Behavioral, Neurocognitive, and Treatment overlap between ADHD and

Mood InstabilitySkirrow, McLoughlin, Kuntsi, Ashwerson, Expert Review.

Neurother.2009

Sogand Ghassemi

Psychiatry Clerkship

MS3, UIC COM

ADHD DSM IV Criteria Attention deficit hyperactivity disorder (ADHD) is a developmentally

inappropriate level of attention, impulsivity, and hyperactivity

Three subtypes: predominantly inattentive type, predominantly hyperactive-impulsive type, and combined type

DSM-IV Criteria: At least 6 symptoms involving inattentiveness, hyperactivity, or both that have persisted for at least 6 months:

Inattentiveness: problems listening, concentrating, paying attention to details, or organizing tasks easily; easily distracted, often forgetful

Hyperactivity-impulsivity: blurting out, interrupting, fidgeting, leaving seat, talking excessively etc.

Onset before age 7

Behavior inconsistent with age and development

ADHD: Chronic and Life-long• Impulsivity, inattention, and hyperactivity present as chronic and

trait like, as opposed to symptomatic increases and declines seen in other psychiatric disorders

• 10-50% have problems adult life with: emotional lability, problems controlling moods and temper, disorganization and distractibility, and problems in sustaining effort and completing tasks

Consistently noted alongside these symptoms is mood instability in the form of irritability, volatility, swift changes in mood, hot temper, and low frustration tolerance.**

Chronic problems and unstable mood have been noted to present up to 90% adult cases.

Mood symptoms are likely to impact social behavior and relationships of adults with ADHD

Unstable and dysregulated mood is predictive of poor social outcome and peer rejection in children.

Mood Instability and ADHD DSM IV considers mood instability as an “associated feature of the

disorder”. Without the formal recognition of mood symptoms in ADHD, differentiating ADHD from other affective disorders difficult, and has lead to misdiagnosis and incorrect treatment in adults.

Stated rational for excluding mood instability from diagnostic criteria for ADHD is: lack of reliability and specificity of mood stability. Mood symptoms (i.e. irritability and dysthymia) are seen in other psych d/o.

Review of recent studies suggest that that there is considerable overlap in behavioral, neurocognitive, and treatment of ADHD and mood instability.

This review article suggests: Mood instability and symptoms of ADHD may be intertwined and mood instability should be considered a CORE and DIAGNOSTIC feature of ADHD syndrome

Mood Instability and Self-regulation of Emotion

Emotional self-regulation: when individual initiates new or alters ongoing emotional responses via regulatory processes to attain social or personal goals

Zeman et al. described self-regulation of emotion as involving management and organization of diverse components:

--internal component (neurophysiologic, cognitive, subjective evaluations)

--behavioral component (facial expression and behavioral actions)

--external/social component (cultural values and social contextual significance)

Difficulties in reacting appropriately to a social situation may stem from different underlying problems: impaired understanding of emotional information (ex facial expressions), a lack of empathetic experience for others, inattentiveness to social cues, or a lack of understanding of social norms. These are functions that are impaired in ADHD.

Studies suggest that individuals with ADHD have problems with emotional self-regulation even when individuals with ADHD understand are aware of the need to regulate emotional behavior, they have difficulty successfully regulating either emotional responses.

Mood Instability and Executive Function Executive dysfunction: deficits in "higher-order" cognitive processes, such as

planning, sequencing, reasoning, holding attention to a task, working memory, inhibition of inappropriate and selection of appropriate behaviors. These supervisory processes control, regulate and manage the "lower-level" cognitive operations, such as language, perception, explicit memory, learning and action.

Barkley, proposed model*: Impairments in cognitive and executive function could be explained by core inhibition deficit in ADHD. This inhibition theory tries to explain classic behavior of ADHD: impulsivity, hyperactivity, and co-occurrence of mood instability. Theory states inhibitory processes are essential to for self-regulation.

Overlap with Mood instability--pts with ADHD are unable to inhibit emotional reactions and so unable to delay responding to factor in social context for appropriate response, resulting in emotionally reactive, irritable and hostile behavior.

Several studies conclude that mood instability is associated with deficits in performance of executive function tasks known to be associated with ADHD. Kids and adults with ADHD due worse on tests of executive functions when compared to controls.

Mood Instability and State Regulation State regulation and cognitive energy models of ADHD highlight

evidence that individuals with ADHD tend to make errors and are slow and more variable in responding in a range of cognitive tasks.

Electroencephalography studies suggest that individuals with ADHD show cortical under arousal, as measured by increased frontal and central theta activity, continuing from childhood in to adulthood. Intra-individual variability in ADHD may be due cerebellar dysfunction, reflecting temporal processing deficits, motor control deficits, or inability to appropriately model very low frequency fluctuations in neuronal activity or dysfunction of executive attention.

Hypothesized: Executive function deficits and variable response seen in ADHD may be secondary to altered arousal or activation states (heart rate, skin conductance, pupil dilation etc).

Relationship between mood instability and executive function caused by deficits in inhibitory or attention processing which in turn is due to problems in state regulation.

State regulation deficits may directly influence mood instability by giving rise to greater variability and performance measures.

