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Background Childhood aggressive antisocial behavior (CD) is one of the strongest predictors of mental health problems and criminal behavior in adulthood. The aims of this study were to describe personality profiles in children with CD, and to determine the strength of association between defined neurodevelopmental symptoms, dimensions of character maturity and CD. Methods A sample of 1886 children with a close to equal distribution of age (9 or 12) and gender, enriched for neurodevelopmental and psychiatric problems were selected from the nationwide Child and Adolescent Twin Study in Sweden. Their parents rated them according to the Junior Temperament and Character Inventory following a telephone interview during which information about the children's development and mental health was assessed with the Autism-Tics, AD/HD and other Comorbidities inventory. Result Scores on the CD module significantly and positively correlated with scores on the Novelty Seeking temperament dimension and negatively with scores on character maturity (Self-Directedness and Cooperativeness). In the group of children with either neurodevelopmental or behavioral problems, the prevalence of low or very low character maturity was 50%, while when these two problems coexisted the prevalence of low or very low character maturity increased to 70%. Neurodevelopmental problems (such as: oppositional defiant disorder, symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder) and low scores on character maturity emerged as independently significant predictors of CD; in a multivariable model, only oppositional defiant symptoms and impulsivity significantly increased the risk for coexisting CD while a mature self-agency in a child (Self-Directedness) remained a significant protective factor. Conclusion These results suggest that children's willpower, the capacity to achieve personally chosen goals may be an important protective factor – even in the presence of neurodevelopmental and psychiatric problems – against progressing into persistent negative outcomes, such as aggressive antisocial behaviors. [ABSTRACT FROM AUTHOR]

Objective: To explore the links between neurodevelopmental disorders – attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) – and personality in a population-based, genetically sensitive study of children. Method: A population-based sample of 1886 twins aged 9 and 12, enriched for childhood mental health problems, was recruited from the Child and Adolescent Twin Study in Sweden (CATSS). Parents were interviewed over the telephone using the Autism-Tics, AD/HD and other Comorbidities (A-TAC) inventory, and in a second step they rated their children according to the Junior Temperament and Character Inventory (JTCI). Results: ADHD was strongly correlated with novelty seeking, while ASD was correlated positively with harm avoidance and negatively with reward dependence. The strongest associations between personality traits and neurodevelopmental disorders were negative correlations between the character dimensions of self-directedness and cooperativeness and ADHD and ASD alike. Cross-twin cross-trait correlations between ADHD, ASD, and personality dimensions in monozygotic twins were more than double those in dizygotic twins, indicating a strong genetic effect behind the phenotypic covariation between neurodevelopmental disorders and personality. Conclusions: Neurodevelopmental disorders are linked specifically to particular temperament profiles and generally to hampered development of the self-governing strategies referred to as "character." Poor self-agency and cooperation may be core functional outcomes in the separation of children with handicapping conditions from those with traits only reminiscent of neurodevelopmental disorders. The associations between neurodevelopmental disorders and personality are at least partly due to genetic effects influencing both conditions. As a consequence, personality must be broadly considered in neuropsychiatry, just as neuropsychiatric disorders and their genetic, neurodevelopmental, and cognitive susceptibilities have to be in personality research and clinical treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Previous studies have found associations between childhood behavior problems and adolescent sexual risk behavior. Using a quasi-experimental approach, we examined the extent to which this association may be due to between-family differences (i.e., unmeasured familial confounds) not adequately explored in prior research. Methods: We used data from a longitudinal, population-based cohort of young twins in Sweden (first assessment: age 9 or 12 years; second assessment: age 15; n = 2,388). We explored the nature of the association between symptom scores for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) at age 9 or 12 and the likelihood of having had sexual intercourse and number of sexual partners by age 15. Two-level mixed-effects models were used to estimate the effect of symptom score on each outcome after controlling for potential unmeasured familial confounds. Results: Higher ADHD, ODD, and CD scores were associated with significantly increased likelihood of sexual intercourse by age 15. Higher ADHD and ODD scores were also associated with increased number of sexual partners. After controlling for unmeasured familial confounds, however, behavior problems were no longer significantly associated with either outcome. Conclusion: The association between childhood behavior problems and sexual risk behaviors may be due to characteristics shared within families. Hence, prevention strategies aimed at reducing these behaviors might need to address broader risk factors that contribute to both behavior problems and a greater likelihood of sexual risk behavior. [ABSTRACT FROM AUTHOR]

