Assessing the Legacy of the GBG Model

A critique of the article by Bryden, McManus, and Bulman-Fleming ("Evaluating the empirical support for the Geschwind-Behan-Galaburda model of cerebral lateralization") is presented. Bryden et al. expose some of the principal weaknesses of the cerebral lateralization model put forth by Geschwind and colleagues and contribute an important meta-analysis of findings concerning the model′s predicted relationship between immune disorders and handedness. Nonetheless, the theory put forth by Geschwind and colleagues retains an important legacy despite a multitude of faulty assumptions and predictive failures. Also offered is a brief synopsis of a new model that explains the many positive relationships found among various neurodevelopmental disorders and medical conditions, as well as why abnormal handedness distributions occur in some but not other neurodevelopmental disorders.     

Anomalous brain dominance and the immune system: Do left-handers have specific immunological patterns?

Geschwind and Behan (1982) and Geschwind and Galaburda (1985a, 1985b, 1985c) suggested a correlation between brain laterality and immune disorders. To test whether this hypothesis holds true not only for the frequency of immune diseases and circulating autoantibodies, but extends also to cellular immunity, we examined the association between handedness and markers of cellular immunity. Twenty-seven left-handed and 37 right-handed subjects were serologically screened for cellular parameters and 22 left-handed subjects were typed for human leukocyte antigen (HLA). When compared to the right-handers, the left-handed group showed a significant decrease in the inflammatory cell types CD3(+) T cells (total T cells), CD4(+) T cells (T-helper cells), and HLA-Dr (MHC-II, antigen-presenting cells) as well as in the CD19(+) cells (B cells) and CD16/CD57(+) cells (natural killer cells). We assume a relationship exists between cerebral hemispheric specialisation and the immune system not only for humoral but also for cellular immunity, and we discuss the role of the major histocompatibility complex in neurological and immunological development.     

Handedness and immune function

Geschwind, Galaburda, and Behan (GBG) have suggested that in utero levels of testosterone influence both cerebral and immune system developments (Geschwind and Behan, 1982; Geschwind and Galaburda, 1984; Geschwind and Galaburda, 1985). According to this theory, high levels of testosterone result in greater incidences of left-handedness, deviations from standard distribution of cerebral functions (known as anomalous dominance), and increased autoimmune dysfunction. While the original data supported these assertions, more recent tests of the hypothesis have been equivocal. One criticism of these studies is that the definition of both handedness and anomalous dominance are too vague. It was one of the aims of this project to investigate and clarify the GBG model by examining four different aspects of handedness as well as a more direct measure of anomalous dominance. In order to extend the GBG model, degree of left-handedness, general immune system functioning, and current testosterone levels were also examined. First, it was predicted and found that left handers had a higher incidence of autoimmune diseases in their immediate families than did right handers. Second, those left handers with an incidence of at least one autoimmune disease were more strongly left-handed than were those with no incidence of autoimmunity. Finally, it was observed that higher testos terone levels were supportive of general immunity. The present findings both support and expand the GBG model.     

A Twin and Family Study of the Association Between Immune System Dysfunction and Dyslexia Using Blood Serum Immunoassay and Survey Data

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.     

Geschwind's theory of cerebral lateralization: developing a formal, causal model

Geschwind and Galaburda (1987) have proposed a complex and influential model of cerebral lateralization that is based on the argument that increased fetal testosterone levels modify neural development, immune development, and neural crest development. The theory can explain many aspects of cerebral lateralization and its relation to learning disorders, giftedness, and immune deficits. This article clarifies the structure of the theory by presenting it as a causal-path model. The internal coherence of the model is then evaluated by assessing the central concept of anomalous dominance, the role of timing in the articulation of the model, and the invocation of nonlinear processes. Finally, the article considers the problems implicit in testing a "grand" theoretical model and derives some principles for assessing the testability of various predictions, given the practical constraints of sample size and the problems of measurement error.     

