ADHD and comorbid conduct problems among adolescents: associations with self-esteem and substance use

Attention-deficit/hyperactivity disorder (ADHD) is a common child and adolescent disorder that is associated with negative outcomes (e.g., emotional and behavioral problems, substance use) and is often comorbid with Conduct Problems (CP). Research findings are mixed as to whether youth with ADHD alone or comorbid ADHD/CP suffer from low self-esteem. Research has also shown links between low self-esteem and ADHD (alone and with CP) with substance use; yet, no research has examined the links between self-esteem and substance use in adolescents with ADHD and CP. The current study examined the relation between ADHD with and without comorbid CP and self-esteem, and whether self-esteem moderated the relation between ADHD and ADHD/CP with substance use among adolescents. We hypothesized that adolescents with comorbid ADHD/CP would experience lower self-esteem than adolescents with ADHD alone or with neither disorder and that self-esteem would moderate the association between ADHD, CP, and substance use. Participants were 62 adolescents who completed the laboratory-based study with a parent. Results suggested that adolescents with comorbid ADHD and CP had significantly lower self-esteem than adolescents with ADHD alone or neither disorder. Self-esteem was not significantly different for adolescents with ADHD alone versus those in the control group. There was one marginally significant interaction between ADHD and self-esteem predicting substance use, such that individuals with comorbid ADHD/CP who also had low self-esteem tended to use more substances. Results have implications for treatments that target adolescents with ADHD and comorbid CP, as these adolescents are at risk for many deleterious outcomes.     

Circadian rhythmicity in substance use disorder male patients with and without comorbid depression under ambulatory and therapeutic community treatment

Although there have been described alterations of circadian rhythmicity both in patients with substance use disorder (SUD) and patients with major depressive disorder (MDD), the circadian characteristics of SUD patients with comorbid MDD (SUD-MDD) are unknown. Likewise, the possible influence of the different modalities of treatments (ambulatory or therapeutic community) upon the circadian rhythmicity of SUD patients has not been characterized. Therefore, this study analyzes the circadian rhythmic profiles of SUD and SUD-MDD patients under ambulatory and therapeutic community treatment. The sample was composed of 40 SUD and 40 SUD-MDD men, aged 22–55 yrs, under treatment and with abstinence for at least three months (including each group 20 ambulatory and 20 from therapeutic community). Patients completed a sociodemographic, clinical and sleep-wake schedules interview, the Composite Scale of Morningness, and wore on the wrist an ambulatory device known as iButton® Thermochron DS1921H, which registered their distal skin temperature every two minutes for 48 hours. All the groups showed a tendency to morningness without differences among them in concordance with their sleep-wake schedules. With regard to distal skin temperature circadian rhythm, SUD patients showed higher values than SUD-MDD in amplitude, relative amplitude, percentage rhythm, and first harmonic power, and lower minimum temperature in 10 consecutive hours (p < .043, in all cases). Therapeutic community group values were lower in minimum temperature and higher in amplitude, relative amplitude, and 12 harmonic accumulated power (p < .028, in all cases) as compared to ambulatory ones. Moreover, all groups showed higher Rayleigh vector and rhythm stability as compared to normative population (p < .043, in both cases). The circadian rhythmic differences observed for diagnosis and type of treatment are indicative of a higher circadian rhythmicity robustness in SUD and therapeutic community patients as compared to SUD-MDD and ambulatory ones, respectively. Although drug consumption exerts a negative effect on the circadian rhythmicity, our results (high amplitude and rhythm stability) are indicative of an adequate circadian functioning as well as of an adjustment to the light-dark cycle in both diagnosis and type of treatment which may constitute a marker of the adherence to treatment and recovery status.     

Protopathic stimulant use among children with symptoms of ADHD

The purpose of the current study was to examine protopathic stimulant use among children with the symptoms of ADHD but do not have a diagnosis of ADHD. Protopathic or prodromal stimulant use refers to the use of stimulants by children with the symptoms of ADHD prior to a diagnosis of ADHD. In the current study, we examined children with the symptoms of ADHD who received stimulant treatment across time and with respect to several background variables. Our results indicate that these children who receive stimulant treatment without a diagnosis of ADHD are significantly more like to be eventually diagnosed with ADHD than not. Results also indicate that these children who receive stimulant treatment but do not yet have a diagnosis of ADHD are significantly more likely to have insurance that does not pay for diagnostic procedures. These results are discussed in view of treatment.     

Bipolar disorder risk alleles in adult ADHD patients

Attention-deficit/hyperactivity disorder (ADHD) has an estimated prevalence of 3-5% in adults. Genome-wide association (GWA) studies have not been performed in adults with ADHD and studies in children have so far been inconclusive, possibly because of the small sample sizes. Larger GWA studies have been performed on bipolar disorder (BD) and BD symptoms, and several potential risk genes have been reported. ADHD and BD share many clinical features and comorbidity between these two disorders is common. We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders. We studied 561 adult Norwegian ADHD patients and 711 controls from the general population. No significant associations or trends were found between any of the single nucleotide polymorphisms (SNPs) studied and ADHD [odds ratios (ORs) ≤ 1.05]. However, a weak association was found between rs1344706 in ZNF804A (OR = 1.25; P = 0.05) and MDQ. In conclusion, it seems unlikely that these six SNPs with strong evidence of association in BD GWA studies are shared risk variants between ADHD and BD.     