Summary: Findings have been divergent regarding the direction of basal cortisol dysregulations resulting from stressor exposure, and seem to differ between young people and adults. Accumulated stress exposure has been suggested to be a risk factor for the development of hypocortisolism. This cross-sectional study aims to examine the impact of cumulative adversity, i.e., the number of adversities, on diurnal salivary cortisol levels, including the cortisol awakening response (CAR), in children without psychiatric disorder. The sample consisted of 130 children (mean age 12.8 years), representing one in each twin pair included in the population-based Child and Adolescent Twin Study in Sweden (CATSS). Information about socioeconomic disadvantage, negative life events and potentially traumatic life events were collected by telephone interview and questionnaires, with parents as informants. Salivary cortisol sampling was performed in the home during two school days: at awakening, +30min post-awakening, and at bedtime. Results showed that the number of adversities was related to the CAR, diurnal decline and +30min post-awakening cortisol levels. Children with a moderate amount of cumulative adversity displayed high cortisol measures, while those with a high amount (3 or more) of adversities instead showed levels similar to the non-exposed group, yielding an inverse U-pattern of the association between cortisol and adversity. These results indicate that the accumulation of adversity might be an explanation of patterns of basal cortisol up-regulation in children and that those most severely exposed can exhibit an early stage of down-regulation, an issue which should be further examined in longitudinal studies. [Copyright &y& Elsevier]

Abstract: Asperger syndrome (AS) and non-verbal learning disability (NLD) are both characterized by impairments in motor coordination, visuo-perceptual abilities, pragmatics and comprehension of language and social understanding. NLD is also defined as a learning disorder affecting functions in the right cerebral hemisphere. The present study investigates if individuals with AS and a cognitive profile consistent with NLD (i.e. verbal IQ>performance IQ) would also have other problems inherent in NLD, visual memory and attention, reading/writing ability and arithmetic in the presence of preserved verbal memory and attention. Forty-four individuals with AS were assessed with a battery of neuropsychological tests. Reading/writing and arithmetic abilities were investigated. Education and global social adaptive levels were studied. Very few AS participants, even though with NLD cognitive profile showed problems with any of the neurocognitive abilities or academic achievements. However, all had poor global social adaptive functioning and few had paid employment, regardless of their cognitive profile. The present study suggests that AS and NLD are two different conditions even though some individuals in both groups have the verbal IQ>performance IQ profile that has been proposed to be typical of both AS and NLD. [Copyright &y& Elsevier]

Abstract: Conforming to a medical disease model rooted in phenomenology and natural science, psychiatry classifies mental disorders according to signs and symptoms considered to be stable and homogeneous across individuals. Scientific studies addressing the validity of this classification are scarce. Following a seminal paper by Robins and Guze in 1970, validity of categories has been sought in specific criteria referring to symptoms and prognosis, aggregation in families, and “markers”, preferentially laboratory tests. There is, however, a growing misfit between the model and empirical findings from studies putting it to the test. Diagnostic categories have not been shown to represent natural groups delineated from the normal variation or from each other. Aetiological factors (genetic and/or environmental), laboratory aberrations, and treatment effects do not respect categorical boundaries. A more adequate description of mental problems may be achieved by: 1) a clear definition of the epistemological frame in which psychiatry operates, 2) a basic rating of the severity of intra- and interpersonal dysfunctions, and 3) empirical comparisons to complementary rather than exclusive dimensions of inter-individual differences in context-specific mental functions, treatment effects, and laboratory findings. Such a pluralistic understanding of mental health problems would fit empirical models in the neurosciences and postmodern notions of subjectivity alike. It would also clarify the assessment of dysfunction and background factors in relation to the requisites for penal law exemptions or insurance policies and make them empirically testable rather than dependent on expert opinion on issues such as whether a specific dysfunction is “psychiatric”, “medical”, or ascribable to “personality”. [Copyright &y& Elsevier]