Overlap of Brain Structures between Mood Instability and ADHD

Neuroimaging and brain injury research has shown overlapping brain structures and networks in the regulation of behavior and the regulation of emotion.

Common brain regions have been associated with inattention, impulsive, hyperactive and emotionally dysregulated behavior.

Frontal lobes –linked with attentional and inhibitory functions

Subcortical limbic and basal ganglia systems—linked with motivational process and emotional learning.

Reciprocal neural connections exist between prefrontal cortical regions and subcortical regions, which may allow for interactions between cognitive and emotional processes.

Functional and structural MRI studies demonstrated altered functional activation and reduced volumes in prefrontal, basal ganglia, and the cerebellum in ADHD pts versus psychiatrically healthy controls.*

Mood Instability and ADHD:Response to Treatment Several studies have found mood instability responds to both stimulant

and non-stimulant treatments of ADHD in the same time frame as core ADHD symptoms in adults with ADHD.

Methylphenidate, a NE & DA reuptake inhibitor, is stimulant medication most commonly used to treat ADH.

Double-blind placebo studies of methylphenidate have found concurrent improvement in both ADHD and mood symptoms. Adult ADHD pts reported feeling happier, less anxious, less depressed, less angry, and with cooler temper as part of treatment response.

Atomoxetine, a NE reuptake inhibitor and most common non-stimulant treatment for ADHD. Double-blind placebo studies of atomoxetine demonstrated mood stability and ADHD symptoms improved with treatment.

Much of study treatment was carried out in adults but needs replication in children.

Top Down and Bottom Up Theories of ADHD Theories of ADHD grouped into pure “top-down” executive function control

and pure “bottom-up” affective/reactive processes related to inattention and hyperactivity, respectively.*

Top-down processes are related to more effortful forms of control. Behaviorally, this kind of control refers to behavior that is goal-directed, resource-demanding, and planful , or when there is a need to overcome immediate stimuli in order to maintain progress toward a goal held in working memory. Neurally, top-down processes are thought to rely primarily on prefrontal circuitry, particularly in its role of suppressing task irrelevant activation elsewhere in the brain.

Bottom-up processes are thought to be related to behavior that does not demand conscious mental resources and which are more heavily influenced by immediate incentive or affective response. This kind of processing is believed to rely on stimulus-driven activation either in parietal cortex (in the case of attentional capture) or subcortically (e.g., in striatum or limbic regions), particularly in its role of interrupting motor or cognitive processing being implemented in frontal cortex, redirecting attention to an immediate salient event.

Bidirectional Multiple Pathway Model Nigg and others: Not just one single process theory can account for the

range of cognitive and neuropsychological impairments associated with ADHD construct.

Propose combination of Top-down executive control (e.g. suppressing competing responses) and bottom-up motivational or state regulation processes (e.g. arousal, activation or delay-reward gradient) may better account for the range of cognitive and neuropsychological problems seen in ADHD.

This approach can help account for heterogeneity in ADHD, as well as association of ADHD with mood instability, which preferentially be associated with deficit in one particular pathway but not within another.

There are number of important limitations to research of ADHD and mood instability, most importantly is contribution of comorbid disorders. Mood instability in ADHD pts may be due to unaccounted for comorbid mood disorder, but it appears highly unlikely, since mood instability is found to improve with treatment for ADHD. Research suggest, mood instability can be attributed to ADHD syndrome.

Key Points ADHD persists to adulthood in many cases

Pts with ADHD often show mood instability characterized by mood changeability, irritability, volatility, hot temper, low frustration tolerance.

ADHD is associated with impairment across a wide range of executive and non-executive tasks, which have been associated with mood instability.

Brain regions involved in emotional regulation and mood stabilization are found to show structural and functional changes in ADHD.

Treatment for ADHD with stimulant medications results in improvement in mood instability alongside ADHD symptomalogy.

Need more research to clarify the relationship between mood instability to ADHD and to clarify the distinction from overlapping disorders, such as borderline personality d/o and Bipolar d/o.

Pts presenting with chronic mood instability associated with core features of ADHD (child or adolescent onset, trait-like course, inattention, hyperactivity, and impulsivity) should be screened for ADHD.

Bibliography Faraone, Biederman, Mick. The Age dependent decline of ADHD: meta-analysis of follow

up studies. Psychol. Med. 2006.

Johnson, Wiersema, Kuntsi, 2009.; Casey 2005; Holroyd and Coles 2002; Nigg and Casey 2005

Barkley, Murphy, Fischer. ADHD in Adults. 2007.

Reimhert, Marchant, Stronge et al. Emotional dysregulation in adult ADHD and response to amoxetine. Biol. Psych. 2005.

Asherson P. Clinical assessment and treatment of ADHD in adults. Expert Rev. Neurother.2005.

Mcloguhlin, Kuntsi, Brandeis. Electrophysiological parameters ADHD. 2005.

Castellanos, Tannock. Neuroscience of ADHD. 2002.

Nigg, Casey, An Integrative theory of ADHD based on cognitive an affective neurosciences. Dev. Psychopathol. 2005.

Sonuga-Barke EJ. The Dual Pathway model of ADHD. Biobehav. Rev. 2003.