Attention-deficit/hyperactivity Disorder In Females Research Articles

Sex differences in attention-deficit hyperactivity disorder diagnosis and clinical care: a national study of population healthcare records in Wales.

Population-based studies have observed sex biases in the diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD). Females are less likely to be diagnosed or prescribed ADHD medication. This study uses national healthcare records, to investigate sex differences in diagnosis and clinical care in young people with ADHD, particularly regarding recognition and treatment of other mental health conditions. The cohort included individuals diagnosed with ADHD, born between 1989 and 2013 and living in Wales between 2000 and 2019. Routine primary and secondary healthcare record data were used to derive diagnoses of ADHD and other neurodevelopmental and mental health conditions, as well as ADHD and antidepressant medications. Demographic variables included ethnicity, socioeconomic deprivation and contact with social services. There were 16,458 individuals diagnosed with ADHD (20.3% females, ages 3-30 years), with a male-to-female ratio of 3.9:1. Higher ratios (4.8:1) were seen in individuals diagnosed younger (<12 years), with the lowest ratio (1.9:1) in those diagnosed as adults (>18). Males were younger at first recorded ADHD diagnosis (mean = 10.9 vs. 12.6 years), more likely to be prescribed ADHD medication and younger at diagnosis of co-occurring neurodevelopmental conditions. In contrast, females were more likely to receive a diagnosis of anxiety, depression or another mental health condition and to be prescribed antidepressant medications, prior to ADHD diagnosis. These sex differences were largely stable across demographic groups. This study adds to the evidence base that females with ADHD are experiencing later recognition and treatment of ADHD. The results indicate that this may be partly because of diagnostic overshadowing from other mental health conditions, such as anxiety and depression, or initial misdiagnosis. Further research and dissemination of findings to the public are needed to improve awareness, timely diagnosis and treatment of ADHD in females.

Review of the Psychosocial Consequences of Attention Deficit Hyperactivity Disorder (ADHD) in Females

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is underrecognised and underdiagnosed in females. As a result, females often navigate years of symptoms without appropriate support, sometimes contributing to adverse outcomes for them and for those who try to support them. This review describes the experience of females with ADHD and explores and explains the main challenges they face. Methods: We distilled the most common themes expressed in the available literature on ADHD in females and used these to develop topic headings for a literature review. We then explored therapeutic options and identified future priorities for clinical research and development. Results: The commonest issues identified and explored related to the following topics: emotional development, friendships and relationships, handling conflict, self-harm and suicidality, creativity and hyperfocus, hypersensitivity, cognition and coordination, physical, psychological, and psychiatric comorbidity, and the effects of masking. We specifically considered the implications for serious self-harm, conflict, and criminal conviction among ADHD females, and explored how these risks may be mitigated with treatment. Discussion: Females with ADHD are both under-diagnosed and undersupported, despite the serious psychosocial consequences of this condition. Given that many of these carry potentially serious complications, recognition of these issues and the provision of appropriate support and intervention is of paramount importance if those who care for them professionally and/or personally are to respond effectively. Treatment mitigates adverse outcomes for many females with ADHD.

Sex Differences in ADHD: Review and Priorities for Future Research.

In childhood, attention-deficit/hyperactivity disorder (ADHD) is diagnosed three to 16 times more frequently in males compared to females, yet in adulthood, nearly equivalent numbers of males and females are diagnosed with ADHD. Relatively few studies have prioritized examination of sex differences in ADHD even though sex differences may have critical implications for the identification and treatment of ADHD in females and males. This review highlights current research on sex differences in ADHD across the lifespan that has emerged from cross-sectional and prospective longitudinal studies of youth, adult-ascertained samples, and registry studies. Accumulating research suggests that both males and females with ADHD experience widespread impairment across the lifespan. Some evidence of sex differences emerged, although effects have generally been modest in size. Continued research that includes females and males with ADHD is needed to clarify the nature of sex differences in ADHD. Research that focuses on equitable identification of ADHD in males and females, disentangles the effects of sex and gender, probes underlying mechanisms of sex differences, and addresses the clinical impact of sex differences in ADHD must be prioritized.

