Five-year outcomes of ADHD diagnosed in adulthood.

There is a dearth of long-term follow-up studies of adults diagnosed with ADHD. Here, the aim was to evaluate long-term outcomes in a group of ADHD patients diagnosed in adulthood and receiving routine psychiatric health care. Adults diagnosed with any type of ADHD (n = 52) and healthy controls (n = 73) were assessed at baseline and at a 5-year follow-up, using Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Brown ADD Scale (BADDS) and Adult ADHD Self-Report Scale (ASRS). A multivariate regression method was used to identify factors predicting 5-year outcomes, including baseline ratings, medication intensity, comorbidity, intelligence quotient (IQ), age, and sex. After 5 years, ADHD patients reported fewer and/or less severe symptoms compared to baseline, but remained at clinically significant symptom levels and with functional deficits. Baseline self-reports of ADHD symptoms predicted their own 5-year outcome and low baseline functioning level predicted improved global functioning at follow-up. Factors previously reported to predict short-term outcomes (i.e., medication, comorbidity, IQ, age, and sex) did not anticipate long-term outcomes in present study.

Neuropsychological profiles of adult bipolar disorder patients with and without comorbid attention-deficit hyperactivity disorder.

BACKGROUND: Comorbid attention-deficit/hyperactivity disorder (ADHD) is common in bipolar disorder and associated with worse outcomes. Cognitive testing might be a tool to identify this group. Here we compare the neuropsychological profiles of bipolar disorder patients with (BD + cADHD) and without (BD - cADHD) childhood attention-deficit hyperactivity disorder. METHODS: Adult patients with BD - cADHD (n = 66), BD + cADHD (n = 32), and healthy controls (n = 112) were tested using a comprehensive battery of neuropsychological tests. Patients underwent rigorous diagnostic assessments for bipolar disorder and ADHD, as well as a parental interview to establish childhood ADHD. RESULTS: The neuropsychological profiles of the groups were similar, except that the BD + cADHD group performed significantly worse on working memory. Working memory did not differ between those in the BD + cADHD group who only had a history of childhood ADHD and those that still met criteria for ADHD in adulthood. CONCLUSIONS: Cognitive testing had limited power to differentiate between bipolar disorder adults with and without childhood ADHD. The BD + cADHD subgroup cannot explain the significant cognitive heterogeneity seen in bipolar disorder patients.

Cortical brain structure and sexual orientation in adult females with bipolar disorder or attention deficit hyperactivity disorder.

BACKGROUND: Nonheterosexual individuals have higher risk of psychiatric morbidity. Together with growing evidence for sexual orientation-related brain differences, this raises the concern that sexual orientation may be an important factor to control for in neuroimaging studies of neuropsychiatric disorders. METHODS: We studied sexual orientation in adult psychiatric patients with bipolar disorder (BD) or ADHD in a large clinical cohort (N = 154). We compared cortical brain structure in exclusively heterosexual women (HEW, n = 29) with that of nonexclusively heterosexual women (nHEW, n = 37) using surface-based reconstruction techniques provided by FreeSurfer. RESULTS: The prevalence of nonheterosexual sexual orientation was tentatively higher than reported in general population samples. Consistent with previously reported cross-sex shifted brain patterns among homosexual individuals, nHEW patients showed significantly larger cortical volumes than HEW in medial occipital brain regions. CONCLUSION: We found evidence for a sex-reversed difference in cortical volume among nonheterosexual female patients, which provides insights into the neurobiology of sexual orientation, and may provide the first clues toward a better neurobiological understanding of the association between sexual orientation and mental health. We also suggest that sexual orientation is an important factor to consider in future neuroimaging studies of populations with certain mental health disorders.

Cerebrospinal fluid monoamine metabolite profiles in bipolar disorder, ADHD, and controls.

Alterations in monoaminergic signaling are suggested as key aspects of the pathophysiology in bipolar disorder and ADHD, but it is not known if the monoamine metabolic profile differs between these disorders. One method to study monoaminergic systems in humans is to measure monoamine end-point metabolite concentrations in cerebrospinal fluid (CSF). Here, we analyzed CSF monoamine metabolite concentrations in 103 adults with bipolar disorder, 72 adults with ADHD, and 113 controls. Individuals with bipolar disorder had significantly higher homovanillic acid (HVA, 264 ± 112 nmol/L, p < 0.001) and 5-hydroxyindoleacetic acid (5-HIAA, 116 ± 42 nmol/L, p = 0.001) concentration, but lower 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG, 38 ± 8 nmol/L, p < 0.001) concentrations than controls (HVA, 206 ± 70 nmol/L; 5-HIAA, 98 ± 31 nmol/L; and MHPG, 42 ± 7 nmol/L). Higher HVA concentrations were associated with a history of psychosis in the bipolar disorder sample. Subjects with ADHD had higher HVA (240 ± 94 nmol/L, p < 0.001) concentrations compared with controls. In addition, SSRI treatment was associated with lower 5-HIAA concentrations in both patient groups. A power analysis indicated that for within-group comparisons, only large effects would be reliably detectable. Thus, there may be moderate-to-small effects caused by medication that were not detected due to the limited size of the sub-groups in these analyses. In conclusion, the present study suggests disorder-specific alterations of CSF monoamine metabolite concentrations in patients with bipolar disorder and ADHD compared with controls; these differences were independent of acute symptoms and medication effects.

