Environmental, epigenetic, psychosocial, or perinatal events are correlated with the severity of the expression of a number of spectrum disorders, such as ADHD, OCD and TS. In other words, these factors don't *cause* the condition, but they may contribute to the severity of the expression of the underlying genetic vulnerability. There are numerous journal articles supporting this relationship for ADHD and OCD, and some evidence for TS as well.
Some definitions from Online Medical Dictionary
epigenetic: Describes something which influences the behaviour of a cell without directly affecting its DNA or other genetic machinery, such as an environmental effect.
perinatal: Pertaining to or occurring in the period shortly before and after birth, variously defined as beginning with completion of the twentieth to twenty eighth week of gestation and ending 7 to 28 days after birth.
psychosocial: Involving both psychological and social aspects; e.g., age, education, marital and related aspects of a person's history.
The current framework for viewing TS (quotes from Leckman/Cohen, 2000 TS book and Advances in Neurology, Volume 85, TS 2001 book):
L/C, p. vii
Often based upon a multigenerational, genetic predisposition, the multifaceted symptoms of Tourette's syndrome unfold during the first years of life as an interaction between biological vulnerability and adverse environmental events. {You can find words to this effect in all good, recent TS literature.}
A/N, p. 273
Great emphasis has been placed on the genetic etiology of Tourette Syndrome. Ironically, those same genetic studies also support a role for nongenetic or environmental factors in the development of TS.
Specific data
A/N and L/C both discuss the well known twin studies, where in all cases of both twins having TS, the twin with the lower birth weight had the higher severity of TS symptoms, suggesting that factors in the womb are at play.
A/N, Chapter 21, Epigenetic and Environmental Risk Factors in Tourette Syndrome, beginning on page 273, also mentions:
A number of studies have implicated very early environmental factors in the expression and severity of TS (see ref. 10 for a comprehensive review). {Ref 10 is to the same chapter in the L/C book}
A more recent study, using a standardized approach to the assessment of obstetrical complications, identified much higher rates of complications in those who developed TS compared to the rates for individuals in the population at large. Two particular complications are of note: 1) Severe nausea and vomiting during the first trimester ... 2) Forceps delivery, which is very common, especially in boys with TS, was associated with an increase risk for OCD in those boys. Very early psychosocial factors were also noted to increase the risk of TS or related conditions. Maternal stress during pregnancy was associated with overall tic severity and level of psychosocial functioning (12). In addition, moderate coffee drinking, cigarette smoking, and alcohol consumption were associated with an increased risk of OCD in persons with TS.
Ref 12 is: Leckman, Dolnansky, Hardin, et al. Perinatal factors in the expression of Tourette's syndrome: An exploratory Study. J Am Acad Child Adolesc Psychiatry 1990; 29:220-226.
L/C, Chapter 12, Environmental Risk and Protective Factors, beginning on p. 213:
These differences in symptom severities cannot be due to genetic influences, because MZ twin pairs are by definition genetically identical. Hence, the inciting events that determine symptom severity differences between these comorbid twins must be nongenetic in nature. As will be seen, these nongenetic determinants appear to include both pre- and postnatal experiences. Certain environmental factors, moreover, appear to be important in determining whether the putative gene is expressed as chronic tics, Tourette's syndrome ... Nongenetic factors also seem to be important in determining whether the severity of symptoms of each clinical syndrome will be mild or severe.
The kinds of risk and protective factors that putatively affect current symptom severity and the long-term outcome of Tourette's-related disorders include perinatal complications, sex-specific factors, stress, infectious and autoimmune processes, stimulant exposure, prior symptom severity and psychological resilience, the presence of comorbid neuropsychiatric disorders, and maturational and developmental factors.
... the severity of maternal life stress during pregnancy and the presence of severe nausea and/or vomiting during the first trimester were found to be significantly associated with current tic severity, accounting for nearly 50% of the variance in tic symptom severity. In addition, the severity of maternal emotional stress during the pregnancy was positively associated with tic severity and the quality of psychosocial functioning.
Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder? J Am Acad Child Adolesc Psychiatry. 1994 Jul-Aug;33(6):795-804. Santangelo SL, Pauls DL, Goldstein JM, Faraone SV, Tsuang MT, Leckman JF.
Department of Epidemiology, Harvard Program in Psychiatric Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA.
OBJECTIVE: To explore the influence of gender and comorbid obsessive-compulsive disorder (OCD) on the phenomenology of Tourette's syndrome (TS).
METHOD: TS proband groups defined by gender and comorbid OCD status were compared on a variety of sociodemographic variables, clinical characteristics, and perinatal complications.
RESULTS: Compared to females, males more often onset with rage and had ever experienced any form of simple tics. Females onset with compulsive tics more often than males. Probands with comorbid OCD were more likely than those without OCD to onset with complex tics. Delivery complications, especially forceps deliveries, were associated with being male and with having OCD. Fetal exposure to relatively high levels of coffee, cigarettes, or alcohol predicted OCD in TS probands. Diagnosis of TS occurred at later ages among females than among males. Males and females displayed different age distributions.
CONCLUSIONS: Males and females tend to experience different kinds of symptoms at onset. However, the overall experience of TS appears to be similar for both groups. Perinatal brain injury is implicated in the etiology of TS in some boys. Early brain injury may cause or exacerbate the development of OCD in some TS sufferers.
PMID: 8083136
Guide to the Diagnosis and Treatment of Tourette Syndrome
http://www.mentalhealth.com/book/p40-gtor.html
Tourette Syndrome Association
Ruth Dowling Bruun, M.D., Donald J. Cohen, M.D., James F. Leckman, M.D., 1984
Based on available information, it is now clear that TS is a genetic disorder. The vulnerability to TS is transmitted from one generation to another. When we speak of "vulnerability," we imply that the child receives the genetic or constitutional basis for developing a tic disorder; the precise type of disorder or severity may be different from one generation to another. That vulnerability is transmitted by either mothers or fathers and can be passed on to either sons or daughters. When one parent is a carrier or has TS, it appears that there is about a 50-50 chance that a child will receive the genetic vulnerability from that parent. That pattern of inheritance is described as autosomal dominant.
However, not everyone who inherits the genetic vulnerability will express any of the symptoms of TS. There is a 70% chance that female gene carriers will express any of the symptoms of TS. For a male gene carrier, there is a 99% chance of showing some clinical expression of the gene. The degree of expression is described as penetrance. In males, the penetrance is higher than in females; thus, males are more likely to have some form of expression of the genetic vulnerability. There is a full 30% chance of female gene carriers showing no symptoms at all. For males, the figure is 1%.
There is a range of forms in which the vulnerability may be expressed that includes full-blown TS, chronic multiple tics, and, as most recently recognized, obsessive-compulsive disorder. Some individuals have TS (or chronic tics) and obsessive-compulsive disorder together; others may have the conditions singly. There are also differences between the sexes in the form of expression of the TS gene. Males are more likely to have TS or tics; females are more likely to have obsessive-compulsive disorder; however, both males and females may have any combination or severity. The severity of the disorder is also highly variable. Most individuals who inherit the TS genetic vulnerability have very mild conditions for which they do not seek medical attention.
Non-Genetic Contributions
The individual variations in character, course, and degree of severity by which TS is manifested cannot be explained by genetic hypotheses alone. Furthermore, it appears that about 10-15% of TS patients do not acquire the disorder genetically. Thus, non-genetic factors are also responsible, both as causes and as modifiers of TS. Non-genetic factors that have been implicated include such stressful processes or events during the prenatal, perinatal, or early life periods as fetal compromise and exposure to drugs or other toxins. Findings from one study in which decreased birth weights were observed in the affected co-twins of discordant monozygotic pairs lend further support to the influence of environmental factors.
