Is ADHD a prodrome of bipolar disorder? Jl of Affective disorder: Dec 2012

19.11.2012

Comorbidity is common between many psychiatric disorders. Many disorders share common symptoms as well. This issue is particularly a problem between ADHD and Bipolar Disorder (BD) . This poses challenges to child and adolescent psychiatrists as well as for those working in adult settings.

Symptoms like poor concentration, restlessness,irritability, aggression, impulsivity seen in both conditions make the distinction extremely difficult at times. As ADHD persist in to adulthood in around two thirds of cases, it is often unclear whether the presentation in adult setting is an exacerbation of ADHD symptoms due to various factors or one of manic episode.Prevalence of ADHD in adults is currently estimated at 2.5–4.3%. The trend of  diagnosing pediatric bipolar disorder further complicates the diagnostic challenges between these two disorders. Failure to make a correct diagnosis can have serious consequences as medication for one disorder can potentially worsen the other.

Skirrow et al reviews these challenges in this article.

Symptoms that make differentiation difficult: distractibility, motor restlessness and over talkativeness are seen in both conditions. Flight of ideas or racing thoughts seen in BD may also be difficult to distinguish from ceaseless distractible thought processes seen in many adults with ADHD. low frustration tolerance, temper outbursts and mood lability, associated with ADHD,  are similar to those seen in mania.

Though similar, the meaning of these symptoms may be quite different. ADHD symptoms are chronic and trait- like whereas BD symptoms are traditionally conceptualised as changes from an individual’s usual premorbid state.Many authors suggest that it is this characteristic periodicity which differentiates BD from conditions such as ADHD and borderline personality disorder.However the broader Bipolar spectrum  conditions like cyclothymia  where clear cut periodicity is less distinct makes the differentiation from ADHD difficult.

Blurring distinctions

BD in youth: High profile research groups  (see  below)  have employed ‘non-classical’ diagnostic criteria for BD, where the requirement for episodicity of symptoms is waived or adapted, and consequently, the similarities with ADHD are likely to be more pronounced.

Washington group’s operational definition/approach : Paediatric mania typically follows a chronic course and therefore infrequently shows the relapsing and remitting course. Paediatric BD is characterised by ultra-rapid  and ultradian cycling in the majority of cases. BD may still be accurately differentiated from ADHD by the presence of mania- specific symptoms (i.e. elated mood, grandiosity, hypersexuality, flight of ideas/racing thoughts and decreased need for sleep).

Massachusetts General Hospital group : Presence of chronic and debilitating irritability is the core symptom. Manic irritability in paediatric BD should show an intensity, severity, frequency and persistence, and a higher association with violence and aggression, that makes it qualitatively distinct from other disorders. Diagnosis does not require any distinct change in the patients’ level of function.

One can see that traditional diagnostic boundaries between ADHD and BD is blurred in the above approaches . With such less conservative definitions and diagnosis of paediatric BD, clinicians in adult psychiatry are going to face the challenge of differentiating Adult ADHD and BD more and more.

Are they really comorbid conditions?

Meta-analysis of seven studies of BD in children and adolescents found that on average 62% also met criteria for ADHD (Kowatch et al., 2005). however, the comorbidity rates between studies ranged from 11% to 98%.

for example: In a sample of 707 6–12 year-old children (OP setting)  selected for elevated manic symptoms the diagnosis of ADHD was made in 76% of the sample, BD in 23%, and a comorbid presentation in 16.5%.(Arnold et al., 2011).

In adulthood, a systematic review of clinical studies reported comorbidity between ADHD and BD to occur in around 5–20% of cases (Wingo and Ghaemi, 2007), regardless of whether comorbidity is assessed in ADHD or BD populations.When  studies where BD1 was more narrowly defined , comorbidity with ADHD is reported in 5.9–8% of cases (Halmøy et al., 2010; Nierenberg et al., 2005; Wilens et al., 2003).

Studies of comorbidity  often do not ensure that ADHD part is assessed while patient is euthymic. Also, inpatient cohorts are not ideally suited to study comorbidity due to obvious reasons. Population studies are essential in estimating the comorbidity rates between ADHD and BD.

Is ADHD a prodrome of BD?

In some cases could ADHD represent a prodrome or early manifestations of BD?  Long term prospective studies are the key to answer this question.

