Substance use disorders in high-risk adolescent offspring.

OBJECTIVE: To examine the risk for substance use disorders (SUD) in offspring of SUD parents who were not selected due to referral to SUD treatment centers. METHODS: The original sample was ascertained through two groups of index children: 140 ADHD probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. RESULTS: We found that: 1) parental SUD was associated with SUD and all SUD subtypes in the offspring; 2) parental alcohol use disorders were associated with alcohol use disorders in the offspring as well as co-occurring alcohol and drug use disorders but not drug use disorders alone in the offspring; and 3) drug use disorders in the parents were associated with drug use disorders but not alcohol use disorders in the offspring. CONCLUSIONS: These findings suggest that alcoholism and drug abuse may breed true from parents to their offspring, but further work with larger samples is needed to confirm this idea. Our findings also suggest a possible common diathesis that is expressed as comorbid alcohol and drug use in the offspring of alcoholic parents. If confirmed, these findings may be useful for the development of preventive and early intervention strategies for adolescents at high risk for SUD based on parental history of SUD.     

A family study of the high-risk children of opioid- and alcohol-dependent parents

In this article, the author sought to use a high-risk study design focused on the children of parents with opioid or alcohol use disorders and children of parents with no substance use disorder (SUD) to evaluate the specificity of the risk conferred by the type of parental SUD. Using structured psychiatric interviews, cognitive assessments, and measures of social, academic, and family functioning, the authors studied 96 families (187 parents and 183 children, mean age of 11.6 years). Sixteen families had parental opioid dependence (22 children, 64% male), 14 families had parental alcohol dependence (22 children; 59% male), and 66 families had no SUD (controls; 139 children; 58% male). Fifty-nine percent of children of opioid-dependent parents had at least one major psychopathological condition, compared to 41% of the alcohol group and 28% of the control group (p < 0.01). The children of opioid- and alcohol-dependent parents were of lower socioeconomic status and had significantly more diffculties in academic, social, and family functioning than did controls. Children of opioid- and alcohol-dependent parents have significantly higher rates of psychopathology as well as more difficulties in academic, social, and family functioning compared to the children of non-SUD parents. In addition, notable trends emerged for the opioid group to have more psychopathology and functional impairment than the alcohol group. With a growing consensus that certain risk factors for later SUD start in childhood with potentially treatable childhood-onset disorders, new preventive approaches for individuals at risk may be developed targeting childhood precursors of     

Risk of mental disorders in children of parents with alcohol or heroin dependence: a controlled high-risk study

Aim: To assess the specific effect of alcohol dependence (AD) or heroin dependence (HD) in patients and their spouses on the risk of psychopathology in their 276 6.0- to 17.9- year-old children (mean 11.3 years). Methods: The sample included 101 offspring of patients with AD, 23 of patients with HD, and 152 of medical controls, as well as their 2 parents. Participants were assessed using semistructured diagnostic interviews and family history reports by psychologists blind to patient diagnoses. Results: Children of HD and AD patients had largely elevated rates of recurrent major depressive disorder. Children of HD patients were also at an increased risk for attention deficit hyperactivity disorder and substance use disorders (SUD). There were interactions between SUD in the 2 parents to increase the risk of SUD in offspring. Conclusions: These results emphasize the need for prompt identification and treatment of these children and highlight the need to pay clinical attention not only to the patient, but also to the co-parent in order to optimize prevention in offspring.     

Characteristics of adults with attention deficit hyperactivity disorder plus substance use disorder: the role of psychiatric comorbidity

The objective of the study was to investigate the characteristics of adults with Attention Deficit Hyperactivity Disorder (ADHD) or substance use disorder (SUD), especially in the context of comorbid psychiatric disorders. Subjects were adults (n = 78) participating in a controlled family study of ADHD and SUD. Four groups were identified based on a diagnosis of ADHD or SUD: ADHD, SUD, ADHD + SUD, and neither ADHD nor SUD. All diagnoses were determined by structured clinical interview for DSM IV. Rates of psychiatric comorbidity were lowest in the controls, intermediate in the ADHD and SUD groups, and highest in the ADHD + SUD group. Relative to controls, the ADHD, SUD, and ADHD + SUD groups had higher rates of major depression (z = 1.98, p = 0.05), conduct disorder (z = 2.0, p = 0.04), antisocial personality disorder (z = 2.6, p = 0.009), agoraphobia (z = 2.5, p = 0.01) and social phobia (z = 2.7, p = 0.007). Higher rates of psychiatric comorbidity, especially mood and anxiety disorders, exist in subjects with SUD + ADHD relative to subjects with SUD, ADHD, or controls. Clinicians need to be attentive to other psychiatric disorders that may occur in the large group of adults with ADHD + SUD.     