The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder.

OBJECTIVE: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder. METHOD: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods. RESULTS: Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted. CONCLUSIONS: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.

Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder and ADHD is aetiologically distinct from the pure disorders. AIMS: To clarify whether ADHD shares genetic and environmental factors with bipolar disorder and schizophrenia. METHOD: By linking longitudinal Swedish national registers, we identified 61 187 persons with ADHD (the proband group) and their first- and second-degree relatives, and matched them with a control group of people without ADHD and their corresponding relatives. Conditional logistic regression was used to determine the risks of bipolar disorder and schizophrenia in the relatives of the two groups. RESULTS: First-degree relatives of the ADHD proband group were at increased risk of both bipolar disorder (odds ratio (OR) = 1.84-2.54 for parents, offspring and full siblings) and schizophrenia (OR = 1.71-2.22 for parents, offspring and full siblings). The risks of bipolar disorder and schizophrenia among second-degree relatives were substantially lower than among full siblings. CONCLUSIONS: These findings suggest that the co-occurrence of ADHD and bipolar disorder as well as ADHD and schizophrenia is due to shared genetic factors, rather than representing completely aetiologically distinct subsyndromes.

Two-year outcome of treatment with central stimulant medication in adult attention-deficit/hyperactivity disorder: a prospective study.

BACKGROUND: Given that adults with ADHD continue to use stimulants for extended periods of time, studies on the long-term effectiveness and adverse events are warranted. The aims of this study were to investigate factors associated with persistence in treatment in an exploratory manner and to document side effects and reasons for discontinuation. METHOD: The current study describes the systematic follow-up of 133 psychiatric patients with DSM-IV-diagnosed ADHD treated with central stimulants at a specialized outpatient unit between January 1, 2001, and August 31, 2006. A standardized questionnaire, derived from the Targeted Attention-deficit Disorder Symptoms Rating Scale, was used in order to measure improvement of the following target symptoms: hyperactivity, impulsivity, irritability, distractibility, structure/organization problems, inattention, and restlessness. RESULTS: Eighty percent of the patients were successfully treated with stimulants at the 6- to 9-month follow-up. Fifty percent remained in treatment after 2 years or more. Forty-five percent were treated for comorbid anxiety and/or depression during the study period. Only 15% dropped out because of lack of efficacy. The amount of clinical response over the first 6 to 9 months (but not at 6 weeks) predicted adherence to treatment at 2 years. The patients' heart rate increased from a least squares mean ± SE of 70 ± 2.2 to 80 ± 2.1 bpm (P = .00003) while blood pressure remained unchanged at the ≥ 2-year follow-up. Severe side effects or drug abuse were not detected in this cohort. CONCLUSIONS: The long-term treatment outcome shows that stimulants are effective in adult ADHD and side effects tend to be mild.

Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD.

Bipolar disorder with childhood attention-deficit hyperactivity disorder (ADHD) is a subphenotype characterized by earlier age of onset, more frequent mood episodes, more suicide attempts, and more interpersonal violence than pure bipolar patients. The aim of this study was to test the biological validity of using childhood ADHD to subgroup bipolar disorder. The monoamine metabolites, homovanillinic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined in the cerebrospinal fluid (CSF) of 53 euthymic patients with bipolar disorder type 1, with (N = 17) and without (N = 36) a history of childhood ADHD. In addition to structured clinical interviews, childhood ADHD was assessed by a next of kin using the Autism-Tics, ADHD and other comorbidities questionnaire (A-TAC), and by patients themselves using the Wender Utah rating scale (WURS-25). Current ADHD symptoms were assessed by the Brown attention-deficit disorder scale (Brown ADD). Bipolar patients with childhood ADHD had significantly lower CSF concentration (mean +/- SD nmol/l) of HVA (89.0 +/- 32.5 vs. 115.8 +/- 47.1, P = 0.039) and 5-HIAA (88.7 +/- 38.5 vs. 116 +/- 47.9, P = 0.021) than pure bipolar patients. CSF MHPG did not differ between the groups. The WURS-25 score correlated negatively with both HVA (r = -0.27, P = 0.048) and 5-HIAA (r = -0.30, P = 0.027). Likewise, the Brown ADD total score correlated negatively with both HVA (r = -0.34, P = 0.013) and 5-HIAA (r = -0.35, P = 0.011). These findings indicate different monoaminergic function in patients with and without childhood ADHD in bipolar disorder type 1. This lends biological support to the notion that those with childhood ADHD represent a valid subphenotype of bipolar disorder.