1.Two studies in 80’s found no cases of  BD in ‘hyperactive’ children (sample size n = 101 and n = 63; age 6–12), followed up for 5 to 15 years into late adolescence and early adulthood (Gittelman et al., 1985; Weiss et al., 1985).

2. 85  ‘hyperkinetic’ boys followed up from a mean age of 7.3 years until 24 years, reported no cases of  BD (Mannuzza et al., 1998)

3. No over- representation of mania in a sample of 147 ‘hyperactive’ children compared to a matched control sample (n = 81), followed up for a mean duration of 13.8 years into their early 20s. Fischer et al. (2002)

4. No cases of BD found in a 6-year follow-up study of 80 ADHD boys, aged 9–13 years (Hazell et al., 2003).

5. Follow-up study of 75 ‘hyperkinetic boys treated with methylphenidate, assessed at ages 6–12 and 21–23 years, found a prevalence of 17.3% of BD in early adulthood (Carlson et al., 2000).

6. Study of 90 children with  ADHD followed- up for an average of 9 years  two individuals (2.2%) developed  BD by late adolescence (Halperin et al., 2011).

7. In an epidemiological sample of 1037 individuals followed up for 15 years mania was only slightly elevated in individuals aged 26 who had a childhood diagnosis of ADHD(Kim-Cohen et al., 2003).

8. MGH group, following up 123 boys with ADHD (aged 6–12 years) for an average of 11 years, identified BD in 10.9% of the sample, versus only 2% in a matched control group (Biederman et al., 2010)

Note that rates of mania are higher in longitudinal studies of ADHD subjects when ‘non-classical’ criteria for BD are utilised.

More ADHD in children of BD?

All of the BD family studies  reported an elevated rate of ADHD among children of BD parents compared to either the offspring of individuals with other psychiatric disorders, or children of healthy controls.

More BD in ADHD relatives?

Elevated rates of BD was found  among the first-degree relatives of children with ADHD, with elevated rates of BD seen in both parents and siblings ( Geller et al., 2006). This is  consistent with a previous meta- analysis (Faraone et al., 1997).

Neurobiology: distinct or shared?

Some early neurobiological studies  suggests  that arousal deficits under low stimulus conditions might be an important underlying mechanism associated with both disorders.

fMRI Study: On a task of inhibitory function,similar performance deficits seen in both clinical groups  (ADHD and BD-1) compared with controls, with differences in the brain regions involved in inhibitory responses.  Overall decreased prefrontal activation was more extensive and more severe in ADHD compared to BD, and was accompanied by subcortical overactivity; suggesting two distinctive pathophysiologies.(Passarotti et al. 2010).

In another fMRI study, distinctive amygdala activation patterns for each of the three clinical groups studied,  (BD, ADHD, SMD (children with chronic rather than episodic mania-like symptoms) , were observed (Brotman et al.2010).

From EEG recordings under eyes-open and eyes- closed resting conditions, Sadatnezhad et al., 2011  were able to classify the groups (ADHD,BD)  with 78–86% accuracy.

Brain structural differences?

Biederman et al., 2008 compared adult BD-I, ADHD and a comorbid BD-I+ ADHD group. ADHD was associated with smaller superior prefrontal cortex, anterior cingulate cortex and cerebellum, while BD was associated with larger thalamic and smaller orbital prefrontal volumes. Both findings were independent of comorbidity status.

Lopez-Larson et al., 2009  identified distinct differences in subcortical regions in individuals with ADHD, with smaller caudate, putamen and amygdala volumes compared to groups of controls and those with BD (including the comorbid group).

Conclusions

Symptomatic similarity is a challenge. They may not be completely unrelated to one another. Comorbidity remains high. Family studies indicate increased familial risk. Children and adolescents identified by  employing ‘non-classical’ modified definitions of BD criteria show significant impairment, but it is not at all clear that these are variants of classical episodic BD . Prospective studies investigating childhood irritability and subthreshold mania suggest that these are unlikely to develop into adult forms of BD.

Summary of the review article:

An update on the debated association between ADHD and bipolar disorder across the lifespan. Skirrow C, Hosang GM, Farmer AE, Asherson P.J Affect Disord. 2012 Dec 10;141(2-3):143-59.

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