ADHD, bruxism and psychiatric disorders: does bruxism increase the chance of a comorbid psychiatric disorder in children with ADHD and their parents?

There is an association between bruxism and ADHD. No published data on psychiatric comorbidities in attention-deficit/hyperactivity disorder (ADHD) children with bruxism were found. There is no satisfying treatment method for children with bruxism. If we understand its comorbidities well, a better treatment method could come out. This study was conducted to compare the frequency of comorbid psychiatric disorders in the parents and their ADHD children with and without teeth grinding. It was hypothesized that there is no association between bruxism and prevalence of comorbid psychiatric disorders in children with ADHD and their parental psychopathology. Eighty-nine ADHD children without teeth grinding were compared with 32 ADHD children with teeth grinding. Their parental psychiatric disorders were also compared. Structured interviews were used to diagnose comorbid psychiatric disorders. The demographic characteristics of the children and their parents were not different between the groups. The only psychiatric disorder in children, which was associated with the groups was oppositional defiant disorder. The rate of conduct disorder, tic disorder, major depressive disorder, separation anxiety disorder, generalized anxiety disorder, enuresis, and obsessive compulsive disorder were not different between the two groups of children. The rate of major depression was more in the mothers of children with teeth grinding than those without such children. These finding were not reported before. ADHD children with teeth grinding have a high prevalence of oppositional defiant disorder. Lack of association between anxiety disorder and presence of teeth grinding might not support the idea that anxiety is associated with teeth grinding. The association of ODD and teeth girding might be a clue about etiology of bruxism. Perhaps, this clue can probably lead to the development of a more satisfying treatment. With consideration of this clue, further studies should survey if there is any association between ODD and sleep micro-arousals.     

Treatment strategies for co-occurring ADHD and substance use disorders

Attention-deficit hyperactivity disorder (ADHD) is a common co-occurring mental disorder among patients with substance use disorders (SUD). Clinicians must be cognizant of the complicated nature of diagnosis and treatment of ADHD when comorbid with SUD. Pharmacotherapy remains the mainstay of treatment for ADHD, although complementary psychotherapeutic approaches have been developed. Psychostimulant medications are the most commonly used medications to treat ADHD, but many clinicians are reluctant to prescribe stimulants to patients with SUD. Recommendations for treatment planning and clinical management for patients with co-occurring ADHD and SUD are discussed.     

Parental history of psychiatric disorders and risk of type 1 diabetes in the offspring

ObjectiveTo examine risk of type 1 diabetes mellitus (T1DM) in the offspring of parents with a psychiatric history at the birth of the child, which would suggest potential shared familial or environmental risk factors between T1DM and psychiatric disorders.MethodsWe established a cohort including all children born in Sweden in 1997–2016, and their parents. Children were followed up from birth until 31 Dec 2017, using national registers. Relative risk for T1DM was estimated by incidence rate ratios (RR) with 95% confidence intervals (CI), calculated from Poisson regression. We examined psychiatric subtypes, T1DM risk within subgroups and in relation to the timing of exposure.ResultsThe study cohort included 1,497,949 children. During follow-up, 7,794 cases of T1DM were identified. Children of mothers with psychiatric disorders at delivery had a higher risk of T1DM (RR 1.10 [95%CI 1.01–1.20]). Psychiatric diagnoses in fathers or assigned after delivery was not associated with increased T1DM risk. The observed association disappeared after adjusting for T1DM in parents; however, remained significant in female offspring. Maternal eating disorder (RR 1.53 [1.17–2.00]) and obsessive-compulsive disorder (RR 1.62 [1.02–2.58]) were associated with offspring T1DM, independent of parental T1DM.ConclusionOur results do not support a strong genetic link between psychiatric conditions and T1DM. However, the risks of offspring T1DM were increased in subgroups of female offspring and in offspring of mothers with a history of eating disorder or obsessive-compulsive disorder, independent of heredity for T1DM, which may warrant further investigation in future studies.     

Attention-deficit/hyperactivity disorder and substance use: symptom pattern and drug choice.

