Summary Review of: Genotype-environment interaction in schizophrenia-spectrum disorder. Published In: The British Journal of Psychiatry (2004) 184: 216-222 (full journal article here)

Introduction and Summary of Results:

Based on our current knowledge of genetics and schizophrenia, no one gene causes the brain disorder on its own.  Many of the common risk genes for schizophrenia are seen in healthy people, and they never develop the disorder.  Researchers believe that this is because schizophrenia requires complex combinations of genes.  But even with all the appropriate genetic risk factors, many (if not most) people may still not develop the disorder.  This has lead to the examination of other influences besides genes, and their role in producing schizophrenia.

Scientists commonly refer to this combination of genetic and other influences as the “nature vs. nurture” debate.  Nature being the genes you were born with, and nurture being every external influence in your environment from conception onward. The theory on how the genetic susceptibility for schizophrenia combines with environmental stressors to result in a person developing schizophrenia is known as the predisposition/stress model, or diathesis-stress model).  Scientists agree that both nature and nurture have a significant role in the development of schizophrenia, but how exactly they interact, or to what degree is not completely understood. 

Because twin studies show approximately a 50% risk of developing schizophrenia in identical twins (meaning siblings with exactly the same genes), environment must have significant influence in the brain disorder.  A well-designed, 40-year longitudinal study from Finland focused on identifying the degree to which family environmental factors might play a protective role in those who are genetically susceptible to schizophrenia. 

Identification of family environmental factors that are protective against developing  schizophrenia offers significant hope for those predisposed to this brain disorder.  The existance of such protective factors would indicate that preventive measures may be taken by parents to reduce the likelihood that their child will develop schizophrenia. The results of this study suggest that there are protective family environmental factors that may reduce the schizophrenia risk for a susceptible child by up to 86%.

This research study suggests that some children, due to their genetics (as well as other factors such as prenatal environment and exposure to stress during pregnancy ), are much more sensitive to certain environmental factors and stress, and as a result of this are more likely to develop schizophrenia and other mental illnesses.  Adoptees with high-genetic risk for schizophrenia-spectrum disorders (see below) have been found to be more sensitive to environmental effects than adoptees with low-genetic risk for the disease.

In this study, 36.8% of high-genetic risk adoptees living in a dysfunctional family environment were found to have developed a schizophrenia-spectrum disorder, compared to only 5.8% of those in a healthy family environment.  The rate of schizophrenia-spectrum disorders in the low-genetic risk adoptees  was similar regardless of the family environment.  This evidence suggests that people with high-genetic risk for schizophrenia-spectrum disorders receive a protective effect of the healthy family environment of 86% decrease in risk.  The study suggests that children with genetic or biological liability for schizophrenia and related disorders may be sensitive to both difficult (volatile, unpredictable, judgmental or hostile) and overly protective or isolated environmental conditions.

Schizophrenia.com Editorial Note   Some readers may interpret this research as harkening back to the “blame the family” era of schizophrenia research.  However, at schizophrenia.com (a group that includes many family members of people who have schizophrenia), we believe this to be a misinterpretation of the study.  Importantly, this research aims to separate the genetic from the environmental factors that are involved in a person developing schizophrenia.  To the degree that the research can help families with a genetic predisposition for schizophrenia identify areas where risk for the disorder can be reduced, we view it as very helpful and important research.  Moreover, please keep in mind what the study suggests, and also what it does not suggest:

 1   Certain children, due to their biological/genetic makeup, are much more sensitive to environmental stressors.  The root cause of schizophrenia is likely to be genetic / biological, but the contributing factors and trigger(s) of schizophrenia is/are likely to be environmental and stress related.

 2   Families with a child who develops schizophrenia are not necessarily less healthy (or more dysfunctional) than other families.  Instead, this research suggests that the genetically-at-risk individual is much more sensitive to any ongoing stress and dysfunction that exists in their given family.

 3   Living in a healthy family environment will not completely eliminate the risk of developing schizophrenia.  Having a healthy family environment was shown in this study to reduce the risk of schizophrenia by about 86%.  However, a significant percentage of children (5.8%) developed schizophrenia even though the family environment was healthy.

