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P J Wickramaratne

Publications and source records attributed to P J Wickramaratne.

At least 19 recordsLinked to original sources
PubMed2000

Selecting early onset MDD probands for genetic studies: results from a longitudinal high-risk study.

Recent studies have found high rates of familial aggregation of major depression (MDD) in relatives of depressed children coming for treatment, leading investigators to suggest that probands for genetic studies of MDD should be selected from samples of depressed children being brought for treatment. Implicit in this recommendation is the assumption that childhood and adult depression are similar disorders. This assumption in turn implies that children with prepubertal or adolescent onset depression are at high risk for having recurrent episodes of MDD that continue into adulthood. The data supporting this latter hypothesis, however, is limited and contradictory. In this article we report results from a high-risk longitudinal family study in which we explored the recurrence and continuity into adulthood of prepubertal or adolescent onset MDD in offspring who were at high or low risk for MDD, by virtue of their parental depression status. One hundred eighteen offspring from 55 families in which one or more parents had MDD and 50 offspring from 21 families in which neither parent had MDD were followed for more than 10 years (all offspring were 20 years or older at the end of follow-up time) and blindly reassessed using a semistructured diagnostic instrument. Offspring with childhood/adolescent onset MDD were at significantly greater risk for recurrence in adulthood (after age 25) as compared with offspring without an onset of childhood/adolescent MDD, if they had a history of parental MDD. In contrast, among offspring without a history of parental MDD, those with childhood/adolescent onset MDD were at no greater risk for continuing to have MDD in adulthood (after age 25) than those without childhood/adolescent onset MDD. Moreover, there was a trend for offspring with childhood/adolescent onset MDD to be at greater risk for recurrence after age 25 if they had a history of parental MDD, as compared with offspring without a history of parental MDD (60 vs. 18%). We conclude that childhood/adolescent onset MDD is a heterogeneous disorder, with family history of MDD appearing to define a subtype of childhood/adolescent onset MDD that is recurrent and continues into adulthood. Our findings suggest that caution should be exercised in selecting depressed children and adolescents brought for treatment as probands in genetic studies of early onset MDD. A conservative strategy would be to select only those depressed children and adolescents with a family history of MDD and reassess the treated sample as they mature, ensuring that they go on to have MDD in adulthood. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:93-101, 2000

Adolescent↗
PubMed2000

Psychiatric disorders in the relatives of probands with prepubertal-onset or adolescent-onset major depression.

OBJECTIVE: To determine whether the familial risk of major depressive disorder (MDD) varies with either onset, recurrence, or continuity of MDD in adulthood in prepubertal- compared with adolescent-onset probands. METHOD: Seventy-six prepubertal-onset MDD, 59 adolescent-onset MDD, and 78 never psychiatrically ill probands were assessed as children or adolescents and were evaluated 10 to 15 years later as adults, by an independent team that was blind to the initial diagnoses. At follow-up, psychiatric disorders among 731 of their first-degree relatives were assessed using direct interviews and family history methods by investigators who were blind to the clinical status of the probands. RESULTS: Both prepubertal- and adolescent-onset MDD were significantly associated with a family history of MDD. The familial rates of MDD and other psychopathology did not vary between the 2 groups. For prepubertal-onset MDD, family history was significantly associated with recurrence and nonsignificantly associated (trend) with continuity into adulthood. In contrast, there was no association between a family history of MDD and either recurrence or continuity into adulthood of adolescent-onset MDD. CONCLUSIONS: Prepubertal- and adolescent-onset MDD are both associated with a family history of MDD, but only in prepubertal-onset MDD is familial loading associated with recurrence and continuity of MDD into adulthood.

Adolescent↗
PubMed1999

Prevalence of suicide ideation and suicide attempts in nine countries.

BACKGROUND: There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data. METHODS: Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand. RESULTS: The lifetime prevalence rates/100 for suicide ideation ranged from 2.09 (Beirut) to 18.51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0.72 (Beirut) to 5.93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married. CONCLUSIONS: While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.

Adolescent↗
PubMed1999

Risk/protective factors among addicted mothers' offspring: a replication study.

There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.

Adolescent↗
PubMed1999

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study.

OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. METHOD: Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. RESULTS: Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.

Adolescent↗
PubMed1999

Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood.