While there has been much recent interest in the relationship between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs), little has been reported about ADHD diagnostic subtypes, persistence of symptoms from childhood into adulthood, and substance of choice in individuals with substance use disorders (SUD+) and comorbid ADHD. To examine the prevalence and subtypes of ADHD in a group of SUD+ individuals, 136 inpatients with an SUD diagnosis (cocaine vs. alcohol vs. cocaine/alcohol) were administered a structured interview for ADHD. Of the SUD+ individuals, 32% met criteria for ADHD, and 35% of those with a childhood diagnosis of ADHD continued to have clinically significant symptoms into adulthood. There were no significant differences in the percentage of ADHD between the SUD+ groups divided by drug choice. Of ADHD subtypes, subjects with combined and inattentive types were significantly more likely to have symptoms continue into adulthood (p < or = .05) than the hyperactive/impulsive subtype. Patients with cocaine use were more likely to have ADHD in childhood only when compared to the alcohol or cocaine-alcohol groups. The findings of this study indicate that ADHD is prevalent in treatment-seeking substance users without difference in prevalence or subtype by drug choice.     

Association of parental hypertension with concentrations of select biomarkers in nonhypertensive offspring

Children of parents with hypertension are at increased risk of developing high blood pressure. We hypothesize that circulating concentrations of putative biomarkers (that may play a role in development of high blood pressure) are higher in nonhypertensive offspring of parents with hypertension. We compared concentrations of 4 different biomarkers (urinary albumin:creatinine ratio, circulating C-reactive protein, aldosterone:renin ratio, and plasminogen activator inhibitor-1) in nonhypertensive Framingham offspring study participants with none (n=233), 1 (n=474), or both (n=322) parents with hypertension. Parental hypertension was defined as onset before age 60 years, based on longitudinal observations of the original Framingham cohort. Serum C-reactive protein concentrations were higher in nonhypertensive offspring with 1 (median: 1.7; Q1 to Q3: 0.8 to 3.6 mg/L) or both parents with hypertension (median: 1.8; Q1 to Q3: 0.7 to 3.6 mg/L) compared with offspring without parental hypertension (median: 1.4; Q1 to Q3: 0.7 to 3.2 mg/L). In multivariable analyses, parental hypertension was associated with higher serum C-reactive protein concentration in offspring (15% increase per parent with hypertension; P=0.004). Prospectively, the relation of parental hypertension to longitudinal changes in blood pressure in the nonhypertensive offspring was attenuated on adjustment for C-reactive protein (P=0.04 for attenuation). The levels of the other biomarkers evaluated did not significantly differ in offspring according to parental hypertension status. In conclusion, serum C-reactive protein concentrations are higher in nonhypertensive offspring of parents with hypertension. These data suggest that inflammation may partly mediate the familial influences on hypertension risk.     

The association of cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) between young parents and their offspring: the Bogalusa Heart Study.

Cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) was examined in a community-based sample of 599 genetically unrelated school-aged children (5-17 years) and their parents. Risk factors used as components of Syndrome X included hyperinsulinemia, obesity, dyslipidemia and high blood pressure defined by values above the age-, sex- and race-specific 75th percentiles of fasting insulin, body mass index, triglycerides/high-density lipoprotein cholesterol ratio and mean arterial pressure, respectively. Based on observed to expected ratio there was an excess of parents (father and/or mother) and their offspring with clusters of three or four disorders (P < 0.05-0.001). In contrast, the number of parents and offspring with two disorders was significantly lower than expected by chance alone (P < 0.05-0.01). Based on paternal, maternal, and parental Syndrome X, the odds ratios (95% confidence interval) for offspring having the same cluster were 7.2 (1.9-27.2), 8.6 (3.1-23.6) and 7.9 (3.5-18.1), respectively. In terms of individual risk factors of parents used as predictors, adverse levels of their insulin and BMI significantly increased the risk of offspring having Syndrome X (P < 0.01-0.001), whereas the effect of parental insulin was considerably reduced after parental BMI was adjusted for. In contrast, parental dyslipidemia and high blood pressure were not associated with the occurrence of Syndrome X in their offspring. These results confirm the familial nature of Syndrome X and suggest that conditions of obesity and the attendant hyperinsulinemia in parents may underlie this familial association.     