Abstract: The assumption that mental disorder is a cause of crime is the foundation of forensic psychiatry, but conceptual, epistemological, and empirical analyses show that neither mental nor crime, or the causation implied, are clear-cut concepts. “Mental” denotes heterogeneous aspects of a person such as inner experiences, cognitive abilities, and behaviour patterns described in a non-physical vocabulary. In psychology and psychiatry, mental describes law-bound, caused aspects of human functioning that are predictable and generalizable. Problems defined as mental disorders are end-points of dimensional inter-individual differences rather than natural categories. Deficits in cognitive faculties, such as attention, verbal understanding, impulse control, and reality assessment, may be susceptibility factors that relate to behaviours (such as crimes) by increasing the probability (risk) for a negative behaviour or constitute causes in the sense of INUS conditions (Insufficient but Non-redundant parts of Unnecessary but Sufficient conditions). Attributing causes to complex behaviours such as crimes is not an unbiased process, and mental disorders will attract disproportionate attention when it comes to explanations of behaviours that we wish to distance ourselves from. Only by rigorous interpretation of what psychiatry actually can inform us about, using empirical analyses of quantified aggressive antisocial behaviours and their possible explanatory factors, can we gain a clearer notion of the relationship between mental disorder and crime. [Copyright &y& Elsevier]

Abstract: Since cross-sectional brain-imaging studies demonstrating frontotemporal cerebral hypoactivity in violent offenders have generally been carried out around the time of trial and sentencing, the findings might be influenced by the stressful situation of the subjects. It seems that no group of offenders with this finding has yet been followed longitudinally. We have re-examined nine offenders convicted of lethal or near-lethal violence in whom single photon emission tomography (SPECT) previously had demonstrated frontotemporal hypoperfusion. The mean interval between the initial and the follow-up examination was 4 years. The initially observed hypoactivity was found to have remained virtually unchanged at follow-up: no mean change in the group exceeded 5% in 12 assessed regions of interest. Although preliminary due to the small sample size, this study suggests that frontotemporal brain hypoactivity is a trait rather than a state in perpetrators of severe violent crimes. [Copyright &y& Elsevier]

Abstract: Neurodevelopmental disorders such as autism and schizophrenia involve social interaction problems and poor mentalizing abilities, associated with abnormal regional cerebral activity. Similar problems may be present in aggressive personality disorders and psychopathy. This paper reviews brain imaging data from research aiming at establishing possible central nervous correlates to aggression and psychopathy. Studies in this field are associated with a range of method problems. Differences between criminal offenders and controls may be confounded by a number of factors unrelated to personality traits or aggression per se. Phenotypical characterisation varies between studies as do the laboratory methods and their interpretation. In spite of these problems, there are some recurrent findings in the present literature. Hypoactivity or structural reduction of the prefrontal cortex is a consistent finding in violent offenders or subjects with antisocial personality disorder. When defined as a personality disorder of social interaction and empathy, psychopathy seems to be associated rather with central abnormalities in the limbic circuitry. Indications of an increased dopaminergic neurotransmission relative to the serotonergic have also been connected to such personality traits, especially to the AD/HD-related behavioural aspects. Further studies using strict phenotypical definitions or experimental models are clearly warranted to establish a pathophysiological background to destructive personality traits and the propensity to violent acting out. [Copyright &y& Elsevier]

Abstract: Swedish penal law does not exculpate on the grounds of diminished accountability; persons judged to suffer from severe mental disorder are sentenced to forensic psychiatric care instead of prison. Re-introduction of accountability as a condition for legal responsibility has been advocated, not least by forensic psychiatric professionals. To investigate how professionals in forensic psychiatry would assess degree of accountability based on psychiatric diagnoses and case vignettes, 30 psychiatrists, 30 psychologists, 45 nurses, and 45 ward attendants from five forensic psychiatric clinics were interviewed. They were asked (i) to judge to which degree (on a dimensional scale from 1 to 5) each of 12 psychiatric diagnoses might affect accountability, (ii) to assess accountability from five case vignettes, and (iii) to list further factors they regarded as relevant for their assessment of accountability. All informants accepted to provide a dimensional assessment of accountability on this basis and consistently found most types of mental disorders to reduce accountability, especially psychotic disorders and dementia. Other factors thought to be relevant were substance abuse, social network, personality traits, social stress, and level of education. [Copyright &y& Elsevier]