OBJECTIVE: To extend findings from several independent reports of an association between maternal smoking during pregnancy and attention-deficit hyperactivity disorder, conduct disorder, and substance abuse in the offspring. METHOD: This is a 10-year longitudinal study of offspring assessed at 3 points in time into adulthood. Fifty offspring of mothers who reported smoking at least 10 cigarettes almost daily during pregnancy and 97 offspring of mothers who reported never smoking during pregnancy were studied. Psychiatric diagnosis in offspring was assessed blind to parental diagnosis. RESULTS: There was a greater than 4-fold increased risk of prepubertal-onset conduct disorder in boys and a greater than 5-fold increased risk of adolescent-onset drug dependence in girls whose mothers smoked 10 or more cigarettes almost daily during pregnancy. These findings could not be explained by maternal substance abuse during pregnancy, parental psychiatric diagnosis, family risk factors, prenatal and early developmental history of offspring, postnatal maternal smoking, or smoking in the offspring. CONCLUSIONS: Maternal smoking during pregnancy may have a long-term effect on specific psychopathology in offspring. The underlying pathophysiology of nicotine on the fetus requires study. The findings suggest the importance of programs aimed at smoking prevention and cessation in women during pregnancy.

Adolescent↗
PubMed1998

Association studies in the presence of comorbidity: design and analysis.

Methods for the design and analysis of allelic association studies in the presence of two comorbid disorders are discussed. These methods are applicable to population-based (i.e., case-control) designs. We first develop probability models that represent pathways to the comorbidity of two disorders when it is hypothesized that at least one of the two disorders is associated with a specific allele. These potential pathways are illustrated with the specific example of the association of the human leptin (OB) gene with obesity and major depressive disorders in humans. We then discuss methods of design and analysis using the well-known methods of log-linear analysis [Bishop et al., 1975: "Discrete Multivariate Analysis." M.I.T. Press, Cambridge, MA] to differentiate between these pathways. With the increasing focus in psychiatric genetics on both association studies and pathways to comorbidity we anticipate that these methods will have wide applications.

Alleles↗
PubMed1998

Familial aggregation of delusional depression: re-examination in a recent family study.

BACKGROUND: Delusional (D-MDD) and nondelusional depression (ND-MDD) differ in clinical presentation, biological abnormalities, course of illness, and treatment response. Family data, however, have been less consistent regarding differential risk both for any major depression (MDD) and specifically D-MDD in relatives of D-MDD probands. In an earlier family study, we observed a 1.5-fold increase in rates of any MDD, specificity of transmission of D-MDD, and increased rates of bipolar disorders in relatives of D-MDD compared to relatives of ND-MDD probands. In a new family study, we attempted to replicate these findings. METHOD: A family study of 361 directly interviewed adult first-degree relatives (FDRs) of 163 probands (118 with MDD and 45 screened normal controls) was used to examine familial aggregation of any MDD, D-MDD, and bipolarity by proband delusional status. RESULTS: Compared to FDRs of ND-MDD probands, FDRs of D-MDD probands were at modestly increased risk for any MDD. These results were unaffected by adjustment for proband ascertainment source, comorbidity, or whether probands had chronologically primary MDD. There was a trend toward increased rates of broadly defined bipolarity (bipolar I, bipolar II, or cyclothymia) in FDRs of D-MDD compared to FDRs of ND-MDD probands. CONCLUSION: Results from the present study were broadly consistent with those from our previous work. While other lines of evidence for D-MDD as a distinct subtype are more compelling than family data, it would be of methodologic interest to identify sources of inconsistency across studies in findings concerning the familial aggregation of delusional depression.

Adolescent↗
PubMed1998

Onset of psychopathology in offspring by developmental phase and parental depression.

OBJECTIVE: To determine the differential effects of parental major depression (MDD) on psychopathology of childhood, adolescent, and early-adult onset in offspring. METHOD: One hundred eighty-two offspring from 91 families in which one or more parents or neither parent had MDD were followed for more than 10 years and blindly reassessed by means of a structured diagnostic instrument. RESULTS: Parental MDD is associated with increased risk in offspring of childhood-onset MDD (eightfold), anxiety disorder (threefold), conduct disorder (fivefold), and early-adult-onset MDD (fivefold) but not adolescent-onset MDD, where there is a marked increase in risk, particularly in girls, regardless of parental diagnosis. These findings were not explained by parental comorbidity, but the association with MDD was explained by parental age at onset of MDD--there was a 13-fold increase in childhood-onset MDD and a 7-fold increase in adult-onset MDD in offspring of parents with MDD of early (before age 30 years) onset. CONCLUSION: Childhood- and early-adult-onset MDD may be etiologically homogeneous and familial subtypes. The reason for the high incidence of adolescent-onset MDD, particularly in girls, regardless of parental diagnosis, needs to be determined. The childhood offspring of depressed parents are a potential target for evaluation, especially when the parent had an early-onset depression.

Adolescent↗
PubMed1998

Psychopathology in children of parents with opiate dependence and/or major depression.