Parental hypertension and proteinuria in Pima Indians with NIDDM

Summary To determine if parental hypertension is associated with proteinuria in offspring with non-insulin-dependent diabetes mellitus (NIDDM), 438 diabetic Pima Indians (172 men, 266 women) aged 20 years or more and both of their parents were examined. Hypertension was defined as a systolic blood pressure 140 mm Hg or more, diastolic blood pressure 90 mm Hg or more, or treatment with antihypertensive medicine. Sixty-three percent of the fathers and 80% of the mothers had diabetes at the time their blood pressure was measured. Families in which either parent had proteinuria, defined as a urine protein-to-creatinine ratio 0.5 g/g were excluded; 73 (16.7%) of the offspring had proteinuria. The prevalence rates of proteinuria in the offspring were similar if neither parent or only one parent had hypertension (8.9 and 9.4%, respectively), but was significantly higher if both parents had hypertension (18.8%), after adjustment for age, sex, duration of diabetes, and 2-h post-load plasma glucose concentration in the offspring and diabetes in the parents by logistic regression. The odds for proteinuria being present in the offspring if both parents had hypertension was 2.2 times (95% confidence interval, 1.2 to 4.2) that if only one parent had hypertension. When mean arterial pressure and blood pressure treatment in the offspring were added to the model the relationship remained (odds ratio =2.2; 95% confidence interval, 1.1 to 4.3). Hypertension in both parents is associated with the development of proteinuria in offspring with NIDDM. This relationship was present even when controlled for the effects of blood pressure and its treatment in the offspring.Abbreviations IDDM Insulin-dependent diabetes mellitus - JNC V Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure - MAP mean arterial pressure - NIDDM non-insulin-dependent diabetes mellitus     

Diabetic nephropathy: a risk factor for diabetes mellitus in offspring

Summary Both non-insulin-dependent diabetes mellitus and diabetic nephropathy show familial aggregation. If diabetes and renal disease have independent determinants (genetic or otherwise), offspring of parents with diabetic renal disease should have a similar risk of diabetes to those offspring of parents with diabetes alone. To test this hypothesis, the prevalence of diabetes was examined in a population-based pedigree study in Pima Indian offspring of three mutually exclusive parental types: 1) diabetic with renal disease, 2) diabetic, but without renal disease and 3) non-diabetic. Among offspring of one diabetic parent and one non-diabetic parent (n=320) the prevalence of diabetes at ages 15–24 years and 25–34 years was 0% and 11%, respectively if the diabetic parent did not have renal disease compared with 6% and 28% respectively if the diabetic parent did have renal disease. Corresponding rates for offspring of two diabetic parents (n=121) were 10% and 17%, respectively if neither parent had renal disease compared with 30% and 50%, respectively if one parent did have renal disease. The presence of renal disease in a parent with diabetes relative to diabetes alone was associated with 2.5 times the odds of diabetes (95% confidence interval 1.4–4.3) in the offspring controlled for age, age at onset of parental diabetes and diabetes in the other parent using logistic regression. These findings provide support for parental diabetic renal disease, independent of age at onset of parental diabetes, conferring an increased risk for diabetes in the offspring. The results are compatible with the hypothesis that the susceptibility to renal disease in the parents and to diabetes in the offspring are due to shared familial environmental factors or to the same gene or set of genes.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - ESRD end-stage renal disease     

Reciprocal influence of parent discipline and child's behavior on risk for substance use disorder: a nine-year prospective study

AIM: This study aimed at determining the association of father's and mother's (parental) substance use disorder (SUD) and discipline styles and son's neurobehavior disinhibition (ND) with son's SUD from childhood (age 10-12) to young adulthood (age 19). It was hypothesized that (1) parental discipline styles and son's ND mediate the association between parental SUD and son's SUD, (2) son's ND mediates the association between parental discipline styles and son's SUD, and (3) parental discipline styles mediate the association between ND and SUD in the son. METHODS: Two-hundred-sixty-three families including a 10-12 year-old son and both parents participated in the study. RESULTS: (1) mother's discipline styles predicted father's discipline styles, (2) son's ND predicted mother's instilling guilt positively and father's punishment negatively, (3) son's ND mediated the association between father's SUD and punishment and son's SUD, and (4) mother's SUD predicted son's ND and SUD. CONCLUSIONS: The reciprocal prediction between son's ND and father's punishment and prediction of father's punishment by mother's punishment point to the need for family-based interventions that take into account the quality of specific dyadic interactions pertaining to discipline behaviors that amplify the risk for SUD in male children.     

