Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%-40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. METHODS: In secondary analyses of a multi-center, prospective, trial of lithium for BD, we examined the relationship between circadian rhythms and therapeutic response to lithium. Using standardized instruments, we measured morningness, diurnal changes in mood, sleep, and energy (circadian rhythm disturbances) in a cross-sectional study of 386 BD subjects with varying lithium exposure histories. Next, we tracked symptoms of depression and mania prospectively over 12 weeks in a subset of 88 BD patients initiating treatment with lithium. Total, circadian, and affective mood symptoms were scored separately and analyzed. RESULTS: Subjects with no prior lithium exposure had the most circadian disruption, while patients stable on lithium monotherapy had the least. Patients who were stable on lithium with another drug or unstable on lithium showed intermediate levels of disruption. Treatment with lithium for 12 weeks yielded significant reductions in total and affective depression symptoms. Lithium responders (Li-Rs) showed improvement in circadian symptoms of depression, but non-responders did not. There was no difference between Li-Rs and nonresponders in affective, circadian, or total symptoms of mania. CONCLUSIONS: Exposure to lithium is associated with reduced circadian disruption. Lithium response at 12 weeks was selectively associated with the reduction of circadian depressive symptoms. We conclude that stabilization of circadian rhythms may be an important feature of lithium's therapeutic effects. CLINICAL TRIALS REGISTRY: NCT0127253.

Religiosity and Chance Beliefs in Persons with DSM-IV Pathological Gambling Enrolled in a Longitudinal Follow-Up Study.

This study investigates the association of public, private and intrinsic religiosity and chance beliefs (superstition, illusion of control) with gambling behavior in a longitudinal follow-up study of younger and older adult subjects with DSM-IV pathological gambling (PG) and an older adult comparison group without PG. One-hundred sixty-three subjects were enrolled including 60 younger adults with PG (≥ 18/< 40 years), 53 older adults with PG (≥ 60 years), and 50 older adults without PG (≥ 60). Subjects were assessed at baseline and every 6 months thereafter. The Duke University Religion Index for Religious Assessment and the Drake Beliefs About Chance scales were administered at baseline. Follow-up was a mean (SD) of 2.6 (1.4) years. Older adults with PG scored lower on measures of public and intrinsic aspects of religiosity than older adults without PG, and scored higher on superstition and illusion of control. Older adults with PG also scored higher than younger adults with PG on private and intrinsic religiosity, but not public religiosity. Superstition predicted intrinsic, but not other aspects of religiosity. Importantly, during follow-up, higher levels of public and intrinsic religiosity were protective against problematic (levels 2, 3) gambling; were protective against chronic PG; and were predictive of PG remission status. Lower illusion of control ratings were protective against problematic gambling and chronic PG; lower superstition ratings were predictive of remission. We conclude that higher levels of public and intrinsic religiosity and lower levels of chance beliefs are associated with a more benign PG course.

Five-year follow-up of people diagnosed with compulsive shopping disorder.

BACKGROUND: The authors assessed clinical symptoms and self-reported shopping and spending behavior in people diagnosed with compulsive shopping (CS) at a 5-year follow-up interview. METHODS: All met the criteria of McElroy et al. for lifetime CS and had the disorder for >1year. Structured and semistructured instruments and self-report questionnaires were used to collect data. RESULTS: Of the original 26 subjects, 17 (65%) were interviewed and are the focus of this report. At follow-up, their ages ranged from 23 to 67years (mean=44years). Lifetime psychiatric comorbidity was common, but few had current psychiatric disorders at follow-up. Interest in shopping and spending decreased for eight (47%), stayed the same for five (29%), and increased for four (24%) subjects. Eleven subjects (65%) reported having attempted to quit their CS and three (18%) reported successfully doing so. Triggers for returning to CS included feelings of pressure/excitement/tension to shop; boredom; negative feelings such as sadness, depression, frustration, or anger; and the desire for positive feelings like happiness, power, or elation. Mean scores on the Compulsive Buying Scale (CBS) and the shopping version of the Yale-Brown Obsessive-Compulsive Scale showed overall improvement in CS symptoms (d=1.16 and d=-1.19, respectively); subjects were also less impulsive (d=-0.48). At baseline and follow-up, those with a lifetime mood disorder tended to have greater CS severity. CONCLUSIONS: While the subjects showed overall improvement, most had ongoing symptoms of CS. The implications of the findings are discussed.