No confirmation of Geschwind's hypothesis of associations between reading disability,immune disorders,and motor preference in ADHD

Geschwind and colleagues have proposed an association among reading disability, immune disorder, and motor preference. Although reading disability commonly overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been previously examined in studies evaluating Geschwind's hypothesis. In this paper we evaluate whether ADHD is associated with either asthma or left motor preference and whether asthma and left motor preference are associated with each other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n= 140) and normal controls (n= 120). Information on reading disability, asthma, and motor preference was obtained in a standardized manner blind to the proband's clinical status. Neither ADHD nor reading disability was associated with either asthma or left motor preference nor was asthma and left motor preference associated with one another. Our results are not consistent with Geschwind's hypothesis linking reading disability, immune disorder, and left motor preference. This work was supported, in part, by USPHS (NIMH) grant RO1 MH-41314-01A2 (J.B.). We thank Drs. Benjamin, Kolodny, and Krauss from the Pediatric Department of the Harvard Community Health Plan and Dr. James Perrin from the Pediatric Service of the Massachusetts General Hospital for their contribution to this work.Address all correspondence, including reprint requests, to Joseph Biederman, M.D., Pediatric Psychopharmacology, ACC-725, Massachusetts General Hospital, 15 Parkman Street, Boston, Massachusetts 02114.     

The Geschwind and Galaburda theory of cerebral lateralisation: An empirical evaluation of its assumptions

The relationship between male gender, left-handedness, high visuo-spatial and mathematical skill, speech problems and increased vulnerability to immune disorders was assessed in a large sample of university undergraduates. The only significant finding was a two-way interaction between hand preference and incidence of speech problems, with “pure” left-handers reporting a three-fold increase in the incidence of speech problems compared to mixed left-handers, mixed right-handers and “pure” right-handers. There was no evidence of an interaction among three or more of the variables. These findings are discussed in relation to the influential theory of cerebral lateralisation proposed by Geschwind and Galaburda (1987).     

Young adult follow-up of hyperactive children: self-reported psychiatric disorders,comorbidity, and the role of childhood conduct problems and teen CD

We report on the psychiatric disorders present at young adult follow-up (Mean age 20–21 years; 13 + year follow-up) and the comorbidity among them for a large sample of hyperactive (H; N = 147) and community control (CC; N = 71) children. The H group had a significantly higher risk for any nondrug psychiatric disorders than the CC group (59% vs. 36%). More of the H group met criteria for ADHD (5%); major depressive disorder (26%); and histrionic (12%), antisocial (21%), passive–aggressive (18%), and borderline personality disorders (14%) at follow-up than the CC group. Severity of childhood conduct problems contributed to the risk for passive–aggressive, borderline, and antisocial personality disorders. But it only affected risk for antisocial personality after controlling for severity of teen conduct disorder (CD), which also contributed to the risk for these same 3 disorders. Examination for comorbidity among these disorders indicated that presence of either borderline or antisocial personality disorder significantly increased the risk for major depression and the other significant personality disorders. More of the hyperactive group had received various forms of mental health treatment during and since leaving high school than the control group. Results suggest that hyperactive children are at significant risk for at least 1 nondrug disorder in young adulthood, principally major depression and several personality disorders, and that this risk is largely mediated by severity of CD at adolescence.     

Testosterone,aggressiveness, and antisocial personality

Testosterone levels were examined in prisoners convicted of violent crimes (n = 13), in men previously convicted of violent crimes but currently not in prison (n = 15), in nonviolent alcoholics (n = 15), and in randomly selected control males (n = 16). Morning, afternoon, and evening testosterone levels were assessed after a minimum alcohol abstinence period of 24 hr. Violent and nonviolent men did not differ in plasma total testosterone level on any sampling occasion. In violent men, however, testosterone levels were significantly correlated with hostility, as measured by the Derogatis Symptom Check List. Most violent men were diagnosed with Antisocial Personality Disorder (ASP) [DSM‐III‐R; 301.70], and the unweighted ASP symptom count also correlated significantly with testosterone levels in these subjects. We suggest that individuals whose life histories involve numerous antisocial behaviors tend to have high testosterone levels even when interpersonal violence is excluded. This, however, does not eliminate the possibility that males who are characterized by high hostility may also have elevated testosterone levels. Violent predisposition and antisocial conduct beginning in early adolescence predict adult aggressive behaviors, which are augmented by power‐related alcohol expectancies and alcohol abuse. Aggr. Behav. 25:113–123, 1999. © 1999 Wiley‐Liss, Inc.     