Motives underlying smoking in college students with ADHD

Background. The positive association between attention deficit hyperactivity disorder (ADHD) symptoms and smoking in youth has been well documented. Less research has examined why individuals with ADHD, particularly college students, are at increased risk for smoking. Objectives. This longitudinal study examined whether smoking motives [cognitive enhancement, tolerance, negative reinforcement (smoking to reduce negative affect or stress), craving, social influences, and weight control] helped to explain the relation between ADHD symptoms (inattention and hyperactivity/impulsivity) and cigarette smoking among college students. Methods. Participants were 889 undergraduates (21% men) and their parents who completed online surveys at the beginning and end of the Fall semester regarding their smoking behaviors, ADHD symptoms, and smoking motives. Structural equation modeling was used to analyze data and answer research questions. Results. Nineteen percent of students reported smoking, while 20% reported one or more inattentive symptoms, 35% reported one or more hyperactive/impulsive symptoms, and 3.3% met criteria for ADHD. All smoking motives significantly moderated the relation between inattentive symptoms and smoking, while most smoking motives (negative reinforcement, tolerance, craving, cognitive enhancement, and weight control) moderated the link between hyperactive/impulsive symptoms and smoking. Results remained significant after controlling for stimulant medication use and conduct disorder symptoms. Conclusions/Importance. Addressing negative reinforcement, craving, social influences, and tolerance in prevention and intervention efforts on college campuses may reduce smoking. Results also highlight the importance of assessing a range of ADHD symptoms in college students as ADHD symptoms, even at subthreshold levels, were associated with increased smoking rates among college students.     

Attention-Deficit/Hyperactivity Disorder and Substance Use: Symptom Pattern and Drug Choice

While there has been much recent interest in the relationship between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs), little has been reported about ADHD diagnostic subtypes, persistence of symptoms from childhood into adulthood, and substance of choice in individuals with substance use disorders (SUD+) and comorbid ADHD. To examine the prevalence and subtypes of ADHD in a group of SUD+ individuals, 136 inpatients with an SUD diagnosis (cocaine vs. alcohol vs. cocaine/alcohol) were administered a structured interview for ADHD. Of the SUD+ individuals, 32% met criteria for ADHD, and 35% of those with a childhood diagnosis of ADHD continued to have clinically significant symptoms into adulthood. There were no significant differences in the percentage of ADHD between the SUD+ groups divided by drug choice. Of ADHD subtypes, subjects with combined and inattentive types were significantly more likely to have symptoms continue into adulthood (p ≤. 05) than the hyperactive/impulsive subtype. Patients with cocaine use were more likely to have ADHD in childhood only when compared to the alcohol or cocaine-alcohol groups. The findings of this study indicate that ADHD is prevalent in treatment-seeking substance users without difference in prevalence or subtype by drug choice.     

Alcohol Expectancies and Drinking Characteristics in Parents of Children with Attention Deficit Hyperactivity Disorder

Alcohol expectancies, drinking characteristics, and their association were examined in 587 adults: 431 parents of children with attention deficit hyperactivity disorder (ADHD) and 156 parents of children without ADHD. In addition to examining both traditional and parenting-specific alcohol expectancies for these adults, risk variables cutting across the two groups were considered: single parenthood and male gender. Few differences in mean expectancy levels were found between parents of children with and without ADHD, between single and married mothers, and between men and women. Furthermore, expectancies did not predict drinking differently across groups. However, there was some support for the utility of assessing parental expectations of alcohol's effects on interactions with children, and there were robust and interesting effects of socioeconomic status on expectancies and drinking. Single mothers also reported consuming higher quantities of alcohol than married mothers. Findings are discussed in terms of the link between ADHD and alcoholism, the ability of alcohol expectancies to explain drinking differences between high risk groups, the effect of socioeconomic status on these variables, and single motherhood as a vulnerability factor for increased drinking.     