 4   Even in a healthy family environment, there are still other environmental factors (for example prenatal stress or toxin exposure, nutritional deficiencies, social stress in peer groups or neighborhoods and schools, substance abuse, etc.) that may contribute to the risk or trigger schizophrenia in those who are genetically-at risk.

 5   In families where there is a history of schizophrenia, the risk of a child developing schizophrenia may be significantly reduced if a healthy low-stress family environment can be created and sustained. For more information on how to lower the risk of schizophrenia in children - read Preventing Schizophrenia.

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 Figure 1. The Percentage of High Genetic Risk Adoptees with Schizophrenia-Spectrum Disorder Diagnosis in Functional versus Dysfunctional Families is shown in the bar graph.  Healthy or Functional families are those that received Low OPAS ratings (below the median) whereas dysfunctional families are those that received High OPAS ratings (above the median).  5.8% (4/69) of the high genetic risk adoptees in a healthy environment developed a schizophrenia-spectrum disorder.  36.8% (28/76) of the high genetic risk adoptees in a dysfunctional environment developed a schizophrenia-spectrum disorder. There is a significant association between dysfunctional family environment and adoptee diagnosis of schizophrenia-spectrum disorder.

Figure 2. The Percentage of Low Genetic Risk Adoptees with Schizophrenia-spectrum Disorder Diagnosis in Functional versus Dysfunctional Families is shown in the bar graph.  Functional families are those that received Low OPAS ratings (below the median) whereas dysfunctional families are those that received High OPAS ratings (above the median).  4.8% (4/83) of the low genetic risk adoptees in a healthy environment developed a schizophrenia-spectrum disorder.  5.3% (4/75) of the low genetic risk adoptees in a dysfunctional environment developed a schizophrenia-spectrum disorder.  There is no significant difference in risk between these two groups.

To be certain that adoptees at high-genetic risk did not have an effect on their families as to increase dysfunction, the proportion of the families’ levels of dysfunction between the low-genetic risk and high-genetic risk adoptee families were compared, and there were no significant differences found.  This means that adoptees with high-genetic risk for schizophrenia-related disorders did not have any measurable impact on parental communication and care giving skills, or on the functioning of the rest of the family, according to the OPAS rating system that was used to evaluate the families in the study.  These results are consistent with earlier findings in the Finnish adoptive study:  Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish adoptive family study of schizophrenia

The Goal of the Study

Previous adoption studies have found conclusive evidence that genetics play a significant role in the development of schizophrenia.  But these adoptive studies have also found that genes do not operate alone; environmental factors must play a significant role as well.  In adoption studies, genetic and rearing environment effects can be separated because the biological parents are not raising the children; this makes them the optimal choice when evaluating “nature vs. nurture”.

Much of environmental influences are a result of family environment.  This is in part due to the developing brains vulnerability to influence during childhood and adolescence, as well as the significant portion of time spent with the family.  Because of this, the current study aims to determine whether the risk for development of schizophrenia in people with genetic predisposition for the disorder is affected by their family environment.  In other words, does having a healthy family environment versus a dysfunctional one have any influence on whether or not a child will develop the disease?   

Background Information on Genes and Environment

Previous studies have provided evidence for a Genetic Contribution to Schizophrenia.  There is a tendency for people to think that genes are ‘hard-coded’ in that if you have the gene for schizophrenia, you will definitely develop the disease.  However, this is not the case; some genes remain latent or hidden in that they never manifest their code in a person’s lifetime.  For example, individuals can be ‘carriers’ for a gene and pass it on to their offspring, but never actually develop the disease themselves.  Certain genes may become activated upon interaction with environmental stressors stress, thus explaining the increased development of schizophrenia-spectrum disorders in high genetic-risk adoptees exposed to adverse environmental conditions.  Researchers call this model of causal factors of schizophrenia the “diathesis – stress” model, where “diathesis” means a hereditary predisposition to a disease.  In fact, recent research suggests that environment interacts with genetics to produce the final ‘expression’ of an individual.  It is now known that people’s experiences, starting from within the womb and continuing into adulthood, can actually change the development of the brain.  Research suggests that the Environmental Contribution to Schizophrenia is much more significant than previously thought. 