Criminal convictions in males and females diagnosed with attention deficit hyperactivity disorder: A Swedish national registry study

AbstractBackgroundIndividuals with Attention‐Deficit/Hyperactivity Disorder (ADHD) face an elevated risk of criminal convictions compared to those without ADHD. However, understanding this link involves considering sex differences, coexisting psychiatric conditions, and unmeasured familial factors. This study aimed to explore the connection between ADHD and criminal convictions (both violent and non‐violent) in males and females, while also assessing the impact of comorbid psychiatric disorders and familial factors.MethodsUsing Swedish national registers, we identified individuals born between 1986 and 1997 (635,391 males and 600,548 females). ADHD was defined through clinical diagnosis and prescribed medications, while criminal convictions were determined based on Swedish lower court records. Unmeasured familial factors were accounted for using a sibling design approach.ResultsFindings revealed that individuals with ADHD had a notably higher absolute and relative risk of both violent and non‐violent criminal convictions compared to those without ADHD. While criminal convictions were more frequent among males with ADHD, females with ADHD exhibited higher relative risks (HR violent 10.50, non‐violent 4.04) than their male counterparts (HR violent 6.03, non‐violent 3.57). Additionally, lower socioeconomic status (SES) in individuals with ADHD was associated with increased relative risks for criminal convictions compared to individuals with ADHD who had higher SES. Adjusting for childhood and internalizing psychiatric disorders partially attenuated these associations, while substance use disorders (SUD) substantially attenuated them. SUD also contributed to an elevated absolute risk of criminal convictions in both male and female individuals with ADHD. Accounting for unmeasured shared familial factors slightly reduced the estimates, but the association between ADHD and criminal convictions persisted.ConclusionIn conclusion, ADHD remains a potent independent risk factor for criminal convictions, with varying effects based on gender. This underscores the importance of tailored crime prevention strategies and early interventions for individuals with ADHD, especially when comorbid SUD is present.

Preterm or early term birth and risk of attention-deficit/hyperactivity disorder: a national cohort and co-sibling study

PurposeTo examine risks of attention-deficit/hyperactivity disorder (ADHD) in preterm and early term birth survivors, and potential sex-specific differences. MethodsA national cohort study was conducted of all 4061,795 singletons born in Sweden in 1973–2013 who survived infancy, followed up for ADHD identified from nationwide diagnoses and medications through 2018. Poisson regression was used to compute prevalence ratios (PRs), adjusting for sociodemographic and perinatal factors. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic or environmental) factors. ResultsADHD prevalences by gestational age at birth were 12.1% for extremely preterm (22–27 weeks), 7.0% for moderately preterm (28–33 weeks), 5.7% for late preterm (34–36 weeks), 6.1% for all preterm (<37 weeks), 5.2% for early term (37–38 weeks), and 4.5% for full-term (39–41 weeks). Adjusted PRs comparing extremely preterm, all preterm, or early term versus full-term, respectively, were 2.35 (95% CI, 2.15–2.57), 1.28 (1.25–1.31), and 1.12 (1.10–1.13) among males, and 2.46 (2.17–2.78), 1.24 (1.20–1.28), and 1.08 (1.06–1.10) among females (P < .001 for each). These associations were virtually unchanged after controlling for shared familial factors. Both spontaneous and medically indicated preterm birth were associated with ADHD (adjusted PRs, 1.21; 95% CI, 1.18–1.24; and 1.39; 1.34–1.43, respectively). ConclusionsIn this large cohort, preterm and early term birth were associated with increased risks of ADHD in males and females, independently of covariates and shared familial factors.

Rare copy number variants in males and females with childhood attention-deficit/hyperactivity disorder.