Prior Mental Disorders and Lifetime Suicidal Behaviors Among US Army Soldiers in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

We report on associations of retrospectively reported temporally prior mental disorders and Army career characteristics with subsequent first onset of suicidal behaviors in a large, representative sample of US Army soldiers who participated in the Consolidated All‐Army Survey of the Army Study to Assess Risk and Resilience in Servicemembers (N = 29,982). Results reveal that among men and women, all self‐reported lifetime disorders measured (some assessed with screening scales) are associated with subsequent onset of suicide ideation. Among men, three disorders characterized by agitation and impulsiveness (intermittent explosive disorder, panic disorder, and substance disorders) predict the transition from suicide ideation to attempt. For both men and women, being in the Regular Army (vs. National Guard or Army Reserve) predicts suicide attempts in the total sample. For men, a history of deployment and junior rank are predictors of suicide attempts after adjusting for preenlistment disorders but not accounting for pre‐ and postenlistment disorders, suggesting that postenlistment disorders account for some of the increased suicide risk among these career characteristics. Overall, these results highlight associations between mental disorders and suicidal behaviors, but underscore limitations predicting which people with ideation attempt suicide.     

Mental Disorders,Comorbidity, and Pre‐enlistment Suicidal Behavior Among New Soldiers in the U.S. Army: Results from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

We examined the associations between mental disorders and suicidal behavior (ideation, plans, and attempts) among new soldiers using data from the New Soldier Study (NSS) component of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS; N = 38,507). Most new soldiers with a pre‐enlistment history of suicide attempt reported a prior mental disorder (59.0%). Each disorder examined was associated with increased odds of suicidal behavior (ORs = 2.6–8.6). Only PTSD and disorders characterized by irritability and impulsive/aggressive behavior (i.e., bipolar disorder, conduct disorder, oppositional defiant disorder, and attention‐deficit/hyperactivity disorder) predicted unplanned attempts among ideators. Mental disorders are important predictors of pre‐enlistment suicidal behavior among new soldiers and should figure prominently in suicide screening and prevention efforts.     

Genetically based correlates of serum oxytocin and testosterone in autism and schizotypy

The hormones oxytocin and testosterone have been implicated in autism spectrum and schizophrenia-spectrum cognition and disorders, but their roles in mediating these psychological phenotypes remain largely unknown. We genotyped a large set of healthy individuals for loci that represent established genetic indicators of serum testosterone and oxytocin levels, and tested for associations of these genetic indices of hormone levels with self-report measures of autistic and schizotypal cognition. A low genetic index of testosterone, a high genetic index of oxytocin, and/or a low ratio of testosterone to oxytocin indices were positively correlated with high imagination (by the Autism Quotient) and high positive and total schizotypy (by the Schizotypal Personality Questionnaire). The genetic indices for oxytocin, and testosterone relative to oxytocin, also showed significant correlations with a metric of positive schizotypy relative to autism, implicating higher oxytocin and lower testosterone in increased positively-schizotypal traits combined with decreased autism-associated traits. These results link genetic indicators of serum hormone levels with measures of schizotypy and autism among healthy individuals.     

An examination of the roles of trauma exposure and posttraumatic stress disorder on emotion regulation strategies of Operation Iraqi Freedom,Operation Enduring Freedom,and Operation New Dawn veterans