More information from TSPlus Website:
http://www.tourettesyndrome.net/tourette_primer3.htm
A more recent study by Eapen et al. (2004) found that for adult patients with TS seen in clinical settings, male patients were significantly more likely to have an earlier onset of TS and to have had birth complications.
http://www.tourettesyndrome.net/tourette_primer4.htm
Tourette's Syndrome (TS) appears to be familial (i.e., it "runs" in families) in the vast majority of cases, suggesting a genetic component or an inherited vulnerability to it, but our understanding of the mode of genetic transmission is incomplete and controversial. At the present time, it appears that there is likely to be a significant genetic factor, although prenatal, perinatal, autoimmune, and environmental factors can affect or modulate the severity of symptoms.
In addition to what appears to be a genetic vulnerability or component, some research also suggests that prenatal events or factors (such as maternal smoking, drug use, exposure to toxins) and perinatal events (such as jaundice, infections) may be associated with severity of TS. While some factors do not necessarily cause TS, they may be correlated with symptom severity in children who do develop TS. Some of the environmental factors that may affect symptom severity are mentioned later in this primer in the section on stress.
More from Canadian Tourette Foundation:
http://www.tourette.ca/articles/article3.html
Paradoxically, the genetic studies on twins with Tourette Syndrome provide the evidence that there may be important environmental factors which interact with the genetic predisposition to produce Tourette Syndrome.
From Recognition and Management of Tourette's Syndrome and Tic Disorders, American Family Physician, Bagheri, Kerbeshian, and Burd, April 1999
http://www.aafp.org/afp/990415ap/2263.html
Etiology
Genetic predisposition is important, but environmental factors influence the risk, the severity and the course of the disorder. Studies show a concordance rate of about 60 percent for Tourette's syndrome in monozygotic twins and 10 percent in dizygotic twins.
From Zinner article:
http://www.tsa-usa.org/research/images/cntped0804_022-036%20T1R2.pdf
Tourette syndrome occurs in all cultures and races. Although a familial basis for TS is well established, its genetic basis remains unclear. What does seem clear is that the syndrome is not explained by a simple gene mutation. Instead, one or more major susceptibility genes are likely involved, probably
of an autosomal dominant inheritance pattern, some genes with minor effect, others more influential. The interaction of these genes with possible environmental influences appears to determine just how the disorder is expressed. Influences may include male gender (TS is four times more common in males than in females) and prenatal or perinatal factors such as lower birth weight or nonspecific maternal emotional stress.
Further data on the effect of family functioning:
Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome
However, ADHD diagnosis, obsessional symptom severity, and family functioning were significantly associated with social and emotional adjustment among TS children. Moreover, family functioning was associated with social and emotional adjustment even after controlling for TS and ADHD diagnostic status. These findings demonstrate that much of the social and behavioral dysfunction in children with TS is ADHD-specific and children with TS alone have a very different social-emotional profile than do those with TS plus ADHD. Finally, social-emotional adjustment in children with TS is best understood within the family context.
Role of the Family in the Onset and Outcome of Childhood Disorders
PMID 11026173
Results: Behavioral genetics research indicates that the shared environment, including issues of parental monitoring and discipline, is important in the development and outcome of externalizing disorders. Differential parental treatments of one sibling are critical in internalizing disorders. Criticism (as measured by expressed emotion) is associated with poor outcome of many childhood medical and psychiatric disorders. Chronic illness in a child changes the family dynamics toward being more structured and less emotionally warm and communicative. The family's role in adherence to treatment is critical, and families with high levels of criticism have more difficulty.
Conclusions: Families can cause problems, but many times the problems families have are in response to a child's problems. There is a continued need to empirically assess which family processes are important for specific childhood disorders.
Parent-Child Conflict and the Comorbidity Among Childhood Externalizing Disorders
http://www.medscape.com/viewarticle/456666_print
Burt SA, Krueger RF, McGue M, Iacono W
Archives of General Psychiatry. 2003;60(5):505-513
"First, parent-child conflict appeared to act as a common vulnerability that increased the risk for multiple childhood disorders. ... Second, the genes common to ADHD, CD, and ODD may be the same genes that influence conflict. ... Third, the shared environmental factor that influences conflicts accounted for roughly a quarter of the shared environmental effects common to ADHD, CD, and ODD. Although the study and its design have limitations, the results have important implications. These results include the probability that the source of psychiatric comorbidity may lie in broad latent factors such as parent-child conflict and family environment."