Intergenerational Childhood Maltreatment in Persons with DSM-IV Pathological Gambling and Their First-Degree Relatives.

This study investigates the characteristics of individuals with DSM-IV pathological gambling (PG) who experienced childhood maltreatment and rates of maltreatment occurring in their first-degree relatives (FDRs). 94 subjects with DSM-IV PG, 91 controls, and 312 FDRs were assessed for childhood maltreatment as part of a family study of PG. Maltreatment was evaluated using the Revised Childhood Experiences Questionnaire. The Family Assessment Device was used to evaluate the functionality of the PG subject's (or control's) family of origin. Data were analyzed using logistic regression by the method of generalized estimating equations. Rates of maltreatment were significantly higher in subjects with PG than controls (61 vs. 25 %, P < 0.001). Subjects with PG who experienced maltreatment were more likely to be female, had more severe PG symptoms, had co-occurring mood and anxiety disorders, and reported greater early family life dysfunction than those with PG who did not experience maltreatment. Rates of maltreatment were higher in FDRs of PG subjects than controls (41 vs. 24 %, P = .002). Rates in FDRs of individuals with PG who experienced maltreatment themselves were still higher that in FDRs of those with PG who did not experience maltreatment (50 vs. 28 %, P = .009). The former were also more likely to have anxiety disorders, substance use disorders, and suicide attempts. The results suggest that childhood maltreatment in persons with PG is common and intergenerational. Rates of maltreatment in FDRs of PG subjects are high, particularly among those who experienced abuse. The implications of the findings are discussed.

Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

BACKGROUND: Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. METHOD: Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. RESULTS: Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. CONCLUSIONS: Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed.

Personality Disorders, Impulsiveness, and Novelty Seeking in Persons with DSM-IV Pathological Gambling and Their First-Degree Relatives.

This study investigates the presence of personality disorders, impulsiveness, and novelty seeking in probands with DSM-IV pathological gambling (PG), controls, and their respective first-degree relatives using a blind family study methodology. Ninety-three probands with DSM-IV PG, 91 controls, and their 395 first-degree relatives were evaluated for the presence of personality disorder with the Structured Interview for DSM-IV Personality. Impulsiveness was assessed with the Barratt Impulsiveness Scale (BIS). Novelty seeking was evaluated using questions from Cloninger's Temperament and Character Inventory. Results were analyzed using logistic regression by the method of generalized estimating equations to account for within family correlations. PG probands had a significantly higher prevalence of personality disorders than controls (41 vs. 7 %, OR = 9.0, P < 0.001), along with higher levels of impulsiveness and novelty seeking. PG probands with a personality disorder had more severe gambling symptoms; earlier age at PG onset; more suicide attempts; greater psychiatric comorbidity; and a greater family history of psychiatric illness than PG probands without a personality disorder. PG relatives had a significantly higher prevalence of personality disorder than relatives of controls (24 vs. 9%, OR = 3.2, P < 0.001) and higher levels of impulsiveness. Risk for PG in relatives is associated with the presence of personality disorder and increases along with rising BIS Non-Planning and Total scale scores. Personality disorders, impulsiveness, and novelty seeking are common in people with PG and their first-degree relatives. The presence of a personality disorder appears to be a marker of PG severity and earlier age of onset. Risk for PG in relatives is associated with the presence of personality disorder and trait impulsiveness. These findings suggest that personality disorder and impulsiveness may contribute to a familial diathesis for PG.

