Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Mentalizing in Adolescents and Young Adults with Attention Deficit Hyperactivity Disorder: Associations with Age and Attention Problems.

INTRODUCTION: Growing, albeit heterogenous evidence questions whether attention deficit/hyperactivity disorder (ADHD) is associated with socio-cognitive impairments, especially beyond childhood. This study focuses on mentalizing - the socio-cognitive ability to attribute and reason in terms of mental states. We aimed to characterize mentalizing performance in terms of correct scores and types of errors in adolescents and young adults with ADHD. METHODS: Forty-nine adolescents and adults with ADHD and 49 healthy controls matched for age and gender completed a computerized naturalistic mentalizing task, the Movie for Assessment of Social Cognition (MASC). Repeated measures analyses of variance examined the effects of age group and ADHD diagnosis on MASC performance. Additionally, associations between mentalizing scores, the severity of attention problems, and the presence of comorbidity were explored in the ADHD group. RESULTS: Results showed an increased prevalence of hypomentalizing errors in adolescents with ADHD. Lower mentalizing scores in adolescents with ADHD were correlated with indices of inattentiveness, impulsivity, and vigilance problems. Hypomentalizing errors in adolescents showed to be particularly associated with inattentiveness, after controlling for age and comorbidity. In contrast, adults with ADHD performed similarly to controls and their scores on the mentalizing task were not correlated to attention problems. CONCLUSION: These findings highlight potential developmental differences in mentalizing abilities in ADHD youths and their association with attentional impairments.

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.

Sexual Function, Sexual Dysfunctions, and ADHD: A Systematic Literature Review.

BACKGROUND: The scientific literature on sexuality among mentally ill patients clearly shows a higher prevalence of sexual disorders for many mental disorders, but little is known about sexuality in individuals suffering from ADHD. Clinicians will often assume that specific difficulties of ADHD are bound to affect sexual functioning. AIM: The aim of this study was to provide a review of the literature to gain better knowledge about sexuality in subjects with ADHD and to discuss screening and management of their potential sexual problems. METHODS: A systematic review of the literature was performed in Pubmed, PsychInfo, and Embase databases. MAIN OUTCOME MEASURES: The main outcome measures were sexual function and sexual dysfunctions. RESULTS: The studies indicated that subjects with ADHD report more sexual desire, more masturbation frequency, less sexual satisfaction, and more sexual dysfunctions than the general population. CLINICAL IMPLICATIONS: Clinicians working with subjects with ADHD should explore the quality of their sexual life. STRENGTHS & LIMITATIONS: This is the first systematic review of the sexuality of individuals with ADHD. However, the results are limited by the small number of studies, by the small sample size of many studies, and the potential for bias. CONCLUSIONS: ADHD is a mental disorder affecting sexual health. Further studies are warranted to learn more about sexuality in subjects with ADHD. Soldati L, Bianchi-Demicheli F, Schockaert P, et al. Sexual Function, Sexual Dysfunctions, and ADHD: A Systematic Literature Review. J Sex Med 2020;17:1653-1664.

Psychiatric disorders among offspring of patients with Bipolar and Borderline Personality Disorder.

OBJECTIVE: As part of a larger study investigating biological risk factors for bipolar disorder (BD) and borderline personality disorder (BPD), we investigated the prevalence of psychiatric diagnoses presented by young BD or BPD offspring. With respect to the scarcity of studies interested in psychiatric disorders among BPD offspring, we have chosen to report these results despite the small sample size for a prevalence study. METHOD: We recruited 21 BD and 22 BPD offspring and 23 control subjects. All subjects were assessed with a structured interview. RESULTS: Our main finding suggests that BPD offspring present a higher rate of psychiatric disorders compared to BD offspring. Attention deficit and hyperactivity disorder was the most prevalent disorder. CONCLUSION: Our results contribute to the evidence that offspring of patients with BPD, are at high risk with regard to their mental health and deserve both more research and special attention at the clinical level.

Insomnia in adult attention-deficit/hyperactivity disorder: A comparison with borderline personality disorder population in a clinical setting and control participants.