• Central ghrelin infusion, but not ghrelin administered systemically, increases aggressive behaviours in male mice. • Aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1A by JMV2959. • Ex vivo biochemical data shows that serotonin in amygdala may have central roles for the ability of JMV2959 to reduce aggression. • JMV2959 cannot decrease aggression following depletion of central serotonin signalling. • In men displaying hazardous alcohol use the Leu72Leu variant in the pre-pro-ghrelin gene are associated with higher aggression. Aggressive behaviour is of crucial importance in the defence for limited resources including food and mates and involves central serotonin as well as dopamine signalling. As ghrelin modulates food intake and sexual behaviour we initially investigated the hypothesis that central ghrelin signalling regulates aggressive behaviour in the resident intruder paradigm in male mice. Moreover, interaction between ghrelin signalling and serotonergic, noradrenergic as well as dopaminergic neurotransmission in aggression was investigated. The relevance of ghrelin for human aggression per se as well as for aggression induced by alcohol was evaluated in a human genetic association study comprising young men (n = 784) from the normal population assessed for anti-social behaviours. The present study demonstrates that central ghrelin infusion, but not ghrelin administered systemically, increases aggression. Moreover aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1 A (GHSR-1A) by JMV2959. As indicated by the ex vivo biochemical data serotonin, rather than dopamine or noradrenaline, in amygdala may have central roles for the ability of JMV2959 to reduce aggression. This link between central serotonin, GHSR-1A and aggression is further substantiated by the behavioural data showing that JMV2959 cannot decrease aggression following depletion of central serotonin signalling. The genetic association study demonstrates that males carrying the Leu72Leu genotype of the pre-pro-ghrelin gene and displaying hazardous alcohol use are more aggressive when compared to the group carrying the Met-allele. Collectively, this contributes to the identification of central ghrelin pathway as an important modulator in the onset of aggressive behaviours in male mice. [ABSTRACT FROM AUTHOR]

This 3-year follow-up study compares background variables, extent of criminality and criminal recidivism in the form of all court convictions, the use of inpatient care, and number of early deaths in Swedish institutionalized adolescents (N=100) with comorbid substance use disorders (SUD) and Attention-Deficit/Hyperactivity Disorder (ADHD) (n=25) versus those with SUD but no ADHD (n=30), and those without SUD (n=45). In addition it aims to identify whether potential risk factors related to these groups are associated with persistence in violent criminality. Results showed almost no significant differences between the three diagnostic groups, but the SUD plus ADHD group displayed a somewhat more negative outcome with regard to criminality, and the non-SUD group stood out with very few drug related treatment episodes. However, the rate of criminal recidivism was strikingly high in all three groups, and the use of inpatient care as well as the number of untimely deaths recorded in the study population was dramatically increased compared to a age matched general population group. Finally, age at first conviction emerged as the only significant predictor of persistence in violent criminality with an AUC of .69 (CI (95%) .54-.84, p=.02). Regardless of whether SUD, with or without ADHD, is at hand or not, institutionalized adolescents describe a negative course with extensive criminality and frequent episodes of inpatient treatment, and thus requires a more effective treatment than present youth institutions seem to offer today. However, the few differences found between the three groups, do give some support that those with comorbid SUD and ADHD have the worst prognosis with regard to criminality, health, and untimely death, and as such are in need of even more extensive treatment interventions. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 ( ESR1 ), steroid-5-alpha-reductase, type 2 ( SRD5A2 ) and sex hormone-binding globulin ( SHBG ) in a subset ( n = 1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS ( n = 10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2 . No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG , especially for language impairment problems in boys, cannot be ruled out. [ABSTRACT FROM AUTHOR]

This study describes the prevalence of adverse events and length of stay in forensic psychiatric patients with and without a restriction order. Detailed clinical and administrative information from medical records and written court decisions was gathered retrospectively from admission until discharge for a Swedish population-based, consecutive cohort of forensic psychiatric patients (n = 125). The median length of stay for the whole cohort was 951 days, but patients with a restriction order stayed in hospital almost five times as long as patients without. Restriction orders were related to convictions for violent crime, but not for any other differences in demographic or clinical variables. The majority of the patients (60%) were involved in adverse events (violence, threats, substance abuse, or absconding) at some time during their treatment. Patients with restriction orders were overrepresented in violent and threat events. Previous contact with child and adolescence psychiatric services, current violent index crime, psychotic disorders, a history of substance, and absconding during treatment predicted longer length of stay. Being a parent, high current Global Assessment of Functioning scores, and mood disorders were all significantly related to earlier discharge. In a stepwise Cox regression analysis current violent index crime and absconding remained risk factors for a longer hospital stay, while a diagnosis of mood disorder was significantly related to a shorter length of stay. [ABSTRACT FROM AUTHOR]