Pathological gambling: relationship to obesity, self-reported chronic medical conditions, poor lifestyle choices, and impaired quality of life.

BACKGROUND: Pathological gambling (PG) is an important public health problem that is prevalent, costly to society, and associated with substance misuse, depression, domestic violence, crime, and suicide. Despite these challenges, little is known about the physical health and medical correlates of PG. The goal of this project was to assess self-reported chronic medical conditions, medication usage, lifestyle choices, health care utilization, quality of life variables, and body mass index (BMI) in persons with and without PG. METHODS: Subjects with PG and community controls were systematically assessed for their medical health, lifestyle choices, medication usage, and health care utilization. We administered the Medical Outcome Study Short-Form 36 Health Survey to assess perceived health and quality of life. BMI was calculated for all subjects. Obesity was defined as having a BMI≥30kg/m(2). RESULTS: We compared 95 subjects with DSM-IV PG (South Oaks Gambling Screen [SOGS] score≥5) and 91 control subjects without PG (SOGS≤2) selected through random digit dialing from the general community. PG subjects and controls were similar in age and gender. Persons with PG had more medical and mental health conditions than controls, and were more likely to avoid regular exercise, smoke≥1 pack/day, drink≥5 servings of caffeine daily, and watch television≥20hours/week. They had more emergency department visits for physical and mental health conditions, were more likely to have been psychiatrically hospitalized in the past year, and were more likely to take psychotropic medication. They were less likely to have had regular dental visits and were more likely to put off medical care due to financial problems. Severity of gambling was positively correlated with number of medical conditions. Persons with PG had poorer self-reported health perceptions on all but one SF-36 subscale. Importantly, persons with PG had a higher BMI than controls and were more likely to be obese. CONCLUSIONS: PG is associated with obesity, chronic medical conditions, poor lifestyle choices, worse quality of life, and the use of costly forms of medical care. Pathological gamblers are less likely to receive regular dental care and are more likely to be unable to pay for medical care. The implications of the findings are discussed.

Prevalence of problem gambling in Iowa: revisiting Shaffer's adaptation hypothesis.

BACKGROUND: Pathological gambling (PG) is an important public health problem. We assessed the prevalence of PG and problem (at-risk) gambling in a random sample of Iowa adults and compared the results to survey data collected in 1989 and 1995. The goal of this study was to examine whether continued expansion of gambling venues is associated with increased rates of problematic gambling behavior. METHODS: A random digit dialing telephone screening was conducted in eastern Iowa of men and women age ≥18. Respondents were administered the South Oaks Gambling Screen (SOGS) to assess lifetime gambling behavior. Demographic and clinical variables were collected. RESULTS: A total of 356 respondents (147 men, 209 women) completed the SOGS, and all reported lifetime gambling participation. PG (SOGS ≥5) was found in 5 (1.4%) and problem gambling (SOGS = 3, 4) in 8 (2.2%) respondents. Disordered gambling (SOGS ≥3) was found in 13 (3.6%) respondents. Risk factors for disordered gambling included age (odds ratio [OR] = 0.64 per 10-year age increase), income (OR = 0.82 per $10,000 increase), minority group status (OR = 5.75), number of lifetime gambling activities (OR = 1.27), and having ever gambled ≥$100 (OR = 13.3). Overall gambling participation was significantly less in the current sample, compared with data collected in 1995. CONCLUSIONS: Recent gambling participation was less than in 1995, despite the continued expansion of gaming opportunities. Disordered gambling was associated with younger age, lower income, and minority group status. The results are consistent with Shaffer's "adaptation" hypothesis, which posits that following an initial increase in gambling participation, problematic gambling stabilizes at a lower level.

An open-label trial of acamprosate in the treatment of pathological gambling.