While childhood attention-deficit/hyperactivity disorder (ADHD) is more prevalent in males than females, genetic contributors to this effect have not been established. Here, we explore sex differences in the contribution of common and/or rare genetic variants to ADHD. Participants were from the Adolescent Brain and Cognitive Development study (N = 1253 youth meeting DSM-5 criteria for ADHD [mean age = 11.46 years [SD = 0.87]; 31% female] and 5577 unaffected individuals [mean age = 11.42 years [SD = 0.89]; 50% female], overall 66% White, non-Hispanic (WNH), 19% Black/African American, and 15% other races. Logistic regression tested for interactions between sex (defined genotypically) and both rare copy number variants (CNV) and polygenic (common variant) risk in association with ADHD. There was a significant interaction between sex and the presence of a CNV deletion larger than 200 kb, both in the entire cohort (β = -0.74, CI = [-1.27 to -0.20], FDR-corrected p = 0.048) and, at nominal significance levels in the WNH ancestry subcohort (β = -0.86, CI = [-1.51 to -0.20], p = 0.010). Additionally, the number of deleted genes interacted with sex in association with ADHD (whole cohort. β = -0.13, CI = [-0.23 to -0.029], FDR-corrected p = 0.048; WNH. β = -0.17, CI = [-0.29 to -0.050], FDR-corrected p = 0.044) as did the total length of CNV deletions (whole cohort. β = -0.12, CI = [-0.19 to -0.044], FDR-corrected p = 0.028; WNH. β = -0.17, CI = [-0.28 to -0.061], FDR-corrected p = 0.034). This sex effect was driven by increased odds of childhood ADHD for females but not males in the presence of CNV deletions. No similar sex effect was found for CNV duplications or polygenic risk scores. The association between CNV deletions and ADHD was partially mediated by measures of cognitive flexibility. In summary, CNV deletions were associated with increased odds for childhood ADHD in females, but not males.

Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder.

ObjectivesTo estimate phenotypic and familial association between early-life injuries and attention deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses.MethodsChildren born in Denmark 1995-2010 (n=786,543) were followed from age five until a median age of 14 (IQR: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward treated injuries by age five. In a subsample born 1995 to 2005 with genetic data available (n=16,580), we estimated incidence rate ratios (IRR) for the association between PRS-ADHD and number of injuries before age five and the genetic correlation between ADHD and any injury before age five.ResultsInjuries were associated with ADHD (HR=1.61; 95% CI 1.55-1.66), in males (HR=1.59; 1.53-1.65) and females (HR=1.65; 1.54-1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs. 3.1% (no injuries).ADHD was also associated with injuries in relatives, stronger in 1st- than 2nd-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR=1.06; 1.00-1.14), with a genetic correlation of 0.53 (0.21-0.85).ConclusionsEarly-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behaviour remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Prenatal maternal stress, child internalizing and externalizing symptoms, and the moderating role of parenting: findings from the Norwegian mother, father, and child cohort study.

Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations. This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques. Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased. This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Annual Research Review: Attention‐deficit/hyperactivity disorder in girls and women: underrepresentation, longitudinal processes, and key directions

Attention-deficit/hyperactivity disorder (ADHD) - and its underlying behavioral dimensions of inattention and hyperactivity-impulsivity - have been understudied in females. We first cover the conceptual issues of prevalence, diagnostic practices, diversity, comorbidity, and causal factors, plus forces limiting awareness of ADHD in females. After a narrative review of cross-sectional and longitudinal findings, we conclude the following. (a) Girls meet diagnostic criteria for ADHD at just under half the rates of boys, a ratio that becomes much closer to equal by adulthood. (b) Girls and women with ADHD show a predominance of inattention and associated internalizing problems; boys and men display greater levels of hyperactive-impulsive symptoms and associated externalizing problems. (c) Sex differences in ADHD symptoms and related outcomes depend heavily on the clinical versus nonreferred nature of the samples under investigation. (d) Females with ADHD experience, on average, serious impairments, with a particularly heightened risk for problems in close relationships and engagement in self-harm. (e) Clinicians may overlook symptoms and impairments in females because of less overt (but still impairing) symptom manifestations in girls and women and their frequent adoption of compensatory strategies. Our review of predictors and mediators of adult outcomes highlights (a) the potential for heterotypically continuous pathways in females with childhood ADHD and (b) developmental progressions to self-harm, intimate partner violence, unplanned pregnancy, and comorbid psychopathology. Focusing on ADHD in females is necessary to characterize causal and maintaining mechanisms with accuracy and to foster responsive interventions, as highlighted in our closing list of clinical implications and research priorities.