Abstract: To the best of our knowledge, the present register is the only nationwide forensic psychiatric patient register in the world. The aim of this article is to describe the content of the Swedish National Forensic Psychiatric Register (SNFPR) for Swedish forensic patients for the year 2010. The subjects are individuals who, in connection with prosecution due to criminal acts, have been sentenced to compulsory forensic psychiatric treatment in Sweden. The results show that in 2010, 1476 Swedish forensic patients were assessed in the SNFPR; 1251 (85%) were males and 225 (15%) were females. Almost 60% of the patients had a diagnosis of schizophrenia, with a significantly higher frequency among males than females. As many as 70% of the patients had a previous history of outpatient psychiatric treatment before becoming a forensic psychiatric patient, with a mean age at first contact with psychiatric care of about 20years old for both sexes. More than 63% of the patients had a history of addiction, with a higher proportion of males than females. Furthermore, as many as 38% of all patients committed crimes while under the influence of alcohol and/or illicit drugs. This was more often the case for men than for women. Both male and female patients were primarily sentenced for crimes related to life and death (e.g., murder, assault). However, there were more females than males in treatment for general dangerous crimes (e.g., arson), whereas men were more often prosecuted for crimes related to sex. In 2010, as many as 70% of all forensic patients in Sweden had a prior sentence for a criminal act, and males were prosecuted significantly more often than females. The most commonly prescribed pharmaceuticals for both genders were antipsychotics, although more women than men were prescribed other pharmaceuticals, such as antidepressants, antiepileptics, and anxiolytics. The result from the present study might give clinicians an opportunity to reflect upon and challenge their traditional treatment methods. [Copyright &y& Elsevier]

Summary: Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n =1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3′-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs. [ABSTRACT FROM AUTHOR]

Abstract: The complexity and consequences of psychopathy are still debated, and its relation to other mental disorders, pathological personality traits, and criminality needs to be further investigated by clinical, longitudinal studies using structured diagnostic instruments. The present study used two groups of mentally disordered offenders (N =153) investigated with in-depth clinical assessments and prospective long-term follow-up to identify the convergence between 1) the four facets of psychopathy defined by the Psychopathy Checklist—Revised (PCL-R; Interpersonal, Affective, Lifestyle, and Antisocial), 2) mental disorders according to SCID I and II interviews, 3) personality traits as measured by the Karolinska Scales of Personality, and 4) criminal recidivism. The Interpersonal facet differed substantially from the other three facets by not being significantly associated with substance use disorders, antisocial personality disorder (the other facets at P ≤0.001 level), or personality traits involving impulsive and aggressive antisocial behaviors (the other facets at P <0.01 level). Furthermore, the interpersonal facet could not predict violent recidivism better than random. The Antisocial facet outperformed not only the other facets but also the total PCL-R score in the prediction of violent recidivism, P <0.001.The findings confirm psychopathy as a heterogeneous phenomenon and have clinical implications for assessments of psychopathy and violence risk assessments in clinical and forensic contexts. [Copyright &y& Elsevier]

Background: In specific vole and primate species the neuropeptide oxytocin plays a central role in the regulation of pair-bonding behavior. Here we investigate the extent to which genetic variants in the oxytocin receptor gene (OXTR) are associated with pair-bonding and related social behaviors in humans. Methods: We first genotyped twelve single nucleotide polymorphisms (SNPs) in the TOSS (Twin and Offspring Study in Sweden) (n = 2309) and the TCHAD (Swedish Twin Study of Child and Adolescent Development) (n = 1240), comprising measures of self-reported pair-bonding behavior. In the TOSS sample we further investigated one of the SNPs for measures of marital status and quality. Moreover, in the TCHAD sample we explored the longitudinal relationship between precursors of pair-bonding during childhood and subsequent behavior in romantic relationships. Finally, in the TCHAD study and in the Child and Adolescent Twin Study of Sweden (CATSS) (n = 1771), the association between the same SNP and childhood behaviors was investigated. Results: One SNP (rs7632287) in OXTR was associated with traits reflecting pair-bonding in women in the TOSS and TCHAD samples. In girls the rs7632287 SNP was further associated with childhood social problems, which longitudinally predicted pair-bonding behavior in the TCHAD sample. This association was replicated in the CATSS sample in which an association between the same SNP and social interaction deficit symptoms from the autism spectrum was detected. Conclusion: These results suggest an association between variation in OXTR and human pair-bonding and other social behaviors, possibly indicating that the well-described influence of oxytocin on affiliative behavior in voles could also be of importance for humans. [ABSTRACT FROM AUTHOR]

