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Home » Bipolar Disorder

Psychiatric Times. Vol. 29 No. 7
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MINE YOUR MIND 

Confounding Factors in TRD (Part 1): The Role of Subtyping and Bipolarity

By Michael I. Casher, MD, Daniel Gih, MD, Joshua D. Bess, MD, and Prachi Agarwala, MD | July 18, 2012
Dr Casher is Director, Psychiatry Adult Inpatient Program, and Clinical Assistant Professor, department of psychiatry, University of Michigan Medical School, Ann Arbor. Dr Gih is Clinical Assistant Professor, Attending, Child and Adolescent Inpatient Psychiatry, University of Michigan Medical School. Dr Bess is Clinical Instructor, Attending, Adult Inpatient Psychiatry, University of Michigan Medical School. Dr Agarwala is Child and Adolescent Psychiatry Hospitalist, Fairview Health Services, Minneapolis. Drs Casher and Bess are co-authors of Manual of Inpatient Psychiatry (Cambridge University Press, 2010), reviewed in Psychiatric Times, February 2011. Dr Casher reports that he is on the Speakers Bureau for Sunovion Pharmaceuticals. Drs Casher and Bess receive royalties from Cambridge University Press. Drs Gih and Agarwala report no conflicts of interest concerning the subject matter of this article.

Personality style characteristics, traits, and temperament

Researchers and psychologists tend to favor dimensional classifications of personality over the categorical approach put forth in DSM texts through DSM-IV-TR. (The upcoming DSM-5 personality section is heavily influenced by the dimensional approach to diagnosis.) An advantage of dimensional approaches is that they include psychological variables that are reliably rated. Some of these factors are inheritable and therefore can be linked with biological markers, specific neurotransmitters, or neuroimaging variations.16 One popular way to conceptualize personality dimensionally is the 5-factor model that includes the polar dimensions of neuroticism-stability, introversion-extraversion, openness-closedness to experience (in other systems, this is called thrill seeking vs harm avoidance), agreeableness-antagonism, and conscientiousness-negligence.17

(MORE: Effective Personalized Strategies for Treating Bipolar Disorder)

A similar dimensional system is Cloninger’s temperament/character model,18 which includes 4 temperament dimensions (harm avoidance, novelty seeking, reward dependence, and persistence) and 3 character dimensions (self-directedness, cooperativeness, and self-transcendence). All are thought to represent significant genetically based contributions to overall personality.

In one study, the Tridimensional Personality Questionnaire was given to patients with major depression to see whether 3 of Cloninger’s dimensions (novelty seeking, harm avoidance, and reward dependence) remained stable with changes in mood. Reward dependence and novelty seeking were stable in the face of affective changes, while harm avoidance tended to be heightened with depressive illness and reduced with treatment.19

Findings from a study using still another dimensional personality model suggest that the distinct personality style traits of perfectionism and anxious worrying contributed to depression in a group of 54 patients. The researchers speculated that these traits also had a role in treatment resistance.20

Drawing from among the various dimensional systems, poor outcome in treatment of depression has also been associated with high levels of neuroticism, high scores on harm avoidance, and a tendency toward introversion.21,22 In patients with TRD, those with high degrees of neuroticism respond better to TCAs than to MAOIs. Introversion includes social inhibition, which reflects a tendency to avoid mixing with others. Social inhibition is overrepresented in patients who have hard-to-treat depressions.23

There is also consistent evidence that the trait of harm avoidance is associated with serotonergic functioning, which suggests that medications that target the serotonin system are useful for patients with TRD who have high harm-avoidance scores.24 Although further associations of different traits with various neurotransmitter systems have been postulated, studies to reliably demonstrate these relationships have been inconsistent.

Axis II comorbidity with TRD

Despite its limitations, the categorical approach to personality disorder diagnosis is firmly ensconced in the practice of American psychiatry and is likely to remain so, even with the anticipated changes in DSM-5. So, does a comorbid personality disorder—as defined by current DSM (pre–DSM-5) criteria—predict a poor treatment outcome in patients with depression?

In a review of the data, Mulder21 concluded that the evidence for worse outcomes in patients with depression and comorbid personality pathology was inconclusive. However, a meta-analysis of 32 studies of depression treatment outcomes in which the presence of personality disorders was also formally assessed found robust evidence for less response to treatment in patients with a concurrent personality disorder.25 Furthermore, recent data from the Collaborative Longitudinal Personality Disorders Study of nearly 2000 patients confirm that many DSM personality disorders, and BPD in particular, are associated with persistence of depressive symptoms.26

Perhaps the strongest evidence for increased treatment resistance in the BPD population is the finding that ECT—arguably the most potent treatment modality for depression—was much less effective in patients with MDD who had comorbid BPD. These patients had a remission rate of only 22% with ECT, compared with 56% for patients with other personality disorders and 70% for patients with no diagnosed personality disorder.27

Speculations about the reason for disparities in responsiveness to ECT and medications in patients with BPD involve a number of issues in the relationship of mood and affect to BPD. First of all, the diagnosis of BPD includes a number of items with mood content. These items overlap considerably with items on depression rating scales: suicidal ideation and behaviors, affective instability with periods of intense dysphoria, and long-term feelings of emptiness. Clinicians can easily get caught up in unsuccessful efforts to eliminate these character-based vulnerabilities through aggressive somatic treatments.

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