Gender differences in externalizing and internalizing problems in Singaporean children and adolescents with attention-deficit/hyperactivity disorder

BackgroundStudies on gender differences in attention-deficit/hyperactivity disorder (ADHD) comorbidities in the Asian populations have been limited and previous studies have shown inconclusive findings. Singapore is a city-state country in Southeast Asia with a population of 5.7 million. This study examined gender differences in internalizing and externalizing problems in Singaporean children and adolescents with ADHD. The plausible social factors underlying the gender differences were discussed.MethodsA total of 773 participants (aged 6 to 18, 88% males) newly diagnosed with ADHD were recruited from the largest public child and adolescent psychiatric center in Singapore. Their internalizing and externalizing problems were assessed using the Child Behavioral Checklist and Teacher’s Report Form by parents and teachers respectively. Demographics and relevant social factors were collected using parent questionnaires.ResultsFemales with ADHD were reported to have less delinquent and aggressive behavior but more depressive symptoms than their male counterparts, similar to findings in the Western literature. Gender remained a significant predictor of externalizing problem after controlling for other factors. Lower socioeconomic status and parental use of physical punishment were significant predictors of both internalizing and externalizing problems.ConclusionsGender differences in ADHD comorbidities do exist in the Asian clinical population. The lack of externalizing symptoms in females with ADHD has made timely referral and diagnosis challenging. More research is needed in understanding the gender differences in ADHD and the biopsychosocial mechanism underlying the differences in order to improve the detection of ADHD in females.

Initial Engagement in Oral Sex and Sexual Intercourse Among Adolescent Girls With and Without Childhood Attention-Deficit/Hyperactivity Disorder.

We investigated initial engagement in oral sex and sexual intercourse, as well as number of sexual partners, among a prospectively followed sample of adolescent girls with and without a thorough childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD). Participants were adolescent girls (ages 12-19) followed longitudinally as part of a study of ADHD in females. A diverse sample of 140 girls with clinician-diagnosed ADHD (47 inattentive, 93 combined) and 88 age- and ethnicity-matched comparison girls were initially recruited and invited to partake in research summer programs. We utilized data on initial engagement in oral sex, sexual intercourse, and number of sexual partners, collected during follow-up interviews conducted 5 and 10years after baseline participation. Girls with a childhood diagnosis of ADHD engaged in oral sex at a significantly younger age and reported nearly twice as many oral sex partners than their typically developing peers. Post hoc tests revealed that group differences were driven largely by girls with the combined presentation of ADHD (i.e., those with childhood histories of both inattention and hyperactivity/impulsivity). No significant differences emerged with respect to age of initial sexual intercourse or number of male sexual intercourse partners. In sum, adolescent girls with ADHD, particularly those with the combined presentation, were more likely to engage in oral sexual activity at a young age and with a greater number of both male and female partners. Findings highlight the need for longitudinal research that quantifies and distinguishes between various forms of sexual behavior and later reproductive and mental health outcomes.

Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study

Several studies have demonstrated associations between neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), and the immune system, including autoimmune diseases. Since ADHD and many autoimmune diseases show sex-specific properties, such associations may also differ by sex. Using Norwegian national registries, we performed a cross-sectional study based on a cohort of 2,500,118 individuals to investigate whether ADHD is associated with common autoimmune diseases. Associations between ADHD and autoimmune diseases in females and males were investigated with logistic regression and effect modification by sex was evaluated. Several subanalyses were performed. The strongest association was found between ADHD and psoriasis in females, adjusted odds ratio (adjOR) = 1.57 (95% confidence interval: 1.46–1.68) and males, adjOR = 1.31 (1.23–1.40); p value for interaction < 0.0001. Furthermore, among females, ADHD was associated with Crohn’s disease, adjOR = 1.44 (1.16–1.79) and ulcerative colitis, adjOR = 1.28 (1.06–1.54). In contrast, males with ADHD had lower odds of Crohn’s disease, adjOR = 0.71 (0.54–0.92), in addition to a trend for lower odds of ulcerative colitis, adjOR = 0.86 (0.71–1.03); p values for interaction < 0.0001 and 0.0023, respectively. In a group of females where information on smoking and body mass index was available, adjustment for these potential mediators did not substantially alter the associations. Our findings support previously reported associations between ADHD and diseases of the immune system. The associations differ by sex, suggesting that sex-specific immune-mediated neurodevelopmental processes may be involved in the etiology of ADHD.

Association of norepinephrine transporter gene polymorphisms in attention-deficit/hyperactivity disorder in Korean population

We investigated the association of three single nucleotide polymorphisms(SNP) of the norepinephrine transporter (NET) gene SLC6A2, T-182C (rs2242446), A-3081T (rs28386840), and G-1287A (rs5569) with the prevalence of attention-deficit/hyperactivity disorder (ADHD), its clinical severity, and other disease-related characteristics in a Korean population. The genotype, allele frequency and haplotype of 103 ADHD patients and 173 controls were analyzed for these three SNPs. All participants completed the Korean version of the ADHD Rating Scale (K-ARS). The ADHD group also completed the Korean Educational Development Institute-Wechsler Intelligence Scale for Children (KEDI-WISC) and the Continuous Performance Test (CPT) in a drug-naive state.The χ2 test and logistic regression analysis revealed no significant differences in the genotype distribution or allele frequencies of each SNP between the ADHD group and the control. In the haplotype analysis, the most common T-A-G haplotype was related to an increased risk of ADHD in females (P=0.002). There was no statistical significance between clinical features of ADHD and any specific allele of each SNP after multiple test correction except lower omission error in non-A girl carriers (GG type) of G-1287A (carrier 76.75±18.74, non-carrier 55.00±9.26, t=3.026, P=0.007, Bonferroni-corrected P=0.042). Some values related A-3081 and G-1287A showed a trend approaching the significance level when analyzed separately by gender. Even though it was not statistically meaningful after multiple test correction, G allele might have some protective effect against development of ADHD symptoms and this finding was consistent with previous studies.

Time trends in incidence rates of diagnosed attention-deficit/hyperactivity disorder across 16 years in a nationwide Danish registry study.

To investigate time trends in incidence rates of first-time diagnosed attention-deficit/hyperactivity disorder (ADHD) in a nationwide sample aged 4-65 years across 16 years and identify potential contributing factors to these time trends. Incidence rates of first-time diagnosed ADHD based on ICD-10 criteria in Danish psychiatric hospitals per 100,000 person years (PY) were calculated for the total population, the 2 sexes, and 4 age groups using data from the Danish Psychiatric Central Research Registry and annual census data. Time trends and the role of contributing factors were analyzed and identified using joinpoint regression procedures by calculating annual percent changes for the time period 1995-2010. A total of 20,281 patients were diagnosed with ADHD and incidence rates increased from 7.3 to 91.2 per 100,000 PY during the study period. Joinpoint analysis suggested that incidence rates for diagnosed ADHD rapidly increased from 1998 to 2002, peaked from 2002 to 2008, and slowed down from 2008 to 2010. Contributing factors to the observed time trends were a general increase in patients seen in psychiatry for any mental disorder and an increased awareness and recognition of ADHD in females, adolescents, and adults. These results provide empirical data needed in the public and professional debate often based on theoretical rather than empirical arguments. Results support the notion of increasing incidence rates of diagnosed ADHD and identify that contributing factors are a general increase in the number of patients assessed in psychiatry and an increased recognition of females, adolescents, and adults with ADHD.