OBJECTIVES: Many adults with attention-deficit/hyperactivity disorder (ADHD) report sleeping difficulties. The relationship between sleep and ADHD is poorly understood, and shows discrepancies between subjective and objective measures. In order to determine the specificity of sleep-associated symptoms in ADHD, subjective sleep assessments among ADHD adult patients were compared with control subjects and with individuals suffering from borderline personality disorder (BPD). METHODS: 129 outpatients with ADHD, 70 with BPD (including 17 patients with BPD and ADHD comorbidity), and 65 control participants were assessed for sleep quality, insomnia, and sleepiness, using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). RESULTS: ADHD- and BPD-sufferers achieved higher insomnia and lower sleep quality scores than control subjects. Clinical groups did not differ in terms of sleep quality, although insomnia was more severe among BPD patients. Depression scores explained most of sleep symptoms, but even when controlling for depression, ADHD sufferers showed higher sleep latency. Inattentive symptoms were associated with somnolence, while hyperactive/impulsive symptoms were associated with insomnia and lower sleep efficiency. CONCLUSION: Sleep-related symptoms associated with ADHD were partly explained by non-specific factors, especially depression symptoms. In a dimensional perspective, hyperactive and inattentive symptoms were associated with specific sleep symptoms.

METHYLATION OF SEROTONIN RECEPTOR 3A IN ADHD, BORDERLINE PERSONALITY, AND BIPOLAR DISORDERS: LINK WITH SEVERITY OF THE DISORDERS AND CHILDHOOD MALTREATMENT.

BACKGROUND: Serotonin 3A receptor (5-HT3A R) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early-life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5-HT3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. METHODS: Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5-HT3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. RESULTS: Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5-HT3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. CONCLUSIONS: This study shows that epigenetic modification of the 5-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.

Personality profiles in adults with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Previous studies suggested that the presence of ADHD in children and young adolescents may affect the development of personality. Whether or not the persistence of ADHD in adult life is associated with distinct personality patterns is still matter for debate. To address this issue, we compared the profiles of the Temperament and Character Inventory (TCI) that assesses personality dimensions in 119 adults ADHD and 403 controls. METHODS: ANCOVA were used to examine group differences (controls vs. ADHD and ADHD inattentive type vs. ADHD combined + hyperactive/impulsive types) in Temperaments and Characters. Partial correlation coefficients were used to assess correlation between TCI and expression and severity of symptoms of ADHD. RESULTS: High novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) scores as well as low self-directedness (SD) and cooperativeness (C) scores were associated with ADHD diagnosis. Low SD was the strongest personality trait associated with adult ADHD. Cases with the ADHD inattentive type showed higher HA and lower SD scores compared to the combined and hyperactive/impulsive types. High HA scores correlated with inattention symptoms whereas high NS and ST scores were related to hyperactive symptoms. Finally low SD and high NS were associated with increased ADHD severity. CONCLUSIONS: Distinct temperaments were associated with inattentive versus hyperactive/impulsive symptoms supporting the heterogeneous nature of the disorder.

Characteristics of Spirituality and Religion Among Suicide Attempters.

Spirituality and religiousness are associated with a lower risk of suicide. A detailed assessment of spirituality among 88 suicide attempters hospitalized after a suicide attempt was performed. Factors associated with the recurrence of suicide attempts over 18 months were looked into. Spirituality was low among most suicide attempters in comparison with the general population. Two groups were identified: those with a high score of depression who featured "low" in spirituality and those with a more heterogeneous profile, for example, involving personality disorders, characterized by a "high" spirituality. At the follow-up, the "meaning in life" score appeared to correlate with recurrence of suicide. Clinical implications are discussed herein.

Spiritual Meaning in Life and Values in Patients With Severe Mental Disorders.

Spirituality and meaning in life are key dimensions of recovery in psychiatric disorders. The aim of this study was to explore spiritual meaning in life in relation to values and mental health among 175 patients with schizophrenia, borderline personality disorder, bipolar disorder, and anorexia nervosa. For 26% of the patients, spirituality was essential in providing meaning in life. Depending on the diagnosis, considering spirituality as essential in life was associated with better social functioning; self-esteem; psychological and social quality of life; fewer negative symptoms; higher endorsement of values such as universalism, tradition (humility, devoutness), and benevolence (helpfulness); and a more meaningful perspective in life. These results highlight the importance of spirituality for recovery-oriented care.

