiences, structural 
poverty, and weak social and emotional ties.
 In closing, an eloquent and meaningful description that I once 
heard from a psychiatrist comes to me, for it applies beautifully to 
depression. He said that there are brain disorders and there are mind 
disorders. Brain disorders are biological and treatable by medication 
and can be traced down to genetic roots. Mind disorders are cognitive, 
personality, and perhaps even spiritual chaos or malfunction and can 
only be solved from within by that individual who has the experience. 
Through reading research on depression from a nature/nurture 
perspective, I cannot help but to conclude that this seems to be a 
disorder that is both a mind and a brain problem. In this scientific 
context, what that observation would translate into, is that depression 
is both an environmental and genetic affliction.        
         
 
References:
	Barlow, D. H., Durand, M. V. (1999). Abnormal Psychology (2nd 
ed.). Pacific Grove, CA: Brooks/Cole.
American Psychiatric Association. (2000). Diagnostic and 
statistical manual of mental disorders (Fourth Edition, Text 
Revision.). Washington, DC, American Psychiatric Association, 2000. 
Kalat, J. W. (1995). Biological psychology  (5th ed.). Pacific 
Grove, CA: Brooks/Cole. 
Carlson, N. R. (1999). Physiology of behavior (6th ed.). Needham 
Heights, MA: A Viacom Company.
Carmelli, D., Swan, G. E., Kelly-Hayes, M., Wolf, P. A., Reed, 
T., Miller, B. (2000). Longitudinal changes in contribution of genetic 
and environmental influences to symptoms of depression in older male 
twins. Psychology and Aging, 15 (3), 505-515
Gatz, M., Pedersen, N. L.,  Plomin, R., Nesselroade, J. R., 
McClearn, G. E. (1992). Importance of shared genes and shared 
environments for symptoms of depression in older adults. Journal of 
Abnormal Psychology, 101(4), 701-708.
Tulle-Winton, E. (1997). Happy in Castlemilk? Deprivation and 
depression in an urban community. Health and Place, 3(3), 161-170.
Psychological Self-Help Http://www.mentalhelp.net