Prevalence of adult ADHD in an all-female prison unit

There is increasing evidence suggesting a link between ADHD and criminality, including a strong association between ADHD symptoms and the likelihood of being on probation or in prison. Most studies investigating the prevalence of ADHD in prison populations have focused on adult male offenders. In the current study, 69 female prisoners were screened for both childhood and adult ADHD symptoms using the Barkley Adult ADHD Rating Scale-IV. The results indicate that 41 % of the prisoners met the diagnostic criteria for ADHD in childhood and continued to meet criteria for ADHD as adults. More importantly, young female prisoners (aged 18–25) were significantly more likely to report symptoms of ADHD than older prisoners. Prisoners who reported symptoms of ADHD also reported high levels of impairment associated with these symptoms. A better understanding of the prevalence of ADHD in female prison units can highlight specific areas for intervention during rehabilitation, as well as the management of serious incidents within prison.     

Skills training groups for men with ADHD in compulsory care due to substance use disorder: a feasibility study

Dialectical behavior therapy (DBT)-based skills training has been developed and previously evaluated for adults with ADHD in a psychiatric outpatient context. The aim of the present study was to evaluate the feasibility of DBT-based skills training as a voluntary intervention for men with ADHD in compulsory care due to severe substance abuse. Forty sufficiently detoxified men with ADHD in compulsory care due to life-threatening substance use disorder (SUD) were included in DBT-based skills training groups. Self- and staff-rating scales were administered before and after the treatment. The refusal rate was 42.9 %. Of those who started the DBT-based skills training, 70 % completed the treatment (attendance at ≥75 % of the sessions). The treatment acceptability was good. Both ADHD and psychiatric symptoms decreased from pre- to post-intervention in self-ratings, but not in staff ratings. The patients reported improved general well-being. The correlation between self- and staff ratings was poor. Motivation for voluntary nonpharmacological treatment was low in a compulsory care context. However, the results indicate that a DBT-based skills training program for adults with ADHD may be feasible for some patients with ADHD in combination with SUD in compulsory care, provided that considerable resources are allocated with adjustments to the target group and compulsory care context.     

Project DyAdd: Fatty acids in adult dyslexia, ADHD, and their comorbid combination

In project DyAdd, we compared the fatty acid (FA) profiles of serum phospholipids in adults with attention deficit hyperactivity disorder (ADHD) (n=26), dyslexia (n=36), their comorbid combination (n=9), and healthy controls (n=36). FA proportions were analyzed in a 2×2 design with Bonferroni corrected post hoc comparisons. A questionnaire was used to assess dietary fat quality and use of supplements. Results showed that ADHD and dyslexia were not associated with total saturated FAs, monounsaturated FAs, or n-3 polyunsaturated FAs (PUFAs). However, those with ADHD had elevated proportions of total n-6 PUFAs (including γ-linolenic and adrenic acids) as compared to those without ADHD. Dyslexia was related to a higher proportion of monounsaturated nervonic acid and a higher ratio of n-6/n-3 PUFAs. Among females none of the associations were significant. However in males, all the original associations observed in all subjects remained and ADHD was associated with elevated nervonic acid and n-6/n-3 PUFA ratio like dyslexia. Controlling for poorly diagnosed reading difficulties, education, dietary fat quality, or use of FA supplements did not generally remove the originally observed associations.     

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive–impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive–impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.     

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Post‐traumatic stress disorder (PTSD) and alcohol‐use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state‐of‐the‐science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co‐occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross‐talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.     

Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review

Molecular Biology Reports - Classical psychedelics are a group of drugs characterized by their activation of the serotonin-2A (5-hydroxytryptamine-2A; 5-HT2A) receptor and the unique hallucinogenic...     

Relationship of self-mutilative behaviour with history of childhood trauma and adult ADHD symptoms in a sample of inpatients with alcohol use disorder

The aim of the present study was to evaluate relationship of self-mutilative behaviour (SMB) with the severity of childhood trauma and adult attention-deficit/hyperactivity disorder (ADHD) symptoms in a sample of inpatients with alcohol use disorder (AUD). Participants included 188 inpatients with AUD. Participants were evaluated with the Self-mutilative Behaviour Questionnaire, the Childhood Trauma Questionnaire (CTQ-28) and the Adult ADD/ADHD DSM-IV Based Diagnostic Screening and Rating Scale (Adult ADHD Scale). Among inpatients with AUD those who have a history of SMB constituted the SMB group (n = 57, 30.3%), and those without a history of SMB constituted the group without SMB (n = 131, 69.7%). Risk of high ADHD risk was 2.5 times higher among those with SMB. Adult ADHD Scale and CTQ-28 scores were also higher in the group with SMB. In the first backward logistic regression model, the severity of ADHD symptoms predicted the presence of SMB, together with the severity of childhood trauma, whereas in the second model, physical neglect and inattentive (IN) dimension of ADHD predicted the presence of SMB. These findings suggest that the higher severity of physical neglect and adult IN dimension of ADHD may be related to SMB among inpatients with AUD.     

