Alan M. Gruenberg

Bio: Alan M. Gruenberg is an academic researcher from Yale University. The author has contributed to research in topics: Schizophrenia & Schizotypal personality disorder. The author has an hindex of 21, co-authored 22 publications receiving 3118 citations.

The Roscommon Family Study. I. Methods, diagnosis of probands, and risk of schizophrenia in relatives.

Abstract: Objectives: We sought to examine, in a rural county in the West of Ireland, the degree of familial relationship between schizophrenia and other nonaffective psychoses and affective illness (AI). Design: A case-controlled epidemiologic family study using DSM-III-R criteria. Participants: This study incuded three proband groups: (1) all cases with a clinical diagnosis of schizophrenia from the Roscommon County Case Register born from 1930 onward (n=285); (2) a random sample of cases from the register with a clinical diagnosis of severe AI (n=99); and (3) a matched, random sample of Roscommon residents ascertained from the electoral register (n=150). Face-toface structured interviews were conducted with 86% of traceable, living relatives (n=1, 753) and 88% of traceable, living probands (n=415). Results: In interviewed relatives, the lifetime risks (±SE) for schizophrenia, as a function of the "blind" proband di- agnosis, were as follows: schizophrenia, 6.5% ± 1.6%; schizoaffective disorder, 6.8%±2.5%; schizotypal personality disorder, 6.9%±3.9%; other nonaffective psychoses, 5.1%±2.4%; psychotic AI, 2.8%±1.2%; nonpsychotic AI, 0.6%±0.6%; and control, 0.5%±0.3%. Individuals with schizophrenia reproduced at a rate about one quarter that of controls and the risk for schizophrenia in parents of probands was much less than that found in siblings. Conclusions: These results support the following hypotheses: (1) in the West of Ireland, as in other populations, schizophrenia is a strongly familial disorder; (2) schizophrenia shares a familial predisposition with a spectrum of clinical syndromes that includes schizoaffective disorder, other nonaffective psychoses, schizotypal personality disorder, and probably psychotic AI, but not nonpsychotic AI; and (3) the diminished reproductive rates associated with schizophrenia have a large impact on the pattern of risk of illness in relatives.

The Roscommon Family Study: III. Schizophrenia-Related Personality Disorders in Relatives

Abstract: Objectives: We sought to clarify the familial relationship between five putative schizophrenia-related personality disorders (schizotypal [SPD], paranoid, schizoid, avoidant, and borderline) and schizophrenia, other nonaffective psychoses, and affective illness. Design: A case-controlled epidemiologic family study using DSM-III-R criteria. Participants: Five hundred thirty-four probands selected from a psychiatric case register or electoral register, of whom 415 were personally interviewed, and 2043 living and traceable relatives, of whom 1753 were personally interviewed. Results: Compared with relatives of unscreened controls, relatives of probands with schizophrenia had a highly significantly increased prevalence of SPD, and modest, but significant, increased prevalences of paranoid, schizoid, and avoidant personality disorders. Borderline personal- ity disorder was rare, with a modest clustering of cases in relatives of affective disorder probands. The prevalence of SPD was also significantly elevated in relatives of probands with SPD and with other nonaffective psychoses but not in relatives of probands with psychotic or nonpsychotic affective illness. In contrast to the pattern seen for schizophrenia, the prevalence rate of SPD was substantially greater in parents than in siblings of schizophrenic probands. Conclusions: Schizotypal personality disorder has a strong familial relationship with schizophrenia. Paranoid, schizoid, and avoidant, but not borderline, personality disorders may have a significant familial relationship with schizophrenia. Schizotypal personality disorder also reflects the familial liability to other psychotic disorders but probably not to affective illness. Fitness effects may substantially influence the pattern of schizophrenia-related personality disorders in relatives.

Psychiatric Illness in First-degree Relatives of Schizophrenic and Surgical Control Patients: A Family Study Using DSM-III Criteria

Abstract: • This report examines the risk for psychiatric illness in 723 first-degree relatives of schizophrenics and 1,056 first-degree relatives of matched surgical control patients. Diagnoses in patients and relatives were made "blind" to one another, using DSM-III criteria. Information on relatives was obtained from personal interview and/or hospital records. Results were analyzed using two levels of diagnostic certainty and with or without relatives on whom only hospital records were obtained. In all analyses, the risk for schizophrenia was significantly greater (at least 18-fold) in the relatives of schizophrenics v controls. Evidence was also found for an increased risk in relatives of schizophrenics for schizoaffective disorder, paranoid disorder, and atypical psychosis but not for unipolar disorder, anxiety disorder, or alcoholism. As defined by DSM-III , schizophrenia is a familial disorder; however, the increased risk for psychotic illness in relatives of schizophrenics does not appear to be confined to schizophrenia alone.