Multigenetic Influences of Major Depression
By Debra Pizzuto

	Making the distinction between cognitive disturbance, a thought 
disorder, and disturbance of emotion is important for classification of 
mental illness.  Mood disorders seem to have a strong genetic 
predisposition.  Psychiatric genetics continues to dissect complexity 
of behavior disorders, though many strategies have delivered false 
starts which have brought to the field, a more critical understanding 
of the difficulties of applying linkage to disease.  The most common 
disorders of mood and affect are depression and mania.  Unipolar (most 
likely several mood disorders) characterized by an unpleasant 
(dysphoric) mood that is present most of the day,day in day out, with 
accompanied mental anguish, the inability to experience pleasure 
(anhedonia), and generalized loss of interest in the world.  Diagnosis 
requires at least three of the following: disturbed sleep, diminished 
appetite and weight loss, or overeating, loss of energy, decreased sex 
drive, restlessness, slowing down of thoughts and actions, difficulty 
concentrating, indecisiveness, feeling of worthlessness, guilt, 
pessimistic thoughts, and thoughts of dying and suicide bipolar (manic 
depressive) have a morbidity rate slightly higher in first degree 
relatives (parents, siblings, and children) of patients with depressive 
illness than that of the general population. Untreated, an episode of 
depression usually lasts about 4-12 months (Kandel et al 1210).  
Melancholic depression (endogenous) is a disorder with the clearest 
subtype among the major depressions, accounting for 40-60 percent of 
people treated for unipolar depression. It cannot easily be associated 
with environmental causal circumstances.  Bebbington et al.,1988 
concludes that melancholic depression symptoms, especially those that 
precede adverse life events, are not that simple. Data remains somewhat 
confusing in terms of supportive and contradictory results.
	Current researchers agree that genes contribute to neural 
circuitry of behavior in their ability to replicate reliably, by making 
precise copies of themselves to all cells in an organism and it's 
future generations.  Each gene in a cell also directs the manufacture, 
function and biological characteristics of the cell.  The human body 
contains approximately 80,000 genes.  DNA of each gene encodes protein 
arranged in an order on structures called chromosomes.  The genetic 
makeup, or specific alleles of one gene is termed (genotype).  The 
appearance and functional expression(phenotype) may change though out 
life.  Certain mutations are pathogenic, leading to disease (Kandel et 
al.,2000).  Many early experiments on single gene alleles encode normal 
behavioral variations in animals.  Defects in single genes can have 
profound effects on complex behaviors. Classic genetic analysis focuses 
on Mendelian traits, normally determined by allelic variation within a 
single gene.  Linking the genetic influence to a chromosome marker has 
not been entirely successful (Martin, 1998).  Most behavioral traits as 
well as common genetic disorders seem to be multigenetic: determined by 
several genes interacting with the environmental factors.  Multigenetic 
includes oligogenic and polygenic traits. Oligogenic is determined by a 
small number of genes, each contributing to the phenotype). and 
polygenic traits.  Oligenic (which is a result of multiple genes, each 
with a small effect on the phenotype).  The basic biological fact 
underlying psychiatric genetic research is the existence of genetic 
polymorphism which alters molecular function and influences behavior 
(Martin 1998).  Multigenetic diseases, including manic depressive 
disorder, are both etiologically (cause or origin)and genetically 
represented by mutant alleles and environmental factors thought to 
produce indistinguishable phenotypes. 
	The basic process of identifying genes related to illness or 
phenotype involves detailed statistical analysis of frequencies 
depicting certain specialized samples including affected individuals 
(Gelernteer & Goldman, 2000). Diagnostic misclassification within the 
diagnostic boundaries of many psychiatric disorders is obscured by a 
spectrum of conditions that are genetically related to the core 
illness.  For example, bipolar I illness may be genetically related to 
bipolar II, major depressive disorder,and schizoaffective disorder, and 
cyclothymic disorder,(alteration of depressed moods with elevated, 