CBT/DBT skills training for adults with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is associated with marked impairments in familial, social, and professional functioning. Although stimulant treatments can be effective in adult ADHD, some patients will respond poorly or not at all to medication. Previous studies demonstrated that cognitive behavioural therapy- (CBT) and dialectical behavior therapy- (DBT) oriented interventions are effective in reducing the burden of the disease, which is mainly marked by depression, interpersonal difficulties, low self-esteem, and low quality of life. In order to determine the effectiveness of this intervention, we assessed the benefits of a CBT/DBT programme to reduce residual symptoms and help patients improve their quality of life. SUBJECTS AND METHODS: 49 ADHD-patients, poor responders to medication, were enrolled in a one-year programme where they received individual therapy, associated with weekly sessions of group therapy with different modules: Mindfulness, Emotion Regulation, Interpersonal Effectiveness and Distress Tolerance, Impulsivity/Hyperactivity and Attention. Each subject was assessed at baseline, at months 3 and 6, and at the end of the treatment for ADHD severity (ASRS v1.1), depression severity (BDI-II), hopelessness (BHS), mindfulness skills (KIMS), anger expression and control (STAXI), impulsivity (BIS-11), quality of life (WHOQOL-BREF), and social functioning (QFS). The 49 ADHD patients were compared with 13 ADHD subjects on a waiting list. Linear mixed models were used to measure response to treatment. RESULTS: Overall, the psychotherapeutic treatment was associated with significant improvements in almost all dimensions. The most significant changes were observed for BDI-II (b=-0.30; p<0.0001), ASRS total score (b=-0.16; p<0.0001), and KIMS AwA (b=0.21; p<0.0001), with moderate to large effect sizes. Compared with the waiting list controls, ADHD patients showed a better, albeit non-significant, pattern of response. CONCLUSIONS: Individual and structured psycho-educational DBT/CBT groups support existing data suggesting that a structured psychotherapeutic approach is useful for patients who respond partially or not at all to drug therapy.

Attachment and coping in psychosis in relation to spiritual figures.

BACKGROUND: Studies have found higher levels of insecure attachment in individuals with schizophrenia. Attachment theory provides a framework necessary for conceptualizing the development of interpersonal functioning. Some aspects of the attachment of the believer to his/her spiritual figure are similar to those between the child and his/her parents. The correspondence hypothesis suggests that early child-parent interactions correspond to a person's relation to a spiritual figure. The compensation hypothesis suggests that an insecure attachment history would lead to a strong religiousness/spirituality as a compensation for the lack of felt security. The aim of this study is to explore attachment models in psychosis vs. healthy controls, the relationships between attachment and psychopathology and the attachment processes related to spiritual figures. METHODS: Attachment models were measured in 30 patients with psychosis and 18 controls with the AAI (Adult Attachment interview) in relationship with psychopathology. Beliefs and practices related to a spiritual figure were investigated by qualitative and quantitative analyses. RESULTS: Patients with psychosis showed a high prevalence of insecure avoidant attachment. Spiritual entities functioned like attachment figures in two thirds of cases. Interviews revealed the transformation of internal working models within relation to a spiritual figure: a compensation process was found in 7 of the 32 subjects who showed a significant attachment to a spiritual figure. CONCLUSIONS: Attachment theory allows us to highlight one of the underlying dimensions of spiritual coping in patients with psychosis.

Adult ADHD and pathological narcissism: A retrospective-analysis.

Adult attention deficit hyperactivity disorder (ADHD) is often associated with personality pathology. However, only few studies have been conducted on the link between ADHD and pathological narcissism (PN), with or without a diagnosis of narcissistic personality disorder (NPD). In order to fill this gap, PN and NPD were assessed in 164 subjects suffering from ADHD, with several other measures including ADHD severity, quality of life, depression, anxiety, impulsivity, and emotion dysregulation (ED). We found that a significant proportion of ADHD patients suffered from NPD, and that both narcissistic grandiosity and vulnerability were associated with ADHD hyperactivity and impulsivity symptoms, but not with inattentive symptoms. These two dimensions seemed to be negatively associated with well-being and positively associated with most of the other studied psychiatric dimensions except ED, the latter being only associated with vulnerability, even after adjustment on borderline symptoms. Overall, despite important limitations that limit the generalizability of our findings to the overall ADHD population (notably linked to selection bias), we believe that this exploratory study sheds light on the potential clinical relevance of narcissistic pathology in adult ADHD patients.

Association between pathological narcissism and emotion regulation: The role of self-mentalizing?

