Cognitive dysfunction, social behavior disorder, cerebellar ataxia, and atypical brain FDG-PET presentation in spinocerebellar ataxia 17: a case report.

BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene. CASE DESCRIPTION: We describe the clinical history, neuropsychological, and neuroimaging findings of a 42-year-old patient who presented for medical attention showing prevalent behavioral and cognitive problems along with progressively worsening gait disturbances. The patient's family history indicated the presence of SCA17 in the maternal lineage. Genetic analysis confirmed a heterozygous 52-CAG pathological expansion repeat in TBP (normal interval, 25-40 CAG. Brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed bilateral hypometabolism in the sensorimotor cortex, with a slight predominance on the right, as well as in the striatal nuclei and thalamic hypermetabolism, a finding similar to what is observed in Huntington's disease. The patient also underwent neuropsychological evaluation, which revealed mild cognitive impairment and difficulties in social interaction and understanding other's emotions (Faux Pas Test and Reading the Mind in the Eyes Test). CONCLUSION: Our report emphasizes the importance of considering SCA17 as a possible diagnosis in patients with a prevalent progressive cognitive and behavioral disorders, even with a pattern of FDG-PET hypometabolism not primarily indicative of this disease.

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice.

Trauma during critical periods of development can induce long-lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety-like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2-5 and 8 hr/day on PD6-16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two-part social interaction task designed to test social motivation (choice between a same-sex novel conspecific or an empty cup) and social novelty preference (choice between the original-novel conspecific vs. a new-novel conspecific). We used chemogenetics to non-selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non-stressed versus ELS mice; social motivation was decreased in non-stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation-for which they were deficient prior-following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma.

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder.

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin's effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.

Lifelong consequences of brain injuries during development: From risk to resilience.

Traumatic brain injuries in children represent a major public health issue and even relatively mild injuries can have lifelong consequences. However, the outcomes from these injuries are highly heterogeneous, with most individuals recovering fully, but a substantial subset experiencing prolonged or permanent disabilities across a number of domains. Moreover, brain injuries predispose individuals to other kinds of neuropsychiatric and somatic illnesses. Critically, the severity of the injury only partially predicts subsequent outcomes, thus other factors must be involved. In this review, we discuss the psychological, social, neuroendocrine, and autonomic processes that are disrupted following traumatic brain injury during development, and consider the mechanisms the mediate risk or resilience after traumatic brain injury in this vulnerable population.

How should we understand the absence of sex differences in the genetic and environmental origins of antisocial behavior?

Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology.

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy.

OBJECTIVE: To examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy. METHODS: In collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA-exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first-choice treatments for many women with epilepsy of childbearing potential. RESULTS: Of the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA-exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA-exposed children had significantly more social problems than those exposed to LTG (-2.8, 95% confidence interval [CI] = -5.2 to -0.4; P = 0.022) or LEV (-3.2, CI: -6.1 to -0.3; P = 0.028), and significantly more attention problems than LEV-exposed children (-3.7, CI: -6.7 to -0.8; P = 0.013). LTG-exposed children had significantly more attention deficit (-9.2, CI: -17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV-exposed children (9.0, CI: 0.3-17.6; P = 0.042). SIGNIFICANCE: Compared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED-exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

A sociocognitive approach to social problem solving in patients with traumatic brain injury: a pilot study.

PRIMARY OBJECTIVE: Patients with traumatic brain injury (TBI) have difficulty dealing with the social world and may display inappropriate social behavior that negatively affects their social and occupational rehabilitation. This difficulty may be explained by a social problem-solving (SPS) impairment, but little is yet known about the cognitive processes involved in the ability to solve social problems. Several publications have demonstrated that executive functions are related to social problem solving, but the role of social cognition needs to be confirmed. The present pilot study examined the expected relationships between SPS ability and both social cognition and social behavioral skills. RESEARCH DESIGN: We compared the performances of 15 patients with TBI on SPS, theory-of-mind and social behavior tasks with those of 25 matched healthy controls. MAIN OUTCOMES AND RESULTS: Our results showed for the first time that impaired social problem solving is associated with a theory-of-mind deficit, but surprisingly not with executive impairment. There was no evidence that SPS deficits predict social behavioral disorders. CONCLUSIONS: Studying social problem solving in patients with TBI may inform the design of more appropriate methods of social rehabilitation.