Some definitions from Online Medical Dictionary
epigenetic: Describes something which influences the behaviour of a cell without directly affecting its DNA or other genetic machinery, such as an environmental effect.
perinatal: Pertaining to or occurring in the period shortly before and after birth, variously defined as beginning with completion of the twentieth to twenty eighth week of gestation and ending 7 to 28 days after birth.
psychosocial: Involving both psychological and social aspects; e.g., age, education, marital and related aspects of a person's history.
The current framework for viewing TS (quotes from Leckman/Cohen, 2000 TS book and Advances in Neurology, Volume 85, TS 2001 book):
L/C, p. vii
Often based upon a multigenerational, genetic predisposition, the multifaceted symptoms of Tourette's syndrome unfold during the first years of life as an interaction between biological vulnerability and adverse environmental events. {You can find words to this effect in all good, recent TS literature.}
A/N, p. 273
Great emphasis has been placed on the genetic etiology of Tourette Syndrome. Ironically, those same genetic studies also support a role for nongenetic or environmental factors in the development of TS.
Specific data
A/N and L/C both discuss the well known twin studies, where in all cases of both twins having TS, the twin with the lower birth weight had the higher severity of TS symptoms, suggesting that factors in the womb are at play.
A/N, Chapter 21, Epigenetic and Environmental Risk Factors in Tourette Syndrome, beginning on page 273, also mentions:
A number of studies have implicated very early environmental factors in the expression and severity of TS (see ref. 10 for a comprehensive review). {Ref 10 is to the same chapter in the L/C book}
A more recent study, using a standardized approach to the assessment of obstetrical complications, identified much higher rates of complications in those who developed TS compared to the rates for individuals in the population at large. Two particular complications are of note: 1) Severe nausea and vomiting during the first trimester ... 2) Forceps delivery, which is very common, especially in boys with TS, was associated with an increase risk for OCD in those boys. Very early psychosocial factors were also noted to increase the risk of TS or related conditions. Maternal stress during pregnancy was associated with overall tic severity and level of psychosocial functioning (12). In addition, moderate coffee drinking, cigarette smoking, and alcohol consumption were associated with an increased risk of OCD in persons with TS.
Ref 12 is: Leckman, Dolnansky, Hardin, et al. Perinatal factors in the expression of Tourette's syndrome: An exploratory Study. J Am Acad Child Adolesc Psychiatry 1990; 29:220-226.
L/C, Chapter 12, Environmental Risk and Protective Factors, beginning on p. 213:
These differences in symptom severities cannot be due to genetic influences, because MZ twin pairs are by definition genetically identical. Hence, the inciting events that determine symptom severity differences between these comorbid twins must be nongenetic in nature. As will be seen, these nongenetic determinants appear to include both pre- and postnatal experiences. Certain environmental factors, moreover, appear to be important in determining whether the putative gene is expressed as chronic tics, Tourette's syndrome ... Nongenetic factors also seem to be important in determining whether the severity of symptoms of each clinical syndrome will be mild or severe.
The kinds of risk and protective factors that putatively affect current symptom severity and the long-term outcome of Tourette's-related disorders include perinatal complications, sex-specific factors, stress, infectious and autoimmune processes, stimulant exposure, prior symptom severity and psychological resilience, the presence of comorbid neuropsychiatric disorders, and maturational and developmental factors.
... the severity of maternal life stress during pregnancy and the presence of severe nausea and/or vomiting during the first trimester were found to be significantly associated with current tic severity, accounting for nearly 50% of the variance in tic symptom severity. In addition, the severity of maternal emotional stress during the pregnancy was positively associated with tic severity and the quality of psychosocial functioning.
Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder? J Am Acad Child Adolesc Psychiatry. 1994 Jul-Aug;33(6):795-804. Santangelo SL, Pauls DL, Goldstein JM, Faraone SV, Tsuang MT, Leckman JF.