BACKGROUND: The efficacy and tolerability of acamprosate has been tested in the treatment of pathological gambling (PG). Acamprosate is known to reduce alcohol craving and use in persons with alcohol dependence, and it has been hypothesized that the drug would have a similar effect in individuals with PG. METHODS: Participants with DSM-IV criteria for PG received acamprosate in an 8-week, open-label trial following a 2-week observation. The primary efficacy measure was the Yale-Brown Obsessive Compulsive Scale modified for PG (Y-BOCS-PG). Secondary efficacy measures included the Gambling Severity Assessment Scale (GSAS), the Clinical Global Impression (CGI) Improvement and Severity Scales, a patient self-rated global rating, the Hamilton Depression Rating Scale (HDRS), the Sheehan Disability Scale (SDS), and the Timeline Follow Back (TLFB). The study was conducted at 2 sites. RESULTS: Twenty-six participants (11 men, 15 women) had at least 1 post-baseline visit and were included in the analysis. Twenty participants (77%) completed the protocol. Significant improvement was observed in Y-BOCS-PG and GSAS scores, both CGI scales, a patient self-rated global scale, all 3 SDS subscales, and number of gambling episodes. Seventeen participants (65%) were considered responders (ie, achieved "much" or "very much" improvement). Improvements on the HDRS, in money wagered, and in time spent gambling were not significant. Few adverse events were reported. CONCLUSIONS: The results suggest that acamprosate is well tolerated and may be effective in the treatment of PG.

Pathological gambling and compulsive buying: do they fall within an obsessive-compulsive spectrum?

Both compulsive buying (CB) and pathological gambling (PG) have been proposed as members of a spectrum of disorders related to obsessive-compulsive disorder (OCD). The spectrum hypothesis originated in the early 1990s and has gained considerable support, despite the lack of empirical evidence. Interest in this hypothesis has become critical because some investigators have recommended the creation of a new category that includes these disorders in DSM-5, now under development. In this article, the authors describe the origin of the obsessive-compulsive (OC) spectrum and its theoretical underpinnings, review both CB and PG, and discuss the data both in support of and against an OC spectrum. Both disorders are described in terms of their history, definition, classification, phenomenology family history, pathophysiology, and clinical management. The authors conclude that: (i) CB and PG are probably not related to OCD, and there is insufficient evidence to place them within an OC spectrum in DSM-V; (ii) PG should stay with the impulse-control disorders (ICDs); and (iii) a new diagnosis of CB should be created and be classified as an ICD.

Increasing Confidence Through the Development of a Transition-to-Practice Orientation Program for the Experienced Nurse.

A formalized orientation program for experienced nurses was modeled after a program for new graduate nurses. Within a year, experienced nurses rotated through teaching stations, including simulations of shock and respiratory failure. Participants completed pre- and postsurveys and scored self-confidence on a Likert scale. Surveys showed a significant increase in participants' confidence related to elements in their new role. Future plans include a retention rate comparison of participants in this program versus nonparticipants.

The association between lithium use and neurocognitive performance in patients with bipolar disorder.

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1-5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1-5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

Internet addiction: definition, assessment, epidemiology and clinical management.

Internet addiction is characterized by excessive or poorly controlled preoccupations, urges or behaviours regarding computer use and internet access that lead to impairment or distress. The condition has attracted increasing attention in the popular media and among researchers, and this attention has paralleled the growth in computer (and Internet) access. Prevalence estimates vary widely, although a recent random telephone survey of the general US population reported an estimate of 0.3-0.7%. The disorder occurs worldwide, but mainly in countries where computer access and technology are widespread. Clinical samples and a majority of relevant surveys report a male preponderance. Onset is reported to occur in the late 20s or early 30s age group, and there is often a lag of a decade or more from initial to problematic computer usage. Internet addiction has been associated with dimensionally measured depression and indicators of social isolation. Psychiatric co-morbidity is common, particularly mood, anxiety, impulse control and substance use disorders. Aetiology is unknown, but probably involves psychological, neurobiological and cultural factors. There are no evidence-based treatments for internet addiction. Cognitive behavioural approaches may be helpful. There is no proven role for psychotropic medication. Marital and family therapy may help in selected cases, and online self-help books and tapes are available. Lastly, a self-imposed ban on computer use and Internet access may be necessary in some cases.