Comparison of the validity of the use of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder in males and females

The spontaneously hypertensive rat (SHR) is a commonly used and well-studied rodent model of attention deficit hyperactivity disorder (ADHD). Sex differences in the cognitive symptoms of ADHD are reported. However, the female SHR rat is much less studied than its male counterpart. The goal of the current study was to assess the validity of the SHR rodent model of ADHD by examining attentional performance, inhibitory control, and hyperactivity in both male and female SHR rats. Adult SHR and control Wistar–Kyoto rats were trained on the 5-choice serial reaction time task, a self-paced test of attention and inhibitory control. This task requires animals to identify the location of a brief light stimulus among five possible locations under several challenging conditions. Analyses of percent correct revealed that attentional performance in SHR females was not significantly different from control females, whereas attentional performance in SHR males was significantly different from control males. Analyses of the number of premature responses revealed that SHR rats made more inhibitory control errors than did control rats and that this decrease in inhibitory control was present in both SHR males and females. Analyses of activity in the open field revealed that SHR rats were more hyperactive than were control rats and that this increased hyperactivity was present in both SHR males and females. The current findings have implications for the study of sex differences in ADHD and for the use of SHR rats as a model of ADHD in females.

Cognitive functions of regularly cycling women may differ throughout the month, depending on sex hormone status; a possible explanation to conflicting results of studies of ADHD in females.

Attention Deficit/Hyperactivity Disorder (ADHD) is considered as a model of neuro-developmental cognitive function. ADHD research previously studied mainly males. A major biological distinction between the genders is the presence of a menstrual cycle, which is associated with variations in sex steroid hormone levels. There is a growing body of literature showing that sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal in ADHD. Thus, it is conceivable to believe that this functional interaction between sex hormones and molecules involved with synaptic plasticity and neurotransmitter systems may be associated with some of the clinical characteristics of women with ADHD. In spite of the impact of sex hormones on major neurotransmitter systems of the brain in a variety of clinical settings, the menstrual cycle is usually entered to statistical analyses as a nuisance or controlled for by only testing male samples. Evaluation of brain structure, function and chemistry over the course of the menstrual cycle as well as across the lifespan of women (premenarche, puberty, cycling period, premenopause, postmenopause) is critical to understanding sex differences in both normal and aberrant mental function and behavior. The studies of ADHD in females suggest confusing and non-consistent conclusions. None of these studies examined the possible relationship between phase of the menstrual cycle, sex hormones levels and ADHD symptoms. The menstrual cycle should therefore be taken into consideration in future studies in the neurocognitive field since it offers a unique opportunity to understand whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive regulation of emotional processing. The investigation of biological models involving the role of estrogen, progesterone, and other sex steroids has the potential to generate new and improved diagnostic and treatment strategies that could change the course of cognitive-behavioral disorders such as ADHD.

Traits of ADHD and autism in girls with a twin brother: a Mendelian randomization study

It has been hypothesized that prenatal exposure to testosterone may be associated with traits of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). We conducted a population-based study of dizygotic female twins to elucidate this hypothesis, assuming that the sex of the co-twin influences the level of prenatal exposure to testosterone. We invited parents of 24,552 3- to 15-year-old twins to answer questionnaires on traits of ADHD and ASD. We analysed the data using a proportional odds model with sex of the co-twin as an instrumental variable for prenatal exposure to testosterone of female twins. We received responses for 6,339 girls from dizygotic twin pairs. Odds ratios for male versus female co-twin were 0.71 (95% confidence interval 0.61-0.81) for ADHD traits and 0.74 (0.66-0.83) for ASD traits, indicating that a twin brother reduces traits of ADHD and ASD in females. In conclusion, we found that female twins with a twin brother scored significantly lower in parent-reported traits of ADHD and ASD than those with a twin sister. The reason for this may be parental reporting bias, or confounding by unmeasured variables, or a causal effect of an intrauterine environment modified by the sex of the co-twin in the opposite direction of what we expected.