Summary: Elevated serum levels of S100B have proven useful as an indicator of brain-injury but have also been shown in patients diagnosed with psychiatric disorders. Recently, associations were found between variations in the S100B gene and schizophrenia as well as bipolar affective disorder. The aim of the present study was to investigate whether some of these genetic variations influence general aspects of human behaviour as portrayed by normal dimensions of personality. Two single nucleotide polymorphisms within the S100B gene, 2757C>G and 5748C>T, were genotyped in two population based cohorts consisting of 42-year-old women (n =270) and 51-year-old men (n =247), respectively. The two polymorphisms were analysed with respect to personality traits assessed using the Temperament and Character Inventory (TCI). In men, the 2757C>G polymorphism was found to significantly influence the TCI dimension self-directedness with higher scores in 2757G homozygotes. A similar tendency towards association was seen in the female cohort; however, this correlation did not remain significant after correction for multiple comparisons. Furthermore, the 5748C>T polymorphism was highly associated with self-directedness in men. Self-directedness is an overall estimate of adaptive strategies to adjust behaviour to conceptual goals as well as coping strategies and is strongly correlated to general mental health and absence of personality disorder. These preliminary findings suggest that the S100B gene may be implicated not only in certain pathological brain conditions but also in processes involved in normal behaviour. [ABSTRACT FROM AUTHOR]

Abstract: The prevention of aggressive behaviours is a core priority for psychiatric clinical work, but the association between the diagnostic concepts used in psychiatry and aggression remains largely unknown. Outpatients referred for psychiatric evaluations of childhood-onset neuropsychiatric disorders (n =178) and perpetrators of violent crimes referred to pre-trial forensic psychiatric investigations (n =92) had comprehensive, instrument-based, psychiatric assessments, including the Life History of Aggression (LHA) scales. Total and subscale LHA scores were compared to the categorical and dimensional diagnoses of childhood and adult DSM-IV axis I and II mental disorders, general intelligence (IQ), Global Assessment of Functioning (GAF), and personality traits according to the Temperament and Character Inventory (TCI). Overall, the two groups had similar LHA scores, but the offender group scored higher on the Antisocial subscale. Higher total LHA scores were independently associated with the hyperactivity facet of attention-deficit/hyperactivity disorder (AD/HD), childhood conduct disorder, substance-related disorders, and low scores on the Cooperativeness character dimension according to the TCI. IQ and GAF-scores were negatively correlated with the LHA subscale Self-directed aggression. Autistic traits were inversely correlated with aggression among outpatients, while the opposite pattern was noted in the forensic group. The findings call for assessments of aggression-related behaviours in all psychiatric settings. [Copyright &y& Elsevier]

Abstract: Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin I to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. [ABSTRACT FROM AUTHOR]

Abstract: Historically, the Swedish criminal justice system conformed to other Western penal law systems, exempting severely mentally disordered offenders considered to be unaccountable. However, in 1965 Sweden enforced a radical penal law abolishing exceptions based on unaccountability. Mentally disordered offenders have since then been subjected to various forms of sanctions motivated by the offender''s need for care and aimed at general prevention. Until 2008, a prison sentence was not allowed for offenders found to have committed a crime under the influence of a severe mental disorder, leaving forensic psychiatric care the most common sanction in this group. Such offenders are nevertheless held criminally responsible, liable for damages, and encumbered with a criminal record. In most cases, such offenders must not be discharged without the approval of an administrative court. Two essentially modern principles may be discerned behind the “Swedish model”: first, an attempted abolishment of moral responsibility, omitting concepts such as guilt, accountability, atonement, and retribution, and, second, the integration of psychiatric care into the societal reaction and control systems. The model has been much criticized, and several governmental committees have suggested a re-introduction of a system involving the concept of accountability. This review describes the Swedish special criminal justice provisions on mentally disordered offenders including the legislative changes in 1965 along with current proposals to return to a pre-1965 system, presents current Swedish forensic psychiatric practice and research, and discusses some of the ethical, political, and metaphysical presumptions that underlie the current system. [Copyright &y& Elsevier]

