aetiology for in X-linked neuroligins G N and N L G N 4 , in siblings with disorders. affect cell adhesion molecules localised the synapse suggest that a defect of synaptogenesis may predispose to autism. in reciprocal and well as restricted and stereotyped of and Asperger higher cognitive abilities more normal language function The recurrence risk of autism in sib-ships approximately 45 times greater in the general and twin studies a higher concordance rate in monozygotic (60%-91%) than in dizygotic twins (0%-6%) . The male-to-female ratio is 4:1 in autism and 8:1 in AS. Male predisposition to autistic disorder remains unexplained, although abnormalities of the sex chromosomes are frequently associated with autistic spectrum disorders 4 . At least two loci for a predisposition to autism have been suggested on the X chromosome. At Xp22.3, de novo chromosomal deletions have been observed in three autistic females 5 and a second locus at Xq13-21 is supported by two independent genome scans, showing increased allele sharing around markers DXS7132 cM) and DXS6789 cM) in affected sib-pair (ASP) 6,7

DNA topoisomerase I (Topo I) is a molecular target for the anticancer agent topotecan in the treatment of small cell lung cancer and ovarian carcinomas. However, the molecular mechanisms by which topotecan treatment inhibits cancer cell proliferation are unclear. We describe here the identification of Topo I as a novel endogenous interaction partner for transcription factor c-Jun. Reciprocal coimmunoprecipitation analysis showed that Topo I and c-Jun interact in transformed human cells in a manner that is dependent on JNK activity. c-Jun target gene epidermal growth factor receptor (EGFR) was identified as a novel gene whose expression was specifically inhibited by topotecan. Moreover, Topo I overexpression supported c-Jun-mediated reporter gene activation and both genetic and chemical inhibition of c-Jun converted cells resistant to topotecan-elicited EGFR downregulation. Topotecan-elicited suppression of proliferation was rescued by exogenously expressed EGFR. Furthermore, we demonstrate the cooperation of the JNK-c-Jun pathway, Topo I, and EGFR in the positive regulation of HT-1080 cell proliferation. Together, these results have identified transcriptional coactivator Topo I as a first endogenous cofactor for c-Jun in the regulation of cell proliferation. In addition, the results of the present study strongly suggest that inhibition of EGFR expression is a novel mechanism by which topotecan inhibits cell proliferation in cancer therapy.

Childhood conduct disorder (CD) and adult psychopathic traits according to the Psychopathy Checklist Revised (PCL-R) were the closest psychiatric covariates to repeated violent crimes and aggression among offenders under forensic psychiatric investigation in Sweden. As psychopathy is not included in the present psychiatric diagnostic systems, we compared total and factor PCL-R scores to Axis I disorders, including childhood-onset neuropsychiatric disorders, and to Axis II personality disorders, to establish the convergence of psychopathic traits with other psychiatric diagnoses, and to identify possible unique features. Psychopathic traits were positively correlated with bipolar mood disorder and negatively with unipolar depression. The total PCL-R scores as well as the Factor 2 (unemotionality) and Factor 3 (behavioral dyscontrol) scores were significantly correlated with attention-deficit/hyperactivity disorder, Asperger's syndrome/high-functioning autistic traits, CD, substance abuse, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Cluster B personality disorders. The interpersonal Factor 1 showed none of these correlations and may capture features that are specific to psychopathy, distinguishing core psychopathy from other diagnostic definitions.

Learning disability is common, affecting 1-2.5% of the general population in the Western world, and encompasses many different conditions. It usually leads to major functional impairment and lifelong need for support and interventions, not the least important of which are medical and health-care services. Rapid progress is being made in the understanding of the cause and pathogenesis of many learning disability syndromes, and these advances are likely to improve targeted interventions in the next decade. Many countries have abolished a learning disability specialty for medical professionals, but there is a great need to revive this niche of medical knowledge. We know little about quality of life and effects on families of people with learning disability, and research is needed to address these issues.

We assessed a total range of peripheral thyroid hormone fractions, binding globulins, and thyroid-active antibodies in 37 medication-free, violent or sexual offenders, aged 17-45 years, to describe possible mechanisms involved in the thyroid metabolism of aggressive men. The ratio between T3 and T4 correlated with ratings of psychopathy, indicating increased peripheral deiodination as a biological covariate to callous personality traits. Autoimmune antibodies, hepatic failure, abnormal binding globulins, or substance abuse did not affect the association.