Theories of posttraumatic stress disorder (PTSD) implicate emotional processes, including difficulties utilizing adaptive emotion regulation strategies, as critical to the etiology and maintenance of PTSD. Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OIF/OEF/OND) veterans report high levels of combat exposure and PTSD. We aimed to extend findings suggesting that emotion regulation difficulties are a function of PTSD, rather than combat trauma exposure or common comorbidities, to OIF/OEF/OND veterans, in order to inform models of PTSD risk and recovery that can be applied to returning veterans. We tested differences in emotion regulation, measured with the Difficulties in Emotion Regulation Scale and Emotion Regulation Questionnaire, among trauma-exposed veterans with (n = 24) or without PTSD (n = 22) and healthy civilian comparison participants (n = 27) using multivariate analyses of covariance, adjusting for major depressive disorder, anxiety disorders, and demographic variables (age, sex, and ethnicity). Veterans with PTSD reported more use of expressive suppression and more difficulties with emotion regulation than veterans without PTSD and healthy comparison participants. Groups did not differ on cognitive reappraisal. Findings suggest the key role of PTSD above and beyond trauma exposure, depression, and anxiety in specific aspects of emotion dysregulation among OIF/OEF/OND veterans. Interventions that help veterans expand and diversify their emotion regulation skills may serve as helpful adjunctive treatments for PTSD among OIF/OEF/OND veterans.     

Quantifying the Strength of General Factors in Psychopathology: A Comparison of CFA with Maximum Likelihood Estimation,BSEM, and ESEM/EFA Bifactor Approaches

Whether or not importance should be placed on an all-encompassing general factor of psychopathology (or p factor) in classifying, researching, diagnosing, and treating psychiatric disorders depends (among other issues) on the extent to which comorbidity is symptom-general rather than staying largely within the confines of narrower transdiagnostic factors such as internalizing and externalizing. In this study, we compared three methods of estimating p factor strength. We compared omega hierarchical and explained common variance calculated from confirmatory factor analysis (CFA) bifactor models with maximum likelihood (ML) estimation, from exploratory structural equation modeling/exploratory factor analysis models with a bifactor rotation, and from Bayesian structural equation modeling (BSEM) bifactor models. Our simulation results suggested that BSEM with small variance priors on secondary loadings might be the preferred option. However, CFA with ML also performed well provided secondary loadings were modeled. We provide two empirical examples of applying the three methodologies using a normative sample of youth (z-proso, n = 1,286) and a university counseling sample (n = 359).     

Prevalence of personality disorders among bulimics,nonbulimic binge eaters,and normal controls

We examined the comorbidity of bulimia and personality pathology among college women. Subjects included women (n=23) meeting DSM-III-R criteria for bulimia nervosa (bulimics), women (n=23) who reported binge eating but did not fulfill the criteria for bulimia nervosa (binge eaters), and women (n=23) who did not binge eat (normals). The subjects completed an assessment battery consisting of the Personality Disorders Examination and the SCID as well as the Beck Depression Inventory, the Rosenberg Self-Esteem Index, and measures of impulsivity and self-defeating tendencies. Fourteen of 23 bulimics (61%) met criterion for a personality disorder using DSM-III-R Axis II criteria. In comparison, 3 of 23 (13%) binge eaters and 1 of 23 (4%) normal subjects received an Axis II diagnosis. Borderline and self-defeating diagnoses were the predominant personality disorders in 96% of the bulimics exhibiting clinically significant personality pathology. Bulimics also exhibited significantly more depression, impulsivity, and self-defeating behavior and lower self-esteem than binge eaters and normals. The findings are discussed within a conceptual framework that posits an interaction between personality pathology and restrained eating.     

Behavioral disordered children's conceptions of moral,conventional, and personal issues

This study employed a series of sorting tasks with 22 normal and 20 children with behavioral disorders (BD) to determine whether BD children discriminate among three classes of social actions viewed by normal children as distinct. These categories are (1) the moral (actions having intrinsic effects upon the rights or well-being of others), (2) the conventional (actions whose propriety is determined by social consensus), and (3) the personal (actions whose propriety is a matter of individual prerogative). Findings were that although BD children distinguished among the three forms of behavior, they differed with normals in the classifications of specific acts and in the reasons given for act classifications. Chief among these differences was the finding that BD children were less likely than normals to identify acts as within their personal domain.We wish to thank Mary Confray, Denise Jaffe, and Christopher Pellikan for their help with the data collection. Thanks are also due to Diana Algminas of the Proviso Area Exceptional Children's Program, Ted Lawrence of the West Suburban Association for Special Education, and Wayne Thorne of the Board of Education District No. 89 (Maywood and Melrose Park, Illinois) for the cooperation of schools in their respective districts. We wish also to thank Mark Oberlander and Ronald Brown for their suggestions regarding identification of the BD sample. Portions of these data were presented at the annual meeting of the American Educational Research Association, Los Angeles, April 1981.     