OBJECTIVE: To evaluate psychiatric disorders and impairment in school-age and adolescent children of opiate-dependent patients. METHOD: One hundred fourteen children, aged 6 to 17 years, of 69 white methadone maintenance patients with (n = 30) and without (n = 39) major depression were evaluated for DSM-III-R diagnoses by the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version and best estimate, and by measures of functioning (Children's Global Assessment Scale, Social Adjustment Inventory for Children and Adolescents, WISC, Peabody Picture Vocabulary Test), and compared with children of historical controls without substance abuse history. RESULTS: Sons of opiate addicts with major depression were at increased risk for conduct disorder and global, social, and intellectual impairment compared with sons of opiate addicts without major depression and/or sons of controls with neither drug dependence nor depression. Sons of opiate addicts without major depression differed little from controls. Daughters of opiate addicts did not differ from controls in rates of disorders but had poorer social adjustment and nonverbal intelligence. CONCLUSIONS: Children of opiate-dependent patients, particularly sons of addicts with depression, may be at risk for a developmental path toward antisocial personality and poor social and intellectual functioning. Treatment settings such as methadone maintenance might afford an opportunity for primary and secondary prevention, both through early detection of childhood disorders and treatment of parental drug dependence and psychopathology.

Adolescent↗
PubMed1997

Familial aggregation and phenomenology of 'early'-onset (at or before age 20 years) panic disorder.

BACKGROUND: While early age at onset has been associated with increased familial risk, increased clinical severity, and distinctive patterns of comorbidity in a range of psychiatric disorders, it has received limited attention in panic disorder, both in family studies and with respect to clinical presentation. METHODS: A family study of 838 adult first-degree relatives of 152 probands in 3 diagnostic groups (panic disorder with or without major depression, subdivided by age at onset at or before 20 and after 20 years, and screened normal controls) was used to examine familial aggregation of panic disorder by proband age at panic disorder onset. Phenomenology of panic disorder in ill probands and their affected adult first-degree relatives was investigated as a function of proband panic disorder onset at or before 20 vs after 20 years of age. RESULTS: Compared with adult first-degree relatives of normal controls, the risks of panic disorder in adult first-degree relatives of probands with panic disorder onset at or before 20 and after 20 years of age were increased 17-fold and 6-fold, respectively. These findings were not explained by the numerous potential confounding factors that we tested. Age at panic disorder onset did not appear to be specifically transmitted within families. The clinical presentation of panic disorder differed little in either probands or affected relatives by proband age at onset. CONCLUSION: The strikingly elevated risk of panic disorder in relatives of probands with panic disorder onset at or before 20 years of age suggests that age at onset may be useful in differentiating familial subtypes of panic disorder and that genetic studies of panic disorder should consider age at onset.

Adolescent↗
PubMed1997

The cross-national epidemiology of panic disorder.

BACKGROUND: Epidemiological data on panic disorder from community studies from 10 countries around the world are presented to determine the consistency of findings across diverse cultures. METHOD: Data from independently conducted community surveys from 10 countries (the United States, Canada, Puerto Rico, France, West Germany, Italy, Lebanon, Taiwan, Korea, and New Zealand), using the Diagnostic Interview Schedule and DSM-III criteria and including over 40,000 subjects, were analyzed with appropriate standardization for age and sex differences among subjects from different countries. RESULTS: The lifetime prevalence rates for panic disorder ranged from 1.4 per 100 in Edmonton, Alberta, to 2.9 per 100 in Florence, Italy, with the exception of that in Taiwan, 0.4 per 100, where rates for most psychiatric disorders are low. Mean age at first onset was usually in early to middle adulthood. The rates were higher in female than male subjects in all countries. Panic disorder was associated with an increased risk of agoraphobia and major depression in all countries. CONCLUSIONS: Panic disorder is relatively consistent, with a few exceptions, in rates and patterns across different countries. It is unclear why the rates of panic and other psychiatric disorders are lower in Taiwan.

Adolescent↗
PubMed1997

Genetic anticipation and imprinting in bipolar I illness.

BACKGROUND: The study focused on: (1) the existence of genetic anticipation in a randomly selected sample of bipolar I patients using broad and narrow definitions of the affection status in the parental generation; (2) the relationship between anticipation and the age at investigation in probands and in their relatives; (3) the relationship between anticipation and imprinting. METHOD: One hundred and fifteen bipolar I patients and their first- to third-degree relatives were diagnosed according to DSM-III-R criteria using the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies. RESULTS: Age at onset was found to be 6-10 years younger in probands with affected parents or uncles/aunts. Two-thirds of these families showed positive anticipation under both the broad and the narrow definitions of affection status in the parents' generation. The age at investigation was younger in probands showing positive anticipation. Anticipation was found only in probands inheriting the disorder from the paternal side. CONCLUSIONS: In spite of the inevitable association between young current age and young age at onset, which could result in spurious anticipation effects, our findings suggest that this phenomenon is not the sole cause of observed anticipation.

