CommentaryThe Pharmacogenetics of Major Depression: Past, Present, and Future
Section snippets
The Past: Small Samples and Few Genes
A MEDLINE search using the terms pharmacogenomics or pharmacogenetics and depression in humans yields about 100 articles, almost half of which are labeled as reviews. This would suggest that since 1968, the year of the first cited article, much has been written but not as much new information has been acquired. This characterization is not confined to the pharmacogenetics of major depression; it applies almost as well to the pharmacogenetics of other fields. In retrospect, without many of the
The Present: Picking Up Speed
There have been two big developments in recent years that have greatly accelerated progress in the field: the availability of large, well-characterized samples and the advent of genomic technologies of unprecedented power and efficiency. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (11) has for the first time provided a sample of well-characterized patients large enough to detect even modest genetic effects. Although not designed specifically to answer
The Future: Knocking at the Clinic Door
Since the recent publication of the first Encyclopedia of DNA Elements (ENCODE) data (19), it has become clear that protein-coding genes are only a very small part of the genome and that most human DNA has significant biological activity: there may be no “junk” DNA. Until we fully understand the mechanisms that regulate gene function, we should maximize the results we obtain from available samples. Near-future technology can add significant amounts of information to what we already have. In
References (22)
Pharmacogenetic studies of antidepressant response: How far from the clinic?
Psychiatr Clin North Am
(2007)Predictors of response to antidepressants: General principles and clinical implications
Psychiatr Clin North Am
(2003)- et al.
Sequenced treatment alternatives to relieve depression (STAR*D): Rationale and design
Control Clin Trials
(2004) - et al.
Genetic associations in large versus small studies: An empirical assessment
Lancet
(2003) - et al.
Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment
Am J Hum Genet
(2006) - et al.
Analysis of association between the serotonin transporter and antidepressant response in a large clinical sample
Biol Psychiatry
(2007) - et al.
Epigenetic marking and neuronal plasticity
Biol Psychiatry
(2007) - et al.
Translating pharmacogenomics: Challenges on the road to the clinic
PLoS Med
(2007) - et al.
Common VKORC1 and GGCX polymorphisms associated with warfarin dose
Pharmacogenomics J
(2005) - et al.
Evidence-based health policy—lessons from the Global Burden of Disease Study
Science
(1996)
Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice
Am J Psychiatry
Cited by (21)
DBH gene as predictor of response in a cocaine vaccine clinical trial
2013, Neuroscience LettersCitation Excerpt :Therefore, the pharmacotherapy of this relapsing brain disease may be better treated using a molecular genetics approach [25,44,45,49]. Tailoring pharmacological treatment to a person's genetic background can enhance therapeutic response [23], increase compliance [33], and decrease drug toxicity [11,26,39]. This study showed an enhanced therapeutic response based on an interaction between a blocking agent that alters the kinetics of cocaine uptake and a patient's genetic background, taking advantage of a genetic risk factor for enhanced and more frequent paranoia from cocaine use.
Pharmacogenetic randomized trial for cocaine abuse: Disulfiram and dopamine β-hydroxylase
2013, Biological PsychiatryThe role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: Data from multicenter, prospective, longitudinal clinic practice
2013, Journal of Psychiatric ResearchCitation Excerpt :Multiple factors, including environmental and genetic, are likely involved in the pathophysiology of TRD. However, mounting evidence has demonstrated that genetic variations associated with antidepressant responses appear to cluster in families, supporting a more critical role for genetic variations in mechanisms underlying TRD (Laje and McMahon, 2007; O'Reilly et al., 1994). Recently, the neurotrophin hypothesis of MDD has attracted more attention (Dunham et al., 2009; Fernandes et al., 2011; Sillaber et al., 2008).
Baseline mood-state measures as predictors of antidepressant response to scopolamine
2012, Psychiatry ResearchCitation Excerpt :Efforts have been made to identify biomarkers that can be used to predict antidepressant treatment response (Leuchter et al., 2010). Measures associated with brain structure (MacQueen et al., 2008), brain function (Salvadore et al., 2009; Leuchter et al., 2010; Pizzagalli, 2011), and genetic factors (Laje and McMahon, 2007; Garriock and Hamilton, 2009) have been evaluated as potential markers of treatment response and may prove to be clinically useful. Evidence suggests that diagnostic subtypes may preferentially respond to medications with a particular mechanism of action (for review see Leuchter et al., 2010).
Genetic variation in the calcium/calmodulin-dependent protein kinase (CaMK) pathway is associated with antidepressant response in females
2012, Journal of Affective DisordersCitation Excerpt :Recent research showed 60–70% of MDD patients fail to reach complete remission even when adequately treated (Sackeim, 2001). Factors associated with the efficacy of antidepressants include genetic factors (Laje and McMahon, 2007), the experience of negative life events (Amital et al., 2008) and adverse childhood experiences (Kaplan and Klinetob, 2000). The mechanisms underlying the actions of antidepressant treatment are still under investigation, but the requirement for long-term, chronic antidepressant treatment has lead to the hypothesis that alterations in neuronal plasticity are necessary for a therapeutic response (Duman et al., 1997; Nestler et al., 2002).