Department of Epidemiology, Harvard Program in Psychiatric Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA.
OBJECTIVE: To explore the influence of gender and comorbid obsessive-compulsive disorder (OCD) on the phenomenology of Tourette's syndrome (TS).
METHOD: TS proband groups defined by gender and comorbid OCD status were compared on a variety of sociodemographic variables, clinical characteristics, and perinatal complications.
RESULTS: Compared to females, males more often onset with rage and had ever experienced any form of simple tics. Females onset with compulsive tics more often than males. Probands with comorbid OCD were more likely than those without OCD to onset with complex tics. Delivery complications, especially forceps deliveries, were associated with being male and with having OCD. Fetal exposure to relatively high levels of coffee, cigarettes, or alcohol predicted OCD in TS probands. Diagnosis of TS occurred at later ages among females than among males. Males and females displayed different age distributions.
CONCLUSIONS: Males and females tend to experience different kinds of symptoms at onset. However, the overall experience of TS appears to be similar for both groups. Perinatal brain injury is implicated in the etiology of TS in some boys. Early brain injury may cause or exacerbate the development of OCD in some TS sufferers.
PMID: 8083136
Guide to the Diagnosis and Treatment of Tourette Syndrome
http://www.mentalhealth.com/book/p40-gtor.html
Tourette Syndrome Association
Ruth Dowling Bruun, M.D., Donald J. Cohen, M.D., James F. Leckman, M.D., 1984
Based on available information, it is now clear that TS is a genetic disorder. The vulnerability to TS is transmitted from one generation to another. When we speak of "vulnerability," we imply that the child receives the genetic or constitutional basis for developing a tic disorder; the precise type of disorder or severity may be different from one generation to another. That vulnerability is transmitted by either mothers or fathers and can be passed on to either sons or daughters. When one parent is a carrier or has TS, it appears that there is about a 50-50 chance that a child will receive the genetic vulnerability from that parent. That pattern of inheritance is described as autosomal dominant.
However, not everyone who inherits the genetic vulnerability will express any of the symptoms of TS. There is a 70% chance that female gene carriers will express any of the symptoms of TS. For a male gene carrier, there is a 99% chance of showing some clinical expression of the gene. The degree of expression is described as penetrance. In males, the penetrance is higher than in females; thus, males are more likely to have some form of expression of the genetic vulnerability. There is a full 30% chance of female gene carriers showing no symptoms at all. For males, the figure is 1%.
There is a range of forms in which the vulnerability may be expressed that includes full-blown TS, chronic multiple tics, and, as most recently recognized, obsessive-compulsive disorder. Some individuals have TS (or chronic tics) and obsessive-compulsive disorder together; others may have the conditions singly. There are also differences between the sexes in the form of expression of the TS gene. Males are more likely to have TS or tics; females are more likely to have obsessive-compulsive disorder; however, both males and females may have any combination or severity. The severity of the disorder is also highly variable. Most individuals who inherit the TS genetic vulnerability have very mild conditions for which they do not seek medical attention.
Non-Genetic Contributions
The individual variations in character, course, and degree of severity by which TS is manifested cannot be explained by genetic hypotheses alone. Furthermore, it appears that about 10-15% of TS patients do not acquire the disorder genetically. Thus, non-genetic factors are also responsible, both as causes and as modifiers of TS. Non-genetic factors that have been implicated include such stressful processes or events during the prenatal, perinatal, or early life periods as fetal compromise and exposure to drugs or other toxins. Findings from one study in which decreased birth weights were observed in the affected co-twins of discordant monozygotic pairs lend further support to the influence of environmental factors.
More information from TSPlus Website:
http://www.tourettesyndrome.net/tourette_primer3.htm
A more recent study by Eapen et al. (2004) found that for adult patients with TS seen in clinical settings, male patients were significantly more likely to have an earlier onset of TS and to have had birth complications.
http://www.tourettesyndrome.net/tourette_primer4.htm
Tourette's Syndrome (TS) appears to be familial (i.e., it "runs" in families) in the vast majority of cases, suggesting a genetic component or an inherited vulnerability to it, but our understanding of the mode of genetic transmission is incomplete and controversial. At the present time, it appears that there is likely to be a significant genetic factor, although prenatal, perinatal, autoimmune, and environmental factors can affect or modulate the severity of symptoms.