[Fetal alcohol spectrum disorder. An underdiagnosed neuro-development disorder of uncertain prognosis]. / Trastorno del espectro alcohólico fetal. Un trastorno del neurodesarrollo infradiagnosticado y de pronóstico incierto.

Prenatal exposure to alcohol is the cause of cognitive and behavioural disorders grouped under the term fetal alcohol spectrum disorders (FASD). The long-term evolution of subjects with FASD is often unfavourable, especially in social and academic fields. Executive dysfunction is a hallmark deficit for children with FASD with increased rates of externalizing behaviours, such as aggressiveness and frequently delinquency in adolescence and adulthood. Deficits in social skills, empathy and communication ability are frequent observed among FASD. Prenatal exposure to alcohol is the most frequent cause of acquired and preventable neurodevelopmental disorder.

La exposición prenatal al alcohol es causa de alteraciones somáticas, cognitivas y conductuales que se agrupan bajo el término de trastorno del espectro alcohólico fetal (TEAF). La evolución a largo plazo de los sujetos afectados a menudo es desfavorable, especialmente a nivel académico y adaptativo social. En el perfil neuropsicológico es característica la disfunción ejecutiva a menudo asociada a trastornos de la conducta que evolucionan en muchos casos hacia la delincuencia a partir de la adolescencia y en la edad adulta. Se han descrito también déficits de las habilidades sociales y la empatía. La exposición prenatal al alcohol constituye la causa más frecuente de trastorno del neurodesarrollo adquirido y prevenible.

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism.

BACKGROUND: Prenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring. RESULTS: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain. CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.

Repeated fluvoxamine treatment recovers early postnatal stress-induced hypersociability-like behavior in adult rats.

Childhood maltreatment is associated with impaired adult brain function, particularly in the hippocampus, and is not only a major risk factor for some psychiatric diseases but also affects early social development and social adaptation in later life. The aims of this study were to determine whether early postnatal stress affects social behavior and whether repeated fluvoxamine treatment reverses these changes. Rat pups were exposed to footshock stress during postnatal days 21-25 (at 3 weeks old: 3wFS). During the post-adolescent period (10-14 weeks postnatal), the social interaction test and Golgi-cox staining of dorsal hippocampal pyramidal neurons were performed. Following exposure to footshock stress, 3wFS rats showed an increase in social interaction time, which might be practically synonymous with hypersociability, and a decrease in spine density in the CA3 hippocampal subregion, but not in CA1. These behavioral and morphological changes were both recovered by repeated oral administration of fluvoxamine at a dose of 10 mg/kg/day for 14 days. These findings suggest that the vulnerability of the hippocampal CA3 region is closely related to social impairments induced by physical stress during the juvenile period and shed some light on therapeutic alternatives for early postnatal stress-induced emotional dysfunction.

Gluten- and casein-free diet and autism spectrum disorders in children: a systematic review.

PURPOSE: Effective treatments for core symptoms of autism spectrum disorders (ASD) are lacking. We systematically updated evidence on the effectiveness of a gluten-free and casein-free (GFCF) diet as a treatment for ASD in children. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up until August 2016, for randomized controlled trials (RCTs); additional references were obtained from reviewed articles. RESULTS: Six RCTs (214 participants) were included. With few exceptions, there were no statistically significant differences in autism spectrum disorder core symptoms between groups, as measured by standardized scales. One trial found that compared with the control group, in the GFCF diet group there were significant improvements in the scores for the 'communication' subdomain of the Autism Diagnostic Observation Schedule and for the 'social interaction' subdomain of the Gilliam Autism Rating Scale. Another trial found significant differences between groups in the post-intervention scores for the 'autistic traits', 'communication', and 'social contact' subdomains of a standardized Danish scheme. The remaining differences, if present, referred to parent-based assessment tools or other developmental/ASD-related features. No adverse events associated with a GFCF diet were reported. CONCLUSIONS: Overall, there is little evidence that a GFCF diet is beneficial for the symptoms of ASD in children.

Psychosocial behaviour management programme for home-dwelling people with dementia: A cluster-randomized controlled trial.

