March 13, 2022
Bipolar disorder is a severe mental illness that afflicts over one in fifty persons worldwide. About a quarter of those with bipolar disorder also has alcohol use disorder (AUD). This in turn complicates the treatment of their bipolar disorder. It exacerbates their symptoms, makes them more likely to be suicidal, and increases the risk of hospitalization.
More than one in five persons with bipolar disorder also have ADHD, which is likewise known to be correlated with AUD. To what extent does ADHD contribute to AUD in persons with comorbid bipolar disorder?
A European study team recently conducted a systematic search of the peer-reviewed medical literature to address that question. The team identified eleven studies with a combined total of 2,734 participants that could be aggregated to perform a meta-analysis.
They found that persons with comorbid ADHD and bipolar disorder were two and a half times more likely to be diagnosed with alcohol use disorder than persons with bipolar disorder but no ADHD.
Between-study heterogeneity was negligible, and there was no sign of publication bias.
The authors concluded, “At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship.â€
Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them. A team of British researchers set out to see whether this association could be further confirmed with objective sleep measures, using cognitive function tests and electroencephalography (EEG).
Measured as theta/beta ratio, EEG slowing is a widely used indicator in ADHD research. While it occurs normally in non-ADHD adults at the conclusion of a day, during the day it signals excessive sleepiness, whether from obstructive sleep apnea or neurodegenerative and neurodevelopmental disorders. Coffee reverses EEG slowing, as do ADHD stimulant medications.
Study participants were either on stable treatment with ADHD medication (stimulant or non-stimulant medication) or on no medication. Participants had to refrain from taking any stimulant medications for at least 48 hours prior to taking the tests. Persons with IQ below 80 or with recurrent depression or undergoing a depressive episode were excluded.
The team administered a cognitive function test, The Sustained Attention to Response Task (SART). Observers rated on-task sleepiness using videos from the cognitive testing sessions. They wired participants for EEG monitoring.
Observer-rated sleepiness was found to be moderately higher in the ADHD group than in controls. Although sleep quality was slightly lower in the sleepy group than in the ADHD group, and symptom severity slightly greater in the ADHD group than the sleepy group, neither difference was statistically significant, indicating extensive overlap.
Omission errors in the SART were strongly correlated with sleepiness level, and the strength of this correlation was independent of ADHD symptom severity. EEG slowing in all regions of the brain was more than 50 percent higher in the ADHD group than in the control group and was highest in the frontal cortex.
Treating the sleepy group as a third group, EEG slowing was highest for the ADHD group, followed closely by the sleepy group, and more distantly by the neurotypical group. The gaps between the ADHD and sleepy groups on the one hand, and the neurotypical group on the other, were both large and statistically significant, whereas the gap between the ADHD and sleepy groups was not. EEG slowing was both a significant predictor of ADHD and of ADHD symptom severity.
The authors concluded, “These findings indicate that the cognitive performance deficits routinely attributed to ADHD … are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. … we would like to propose a simple working hypothesis that daytime sleepiness plays a major role in cognitive functioning of adults with ADHD. … As adults with ADHD are more severely sleep deprived compared to neurotypical control subjects and are more vulnerable to sleep deprivation, in various neurocognitive tasks they should manifest larger sleepiness-related reductions in cognitive performance. … One clear testable prediction of the working hypothesis would be that carefully controlling for sleepiness, time of day, and/or individual circadian rhythms would result in a substantial reduction in the neurocognitive deficits in replications of classic ADHD studies.”
Israel has a military draft that applies to males and females alike, except orthodox women and orthodox male seminary(yeshiva) students, who are exempt. Upon turning 17 every Israeli undergoes a medical review, including both a physical and psychiatric assessment, in preparation for the draft. The Draft Board Registry maintains comprehensive health information on all unselected Israelis until they turn 21. The registry also tracks all family members of draft registrants, including full siblings.
An Israeli study team used registry records from 1998 through2014 to obtain data for a total of over a million individuals (1,085,388). Because of the exemption for orthodox women, 59% were male.
The team identified 903,690 full siblings in the study population (58% males), including 166,359 male-male sibling pairs, 104,494 female-female sibling pairs, and 197,571 opposite-sex sibling pairs.
Next, the team identified all cases in the study population with a diagnosis of a psychiatric disorder, low IQ (≥ 2 standard deviations below the population mean), Type-1 diabetes, hernia, or hematological malignancies. It matched each case with ten age- and sex-matched controls selected at random from the study population. Then, for each case and case-matched controls, it identified all siblings.
There were 3,272 cases receiving treatment for ADHD, 2,128 with autistic spectrum disorder, 9,572 with severe/profound intellectual disability, 7,902 with psychotic disorders, 9,704 with mood disorders, 10,606with anxiety disorders, 24,815 with personality disorders, 791 with substance abuse disorders, 31,186 with low IQ, 2,770 with Type-1 diabetes, 30,199 with a hernia, and 931 with hematological malignancies.
Draftees with ADHD were five and a half times more likely to have a sibling with ADHD than controls.
There were no significant associations between ADHD and any of the somatic disorders – Type-1 diabetes, hernia, or hematological malignancies –nor between ADHD and low IQ.
There were also no significant associations between ADHD and autism spectrum disorder, severe/profound intellectual disability, mood disorders, and substance use disorders.
On the other hand, draftees with ADHD were more than 40% more likely to have siblings with anxiety or personality disorders than controls.
Surprisingly, draftees with ADHD were less than half as likely to have siblings with psychotic disorders than controls.
There were some limitations. The psychiatric classification system used by the Israeli military did not permit assessing the risk of bipolar disorder and depression separately. That meant having to use a broader category of mood disorders, including both disorders. In addition, the military diagnostic system does not allow diagnosis of comorbid psychiatric disorders in the same individual, instead of assigning only the most severe diagnosis.
Neurofeedback, also known as EEG (electroencephalogram)biofeedback, is a treatment that seeks to alleviate symptoms of various neurological and mental health disorders, including ADHD. It does this through immediate feedback from a computer program that tracks a client’s brainwave activity, then uses sound or visual signals to retrain these brain signals. This in principle enables patients to learn to regulate and improve their brain function and reduce symptoms.
An Iranian study team recently performed a systematic search of the peer-reviewed medical literature. It identified seventeen randomized-controlled trials (RCTs) of neurofeedback treatment for children and adolescents with ADHD that could be aggregated for meta-analysis.
A meta-analysis of twelve RCTs with a combined total of 740 youths looked at parent ratings of changes in hyperactivity/impulsivity symptoms, and separately of changes in inattention symptoms. In both instances, the net pooled effect centered on zero.
A meta-analysis of nine RCTs with a combined total of 787 youths examined teacher ratings. Once again, the pooled change hyperactivity/impulsivity symptoms centered on zero. For inattention symptoms, the teacher ratings centered on a tiny improvement, but it did not approach statistical significance. The 95% confidence interval stretched well into negative territory.
There was no sign of publication bias. Between-study heterogeneity, on the other hand, was high, with some small sample size RCTs pointing to reduced symptoms, and other small sample size RCTs pointing to increased symptoms. However, the RCTs with the larger sample sizes clustered close around zero effect size.
The authors concluded, “The results provide preliminary evidence that neurofeedback treatment is not an efficacious clinical method for ADHD.â€