Schizotypal Symptoms and Signs in the Roscommon Family Study: Their Factor Structure and Familial Relationship With Psychotic and Affective Disorders

Abstract: Background: Although schizotypal personality disorder aggregates in relatives of schizophrenic probands, the criteria for this disorder may not be optimal either in describing the dimensions of schizotypal phenomena or in identifying those with a high familial liability to schizophrenia. Methods: In the Roscommon Family Study, an epidemiologically based family study of major psychiatric disorders conducted in the west of Ireland, we examined 25 individual schizotypal symptoms and signs, assessed by structured personal interview, in 1544 first-degree relatives (without chronic psychosis or mental retardation) of five proband groups: schizophrenia; other nonaffective psychoses; psychotic affective illness; nonpsychotic affective illness; and matched, unscreened controls. Results: We obtained seven meaningful schizotypal factors: negative schizotypy, positive schizotypy, borderline symptoms, social dysfunction, avoidant symptoms, odd speech, and suspicious behavior. Taken individually, all of these factors, except borderline symptoms, significantly discriminated relatives of schizophrenic pro-bands from relatives of controls; in descending order of the odds ratios, they were odd speech, social dysfunction, suspicious behavior, negative schizotypy, avoidant symptoms, and positive schizotypy. In a multivariate analysis, four of these factors remained significant: odd speech, negative symptoms, social dysfunction, and avoidant symptoms. These schizotypal factors differed in their specificity. Three of the four most predictive schizotypal factors also significantly discriminated relatives of probands with other nonaffective psychoses from relatives of controls. Conclusion: "Schizotypy" is a complex, multidimensional clinical construct, whose various dimensions differ widely both in the degree and specificity with which they reflect the familial liability to schizophrenia. Sub-psychotic thought disorder; negative schizotypal signs, such as poor rapport and odd behavior; deficient occupational functioning; and social isolation/avoidance best characterized relatives of schizophrenic probands compared with relatives of matched controls.

An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. II. The relationship between schizotypal personality disorder and schizophrenia.

Abstract: To assess the relationship between schizophrenia and schizotypal personality disorder (SPD) as defined in DSM-III, the interviews of relatives from the Danish Adoption Study of Schizophrenia were independently and blindly reevaluated. The prevalence of SPD was significantly higher in the biologic relatives of the schizophrenic adoptees than in the biologic relatives of matched controls and was low and equal in the two groups of adoptive relatives. Compared with "borderline" and uncertain borderline schizophrenia as defined by Kety and co-workers, the criteria for SPD were more specific but less sensitive in identifying biologic relatives of schizophrenics. In this sample, SPD has a strong genetic, but no familial-environmental, relationship to schizophrenia. These results replicate the findings of Kety and co-workers on borderline schizophrenia and support the validity of the diagnosis of SPD.

Children of depressed parents: an integrative review.

Abstract: This article reviews the various literatures on the adjustment of children of depressed parents, difficulties in parenting and parent-child interaction in these families, and contextual factors that may play a role in child adjustment and parent depression. First, issues arising from the recurrent, episodic, heterogeneous nature of depression are discussed. Second, studies on the adjustment of children with a depressed parent are summarized. Early studies that used depressed parents as controls for schizophrenic parents found equivalent risk for child disturbance. Subsequent studies using better-defined samples of depressed parents found that these children were at risk for a full range of adjustment problems and at specific risk for clinical depression. Third, the parenting difficulties of depressed parents are described and explanatory models of child adjustment problems are outlined. Contextual factors, particularly marital distress, remain viable alternative explanations for both child and parenting problems. Fourth, important gaps in the literature are identified, and a consistent, if unintentional, "mother-bashing" quality in the existing literature is noted. Given the limitations in knowledge, large-scale, long-term, longitudinal studies would be premature at this time.

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Diagnostic Interview for Genetic Studies: Rationale, Unique Features, and Training

Abstract: This the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria—based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder Reliabilities using algorithms were excellent (073 to 095), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions

A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder

Abstract: A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.