In addition to what appears to be a genetic vulnerability or component, some research also suggests that prenatal events or factors (such as maternal smoking, drug use, exposure to toxins) and perinatal events (such as jaundice, infections) may be associated with severity of TS. While some factors do not necessarily cause TS, they may be correlated with symptom severity in children who do develop TS. Some of the environmental factors that may affect symptom severity are mentioned later in this primer in the section on stress.
More from Canadian Tourette Foundation:
http://www.tourette.ca/articles/article3.html
Paradoxically, the genetic studies on twins with Tourette Syndrome provide the evidence that there may be important environmental factors which interact with the genetic predisposition to produce Tourette Syndrome.
From Recognition and Management of Tourette's Syndrome and Tic Disorders, American Family Physician, Bagheri, Kerbeshian, and Burd, April 1999
http://www.aafp.org/afp/990415ap/2263.html
Etiology
Genetic predisposition is important, but environmental factors influence the risk, the severity and the course of the disorder. Studies show a concordance rate of about 60 percent for Tourette's syndrome in monozygotic twins and 10 percent in dizygotic twins.
From Zinner article:
http://www.tsa-usa.org/research/images/cntped0804_022-036%20T1R2.pdf
Tourette syndrome occurs in all cultures and races. Although a familial basis for TS is well established, its genetic basis remains unclear. What does seem clear is that the syndrome is not explained by a simple gene mutation. Instead, one or more major susceptibility genes are likely involved, probably
of an autosomal dominant inheritance pattern, some genes with minor effect, others more influential. The interaction of these genes with possible environmental influences appears to determine just how the disorder is expressed. Influences may include male gender (TS is four times more common in males than in females) and prenatal or perinatal factors such as lower birth weight or nonspecific maternal emotional stress.
Further data on the effect of family functioning:
Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome
However, ADHD diagnosis, obsessional symptom severity, and family functioning were significantly associated with social and emotional adjustment among TS children. Moreover, family functioning was associated with social and emotional adjustment even after controlling for TS and ADHD diagnostic status. These findings demonstrate that much of the social and behavioral dysfunction in children with TS is ADHD-specific and children with TS alone have a very different social-emotional profile than do those with TS plus ADHD. Finally, social-emotional adjustment in children with TS is best understood within the family context.
Role of the Family in the Onset and Outcome of Childhood Disorders
PMID 11026173
Results: Behavioral genetics research indicates that the shared environment, including issues of parental monitoring and discipline, is important in the development and outcome of externalizing disorders. Differential parental treatments of one sibling are critical in internalizing disorders. Criticism (as measured by expressed emotion) is associated with poor outcome of many childhood medical and psychiatric disorders. Chronic illness in a child changes the family dynamics toward being more structured and less emotionally warm and communicative. The family's role in adherence to treatment is critical, and families with high levels of criticism have more difficulty.
Conclusions: Families can cause problems, but many times the problems families have are in response to a child's problems. There is a continued need to empirically assess which family processes are important for specific childhood disorders.
Parent-Child Conflict and the Comorbidity Among Childhood Externalizing Disorders
http://www.medscape.com/viewarticle/456666_print
Burt SA, Krueger RF, McGue M, Iacono W
Archives of General Psychiatry. 2003;60(5):505-513
"First, parent-child conflict appeared to act as a common vulnerability that increased the risk for multiple childhood disorders. ... Second, the genes common to ADHD, CD, and ODD may be the same genes that influence conflict. ... Third, the shared environmental factor that influences conflicts accounted for roughly a quarter of the shared environmental effects common to ADHD, CD, and ODD. Although the study and its design have limitations, the results have important implications. These results include the probability that the source of psychiatric comorbidity may lie in broad latent factors such as parent-child conflict and family environment."