expansive, or irritable moods without psychotic features).  This proves 
to be problematic because relationships introduce heterogeneity into 
the research study.  At present, according to Raymond Crowe, M.D., none 
of the biological markers in psychiatry can replace or extend clinical 
diagnosis in linkage studies.  He states that diseases as common as 
depression and alcoholism are likely to include a large proportion of 
phenocopies (environmental copies of genetic traits).  Inappropriately, 
they create a broad range of definitions.  The net effect of 
phenocopies weakens the power to detect linkage. 
	Biological facts underlying psychiatric genetic research is the 
existence of genetic polymorphism which alters molecular function and 
influences behavior. DNA variation inherited from parents to offspring 
accounts for heritability traits are usually measured as a proportion 
of population variance.  Kendal(2001) terms this as a prekindling 
effect.  His genetic studies of monozygotic and dizygotic twins, 
siblings, and parents with kindled state may be provoked by episodes 
reached by two pathways: many previous depressive episodes, perhaps 
driven by multiple adversities and high genetic risk.  Gender effect 
does not apply.  Both men and women are susceptible to major 
depression.  Gene expression is modified by biological and cultural 
differences between the genders (Kendler 2001).  
	Genetic mapping and linkage analysis provides researchers with a 
full range of expression from family, twin, and adoption studies.  
McGuffin and Katz (Crowe) studied twelve families with bipolar illness 
reporting the average risk among first degree relatives(parents, 
siblings, and children) to be 7.8% for bipolar and 11.4% for unipolar 
illness.  In comparison, they concluded that over the respective 
population approximately 1% to 3%.  Bipolar illness for monozygotic 
twins ranged from 62 to 72 percent, with an additional unipolar range 
from zero to 11%.  Their observations of adoptees supports the role of 
genes in bipolar illness.  Increased rates are seen in biological 
parents but not in adoptive parents of bipolar adoptees.  
	Large bipolar pedigrees have been discovered among Old Order 
Amish.  Genetically isolated populations are ideal for linkage studies.  
Their gene pools are typically homogenous (Crowe).  A gene appears to 
be found for bipolar illness with two DNA markers (HRAS and INS) on the 
short arm of chromosome 11.  Later studies have failed to replicate 
this finding.  One possible explanation for these newer findings is the 
possible inclusion of unipolar depression in the affected phenotype.  
Unipolar depression is an expression of bipolar genotype.  The high 
population prevalence of depression could introduce cases into the 
pedigree that are unrelated to the bipolar gene because of marriage.  
The failure of other linkage supports this explanation (Crowe).  
	The X-linkage hypothesis for manic depressive illness was 
introduced over twenty five years ago.  Pekkarinen et al. found 
evidence for susceptibility locus in a large bipolar pedigree in 
Finland.  Continued research will most likely explain genetics by 
multiple genes of small effect acting in concert to cause disease.  
Now, the most promising region for manic depression is the 
pericentromeric region of chromosome 18.  Most of these studies have 
evolved from linkage from the fathers side of the family (Crowe).  
According to Dr. Crowe, genome significance of 0.05 level could be 
expected to occur by chance in one out of twenty genome searches.  The 
significance levels reported in his data for these broad regions on 
chromosome 18 do not support confirmed linkage.  It is premature to 
conclude at this time(Crowe).  His meta analysis retains also some 
significance of another region on the long arm of chromosome 21.
	The process of discovering disease genes in psychiatry is likely 
to require collaboration of the sciences with productive interaction of 
existing methods and strategies. Certain major depressive illnesses may 
be the result of genetically determined defects in chemical synaptic 
transmission involving at least two major transmitter pathways of the 
brain, the serotonergic and noradrenergic systems.  Variations in 
genes, DNA systems, represent the basis for evolutionary change and the 
basis for individual differences in risk for many genetically complex 
diseases that confront neurology and psychiatry.