Abstract: Parkinson’s disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], β2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general. [ABSTRACT FROM AUTHOR]

abstract: Neurobiological markers in cerebrospinal fluid (CSF) and in serum, previously found to co-vary with destructive personality traits in violent offenders, were explored in a general population sample of 21 patients undergoing knee surgery. Results on the Karolinska Scales of Personality (KSP) and the Temperament and Character Inventory (TCI) were compared with CSF/serum albumin ratios and serum concentrations of beta-trace protein (βTP) (as markers for blood–brain barrier (BBB) permeability), to CSF/serum albumin ratios between the dopamine and serotonin metabolites homovanillic acid (HVA)/5-hydroxyindoleacetic acid (HIAA) and to CSF and serum ratios between activated thyroid hormone (T3) and its precursor T4. Serum βTP concentrations correlated with CSF/serum albumin ratios (P =0.018), but not with preoperative serum creatinine concentrations. Serum βTP correlated significantly with Monotony Avoidance and Impulsiveness; CSF HVA/5-HIAA ratios with Irritability and low Cooperativeness. The βTP is a potential serum marker for the integrity of the BBB that does not necessitate lumbar puncture. Thyroid hormones did not correlate with personality traits. As reported in forensic psychiatric patients, aggressive, unempathic personality traits were thus associated with increased dopaminergic activity in relation to the serotonergic activity and impulsivity to increased BBB permeability also in a general population group. [ABSTRACT FROM AUTHOR]

Abstract: The development of forensic psychiatric risk assessments is discussed from a clinical point of view using the example of Sweden. A central task in forensic psychiatry has traditionally been to identify dangerous, mentally disordered subjects considered to be prone to commit violent acts. Over time, “dangerousness” has been reworded into “risk”. Nevertheless, such assessments have generally been based on the psychiatric factors characterising the individual patient, while group interaction, situational factors, or social and cultural circumstances, such as the availability of alcohol and drugs, have been largely overlooked. That risk assessments have a focused on people with a diagnosis of “mental disorder” and been used as grounds for coercive measures and integrity violations has somehow been accepted as a matter of course in the public and political debate. Even the basic question whether offenders with a mental disorder are really more prone to criminal recidivism than other offenders seems to have been treated light-handedly and dealt with merely by epidemiological comparisons between groups of persons with broad ranges of psychosocial vulnerability and the general population. Legal texts, instructions and guidelines from the authorities in charge are often vague and general, while actors in the judicial system seem to put their trust in psychiatric opinions. The exchange of professional opinions, general public expectations, and judicial decision processes poses a huge risk for misunderstandings based on divergent expectations and uses of terminology. [Copyright &y& Elsevier]

Abstract: Aiming to clarify the adult phenotype of antisocial personality disorder (ASPD), the empirical literature on its childhood background among the disruptive behaviour disorders, such as attention deficit/hyperactivity disorder (AD/HD), oppositional defiant disorder (ODD), conduct disorder (CD), or hyperkinetic conduct disorder (HKCD), was reviewed according to the Robins and Guze criteria for nosological validity. At least half of hyperactive children develop ODD and about a third CD (i.e. AD/HD+CD or HKCD) before puberty. About half of children with this combined problem constellation develop antisocial personality disorder (ASPD) in adulthood. Family and adoption/twin studies indicate that AD/HD and CD share a high heritability and that, in addition, there may be specific environmental effects for criminal behaviours. “Zones of rarity” delineating the disorders from each other, or from the normal variation, have not been identified. Neurophysiology, brain imaging, neurochemistry, neurocognition, or molecular genetics have not provided “external validity” for any of the diagnostic categories used today. Deficient mental functions, such as inattention, poor executive functions, poor verbal learning, and impaired social interaction (empathy), seem to form unspecific susceptibility factors. As none of today''s proposed syndromes (e.g. AD/HD or psychopathy) seems to describe a natural category, a dimensional behavioural phenotype reflecting aggressive antisocial behaviours assessed by numbers of behaviours, the severity of their consequences and how early is their age at onset, which will be closely related to childhood hyperactivity, would bring conceptual clarity, and may form the basis for further probing into mental, cognitive, biological and treatment-related co-varying features. [Copyright &y& Elsevier]