High and Low Neurobehavior Disinhibition Clusters within Locales: Implications for Community Efforts to Prevent Substance Use Disorder

Background: Knowledge of where substance use and other such behavioral problems frequently occur has aided policing, public health, and urban planning strategies to reduce such behaviors. Identifying locales characterized by high childhood neurobehavioral disinhibition (ND), a strong predictor of substance use and consequent disorder (SUD), may likewise improve prevention efforts. Objectives: The distribution of ND in 10–12-year olds was mapped to metropolitan Pittsburgh, PA, and tested for clustering within locales. Methods: The 738 participating families represented the population in terms of economic status, race, and population distribution. ND was measured using indicators of executive cognitive function, emotion regulation, and behavior control. Innovative geospatial analyzes statistically tested clustering of ND within locales while accounting for geographic barriers (large rivers, major highways), parental SUD severity, and neighborhood quality. Results: Clustering of youth with high and low ND occurred in specific locales. Accounting for geographic barriers better delineated where high ND is concentrated, areas which also tended to be characterized by greater parental SUD severity and poorer neighborhood quality. Conclusions and Significance: Offering programs that have been demonstrated to improve inhibitory control in locales where youth have high ND on average may reduce youth risk for SUD and other problem behaviors. As demonstrated by the present results, geospatial analysis of youth risk factors, frequently used in community coalition strategies, may be improved with greater statistical and measurement rigor.     

Characteristics of Framingham offspring participants with long-lived parents

BACKGROUND: Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity. METHODS: We studied 1697 Framingham Heart Study (FHS) offspring members 30 years or older, whose parents (1) participated in the original FHS cohort and (2) achieved age 85 years or died before January 1, 2005. Offspring participants (mean +/- SD age, 40 +/- 7 years; 51% women) were grouped according to whether neither (n = 705), one (n = 804), or both parents (n = 188) survived to 85 years or older. We examined offspring risk factors at examination cycle 1 (1971-1975) including age, sex, education, cigarette smoking, systolic and diastolic blood pressures, total-high-density lipoprotein cholesterol ratio, body mass index, and Framingham Risk Score. Participants returning for examination cycle 3 (1983-1987; n = 1319) were eligible for inclusion in longitudinal analyses evaluating risk factor progression from baseline to a higher follow-up risk category. RESULTS: For all factors studied, except body mass index, we observed statistically significant linear trends for lower offspring examination 1 risk factor levels with increasing parental survival category. The mean Framingham Risk Score was most favorable in offspring with both parents surviving to 85 years or older and was progressively worse in those with one or no long-lived parent (0.55, 1.08, and 1.71, respectively; P value for trend, <.001). Longitudinally, offspring of parents who lived longer had lower risk of blood pressure and Framingham Risk Score progression. CONCLUSIONS: Our findings suggest that individuals with long-lived parents have advantageous cardiovascular risk profiles in middle age compared with those whose parents died younger. The risk factor advantage persists over time.     

Effects of Deviant Child Behavior on Parental Alcohol Consumption: Stress-Induced Drinking in Parents of ADHD Children

Distress and ad lib alcohol consumption after interactions with child confederates were investigated in parents of children with externalizing disorders—attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD), or oppositional defiant disorder (ODD). Sixty subjects interacted with boys trained to act like either normal children or children with ADHD/CD/ODD. Interactions with deviant confederates resulted in feelings of inadequacy and produced negative affect but had no effect on alcohol consumption. Post hoc analyses showed that parents with a family history of alcohol problems (FH+) showed increased drinking after interaction with a deviant confederate, compared with FH+ parents who interacted with the normal confederate. FH- parents showed the opposite pattern of results. (Am J Addict 1998; 7:103–114)     

Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure.

AIM: To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young people. SUBJECTS: Eight hundred and sixty-four people aged 16-24 years and their parents. SETTING: Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD: Blood pressure was measured in 864 young adults and in both of their parents. Four groups of approximately 50 offspring were selected from the corners of a scatter diagram, with offspring blood pressure scores on one axis and combined parental blood pressure scores on the other. Blood and urine samples were taken for biochemical and genetic analyses. RESULTS: Two groups of offspring had parents with high blood pressure and two groups had parents with low blood pressure. When parental blood pressure was low, comparison of offspring with high and low blood pressure revealed significantly higher mean body mass index in offspring with high blood pressure, but no significant elevation of biochemical or hormonal variables. When parental blood pressure was high, comparison of offspring with high and low blood pressure also revealed a significant difference in body mass index, but in addition, offspring with high blood pressure and high parental blood pressure had higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction fragment length polymorphism analysis revealed that 27% of offspring at the greatest genetic risk (high personal and parental blood pressure) were homozygous for the larger allele of the glucocorticoid receptor gene compared with only 9% of those at lowest genetic risk (low personal and parental blood pressure). CONCLUSION: The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure. The new sampling method is practicable and could be applied to the investigation of other continuously distributed variables which show familial aggregation.