It is neither nature nor nurture alone that is responsible for brain chemistry and development; rather it is the interaction between both genes and environment that is responsible for the brain development of an individual  Research suggests that if a person has the genes for schizophrenia, but doesn’t experience the environmental factors necessary to “trigger” or express these genes then the likelihood is low that they will develop schizophrenia.  Similarly, if they do not have the genes, and do experience environmental risk factors, then it is also unlikely that they will develop schizophrenia.  Schizophrenia research today suggests that t is only when a person has the genes related to schizophrenia, and also experiences the environmental triggers, that the risk for schizophrenia increases significantly.

Importantly, this study attempts to understand more fully the contribution of genetics and environment in the development of schizophrenia-spectrum disorders.  In fact, the reported findings are consistent with a large body of scientific research suggesting that schizophrenia is the result of a genetic or biological predisposition, with secondary factors (such as prenatal environment, complications at birth, family or social stress, social isolation, brain trauma, drug/substance abuse, etc.) that ultimately trigger the disorder (cause the genotype to be expressed).  Of utmost significance,  these findings and those from other studies examining the diathesis-stress model indicate that if a genetically-at-risk individual does not experience the negative environmental factors they may not develop schizophrenia or, at the very most, may develop a far less serious form of difficulties thought possibly related to the “schizophrenia genotype” (e.g., idiosyncratic use of language).

How They Did the Study

A Finnish national sample of adoptees whose biological mothers were diagnosed with schizophrenia-spectrum disorders was blindly compared to a demographically (age, sex, location, ect) matched sample of adoptees whose biological mothers did not have a schizophrenia-spectrum psychiatric diagnosis. By ‘blindly compared’, we mean that the interviewers were not aware of who belonged to which group, low- or high-genetic risk.  This is a commonly used and highly beneficial practice in many research studies that helps to eliminate experimenter bias.  Conversely, the mental health status of the adoptees was unknown to the diagnosticians who rated the biological mothers.  This prevented bias in diagnosis from occurring, as the interviewers would have no reason to anticipate psychotic tendencies in the subject.   The final sample of high-risk offspring were born to mothers with severe spectrum disorders rather than to a broad sampling of  mothers who had other disorders in the spectrum, specifically leaving out the personality disorders.  Thus, the high-genetic risk group in this study only applies to individuals with severely psychotic mothers.  More information about the selection of the high-risk offspring can be found in this article: Sample selection in Finnish Adoptive Family Study

The adoptees were evaluated on three separate occasions by interviewing psychiatrists that did not know the mental health status of the biological parents.  The first evaluation occurred in 1977 with semi-structured personal interviews of the adoptees.  Approximately 12 years later the adoptees were re-evaluated by new psychiatrists that were blind to all prior mental health assessments of the adoptees and their biological and adoptive parents.  A final psychological evaluation of the adoptees was done 21 years after the initial assessment.  The diagnoses were assigned based on meeting the criteria of DSM III R (Diagnostic Statistical Manuel which is the industry standard for categorizing and evaluating mental illnesses) for Axis I (major mental disorders, developmental disorders and learning disabilities) or Axis II (underlying pervasive or personality conditions, as well as mental retardation) psychiatric disorders.  Adoptees diagnosed with schizophrenia and ten other disorders that have been considered genetically linked to schizophrenia in previous reports were the focus of the study.  These disorders make up what the author’s refer to as their ‘broad’ schizophrenia-spectrum (see box below). 

The adopted families were investigated in their homes by experienced psychiatrists over extended home visits.  The procedure included joint interviews with the whole family and the parents, as well as personal interviews with extended family members.  A wide range of observations, especially about non-verbal behavior and alienation of a family member, could be made more easily in the home than in the clinic.  Each session was tape recorded and lasted between 14 and 16 hours; the huge amount of time spent in the home was such that habitual patterns of interaction were likely to emerge, even in families that may normally be a bit guarded.  From these interviews several measures of the adoptive family environment were taken, including the psychiatric diagnosis of the adoptive parents, test measures of their level of communication deviance, global family functionality ratings and specific family rating scales.  Since all of the interviews were tape recorded it was possible for several different investigators to evaluate and rate each family’s behavior, thus allowing for studies on the reliability of ratings and creation of mean scores for each family.

