Behavioral, Neurocognitive, and Treatment overlap between ADHD and

							      Behavioral, Neurocognitive, and
Treatment overlap between ADHD and
                     Mood Instability
      Skirrow, 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.