Extended release carbamazepine in the treatment of pathological gambling: an open-label study.

BACKGROUND: The efficacy and tolerability of extended release carbamazepine was tested in the treatment of pathological gambling (PG). METHOD: Non-depressed outpatients with DSM-IV PG received flexibly dosed extended release carbamazepine in a prospective 10-week open-label trial following a two-week observation period. Subjects were evaluated at baseline and at one week intervals during a four week titration period, and every two weeks thereafter for assessment of gambling behavior, mood, and adverse experiences. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale modified for PG (YBOCS-PG). RESULTS: Eight subjects (6 men, 2 women) had at least one post-baseline visit, and five subjects (63%) completed the protocol. Significant improvement was found on the YBOCS-PG (P< .001). Seven of the eight subjects with post-baseline assessment (88%) were considered responders (i.e., achieved "much" or "very much" improvement on the CGI). Four subjects (50%) abstained from gambling during their final month of study participation. Several patients were dropped because of adverse experiences. CONCLUSION: The results suggest that extended release carbamazepine may be effective in the treatment of PG.

Neuropsychological characteristics and personality traits in pathological gambling.

INTRODUCTION: Pathological gambling disorder (PG) has been associated with fronto-temporal dysfunction and maladaptive personality traits, such as impulsivity and novelty seeking. The purpose of this study was to examine the predictive variance of neuropsychological and personality characteristics in PG. METHODS: Persons with PG (n=25) and a comparison group (n=34) were administered a battery of neuropsychological tests, the Temperament and Character Inventory, and the Barratt Impulsiveness Scale. Subjects with PG had evidence of fronto-temporal dysfunction as assessed by the Stroop, Wisconsin Card Sorting Test-64, Wechsler Adult Intelligence Scale Letter-Number Sequencing, Controlled Oral Word Association Test, and Boston Diagnostic Aphasia Examination Animal Naming Test. RESULTS: Subjects with PG also had impaired decision making on the Iowa Gambling Task. PG subjects had elevated levels of impulsivity, novelty seeking, and harm avoidance, and lower levels of self-directedness and cooperativeness. Logistic regression analyses indicated that neuropsychological variables did not add significant incremental variance over personality traits in predicting PG (Block chi-square=5.19, P=.074), while personality variables added significant incremental variance over neuropsychological traits in predicting PG (Block chi-square=25.13, P<.001). CONCLUSION: These results suggest that personality traits are better predictors than neuropsychological characteristics of whether someone has PG.

An open-label trial of escitalopram in the treatment of pathological gambling.

BACKGROUND: The effectiveness and tolerability of escitalopram was tested in the treatment of pathological gambling (PG). METHOD: Nondepressed outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PG received flexibly dosed escitalopram in a prospective, 10-week, open-label trial after a 2-week observation period. Subjects were evaluated at baseline and at 2-week intervals for assessment of gambling behavior, mood symptoms, and adverse experiences. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale modified for PG. Secondary efficacy measures included the Clinical Global Impression (CGI) Improvement and Severity Scales, a patient self-rated global rating, the Sheehan Disability Scale, and the Timeline Follow Back. RESULTS: Nineteen subjects (12 men and 7 women) had at least 1 postbaseline visit and were included in the analysis; 16 subjects (84%) completed the protocol. Significant improvement was found in all measures, including the Yale-Brown Obsessive-Compulsive Scale modified for PG, both CGI Scales, a patient self-rated global scale, the Timeline Follow Back, the Attention-Deficit/Hyperactivity Disorder Checklist, the Hamilton Depression Rating Scale, and all 3 Sheehan Disability Scale subscales. Fourteen subjects (73.7%) were considered responders (ie, achieved "much" or "very much" improvement on the CGI). Few adverse experiences were reported. CONCLUSION: The results suggest that escitalopram is well tolerated and may be effective in the treatment of PG.