The family observations were used to rank the families on a scale from ‘healthy’ to ‘severely dysfunctional’ by means of the Finnish family emotional health rating scale (OPAS).  The scale was specially constructed to tap into concepts that may be relevant for families with offspring suffering from schizophrenia and is heavily based off of the Beavers-Timberlawn Family Evaluation Scale.  The family emotional health rating scale consists of 33 sub-scales of behaviors that could be rated at five levels from ‘healthy’ to ‘severely dysfunctional’.  Ratings above the median (the number that divides the population in half; where half of the sample has scores higher than the median, and half has scores below the median) were considered dysfunctional, while ratings below the median were considered functional.  The following Table lists 21 of the subscale behavior categories that proved reliable for statistical analysis and the characteristics of families that warrant a healthy, intermediate, or dysfunctional rating: 

The OPAS Rating Scale: What patterns of behavior within families are considered healthy or dysfunctional? 

The information in this table can be found in the appendix of the OPAS Scale Manual: Observing relationships in Finnish adoptive families.  Published in the Nordic Journal of Psychiatry (2005) 59(4): 253-263. 

What does this study suggests for families affected by schizophrenia?

Whether your family is genetically susceptible to schizophrenia or there is a person with schizophrenia in your home, this study indicates that a healthy and stable family environment may provide protective effects against development of schizophrenia-spectrum disorders.  Similarly, a dysfunctional rearing environment may increase the risk for development of schizophrenia-spectrum disorders in those with genetic susceptibility.  Disordered parenting and stress in the home is also known to contribute to depression, antisocial behavior, substance abuse and alcoholism, and other mental health problems – so there are many very good reasons to make extra effort to resolve family issues and make the family environment as healthy and safe as possible.  If an individual who is genetically susceptible to psychotic disorders is forced to cope in such an environment, he or she is more likely to develop schizophrenia and related disorders. 

This does not mean that all individuals who develop schizophrenia-spectrum disorders have come from a broken home or even a family that is more dysfunctional than families where schizophrenia has not been diagnosed; what it does mean, however, is that some children – due to their genetics – are much more sensitive to some environmental factors, and the good news is that this study suggests that we have more power over our genetic expression than previously thought. 

This paper suggests, for families with a history of schizophrenia or who are concerned about mental health risks, a decrease in the risk of schizophrenia may be achieved by reducing dysfunctional interactions in the family environment through family therapy or education. 

This study is stronger than others of its kind for a few reasons.  The first is that the Finnish national database that was consulted for sampling purposes is so extensive that they were able to find adoptees and families at high- and low-genetic risk for schizophrenia-spectrum disorders that were matched on demographic variables (age, education, income level, household size, etc.).  This makes the evidence stronger for a difference between the two risk groups based upon the family environment, since the families in consideration were of similar backgrounds.  In addition to this, the study was performed with the public interest in mind and had no corporate or pharmaceutical funding with a long term, blind design that prevented bias from being incorporated into the results.  Lastly, the study was done over a long period of time (~30 years) which allowed for the appearance of psychiatric diagnoses which would not have been caught in a shorter period of time.  This means that the relative risk found in the study is more applicable to a person’s lifetime than it would have been had the study only lasted a few years. 

On the flip side, the fact that the study lasted so long is also one of its limitations.  When the study began in the 1970s family therapists favored observational methods rather than self reporting of family behaviors.  By the 12-year follow up of the adoptees’, this viewpoint had changed, and Beaver’s Self Report Questionnaire was given to the adoptees in an attempt to compare the adoptee’s view of the family at the time with earlier assessments.  The psychiatrists that designed the family emotional health rating scale (OPAS) used major hypotheses regarding the disorder at the time to develop the methods for evaluating the functioning of the family.  Since theories have changed and practices for evaluating families have as well, the reviewer’s perspectives over time may have been inconsistent.  For this reason, families were scored by several different investigators, and in the end were given an average rating.  This enabled the investigators to create interrater reliability statistics to show that the observational data still held significant merit. 