                        References
	Crowe, Raymond R. (2000). Genetics: A hypertext. Retrieved from 
the web 03/03/01. http://www.acnp.org/G4/GN401000091/CH.html
	Gelernter, Joel, & Goldman, David.  Psychiatric Genetics: A 
hypertext. Retrieved from the web 03/03/01.  
http://www.acnp.org/G4/GN401000091/CH.html
	Kandel, Eric R., Schwartz, James H., & Jessell, Thomas M.(2000). 
Principles of Neural Science 4th ed. Chicago: University of Chicago 
Press.
	Kendler,K.S., Thorton, L.M., & Gardner, C.O.(2001).Genetic risk, 
number of previous episodes, and stressful life events in predicting 
onset of major depression.  American Journal of Psychiatry 
Apr;158(4):582-6
	Martin, Neil G. (1999) Human Neuropsychology. Great Britain: 
Prentice Hall
	Weissman, M.M. & Wickramaratne, P. (2000). Age of onset and 
familial risk in major depression.  General Psychology May vol.57(5)

Research designs utilized to investigate the effects of genes & 
behavior.
By Teena George
	
In 1989 Congress passed Public Law 101-58 declaring the "Decade 
of the Brain", which opened the doors for more quality research on 
brain disorders.  Rapid advancement proved several research advances in 
the identification of complex anatomical connections: understanding the 
biochemical molecular and genetic mechanisms that control brain 
structure and functions; the ability to measure and visualize human 
brain functioning during mental activity; and the capacity to monitor 
neural activity simultaneously in complicated networks of neurons. 
(Blank, 1998) The 1990's proved to show great strides in treating 
neural diseases and disorder, increasing global knowledge, and the 
ability to help predict, modify, and control behaviors.  
Research that implicates specific mental or mood disorders often 
turn to genes and environment.  Determining the effects of whether it 
is heredity, upbringing, or environment is rather hard to pinpoint 
because there is no way to test such pure singularities.  There is also 
the genetic complexity in which non-genetic factors act together with 
multiple genes to produce a mental disorder like depression.  Research 
for such a disorder might want to look at timing and expression of risk 
genes, possibly BRCA1 and BRCA2 since they are known to be gene 
mutations, during brain development.  People are highly unique, but 
there are enough similarities between each individual to facilitate an 
investigation of cause and effect of specific behaviors and mental 
disorders.  

Genetic research is described through several different kinds of 
designs.  Other research designs are looking for genetic connections.  
It has been well established that mental illnesses run in families.  
Family, twin, and adoption studies have been used to prove these 
genetic connections.  Genetic research discovers a multitude of 
biological reasons for our behaviors. Genetic research examines 
phenotypes, observable characteristics or behaviors, and genotypes, 
unique genetic makeup of an individual.  The transmission of risk is 
due to heredity.  Different combinations of genes may influence 
vulnerability in different families.  The basic need for genetic 
studies are helpful to identify and clone genes that contribute to such 
disorders.  Information is often obtained from an identified affected 
individual, the family, or and entire population of individuals 
affected.  They tend to look for the risk or candidate genes.  
Future Research 