Summary: Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case–control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition. [Copyright &y& Elsevier]

Abstract: To examine age at onset of substance abuse in relation to other factors of relevance to criminal behavior, we compared Life History of Aggression (LHA) scores, traits of psychopathy according to the Psychopathy Checklist — Revised (PCL-R), and violent recidivism in 100 violent offenders with early (before the age of 18) versus late onset of abuse or dependence. Of 56 subjects with a history of alcohol and/or drug abuse, an early onset was ascertained in 31. The duration of abuse did not correlate with the LHA and PCL-R scores or with violent recidivism, but the age at onset correlated strongly with all these factors and also remained their strongest correlate in multivariate models including childhood-onset attention deficit/hyperactivity disorder, conduct disorder, and drug abuse as covariates. Strong mathematical associations with aggression, psychopathy, and recidivism pointed to age at onset of substance abuse as a marker of possible complications that require preventive social, educational and medical measures. [Copyright &y& Elsevier]

Summary: Background: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. Methods: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. Results: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T3/T4 ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T3/T4 ratio decreased (p<0.0001), while the CSF T3/T4 ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T3 and T4 at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. Conclusions: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress. [Copyright &y& Elsevier]

Abstract: In several twin studies the relative contribution of genetic factors for personality traits has amounted to figures between 40 and 60%. In the present study we investigated to which degree polymorphisms in the 5-HTT and AP-2β genes are implicated in the neural processes involved in the formation of Temperament and Character traits, as estimated by Cloninger''s TCI. Considering the background of previous reports, associations with the character Self-Transcendence and its sub-scale Spiritual Acceptance in particular, were of interest. A stratified random sample of 200 individuals (total population=5173), matched for age, gender and risk behaviors, from volunteering 16- and 19-year-old adolescents students in Sweden was investigated. Cloninger''s TCI inventory was used for investigation of temperament and character traits. Blood samples were used for analyses of a promoter serotonin transporter polymorphism (5-HTTLPR) and an intron 2 polymorphism in the transcription factor AP-2β gene. Among boys individuals with presence of the short 5-HTTLPR genotype showed lower scores, whereas individuals with presence of the short AP-2β genotype showed higher scores of personality character Self-Transcendence and its sub-scale Spiritual Acceptance. Among girls no effect of either genotype was found. Both among boys and girls, significant interactive effects were found between 5-HTTLPR and AP-2β genotypes, with regard to Self-Transcendence and Spiritual acceptance. Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2β genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance. [Copyright &y& Elsevier]

Objective: Attention-deficit/hyperactivity disorder (ADHD) is more frequent in males than in females. The "female protective effect" posits that females undergo greater exposure to etiological factors than males in order to develop ADHD, leading to the prediction that relatives of females with ADHD will display more ADHD behaviors. We thus tested whether cotwins of females displaying extreme ADHD traits would display more ADHD traits than cotwins of males displaying extreme ADHD traits.Method: Parents of approximately 7,000 pairs of nonidentical twins in Sweden, and approximately 4,000 pairs of twins in England and Wales, completed dimensional assessments of ADHD traits. Probands were selected on the basis of scoring within the highest 10% of the distribution in each sample. Dimensional scores of cotwins of probands, as well as the categorical recurrence rate, were investigated by proband sex.Results: Cotwins of female probands displayed higher mean ADHD trait scores (mean = 0.62-0.79) than cotwins of male probands (mean = 0.38-0.55) in both samples. This trend was significant in the Swedish sample (p < .01) and when the 2 samples were merged into a single, larger sample (p < .001). When the samples were merged, there was also a significant association between proband sex and cotwin's categorical status, with more cotwins of female probands also being probands than cotwins of male probands.Conclusion: These findings support a female protective effect against ADHD behaviors, suggesting that females require greater exposure to genetic and environmental factors associated with ADHD in order to develop the condition. [ABSTRACT FROM AUTHOR]