Another weakness of the study is the fact that the levels of dysfunction and the particular behaviors that are most detrimental to high-risk groups are not clearly defined.  In fact, the rating system is overall pretty nonspecific.  It is difficult to tap into crucial developmental changes and events when families are only observed at a given point in time.  It is also highly open to interpretation whether or not a particular behavior is beyond the scope of normal problems within a family.  Some families may have happened to be at a rough ‘patch’ at all instances of observation, whereas others may not have appeared that dysfunctional at the time but generally functioned on a tense and unhealthy level.  Lastly, the rating scales were specially constructed to “tap major concepts thought to be relevant for families with offspring with schizophrenia”.  Whether constructing the scales in such a way somehow biased the results is unknown and not discussed in the paper

Finally, while this study included an exceptional database (Finnish nationwide sample of adopted-away offspring) with low attrition (drop-out or non-participation), adopted individuals represent only a very small number of the general population, and schizophrenia-spectrum disorder is likewise relatively rare; thus, the subsample of the low-genetic-risk adoptees who received a broadly defined schizophrenia-spectrum disorder was small (n = 8).  This number, when divided into the healthy and dysfunctional families, becomes even smaller (4 each).  The authors do not address whether such a small sample size in the low-genetic risk group could influence the results.    

Additional Resources

Further Reading about Functional and Dysfunctional Family Behaviors:

Some characteristics of healthy families as hypothesized by family relationship expert Dr. D. Reiss, of George Washington University:

1. These healthy families speak clearly. They are not rigid in their discussions, nor are they confused and chaotic.

2. They tend to agree more often than disagree and are able to assert themselves without offending others.

3. They have a friendly environment and are able to disagree without upsetting other members.

4. They show variation in affect; they can express happiness or sadness to each other.

5. They have a good sense of humor and have the ability to laugh at themselves.

6. They respect each other's need for privacy and do not engage in mind reading (thinking that they can tell exactly what a person is thinking).

7. They negotiate and compromise.

8. In families that function effectively, grudges are not held very long. Arguments are short and followed by more friendly interactions.

“Dysfunctional families: What exactly does that mean?”

This article discusses the characteristics of healthy families and dysfunctional families, with lists of particular symptomatic behaviors.  It provides a list of suggestions for preventing families from becoming dysfunctional during times of stress and change by focusing on meeting basic human emotional needs within the family. 

Recommended Reading:

Child and Teen Brains Very Sensitive to Stress, Likely a Key Factor in Mental Illness

Social Intelligence More Useful Than IQ? Important for Mental Health

Recommended Relationship Books to Help Create a Healthy Family Environment

The Relationship Cure: A 5 Step Guide to Strengthening Your Marriage, Family, and Friendships - By Dr. John M. Gottmann

Love Is Never Enough: How Couples Can Overcome Misunderstandings, Resolve Conflicts - By Dr. Aaron T. Beck

The Seven Principles for Making Marriage Work - By Dr. John M. Gottmann

20 Communication Tips for Families: A 30-Minute Guide to a Better Family Relationship
this is a simple book of really short tips for getting along better as a family.  it's a solution-focused way of addressing things

How to Talk So Kids Will Listen & Listen So Kids Will Talk

104 Activities That Build: Self-Esteem, Teamwork, Communication, Anger Management, Self-Discovery, Coping Skills

A book with a more academic flavor:

“A General Theory of Love” By Thomas Lewis, Fari Amini, Richard Lannon

This book discusses the science of human emotions and how love changes and guides who we are and what we become.  It explains how relationships function and how parents shape a child’s developing self, with emphasis on the idea that our emotional ties determine our mood, stabilize and maintain our health, and change the structure of our brains.

Early Childhood Educational Programs for Parents:

Improving Baby Mental Health – Programs for Parents

Recommended Books on Child Care and Child Development

Sample of Related Research

Schizophrenia: genes and environment - Biological Psychiatry. 2000 February

Book: The Relationship Code: Deciphering Genetic and Social Influences on Adolescent Development - a report of a longitudinal study, conducted over a ten-year period, of the influence of family relationships and genetic factors on competence and psychopathology in adolescent development. The sample for this landmark study included 720 pairs of same-sex adolescent siblings--including twins, half siblings, and genetically unrelated siblings--and their parents. (Harvard Press).