Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

Lester, Kathryn J; Eley, Thalia C

doi:10.1186/2045-5380-3-4

Table 1 Summary of studies investigating associations between genetic variation and response to psychological therapy in mood and anxiety disorders

From: Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

Authors	Diagnosis	Sample	Treatment	Results
5HTTLPR/rs25531
Wang et al. [58]	PTSD	N = 35	12wk prolonged exposure therapy or 12 wk Escitalopram (N = 20)	No significant association with treatment response in exposure therapy group
Bryant et al. [56]	PTSD	N = 45, Caucasian,	8 × 90 min weekly individual CBT	No significant association at post-treatment. At 6mth follow-up, higher % of Sⁱ allele than L allele carriers met PTSD criteria and had significantly higher symptom scores
Bryant et al. [56]	PTSD	M_age = ~ 43 yrs, 33% female	8 × 90 min weekly individual CBT
Lonsdorf et al. [59]	PD ± AG	N = 69, Caucasian,	10 × 2 hr weekly group (N = 38) or internet-delivered (N = 31) CBT	No significant association with treatment response
Lonsdorf et al. [59]	PD ± AG	M_age = ~ 35 yrs, 62% female		No significant association with treatment response
Furmark et al. [60]	SAD	N = 204, M_age = 38 yrs,	9 wk internet delivered CBT or waitlist control	No significant association with treatment response
Furmark et al. [60]	SAD	60% female	9 wk internet delivered CBT or waitlist control	No significant association with treatment response
Kohen et al. [61]	DEP (post- stroke)	N = 61, mixed ethnicity	9 × positive problem solving plus antidepressant vs. usual care plus antidepressant	SS and SL carriers had a significantly greater mean percentage reduction in depression ratings and more likely to be in remission at 9-week follow-up than those in the control group
Sakolsky et al. [62]	SEP; GAD; SAD	N = 211, Caucasian,	Sertraline, 14 sessions of CBT, combination therapy or 12 wk placebo	No significant association with treatment response
Sakolsky et al. [62]	SEP; GAD; SAD	7-17 yrs,		No significant association with treatment response
Eley et al. [10]	ANX	N = 359, Caucasian,	10-12 session group or individual CBT or guided self-help	No significant association at post treatment. At follow-up, higher % of SS genotype carriers free of anxiety diagnoses than SL/LL genotype carriers. SS genotype carriers had significantly greater reduction in symptom severity scores
Eley et al. [10]	ANX	M_age = 9.44 yrs, 49% female	10-12 session group or individual CBT or guided self-help
Hedman et al. [63]	SAD	N = 126, 98% Caucasian, M_age = ~ 35 yrs, 36% female	15 × 2.5 hr weekly group (N = 62) or internet-delivered (N = 64) CBT	No significant association with treatment response
Bockting et al. [64]	Recurrent DEP	N = 180, Caucasian,	Brief CBT vs. treatment as usual	No significant association with time to recurrence
Bockting et al. [64]	Recurrent DEP	M_age = 45 yrs, 74% female	Brief CBT vs. treatment as usual	No significant association with time to recurrence
STin2 VNTR
Kohen et al. [61]	DEP (post- stroke)	N = 64, mixed ethnicity	9 × positive problem solving plus antidepressant vs. usual care plus antidepressant	9/12 and 12/12 genotype carriers in intervention group had a significantly greater mean percentage reduction in depression scores and greater likelihood of remission at 9 wk follow-up than controls
Sakolsky et al. [62]	SEP; GAD; SAD	N = 211, Caucasian,	Sertraline, 14 sessions of CBT, combination therapy or 12 wk placebo	At 12-week assessment STin2 12-copy variant carriers showed significantly greater improvement.
Sakolsky et al. [62]	SEP; GAD; SAD	7-17 yrs
HTR2A rs7997012
Kotte et al. [65]	DEP	N = 58, 100% male	16-wk group CBT	G allele predicted significantly larger reduction in BDI scores across treatment compared to A allele carriers
TPH2 G-703T
Furmark et al. [60]	SAD	N = 204, M_age = 38 yrs,	9 wk internet delivered CBT or waitlist control	In the CBT group, a better treatment response was observed in TPH2 GG homozygotes relative to T allele carriers