Pathological narcissism (PN) is a common psychopathological issue leading to maladaptive strategies to cope with self-esteem threats, including self-enhancement and exploitation (grandiose strategies) or internalized shame, depression, and social withdrawal (vulnerable strategies). Mentalizing is a key process for regulating self and other representations and their associated emotions. Patients with PN further struggle with emotion dysregulation (ED), which during development is intertwined with the growing capacity to mentalize. We seek to contribute to emerging empirical data documenting the associations between PN and ED and between PN and mentalizing, and to provide information on the nature of their mutual relationships. In the present study, we assessed PN, ED, and three mentalizing dimensions (mentalizing self, other, and motivation to mentalize) in 183 patients consulting in our outpatient unit specialized in ED. We found that narcissistic vulnerability was negatively associated with self-mentalizing and positively associated with overall ED, both even after adjustment for borderline and attention deficit hyperactivity disorder (ADHD) symptoms. However, the association with ED was not maintained after further adjustment for self-mentalizing or overall-mentalizing, which suggests that mentalizing may play a mediating role in this relationship. On the other hand, narcissistic grandiosity was positively associated with other-mentalizing and ED and negatively associated with self-mentalizing in bivariate analyses, but these last two associations were not maintained after adjustment for comorbid borderline and/or ADHD symptomatology. This study provides new information on the link between PN and ED and on key mentalizing dimensions meaningfully relating to PN, notably through a potential role of self-mentalizing processes between PN and ED.

Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Partial dissociative identity disorder and gender incongruence: a case report.

Introduction: Gender incongruence (GI) is characterized by a marked and persistent incongruence between an individual's experienced gender and assigned sex, which often leads to a desire to "transition" and a demand for medical treatments. Dissociative identity disorder and partial dissociative identity disorder (PDID) are poorly known mental disorders whose clinical presentation can be confused with GI. Aims: To provide a case report of a patient with PDID and GI who required treatment for GI. Methods: A case report and follow-up were described. Results: The case report describes a person suffering from PDID and GI and asked for hormonal treatment for GI. In view of the complexity of the case, it was decided to start a follow-up to investigate the gender experience of the different personalities. After 4 months of follow-up, the symptomatology changed, and the patient waived treatment for GI and continued psychotherapeutic treatment for PDID. Conclusion: Our case report shows the complexity of providing treatment for patient with PDID and GI.

Body modifications in borderline personality disorder patients: prevalence rates, link with non-suicidal self-injury, and related psychopathology.

BACKGROUND: Borderline Personality Disorder (BPD) is a potentially severe personality disorder, characterized by difficulties in emotion regulation and control of behaviors. It is often associated with non-suicidal self-injury (NSSI). Borderline personality features have also been linked to body modifications (BMs). However, the prevalence of BMs, the link between BMs and NSSI, and between BMs and several psychopathology dimensions (e.g. borderline severity, emotion regulation, impulsivity …) remains understudied in patients with BPD. This study aims to fill this gap, and to provide further evidence on the link between NSSI and BMs. METHODS: We used data from a psychiatric outpatient center located in Switzerland (n = 116), specialized in the assessment and treatment of BPD patients. Patients underwent several semi-structured interviews and self-report psychometric scales at the arrival, and the data were retrospectively analyzed. RESULTS: We found that 70.69% of the patients had one piercing or more, and 69.83% were tattooed. The total score of body modifications and the total number of piercings score of piercings were significantly positively associated with NSSI and the SCID BPD total score. The association with the SCID score was mainly driven by the "suicide and self-damaging behaviors" item and the "chronic feeling of emptiness" item. A significant association was found between total number of piercings and emotion dysregulation. On the other hand, the self-reported percentage of body covered by tattoos score was specifically associated with the sensation seeking subscale of the UPPS-P. CONCLUSION: This study provides evidence on the prevalence of BMs in BPD patients, and on the link between BMs and NSSI in this population, suggesting a role of emotion regulation in the link between both constructs. These results also suggests that tattoos and piercings may be differentially linked to specific underlying psychological mechanisms. This calls for further considerations of body modifications in the assessment and care of BPD patients.

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3ß. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.

Exploring the genetics of lithium response in bipolar disorders.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

The utility of the autism-spectrum quotient to screen for autism spectrum disorder in adults with attention deficit/hyperactivity disorder.

The co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has been reported to be highly prevalent in adults. However, very few studies have assessed the usefulness of screening instruments to detect this co-occurrence, particularly when screening for ASD in the context of ADHD. Our study aimed at assessing the utility of the autism-spectrum quotient (AQ) as a screening tool of ASD in a sample of 153 adults referred for ADHD assessment. Our results showed that the AQ is of limited use in this context as its positive predictive value was low (47%). Particularly, the more severe the attentional deficits the more likely individuals with ADHD were to be misclassified as having a co-occurring ASD based on the AQ. However, the "imagination" subscale of the AQ was able to discriminate those who met ASD criteria from those who did not, suggesting that targeting imagination impairments might be useful when assessing for the ADHD+ASD co-occurrence in clinical settings.