Little is known about the effectiveness of a psychosocial behaviour management programme on home-dwelling people with dementia. We developed a Behaviour Analytics & Support Enhancement (BASE) programme for care managers and professional caregivers of home care services in Japan. We investigated the effects of BASE on challenging behaviour of home-dwelling people with dementia. METHODS: A cluster-randomized controlled trial was conducted with home care providers from 3 different districts in Tokyo. Each provider recruited persons with dementia aged 65 years or older to receive home care in the BASE programme in August 2016. An online monitoring and assessment system was introduced to the intervention group for repeated measures of challenging behaviour with a total score of the Neuropsychiatric Inventory. Care professionals in both the intervention and control groups evaluated challenging behaviour of persons with dementia at baseline (September 2016) and follow-up (February 2017). RESULTS: A majority of persons with dementia had Alzheimer disease (59.3%). One-hundred and forty-one persons with dementia were included in the intervention group and 142 in the control group. Multilevel modelling revealed a significant reduction in challenging behaviour in the intervention group after 6 months (mean score, 18.3 to 11.2) compared with that of the control group (11.6 to 10.8; P < .05). CONCLUSION: The implementation of the BASE programme resulted in a reduction of challenging behaviour of home-dwelling people with dementia. Future research should examine the long-term effects of behaviour management programmes on behaviour, nursing home placement, and hospital admission of home-dwelling people with dementia.

Clinician modifiable factors associated with better quality of life in children with acquired brain injury undergoing rehabilitation.

OBJECTIVES: To identify clinician-modifiable factors related to quality of life (QOL) in children with acquired brain injury (ABI). PARTICIPANTS AND METHODS: Thirty-nine children attending an ABI rehabilitation program (5-18 years) were assessed using the Personality Inventory for Children-2, Vineland Adaptive Behavior Scale-2, Handicap-Related Problems for Parents Inventory and Children's Assessment of Participation and Enjoyment. The Pediatric Quality of Life Inventory was completed by children and parents six months later. RESULTS: Children with lower levels of internalising and externalising behaviours, health and social skill problems, and higher family functioning had significantly higher levels of total QOL (child and parent rated) (r = -.47 to -.79). In addition, children with higher levels of adaptive behaviour had significantly higher parent rated total QOL (r = .46). Measures of mother's stressors had moderate but not statistically significant relationships with the child's total QOL (r = -.31 to -.35). There were moderate and statistically significant relationships between measures of participation in physical activities and total QOL as rated by children (r = .42-.48) but not parents (r = .11-.30). CONCLUSIONS: These findings suggest potential targets to be investigated in future clinical research in rehabilitation following ABI in children to optimise QOL.

Cognitive behavioural therapy for aggression among individuals with moderate to severe acquired brain injury: a systematic review and meta-analysis.

BACKGROUND: Aggression is common after an acquired brain injury (ABI). Cognitive behavioural therapy (CBT) is a form of psychotherapy, in which therapists help patients to identify their maladaptive behaviours. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the effectiveness of CBT interventions in treating aggression in an ABI population. METHODS: A systematic literature search was conducted using: PubMed/MEDLINE, CINAHL, EMBASE and PsycINFO from database inception to August 2016. English articles were included if: at least 50% of the study sample had a moderate to severe ABI, there were at least three adult human participants, and use of a CBT intervention for the treatment of aggression. RESULTS: Seven articles met inclusion criteria: one RCT, an RCT crossover and five pre-post trials. Of these, four articles were included in a pre-post meta-analysis for treatment efficacy on subscales of the State Trait Anger Expression Inventory (STAXI) and STAXI-2 outcome measures. The meta-analysis found CBT was effective in moderating the external behaviours of aggression, but not internal anger. CONCLUSION: The differences in outcomes may be related to the differential management of anger expression and anger suppression. CBT shows promise, but further studies with comparator groups are needed before conclusions about its efficacy can be made.

Examining the effect of social bonds on the relationship between ADHD and past arrest in a representative sample of adults.

BACKGROUND: Several studies have found a connection between attentional deficit hyperactivity disorder (ADHD) and criminal behaviour in clinical and prison samples of adults, but there is a lack of representative general population data on this. AIM: To test relationships between histories of ADHD and arrest. Our main research question was whether any such relationship is direct or best explained by co-occurring variables, especially indicators of social bonds. METHOD: Data were from a sample of 5,376 adults (18+) representative of the general population of Ontario, Canada. Logistic regression analysis was used to explore the relationship between self-reported arrest on criminal charges and ADHD as measured by the Adult Self Report Scale (ASRS-v1.1). Indicators of strong social bonds (post secondary education, household size) and weak bonds (drug use, antisocial behaviours, alcohol dependence) were also obtained at interview and included in the statistical models. RESULTS: In a main effects model, screening positive for ADHD was twice as likely (OR 2.05 CI 1.30, 3.14) and past use of medications for ADHD three times as likely (OR 3.94 CI 2.46, 6.22) to be associated with ever having been arrested. These associations were no longer significant after controls for weak and strong social bonds were added to the models. In the best fitting statistical model, ever having been arrested was not associated with ADHD, but it was significantly associated with indicators of strong and weak social bonds. CONCLUSIONS: The observed connection between ADHD and criminality may be better understood through their shared relationships with indicators of poor social bonds. These include antisocial behaviour more generally, but also drug use and failure to progress to any form of tertiary education, including vocational training. Copyright © 2017 John Wiley & Sons, Ltd.