Adjunctive atomoxetine to SSRIs or SNRIs in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety (GA): an open-label study

To examine changes in partially responsive anxiety symptoms utilizing adjunctive treatment with atomoxetine in the treatment of adult ADHD patients with comorbid partially responsive anxiety symptoms. Consenting adult patients (n=29) with confirmed diagnosis of generalized anxiety and comorbid attention deficit hyperactivity disorder (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A>7) and failed to respond to 8-week trials of selective serotonin reuptake inhibitors (SSRIs) or noradrenaline reuptake inhibitors (SNRIs). All patients were treated with atomoxetine as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary outcome measure was the Clinical Global Impression severity subscale. Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's Disability Scale. Baseline measures prior to the treatment with atomoxetine were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. Twenty-seven patients (93%) completed this open-label study. There was significant resolution of symptoms of all outcome measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 12 weeks (P<.001). Also, there was significant reduction in the disability score at 12 weeks. Patients completed the study, tolerated the adjunctive treatment, and there were no significant cardiovascular or weight changes. Two patients withdrew from the study during the first 4 weeks of treatment due to side effects. Atomoxetine can be used as an adjunctive treatment in adult patients with ADHD and comorbid partially responsive anxiety symptoms.     

A cost-effectiveness analysis of off-label atypical antipsychotic treatment in children and adolescents with ADHD who have failed stimulant therapy

The objectives of this study are: (1) to estimate the expected health outcomes of atypical antipsychotics (AAPs) and other non-stimulant attention-deficit/hyperactivity disorder (ADHD) medications and (2) to evaluate the cost-effectiveness of AAPs compared to other non-stimulant ADHD medications. We used decision analysis to compare three alternatives for treating children and adolescents with ADHD who failed initial stimulant treatment: (1) AAPs, (2) a selective norepinephrine reuptake inhibitor (atomoxetine), and (3) selective α2-adrenergic agonists (clonidine and guanfacine). Probability estimates and quality-adjusted life year (QALY) weights were derived from a literature review. Cost-effectiveness was estimated using the expected health outcomes derived from the decision analysis and expected costs from the literature. The study was conducted from the third-party payer perspective, and the study period was 1 year. One-way deterministic sensitivity analysis and a Monte Carlo simulation were performed. Over the course of 1 year of ADHD pharmacotherapy, the highest QALY was for clonidine/guanfacine (expected QALY = 0.95) followed by atomoxetine (expected QALY = 0.94). Atypical antipsychotics yielded the lowest health outcome with an expected QALY of 0.84. In the cost-effectiveness analysis, the AAP strategy was dominated as it was less effective and more costly than other two strategies. Compared to clonidine/guanfacine, AAPs provided lower QALYs (0.11 QALY lost) at an additional cost of $2186 on average. Compared to atomoxetine, AAPs resulted in 0.10 QALYs lost at an additional cost of $2186. In this decision analysis model, AAPs provide lower expected health outcomes than other ADHD medications in children and adolescents who failed prior stimulant therapy. Furthermore, AAPs were not a cost-effective option.     

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients.     

The preservation of Mullerian inhibiting substance during long-term freezing of testicular fragments

Mullerian Inhibiting Substance, a fetal testicular hormone found in most mammalian species, causes regression in the male of the Mullerian duct, the anlagen of the fallopian tube, uterus, and upper vagina. Limitations to study of this substance in the past have been posed by its short period of production and by its localized and specific action. We have been able to store testicular fragments that continue to demonstrate detectable Mullerian Inhibiting Substance activity for up to 5 months by using techniques of slow freezing which approximate 1 °C/min, cryoprotective additives, storage in liquid nitrogen, and rapid thawing. These fragments then can be pooled for biochemical and endocrinological studies. In addition, unknown fragments can be transported long distances for assay of Mullerian Inhibiting Substance.     

Effects of long-term use of fluoxetine on fertility parameters in adult male rats

The effects of long-term ingestion of fluoxetine on fertility were investigated in Sprague-Dawley male rats. Adult male rats were exposed to fluoxetine at a concentration of 200 mg/kg for 60 days. Long-term ingestion of fluoxetine for 60 days caused a great decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The weights of reproductive organs (testes, epididymides, ventral prostrate and seminal vesicle) were decreased considerably. The hormonal assay also showed significant decrease in testosterone levels and FSH levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocystes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term fluoxetine diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested fluoxetine. Fluoxetine caused a slight decrease in body weight, when initial and final body weights were compared in the experimental groups. Levels of ALT and AST were found to be significantly increased in the treated group when compared to the control. Histometery of reproductive organs confirmed these results. In conclusion, these results confirm that the long-term fluoxetine ingestion produce adverse effects on fertility and reproductive system in adult male rat. Thus, it would be of great interest to investigate the impact via long -term treatment with fluoxetine in male human fertility.