BACKGROUND:It is only recently that "comorbidity" in ADHD has come to the forefront as one of the most important aspects of the disorder. It is agreed that, often, these problems are at least as important as ADHD in contributing to the longer term outcome in the individual child.OBJECTIVE:To provide the reader with basic information about clinics and treatment of "comorbidity" in ADHD.METHOD:Review of the empirically based literature.RESULTS:ADHD exists in a surprisingly high frequency together with a broad range of child neuropsychiatric disorders. This is accompanied with many still unresolved treatment problems.CONCLUSION:It would not be appropriate to develop ADHD-services where clinicians would only have expertise in ADHD as such. Anyone working with children, adolescents and adults with ADHD would need to have training in general neuropsychiatry. Further research in this field is urgently needed.

Changes in the metabolism of tryptophan, other amino acids, and steroid hormones have been implicated in aggression. We compared tryptophan, competing long amino acids (CAAs), and cortisol in serum (S) and CSF in 22 violent offenders and 15 healthy controls. Offenders had significantly increased S-L-tryptophan, S-free tryptophan, S-CAAs, S-cortisol and CSF-cortisol, indicating abnormal neurophysiological processes. Larger studies on the interplay between violence, serotonin precursors, and stress hormones need to integrate personality traits, life situations, and physiological adaptation.

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Borg and Colleagues ReplyJACQUELINE BORG, Psychol., M.Sc., BENGT ANDRÉE, M.D., Ph.D., HENRIK SÖDERSTRÖM, M.D., Ph.D., and LARS FARDE, M.D., Ph.D., JACQUELINE BORGSearch for more papers by this author, Psychol., M.Sc., BENGT ANDRÉESearch for more papers by this author, M.D., Ph.D., HENRIK SÖDERSTRÖMSearch for more papers by this author, M.D., Ph.D., and LARS FARDESearch for more papers by this author, M.D., Ph.D., Stockholm, SwedenPublished Online:1 Sep 2004https://doi.org/10.1176/appi.ajp.161.9.1721AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We appreciate that Dr. Hall and colleagues draw attention to the problem of defining the concepts of “spirituality” and “religion.” Several multidimensional or pluralistic definition systems of religion have indeed been proposed over the years. However, none of them offers a perfect solution to the need of operational tools in research on a possible biological underpinning of religious and spiritual behavior.The authors criticize our article for using the terms “religion” and “spirituality” interchangeably. However, we did not use the concept “religion” in the article. Rather, the concept “religious behavior,” which is operationally defined in the literature (1), denotes cognitive and emotional behavior associated with (the individual’s relationship to their) religious beliefs. The term “spirituality” has been used in a wider context, including internal, subjective experiences, and has not been consistently defined by operational criteria. It is worth noting that the concept of spirituality is not necessarily linked to organized religion.“Religious behavior” and “spirituality” are both covered by the personality subscale of the Spiritual Acceptance Scale, which was used in our study. The Spiritual Acceptance Scale consists of 13 items that include cognitive affirmation and values as well as subjective experiences of mystical quality. Thus, the definition of religion at a sociocultural level, as suggested by Dr. Hall and colleagues, is not covered by the scale used in our study and belongs to a different discussion.Another part of Dr. Hall and colleagues’ criticism is their interpretation that aspects of mystical experiences can be mediated by the central serotonin system. We do not suggest that the serotonin system per se mediates mystical experiences but instead may act as a sensory filter (2). Low serotonin 5-HT1A receptor binding potential may be associated with a low filter function, thus paving the way for sensory stimuli otherwise not experienced. The more narrow focus on mystical experiences in this part of the discussion in our article (pp. 1967–1968) was given by comparisons made with pharmacological mechanisms causing similar experiences in man.Finally, we agree with Dr. Hall and colleagues that it would be interesting to repeat this study in different populations. Epidemiological studies provide support for the view that religious behavior (in a more narrow sense) and spirituality (in a wider sense) are influenced by both genetic and environmental factors (3, 4). Given the previously demonstrated genetic contribution to religious behavior and spirituality, it is a promising strategy to use interindividual variability in neuroreceptor binding as a tool to approach the multifaceted question of why people vary in spiritual zeal and also within the same religious belief system.References1. Hood RW, Spilka B, Hunsberger B, Gorsuch R: The Psychology of Religion: An Empirical Approach, 2nd ed. New York, Guilford, 1996, pp 4–40Google Scholar2. Albert DJ, Walsh ML: Neural systems and the inhibitory modulation of agonistic behavior: a comparison of mammalian species. Neurosci Biobehav Rev 1984; 8:5–24Crossref, Medline, Google Scholar3. Bouchard TJ Jr, Lykken DT, McGue M, Segal NL, Tellegen A: Sources of human psychological differences: the Minnesota Study of Twins Reared Apart. Science 1990; 250:223–228Crossref, Medline, Google Scholar4. Kirk KM, Eaves LJ, Martin NG: Self-transcendence as a measure of spirituality in a sample of older Australian twins. Twin Res 1999; 2:81–87Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 161Issue 9 September 2004Pages 1721-1721 Metrics PDF download History Published online 1 September 2004 Published in print 1 September 2004

