Mental Disorders: Diseases or Behavioral Conditions?

Clinical neuroscience conditions represent a heterogeneous group of conditions with varying contributions from genetic and environmental influences.  It has been common to view some of these conditions under the disease model presumed to represent a specific pathophysiology, tissue pathology (i.e. Alzheimer’s disease, Huntington’s disease).  Other conditions have been classified as representing primarily a disorder of behavior (i.e. anorexia nevosa, substance use disorders).

The disease model is thought to be something outside of an individual’s control—individuals have the condition and the manifestations of the disease represent the effects of the underlying pathology.   More behavioral disorders are thought to have a volitional component.  Individuals with behavioral disorders are thought to contribute more to their condition and therefore assume some responsibility for having the condition.

Bienvenu, Davydow and Kendler recently published an examination of the validity of this type of classification approach.  They noted that diseases with involuntary symptoms would typically have a stronger genetic contribution that behavioral disorders where personal choices contribute to the condition.   One method to examine the genetic contribution to a particular disorder is the twin study.  Using identical and fraternal twin, examination of the concordance rates for a particular illness will provide an estimate of the relative contribution of genetic factors in the illness.  Heritability ranges between zero (no genetic contribution) to 1 (purely genetic condition). 

The authors reviewed high-quality twin studies in six clinical neuroscience conditions felt to be diseases and six clinical neuroscience conditions with a strong behavioral contribution.   The heritability estimates for the 12 conditions are shown in the graph adapted from data in the manuscript:

The authors note that the review fails to support the disease versus behavior distinction.  Behavioral disorders appear to have as significant of a genetic contribution as a group as do those more typically classified as diseases.  They note that some may argue that the diseases with lower heritabilities (major depression and generalized anxiety) are really not diseases.  If you take away major depression, panic disorder and generalized anxiety disorder from the analysis, you do get the three remaining diseases as having the highest heritability.

Nevertheless, the authors correctly point out that many behavioral disorders carry significant genetic contributions to risk.   This finding should reduce some of the stigmatization of these behavioral disorders.  They note “we humans do not seem to be equally free in our decisions”. 

The study also underscores that mental disorders considered the most disease-like, bipolar disorder and schizophrenia, have heritabilities as high as Alzheimer’s disease.  Few would argue that Alzheimer’s disease is just a behavioral disorder without a brain-based pathological contribution.  Increasing evidence supports incorporating bipolar disorder and schizophrenia in the brain disease model category. 

Bienvenu OJ, Davydow DS, & Kendler KS (2011). Psychiatric 'diseases' versus behavioral disorders and degree of genetic influence. Psychological medicine, 41 (1), 33-40 PMID: 20459884

The Neurobiology of Anxiety Disorders

A key question in the classification of anxiety disorders is whether the DSM-IV classification system describes distinct useful categories.  There is a great deal of overlap in clinical populations.  You do not find many individual who have one unique disorder.  Typically, someone with say panic disorder is likely to have one or more additional anxiety disorder such as social phobia or PTSD.  A key question is whether there is a broader anxiety disorder phenotype that might include a variety of symptoms found in specific anxiety disorders.

If specific anxiety disorders describe specific phenotypes, there should be evidence from what we know about the neurobiology of these disorders.  A recent comprehensive review of this issue has been published in the 2009 September issue of Psychiatric Clinics of North America and has been republished in Clinical and Laboratory Medicine.  The authors of this review make the argument that “there exist many distinguishing features that support the continued classification of individual anxiety disorders that are distinct from each other and from major depression.”  I will summarize some of their highlights for several of the individual anxiety, disorders.  The authors group their findings into anatomical and functional imaging findings, neuroendocrine and neurotransmitter, and genetic domains.  I will focus on the anatomical and functional imaging domains and refer the reader to the original manuscript for the other domains.

Panic Disorder

• Decreased glucose metabolism in parietal lobe and overall decreased cerebral blood flow
• Elevated glucose metabolism in amygdale, hippocampus, thalamus, midbrain and cerebellum
• Elevations normalize with successful treatment with behavioral or pharmacotherapy
• Panic attacks are linked with hyperactivity burst in right amygdale
• Anxious visual stimuli provoke increased activity in inferior frontal cortex, hippocampus, anterior and posterior cingulated cortex and orbitofrontal cortex

Posttraumatic Stress Disorder

• Severity of PTSD linked to greater activation of amygdale in response to fearful faces
• Ventral activation of anterior cingulate cortex with fearful faces predicts poor response to cognitive behavioral therapy
• PTSD patients activate the executive function network with combat-related images—this network is typically not activated in normals for emotional/affective processing tasks
• PTSD patients anxiety overwhelms brain inhibitory network producing more errors with cognitive tasks

Social Phobia

• Anticipation of public speaking tasks excessively elevates activation of subcortical, limbic and lateral paralimbic regions
• Response to trazodone in social phobia linked to decreased blood flow to ventral and dorsl anterior cingulate cortex and prefrontal cortex and increased cerebral blood flow to middle cingulated cortex, left hippocampus and parahippocampal gyrus
• Misinterpretation of social cues due to dysfunction of the cortico-striato-thalamic network

Generalized Anxiety Disorder

• Pediatric patients with generalized anxiety show enlargement of amygdale
• Elevated prefrontal cortex resting activity felt to be an anxiety compensatory response
• Elevated amygdala and insular cortex activation with angry faces
• Venlafaxine drug response tied to lower pretreatment amygdala activity and higher anterior cingulated activity

One of the methodological problems with imaging, neurotransmitter and genetic studies in anxiety disorders is the issue of identifying individuals with a unique anxiety disorder.  Even this strategy may be problematic.  Studying a young adult patient with a unique panic disorder diagnosis does not account for the possibility of later development another anxiety disorder such as social phobia or PTSD.

Although a great deal of progress has been made in the neurobiology of anxiety disorders, the challenge of understanding the best classification strategies remain.  Clinicians are typically, left with a implementing a trial of a selective serotonin re-uptake inhibitor or cognitive behavior therapy in patients with a single or multiple anxiety disorder diagnoses.  The jury is out whether neurobiology can lead to improved and more specific treatments.  

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Martin EI, Ressler KJ, Binder E, & Nemeroff CB (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32 (3), 549-75 PMID: 19716990