Familial risk analysis of the association between attention‐deficit/hyperactivity disorder and psychoactive substance use disorder in female adolescents: a controlled study

A robust and bi-directional comorbidity between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the findings may not generalize to females. First-degree relatives from a large sample of pediatrically and psychiatrically referred girls with (123 probands, 403 relatives) and without ADHD (112 probands, 359 relatives) were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first-degree relatives for ADHD and PSUD (alcohol or drug abuse or dependence) after stratifying probands by the presence and absence of these disorders. ADHD in the proband significantly increased the risk for ADHD in relatives independently of the comorbidity with PSUD. PSUD in the proband was associated with a significantly increased risk for PSUD in relatives regardless of ADHD status. There was no evidence of co-segregation or non-random mating in the families of probands with ADHD and PSUD. Patterns of familial risk analysis suggest that the association between ADHD and PSUD in adolescent females is most consistent with the hypothesis that these disorders are independently transmitted, although the hypothesis of variable expressivity could not be ruled out. These findings are consistent with previously reported patterns of familial associations between ADHD and PSUD found in adolescent males. Longer follow-up periods are needed to more fully clarify the relationship between ADHD and PSUD, as well as provide adequate power for separate analyses of alcohol and drug use.

New Insights Into the Comorbidity Between ADHD and Major Depression in Adolescent and Young Adult Females

The main aim of this study was to evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD) in adolescent and young adult females. Subjects were females with (n = 140) and without (n = 122) ADHD ascertained from pediatric and psychiatric settings. Subjects were followed prospectively for 5 years into adolescence and young adulthood and reassessed in multiple nonoverlapping domains including psychiatric, cognitive, interpersonal, family, and educational functioning. Females with ADHD had a 2.5 times higher risk for MD at adolescent follow-up compared with control females, adjusting for psychiatric comorbidity. MD in females with ADHD was associated with an earlier age at onset, greater than twice the duration, more severe depression-associated impairment, a higher rate of suicidality, and a greater likelihood of requiring psychiatric hospitalization than MD in control girls. Parental MD and proband mania were significant predictors of MD among females with ADHD, independently of other predictors. MD emerging in the context of ADHD in females is an impairing and severe comorbidity worthy of further clinical and scientific considerations.

Sex differences in tactile defensiveness in children with ADHD and their siblings

Tactile defensiveness (TD) is a disturbance in sensory processing and is observed in some children with attention-deficit-hyperactivity disorder (ADHD). TD has been examined in male children with ADHD and in children with ADHD without differentiating by sex. As males and females with ADHD may differ in the clinical expression of the disorder and associated deficits, the aim of this study was to examine sex differences in TD in males and females with ADHD. Non-affected siblings were also examined to investigate familiality of TD. The Touch Inventory for Elementary-School-Aged Children was administered to 47 children with ADHD (35 males, 12 females; mean age 9y 8mo [SD 1y 11mo]), 36 non-affected siblings (21 males, 15 females; mean age 8y 10mo [SD 2y 4mo]), and 35 control children (16 males, 19 females; mean age 9y 5mo [SD 6mo]). Results indicated that females with ADHD displayed higher levels of TD than males with ADHD (who did not differ from control males). This suggests that TD is sex specific and may contribute to the identification of ADHD in females, thus improving diagnostic and therapeutic strength in this under-referred group. Non-affected siblings were unimpaired, regardless of sex, which suggests that TD is specific to the disorder and not part of a familial risk for ADHD.