A researcher that is looking for a mood-gene would design a 
research around a single family or an isolated population that is prone 
to manic-depressive, then analyze their DNA for a comparison between 
genetic markers and pre-existing disorder.  If there is a link then the 
researcher knows a mood gene appears close to that marker on a 
particular chromosome.  The mood-gene testing is still fairly new but 
has proven to be useful in diagnosing manic-depression.  Other 
fascinating discoveries are just around the corner with this new 
research because once they are able to determine an understanding of 
the proteins, enzymes, and hormones genes produce then they can create 
a new category of drugs with completely different molecular targets.  
They have already found evidence of "hot spot" for mood-genes located 
in the "long arm" of chromosome 18, and other studies reveal areas on 
chromosome 4, 6, 13, and 15.  Samuel H. Barondes writes; "In the long 
run a major benefit of mood-gene discovery may be the prevention of all 
symptoms of manic-depression – even initial attacks, may not just be 
used to foretell our destinies, but also to forestall them," (Barondes, 
1999).
Genetic epidemiology is the study of aetiology, distribution, and 
control of disease in groups of relatives and of inherited causes of 
disease in populations.  Currently, there are several intensive studies 
being conducted on genes affecting people's susceptibility to disease.  
Family studies help reveal backgrounds of genetic traces, give a better 
understanding of the genetic contribution to the intermediate 
phenotypes linking genes and disease, and the overall biology of the 
disorder.  They believe they will be able to predict developments in 
the next 5-10 years using genetic epidemiology research.  Twin studies 
are comparisons of similarities between monozygotic and dizygotic twin 
pairs (see the website of International Society for Twin Studies, 
www.ists.qimr.edu.au ).  Adoption studies are equally used to show a 
comparison of disease rates in the biological parents and foster 
parents of adoptees, and in their biological and adopted siblings.  
Many times the reported associations between a gene and disease are not 
consistently replicated, and then the need to use both meta-analyses 
and large studies to establish their true existence.
Animals render very helpful in determining information about 
human beings.  Scientists have invented several components to exploring 
the brain of an animal.  The stereotaxic instrument is useful for 
recording brain activity.  These devices can be used on many animals 
but the most common animals are the rat, mouse, cat, and monkey. When 
scientists are looking for neurochemical answers they often use 
specific designs for measuring animals brain activity.  Microdialysis, 
measuring the concentration of chemicals in a small area and 
autoradiography is method used to determine where a chemical is 
located.  Immunohistochemistry is used to label types of tissues in the 
immune system.  Research on animals have given us many answers to 
questions about behavior and disabilities.  The most common research 
techniques for examining behaviors are: before and after brain damage; 
behavior after extra stimulation to an area in the brain; and 
correlational findings can inform us about a relationship.  Whether it 
exists between two variables or not.  One way of looking at 
correlations could be between spontaneous brain activity (one variable) 
and spontaneous behavior (another variable).  Epidemiology research 
reveals incidences, distribution, and consequences of a particular 
problem in one or more populations using correctional studies.  
Tracking a disorder among many people helps give clues as to why the 
disorder exists.  Experiments also give us a chance to control a 
situation and determine an outcome.  Sometimes the outcome may not be 
what the research is expecting to find but through trial & error and 
replication we can overcome these inconsistencies. Another type of 
research is called descriptive; this is designed to describe the 
thoughts, feelings, and behaviors of individuals.  We can use case 
studies, questionnaires, surveys, and scales to enhance the study.  
Other forms of research include cross-sectional (comparisons made 
across different age groups at the same time) and longitudinal 
(individuals measured over a long period of time).  All research is 
used in conjunction with another enabling the designer to manipulate 
the situation to fit the needs of the design.  The main purpose of 
research is to gain specific methods of collecting, analyzing, and 
interpreting data. 
When measuring human activity much information has been 
contributed by the inventions of measure through magnetic imaging.  
Electroencephalography (EEG) records electrical activity through 
electrodes attached to the scalp.  Magnetoencephalography (MRI) is used 
to measure magnetic fields in the brain and positron-emission 
tomography (PET) provides a high-resolution image of the brains 
activity.  These designs are used to show differences in the brains 
activity.  Another research solution, the Gavenic Skin Response, was 
invented to measure the skin reactions to various stimuli.  These 
devices are all used in conjunction of tasks being given, causing 
stimulation, or verbal expressions.  
Ethics in research has important rules and regulations for 
subjects, people or animals, which participate in these studies.  The 
Code of Ethics (APA, AMA) must ensure the well being of its subjects 
both mentally and physically.  The APA published the Ethical Principles 
of Psychologists, which are the general guidelines for conducting 
research.  The Society for Research in Child Development has guidelines 
of their own for children.  
In conclusion, depression has a cascade of affects that have a 
spurious relationship (explains the relationship between the predictor 
and outcome variables) with the environment, upbringing, as well as 
genetic factors.  The brain is very complex to investigate that it is 
essential to use devices and research practices on humans and on 
animals to discover new information.  There are so many interactions 
between mental illnesses that developing research to investigate 
combinatorial interactions like non-linear, gene-gene, and gene-
environment.  This is why establishing critical information about genes 
and environment is most effective for finding clues on mental 
illnesses, such as depression.  Genes are critical to the development 
of the overall circuit maps and functions of the brain.  Variations and 
fluctuations in the environment contribute to these various functions.  
Some designs are able to measure and investigate different behaviors or 
genes better than others are, but the information retrieved or 
discovered from all of the designs is what makes all research 
indispensable.  There has to be reasons for why everyone doesn't get 
depressed like everyone else and these are questions that are being 
answered everyday in the sciences.  Research is essentially the best 
way of gaining knowledge.