The effect of pathological gambling on families, marriages, and children.

Pathological gambling (PG) is widely reported to have negative consequences on marriages, families, and children. Empirical evidence is only now accumulating but when put together with anecdotal information, the extent of these problems is clear. PG contributes to chaos and dysfunction within the family unit, disrupts marriages, leading to high rates of separation and divorce, and is associated with child abuse and neglect. Divorce rates are high, not surprising in light of reports that these marriages are often abusive. Research shows that the families of pathological gamblers are filled with members who gamble excessively, suffer from depressive or anxiety disorders, and misuse alcohol, drugs, or both. Families of persons with PG are also large, a variable independently related to family dysfunction. The authors review the evidence on the impact of PG on families, marriages, and offspring, and make recommendations for future research targeting these problems.

A prospective follow-up study of younger and older subjects with pathological gambling.

Pathological gambling (PG) is a common and costly public health problem associated with impaired quality of life and high suicide rates. Despite its frequency in the general population, PG course is poorly understood in older adults who are especially vulnerable to its devastating consequences. We enrolled 175 subjects in a longitudinal study of gambling behavior: our case group of 53 older adults with PG (≥ 60 years), and two comparison groups including 72 younger adults with PG (< 40 years) and 50 older adults without PG (≥ 60 years). Subjects with PG met lifetime criteria for DSM-IV PG and had a South Oaks Gambling Screen (SOGS) and National Opinion Research Center DSM Screen for Gambling Problems (NODS) scores ≥ 5. Subjects were evaluated at intake and reassessed every 6 months and drop outs were replaced. Follow-up lasted a mean (SD) of 2.6 (1.4) years. At intake older PGs were more likely to be female, Caucasian, divorced, and to have a lower level of education. Older and younger PGs were similar in gambling severity, but older PGs were more likely to have sought PG treatment. Older PGs had lower rates of lifetime drug use disorders, attention deficit/hyperactivity disorder, and obsessive-compulsive disorder. They preferred slots, were more likely to receive PG treatment, and were less likely to discontinue participation in the study. Week by week gambling activity levels showed a significant general downward movement for older and younger PGs, although there were no differences between the groups. Elders without PG had no change in their level of gambling activity. We conclude that younger and older PGs moved toward a reduced level of gambling activity during follow-up. Our data challenge the notion that PG is chronic and progressive.

A family study of pathological gambling.

The cause of pathological gambling (PG) is unknown. The current study was conducted to determine whether PG is familial, and to examine patterns of familial aggregation of psychiatric disorder. To that end, 31 case probands with DSM-IV PG and 31 control probands were recruited and interviewed regarding their first degree relatives (FDRs). Available and willing FDRs were directly interviewed with structured instruments of known reliability, and best estimate final diagnoses were blindly assigned for 193 case and 142 control relatives over age 18 years. The results were analyzed using logistic regression by the method of generalized estimating equations. The lifetime rates of PG and "any gambling disorder" were significantly greater among the relatives of case probands (8.3% and 12.4%, respectively) than among the control relatives (2.1% and 3.5%, respectively) (OR=3.36 for "any gambling disorder"). PG relatives also had significantly higher lifetime rates of alcohol disorders, "any substance use disorder," antisocial personality disorder (ASPD), and "any mental disorder". "Any gambling disorder," alcohol disorder, and "any substance use disorder" remained significant after a conservative Bonferroni correction. Interestingly, PG families were significantly larger than control families. We conclude that gambling disorders are familial and co-aggregate with substance misuse. The data are also suggestive that PG co-aggregates with ASPD. Further research on the heritability of PG is warranted.