Individuals with attention-deficit/hyperactivity disorder (AD/HD) and autism spectrum disorders (ASD) often display symptoms from other diagnostic categories. Exclusion criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Statistical Classification of Diseases and Related Health Problems (ICD-10) impede the use of categorical diagnoses to describe the particular problem constellation in a patient. In this study, we describe the prevalence and patterns of comorbid bipolar and psychotic disorders in 241 consecutively referred adult patients with AD/HD and/or ASD. Thirty per cent of patients with AD/HD had comorbid ASD and 38% of patients with ASD had comorbid AD/HD. Of the subjects with ASD, 7% had bipolar disorder with psychotic features, and 7.8% had schizophrenia or another psychotic disorder. The corresponding figures for the patients with AD/HD were 5.0% and 5.0%, respectively. Current diagnostic criteria have to be revised to acknowledge the comorbidity of bipolar and/or psychotic disorders in AD/HD and ASD.

BACKGROUNDThe brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance.OBJECTIVETo elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women.DESIGNTwo independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated.RESULTSA significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity.CONCLUSIONThe C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.

OBJECTIVE The serotonin system has long been of interest in biological models of human personality. The purpose of this positron emission tomography (PET) study was to search for relationships between serotonin 5-HT(1A) receptor density and personality traits. METHOD Fifteen normal male subjects, ages 20-45 years, were examined with PET and the radioligand [(11)C]WAY100635. Personality traits were assessed with the Swedish version of the Temperament and Character Inventory self-report questionnaire. Binding potential, an index for the density of available 5-HT(1A) receptors, was calculated for the dorsal raphe nuclei, the hippocampal formation, and the neocortex. For each region, correlation coefficients between 5-HT(1A) receptor binding potential and Temperament and Character Inventory personality dimensions were calculated and analyzed in two-tailed tests for significance. RESULTS The authors found that the binding potential correlated inversely with scores for self-transcendence, a personality trait covering religious behavior and attitudes. No correlations were found for any of the other six Temperament and Character Inventory dimensions. The self-transcendence dimension consists of three distinct subscales, and further analysis showed that the subscale for spiritual acceptance correlated significantly with binding potential but not with the other two subscales. CONCLUSIONS This finding in normal male subjects indicated that the serotonin system may serve as a biological basis for spiritual experiences. The authors speculated that the several-fold variability in 5-HT(1A) receptor density may explain why people vary greatly in spiritual zeal.

Do the CNS monoaminergic (MA) systems regulate thyroid hormone metabolism in humans? In 23 unmedicated, male, violent offenders without signs of thyroid disease, we found positive correlations between the catecholaminergic CSF metabolites HVA and MHPG and the peripheral T3/T4 ratio (rho=0.55, p=0.010 and 0.51, p=0.018), indicating that increased activity in the brain MA systems, especially the dopaminergic, is associated with increased peripheral thyroid hormone activity.

To describe lifetime mental disorders among perpetrators of severe inter-personal crimes and to identify the problem domains most closely associated with aggression and a history of repeated violent criminality, we used structured interviews, clinical assessments, analyses of intellectual functioning, medical and social files, and collateral interviews in 100 consecutive subjects of pretrial forensic psychiatric investigations. Childhood-onset neuropsychiatric disorders [attention-deficit/hyperactivity disorder (AD/HD), learning disability, tics and autism spectrum disorders] affected 55% of the subjects and formed complex comorbidity patterns with adult personality disorders [including psychopathic traits according to the Psychopathy Checklist (PCL-R)], mood disorders and substance abuse. The closest psychiatric covariates to high Lifetime History of Aggression (LHA) scores and violent recidivism were the PCL-R scores and childhood conduct disorder (CD). Behavioral and affective PCL-R factors were closely associated with childhood AD/HD, CD, and autistic traits. The results support the notion that childhood-onset social and behavioral problems form the most relevant psychiatric symptom cluster in relation to pervasive adult violent behavior, while late-onset mental disorders are more often associated with single acts of violent or sexual aggression.