References
Carlson, Neil R. (1998)Physiology of Behavior, sixth edition.  Allyn 
and Bacon.  University of Massachusetts
Barlow, David H./Durand, Mark V. (1999) Abnormal Psychology, 
Brolks/Cole Publishing.  Boston University/State University of New York
Kalat, James W. (1998) Biological Psychology, sixth edition.  
Brooks/Cole Publishing.  North Carolina State University
Stangor, Charles (1998) Research Methods.  Houghton Mifflin Company.  
University of Maryland
Mood Genes: Hunting for Origins of Mania and Depression by Samuel H. 
Barondes.  www.wfs.org/specials.htm on the web.

Advantages and Disadvantages of Specific Research Designs of Depression
Tara Thelen

	Many research designs have been conducted over the past several 
years in order to determine the genetic basis of depression.  Different 
types of studies enable researchers to explore risk factors of 
depression, and formulate theories for further research.  When 
conducting studies on depression, one will find some research designs 
to be more advantageous than others depending on what they are looking 
at.  Advantages and disadvantages of specific research designs to 
determine the risk factors for depression will be discussed.  
	The first study I examined was "Genetic Risk, Number of Previous 
Episodes, and Stressful Life Events in Preceding Onset of Major 
Depression" by Kendler, Thorton, et al..  This was a longitudinal 
population based twin study to examine the interaction between genetic 
risk, stressful life events, and previous depressive episodes in the 
prediction of onset of major depression.  The researchers interviewed 
Caucasian female twins four times over a nine-year period.  Subjects 
were asked to date the onset and offset of each depressive episode they 
encountered over the nine year period.  
	There are many advantages of conducting a longitudinal twin 
study.  First, twin studies compare the concordance rates of 
monozygotic and dizygotic twins for depression (Carlson). Therefore, 
the researcher is able to determine whether depression is actually 
influenced by heredity or the environment.  Second, a longitudinal 
study enables the researcher to examine subjects over a long period of 
time.  Therefore, researchers are able to estimate the heritability of 
depression symptoms at a baseline and follow up, test for an increase 
in heritability with and increase in age, and determine the extent to 
which genetic and environmental influences at an early age are 
transmitted to an older age(Carmelli, et al).
	Longitudinal studies often pose a threat to the internal validity 
of the design.  Three of these threats include maturation, changes in 
the participants over time, test sensitization, subjects learning from 
prior tests or interviews, and attrition, subjects leaving the study 
over time.  Subject attrition in this study was about 12 percent.  In 
addition to these disadvantages common to all longitudinal research 
designs, there were several limitations specific of this study.  First, 
this study was limited to female Caucasians and may not extrapolate to 
male subjects or other ethnic groups.  Second, the researchers treated 
all stressful life events as equal despite the fact that they greatly 
differ in strength of their association with major depression.  The 
study contained no direct measure of the pattern of depressive episode 
onsets as they became autonomous and less linked to environmental 
adversity.   Despite these limitations, this study was well conducted, 
and the final results were consistent with the hypothesis. 
	The second research study I examined was "Genetic Epidemiology of 
Major depression: Review and Meta-Analysis" by Sullivan, et al..  A 
meta analysis of data from primary studies of the genetic epidemiology 
of major depression was conducted.  The researchers viewed previous 
articles on family, adoption, and twin studies and derived quantitative 
summary statistics of this data.  
	There are many advantages of a meta analysis. It enables 
researchers to study existing scientific research and then using this 
existing knowledge to generate new research information. In addition, 
research that is based on previous research findings tends to advance 
science more rapidly because it contributes to the accumulation of an 
integrated body of knowledge.  Another advantage of a meta analysis is 
the potential to yield a less biased quantitative summary of the data 
(Sullivan, et al).
	This meta-analysis focused on three specific reviews including 
family, adoption, and twin studies.  These are all powerful methods for 
estimating the influence of heredity on depression.  In family studies, 
the researcher is able to determine whether there is an association 
between major depression in subjects and in their first-degree 
relatives.  One disadvantage of this type of study, known as a case 
control study, is that the subjects are often not matched with a 
comparison group on the basis of age, gender, and the prevalence of 
major depression in biological relatives.  Adoption studies compare 
people who were adopted early in life with their biological and 
adoptive parents.  If the subjects resemble their biological parents, 
evidence is seen for genetic factors.  If the subjects resemble their 
adoptive parents, evidence is seen for a role of factors in the family 
environment (Carlson).  Finally, twin studies compare the rate of 
depression in monozygotic and dizygotic twins.  Again, this enables the 
researcher to identify to what degree heredity or environment is the 
cause of depression.  One potential threat to twin studies is the equal 
environment assumption.  This assumption relies on the fact that 
monozygotic and dizygotic twins share very similar environments.
Similarities between monozygotic versus dizygotic twins for expression 
of major depression could result from environmental and not genetic 
factors (Sullivan, et al). This has been controlled to some extent by 
studies involving one group of twins raised together and another group 
of twins separated some time during infancy or early childhood.
	Although a meta analysis is an excellent way to take existing 
research and improve it, there are some disadvantages.  First, there 
may be published or unpublished studies that are not included in the 
meta-analysis.  Second, there may be specific limitations of a study 
that the researcher is examining that may limit the results to the meta 
analysis.  For example, the studies in this meta analysis focused on 
predominantly Caucasian subjects from developed nations.  It is not 
known whether the results would generalize across the world.   
	The research designs mentioned above are only a few of the main 
methods conducted in order to determine the influence of heredity on 
depression.  They are all beneficial for showing the effects of 
heredity.  However, some have more advantages than other.  Combining 
several studies together such as twin, family, and adoption studies is 
one way to eliminate some bias and disadvantages. Overall, there are 
several research designs shown to be effective for estimating the 
influence of genetics on depression, and new research furthering these 
designs is constantly being presented. 


References
Carlson, Neil R., Physiology of Behavior 7th ed. 
	Massachusetts: Allyn and Bacon, 2001.
Carmelli, Dorit., Swan, Gary E., Kelly-Hayes, Margaret.,
Wolf, Philip A., Reed, Terry and Miller, Bruce. 
(2000).Longitudinal changes in the contribution of genetic and 
influence to symptoms of depression in older male twins. American 
Psychological Association, Inc 15,505-510.
Kendler, Kenneth S., M.D., Thornton, Laura M., Ph.D., and  
Charles O. Gardner, Ph.D. (2001). Genetic risk, number of 
previous genetic episodes, and stressful life events in 
predicting onset of major depression. American Journal of 
Psychiatry 158, 582-586.
Sullivan, Patrick F., M.D., Michael C. Neale, Ph.D., and     
Kenn often eth S. Kendler, M.D. (2000). Genetic epidemiology of 
major depression: review and meta-analysis. American Journal of 
Psychiatry 157, 1552-1571.
Vincent, John B., Ph.D., Masellis, Mario., Choi, Victor.,    
Gurling, Hugh, M.D., Phil, M., Parikh, Sagar, M.D., Kennedy, 
James, M.D. (1999). Genetic association analysis of seratonin 
system genes in bipolar affective disorder. American Journal of 
Psychiatry 156, 136-138.

Copyright © 2001, Dr. John M. Morgan, All rights reserved - This page last edited 8 May, 2001
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