Salivary testosterone and cortisol among late adolescent male offenders

The relationship of salivary testosterone and cortisol concentrations to personality, criminal violence, prison behavior, and parole board decisions was examined among 113 late-adolescent male offenders. Offenders high in testosterone committed more violent crimes, were judged more harshly by the parole board, and violated prison rules more often than those low in testosterone. No main effects for cortisol emerged. However, as expected, a significant interaction between testosterone and cortisol was found, in which cortisol moderated the correlation between testosterone and violence of crime. Cortisol may be a biological indicator of psychological variables (e.g., social withdrawal) that moderate the testosterone-behavior relationship. Paper and pencil measures of personality and behavior showed little relationship to hormones.This research was supported in part by NIMH grant MH42525 and by a Vice-President's grant from Georgia State University. We wish to thank the Georgia Department of Corrections and the Georgia Board of Pardons and Paroles for making the research possible. In addition, we specifically extend thanks to Tim Carr (Department of Corrections); to Sue Aiken, Tom Morris, and Sheila Thompson (Board of Pardons and Paroles); and to Debra Plyler and Paula Williams for coding inmate records.     

Self-criticism,interpersonal conditions,and biosystemic inflammation in suicidal thoughts and behaviors within mood disorders: A bio-cognitive-interpersonal hypothesis

We review the theoretical and empirical literature on the role of self-concept in suicidal behavior in the context of mood disorders (i.e., unipolar depression and bipolar spectrum disorders). The main themes emanating from this review are then juxtaposed against (a) the Interpersonal-Psychological Theory of Suicide and (b) biological research on the role of inflammatory processes in suicidality. Such a juxtaposition paves the way for a bio-cognitive-interpersonal hypothesis. Pathologies of the self-concept—primarily self-criticism—propel mood disorder sufferers to generate interpersonal stress that culminates in two proximal causes of suicidality: thwarted belongingness and perceived burdensomeness. In turn, these two interpersonal conditions set in motion systemic biosystemic inflammation, serving as a proximal cause for suicidality in mood disorders. We conclude by describing a research project aimed at testing this hypothesis, and by outlining pertinent implications for assessment, treatment, and prevention.     

Prayer,God Imagery,and Symptoms of Psychopathology

Researchers have shown a longstanding interest in the relationship between religion and mental health. Here, we outline a series of hypotheses linking personal prayer, images of God, and mental health. We then empirically test the hypotheses using data from an online survey of U.S. adults (N= 1,629) conducted in 2004 by Spirituality and Health magazine. We find a positive correlation between both frequency of prayer and the perception of God as remote and several different forms of psychopathology; a perceived intimate relationship with a loving God is inversely related. The positive association between prayer and psychopathology manifests itself primarily among individuals who experience God as either (a) remote or (b) not loving. We also find an inverse correlation between prayer and psychopathology among individuals who believe that they are praying to a close (the inverse of remote) God. We discuss the implications of these findings for research on the religion-mental health connection and outline an agenda for future research.     

Fetal Testosterone,Socio‐Emotional Engagement and Language Development

The present study investigated the relations among fetal testosterone, child socio‐emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly negatively correlated with socio‐emotional engagement and vocabulary development for boys but not for girls. Socio‐emotional engagement mediated the effect of boys' fetal testosterone levels on their vocabulary development. However, the size of the effects was small, and fetal testosterone and socio‐emotional engagement were no longer significant predictors of boys' vocabulary scores after accounting for the effects of other predictors including maternal age and education, parity, and parent–child book reading. It is concluded that further research into these associations is warranted in both typical and atypical development and that this research would profit from including a broader focus on the role that proximal processes such as socio‐emotional engagement, joint attention and imitation have in mediating the developmental effects of prenatal factors such as fetal testosterone exposure. Copyright © 2012 John Wiley & Sons, Ltd.