Adolescent↗
PubMed1996

The cross-national epidemiology of social phobia: a preliminary report.

We present a preliminary report on cross-national rates, age at onset, comorbidity, suicide attempts and symptom profiles of social phobia. These data are based on epidemiologic community surveys using similar methods from the United States, Canada, Puerto Rico and Korea. The lifetime rate of social phobia (cases per 100 persons) varies by country, from 2.6 in the United States to 0.5 in Korea. Rates are higher in females than in males in all countries. The age of onset for any phobia is mid-teens to early twenties, and social phobia usually has its first onset before other psychiatric disorders. Only a third or fewer cases of social phobia are uncomplicated by another psychiatric disorder. The presence of social phobia increases the risk of suicide attempts in persons with any other psychiatric disorder. Symptom profiles vary by country. Our data indicate consistent patterns but different cultural expressions of social phobia in the countries studied. The early age of onset of social phobia followed subsequently by another psychiatric disorder raises the possibility that early treatment of social phobia could prevent the onset of other psychiatric disorders.

Adolescent↗
PubMed1995

Selecting control groups for studies of familial aggregation of disease.

In genetic-epidemiologic studies to determine the association between the disease status of family members, this association is measured by comparing rates of the disease in relatives of probands (index cases) with the disease, with the rates of the disease among individuals in a control group. Either of two types of control groups are generally used: (1) a control group consisting of a random sample from the population or the entire population if available or (2) a control group consisting of relatives of individuals without the disease under study. We examine the advantages and disadvantages of using these different types of control groups. We show two major results for family studies: (1) when there are no other factors associated with the disease status of an individual other than the disease status of a family member, both types of control groups will give a valid test of the null hypothesis of no familial aggregation. However, tests using a population control group will always be less efficient statistically, than those performed with a control group of relatives of probands without the disease under study, the degree of efficiency decreasing with increasing population prevalence of the disease. (2) When factors other than the disease status of a family member are also associated with the disease status of an individual, if this factor is a proband characteristic (which is not shared by relatives) population control groups cannot be adjusted to eliminate possible bias due to the potential confounding effect of this factor (unlike control groups consisting of relatives of probands without the disorder).

Bias↗
PubMed1995

Sample size determination in epidemiologic studies.

Sample size determination is an important issue in epidemiologic studies. Standard methods for determining sample size in cohort and case-control studies have generally been restricted to dichotomous disease and exposure variables and discrete confounding variables, and are based on simplifying assumptions that could often be unrealistic. Methods for sample size determination that make less restrictive and more realistic assumptions regarding the distribution of disease, exposure and confounding variables and which more closely parallel the analyses that are performed on the data, after the study has been conducted, have been developed in recent years. In this article some recent developments in the methodology for sample size determination in epidemiologic studies are reviewed.

Case-Control Studies↗
PubMed1994

Psychiatric disorders in relatives of probands with panic disorder and/or major depression.

BACKGROUND: Panic disorder and major depression (MDD) are both highly familial disorders that co-occur in individuals but do not cosegregate in families. Evidence concerning their familial aggregation with other psychiatric disorders, including phobias, substance abuse, and antisocial personality, has been contradictory. In part, the contradictory findings may be due to failure to account for the effects of proband comorbidity on risks in relatives. METHODS: A family study of 1047 adult first-degree relatives of 193 probands in four diagnostic groups (panic disorder without MDD, panic disorder plus MDD, early-onset MDD, and screened normal controls) was used to determine the range of psychiatric disorders associated with panic disorder and MDD and the effects of proband comorbidity on the rates of disorders in relatives. RESULTS: Compared to relatives of normal controls, relatives of probands with panic disorder or panic disorder and MDD showed significantly increased risks of panic disorder, but relatives of probands with early-onset MDD did not. After proband comorbidity was controlled for, relatives of probands with panic disorder were also at a significantly increased risk for social phobia but not for any other psychiatric disorders. Relatives of probands with early-onset MDD were at significantly increased risk for MDD, dysthymia, abuse of or dependence on alcohol and other drugs, and antisocial personality disorders but not for any other psychiatric disorders. CONCLUSIONS: We conclude that panic disorder is a specific familial entity that is not associated with a broad range of other anxiety or other psychiatric disorders, with the possible exception of social phobia. Dysthymia, substance abuse, and antisocial personality appear to be on the spectrum of early-onset MDD.

Adolescent↗