Subtyping Schizophrenia by Social Functioning - a Pragmatic Proposal for Clinics and Research.

Schizophrenia has been claimed to be a "heterogeneous" disorder despite the fact that a diagnosis is made without reliable biomarkers but sorely with a constellation of "common" observable symptoms that however may be overlooked. Alternatively functional impairments are the prerequisite to make a diagnosis and may be simpler and more pragmatic to express objectively. It would then be reasonable to categorize patients according to the magnitude of psychosocial impairments, as has been done in terms of the severity of "classical" symptoms. In this context the author proposes a new paradigm in which patients with schizophrenia are classified into three functional subtypes using the anchors for the Clinical Global Impression Functioning subscale (CGI-F, adopted from the CGI) and the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz): Class 1 patients are those with no to mild functional impairments (a score of 1-3 in the CGI-F and a score of 60-100 in the FACT-Sz), Class 2 patients are those with moderate to marked impairments (4 or 5 in the CGI-F and 40-59 in the FACT-Sz), and Class 3 patients are those with severe to most severe impairments (6 or 7 in the CGI-F 6,7 and 0-39 in the FACT-Sz). The author has no intention to ignore the importance of other domains of the illness but instead provides a simple framework as what the patient is actually doing is considered to represent the proximal "hard outcome" and certainly has the relevance in the management of schizophrenia. Implications of this pragmatic classification system for clinics and research are discussed.

mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus.

Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1 +/- and Tsc2 +/- mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2 +/- (Eker)-rats express social deficits similar to Tsc2 +/- mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2 +/- (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels.

A Survey of Clinicians Working in Brain Injury Rehabilitation: Are Social Cognition Impairments on the Radar?

OBJECTIVES: To examine the social cognition assessment practices of clinicians working with children and adults with traumatic brain injury. MAIN MEASURES: Online survey addressing frequency of social cognition impairments, how these are assessed and obstacles to same, and treatment practices. PARTICIPANTS: A total of 443 clinicians worldwide working in inpatient and outpatient settings. RESULTS: While 84% of clinicians reported that more than half of their clients with severe traumatic brain injury had social cognition impairments, 78% of these reported that they infrequently or never assessed these domains using a formal assessment tool. Lack of reliable tests was most frequently (33% of respondents) cited as the greatest barrier to undertaking social cognition assessment. CONCLUSIONS AND IMPLICATIONS: Improvements are needed in the development and norming of instruments capable of detecting social cognition impairments in the traumatic brain injury population. Additional training and education is needed in the use of social cognition assessment tools.

Functional changes of the reward system underlie blunted response to social gaze in cocaine users.

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants' gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.

The occurrence of early impaired self-awareness after traumatic brain injury and its relationship with emotional distress and psychosocial functioning.

OBJECTIVE: To describe the occurrence of impaired self-awareness (ISA) after traumatic brain injury (TBI) and its association with emotional distress and psychosocial functioning following discharge. DESIGN: Prospective cohort design with data collection at discharge and 1-, 3- and 6-month follow-up. PARTICIPANTS: 81 adults with TBI. MEASURES: Self-awareness was measured using a discrepancy score generated from the Mayo-Portland Adaptability Index (MPAI-4) Ability subscale, and significant other's ratings of Item 20 on the MPAI-4. Other measures were the Depression Anxiety Stress Scale-21 and Sydney Psychosocial and Reintegration Scale. RESULTS: The discrepancy score method identified more cases of ISA than the single-item rating by significant others. Using discrepancy scores, the occurrence of ISA was 69.1% at discharge, and for those remaining in the study 6 months later, it was 54.3%. Better self-awareness was associated with greater anxiety at discharge, and stress at discharge, 3 and 6 months later, and better psychosocial functioning at all time points. Participants with ISA had significantly poorer relationships at 6 months post-discharge after controlling for injury severity. CONCLUSION: Whilst self-awareness is associated with greater stress in patients with TBI, it is also associated with better outcomes, indicating the importance of targeting ISA in rehabilitation.