Furmark et al. [60]	SAD	60% female	9 wk internet delivered CBT or waitlist control
MAOA-u VNTR
Reif et al. [66]	PD + AG	N = 288, Caucasian	12 × twice weekly CBT	Carriers of the long, higher activity alleleⁱⁱ had significantly worse treatment outcome, elevated heart rate, greater fear and panic attacks during a behavioral avoidance task and failure to habituate during repetitive exposure
COMT val158met
Lonsdorf et al. [59]	PD ± AG	N = 69, Caucasian,	10 × 2 hr weekly group (N = 38) or internet-delivered (N = 31) CBT	No significant effect of COMTval158met genotype on change in anxiety or depression scores across cognitive modules (weeks 1-3). met/met genotype carriers had significantly smaller reduction in anxiety scores across exposure modules (weeks 4-9) compared to val-carriers
Lonsdorf et al. [59]	PD ± AG	M_age = ~ 35 yrs, 62% female
Hedman et al. [63]	SAD	N = 126, 98% Caucasian, M_age = ~ 35 yrs, 36% female	15 × 2.5 hr weekly group (N = 62) or internet-delivered (N = 64) CBT	No significant association with treatment response
NGF rs6330
Lester et al. [57]	ANX	N =374, Caucasian,	10-12 session group or individual CBT or guided self-help	No significant association with treatment response at post treatment. At follow-up, children with one or more copies of T allele of NGF rs6330 were significantly more likely to be free of anxiety diagnosis
Lester et al. [57]	ANX	M_age = 9.46 yrs, 49% female	10-12 session group or individual CBT or guided self-help
BDNF val66met; rs7934165; rs1519480; rs11030104
Sakolsky et al. [67]	SEP; GAD; SAD	N = 211, Caucasian,	Sertraline, 14 sessions of CBT, combination therapy or 12 wk placebo	No significant association with treatment response
Sakolsky et al. [67]	SEP; GAD; SAD	7-17 yrs		No significant association with treatment response
Lester et al. [57]	ANX	N = 374, Caucasian,	10-12 session group or individual CBT or guided self-help	No significant association with treatment response
Lester et al. [57]	ANX	M_age = 9.46 yrs, 49% female	10-12 session group or individual CBT or guided self-help	No significant association with treatment response
Hedman et al. [63]	SAD	N = 126, 98% Caucasian, M_age = ~ 35 yrs, 36% female	15 × 2.5 hr weekly group (N = 62) or internet-delivered (N = 64) CBT	No significant association with treatment response
Fullana et al. [68]	OCD	N = 106, Caucasian,	20 × 45 min weekly exposure based CBT plus SSRI	Met allele carriers significantly less likely to respond to treatment than non-met allele carriers. Genotype predicted response only and not change in severity scores
Fullana et al. [68]	OCD	M_age = 33 yrs, 50% female	20 × 45 min weekly exposure based CBT plus SSRI
GRIN2B rs1019385
Sakolsky et al. [67]	SEP; GAD; SAD	N = 211, Caucasian,	Sertraline, 14 sessions of CBT, combination therapy or 12 wk placebo	No significant association with treatment response
Sakolsky et al. [67]	SEP; GAD; SAD	7-17 yrs		No significant association with treatment response
GRIK4 rs1954787
Sakolsky et al. [67]	SEP; GAD; SAD	N = 211, Caucasian,	Sertraline, 14 sessions of CBT, combination therapy or 12 wk placebo	Significant association with treatment response at 12 week assessment
		7-17 yrs

PTSD = post-traumatic stress disorder; PD ±AG = panic disorder with or without agoraphobia; SAD = social anxiety disorder; DEP = depression; SEP = separation anxiety disorder, GAD = generalized anxiety disorder; ANX = all anxiety disorders; OCD = obsessive compulsive disorder.
^IS allele group defined as S_AS_A, S_AL_A, S_AL_G, S_GL_G, L_AL_G, L_GL_G and L allele group defined as L_AL_A.ⁱⁱ Long, high activity risk allele group defined as 3.5, 4 and 5 copy repeat allele males, and 2/4, 3/4, 3.5/4, 4/4, and 4/5 copy repeat allele females. Short, low activity allele group defined as 2 or 3 copy repeat allele males and 2/2, 2/3 and 3/3 females.

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