Table 3 Overview of important specifications of the sample for the experimental and clinical studies

From: A review on experimental and clinical genetic associations studies on fear conditioning, extinction and cognitive-behavioral treatment

Author ^ref.	Polymorphism	Ethnicity	Screening	Study	N	F/M	Genotypes	HWE	Age	Genotyping	Measure	Results
Garpenstrand et al.²⁷	5-HTTLPR	Swedish Caucasian	No	E	40	14/26	24s+/16ll	?	29.7	Post	SCR	• Participants good in acquisition had a higher frequency of the s-allele as compared to those with bad acquisition performance • No differences during (immediate) extinction
Lonsdorf et al.³⁶	5-HTTLPR	German Caucasian	Yes^a	E	48	25/23	30s+/18ll	N/Aa	23.9	Pre and post	FPS SCR	• CS+ potentiation s-carriers >l/l (FPS) during acquisition and (delayed) extinction • CS− inhibition s-carriers <l/l (FPS) during extinction
Crisan et al.²⁹	5-HTTLPR	Probably Romanian Caucasian	Yes^a	E	32	6/26	18s+/14ll	Yes	26.8	Post	SCR	• Observational fear learning s-carrier >l/l • SCR reactivity during observation s-carrier >l/l
Bryant et al.³⁵	5-HTTLPR^b	Australian Caucasian	N/A	C	42^c	30/15^d	29s+/13ll^e	Yes	∼42	Post	CAPS	• More s-carriers than l/l fulfill criteria for PTSD diagnosis 6 months after CBT, despite no differences right after treatment
Lonsdorf et al.⁷³	5-HTTLPR	Swedish Caucasian	N/A	C	73	26/43	51s+/22ll 60s+/13ll^e	Yes	35.4	Post	HADS	• No differences in response to exposure-based CBT after treatment or at 6 months follow-up • Main effect of symptom severity over time (s-carrier >l/l)
Kilpatrick et al.³²	5-HTTLPR^b	Mainly Caucasian	N/A	C	Total:589 PTSD:19	36.5%/63/5%	ss: 120/sl:315/ll:154	?	?	Post	PTSD risk	• An association of the s/s genotype with PTSD in highly exposed adults with low social support
Koenen et al.³³	5-HTTLPR	Mainly Caucasian	N/A	C	Total:590 PTSD:19	375 female	ss: 120/sl:316/ll:154	?	?	Post	PTSD risk	• The s/s genotype to be associated with PTSD in high-risk environments (e.g., crime, unemployment), whereas the opposite was found for low-risk environments
Kolassa et al.³⁴	5-HTTLPR	African	N/A	C	Total:408	190/218	ss:16/sl:109/ll:283 (whereof 8 ultra-l/l)	Yes	34.7	Post	PTSD risk	• s-carriers exhibited an enhanced risk for lifetime PTSD irrespective of trauma load, whereas non-carriers exhibited a dose–response relationship
Lonsdorf et al.³⁶	COMTv158met	German Caucasian	Yes^a	E	48	25/23	39val+/9mm	N/A	23.9	Pre and post	FPS, SCR	• No differences during acquisition • CS+ potentiation met/met>val-carrier during extinction (FPS)
Kolassa et al.⁴⁸	COMTv158met	African	N/A	C	424	198/226	188vv/190vm/46mm	?	34.8	Post	PTSD risk	• met/met higher risk for lifetime PTSD even at low trauma load
Lonsdorf et al.⁷³	COMTv158met	Swedish Caucasian	N/A	C	69	26/43	40val+/29mm	No	35.4	Post	HADS	• met/met less reactive to exposure-based CBT as compared to val-carrier
Valente et al.⁵⁰	COMTv158met	Brazilian	Yes^f	C	99 PTSD 335 CS^g	50/59 ?/?	20mm42vm/37vv 26mm/185vm/124vv	Yes/No^h Yes	18–60	Post	CAPS	• Significantly higher frequency of the COMT met-allele in Brazilians that had developed PTSD as compared to those that had not developed PTSD after being exposed to a single urban trauma, as well as compared to a general community sample
Hajcak et al.⁷²	BDNFv66met	?	No	E	57	26/31	44vv/13m+	?	?	Post	FPS Shock likelihood	• FPS to the CS+ only in val/val- not in met-carriers
Lonsdorf et al.³⁷	BDNFv66met	German Caucasian	Yes^a	E	48	25/23	43vv/14m+	Yes	23.9	Post	FPS, SCR	• CS+ potentiation and CS discrimination val/val>met-carrier during late acquisition (FPS) • CS+ potentiation val/val>met-carriers during early extinction (FPS)
Soliman et al.⁷⁴	BDNFv66met	Mixed	Yes^d	E	70/−72ⁱ	34/36 33/39	35vv/35m+ 36vv/36m+	?	25.9 25.6	Post?^j	SCR, fMRI	• Resistance to extinction in met/met (fMRI, SCR see text for severe problems interpreting these results due to methodological shortcomings)
Garpenstrand et al.²⁷	DRD4 exon III	Swedish Caucasian	No	E	40°	14/26	29 Short/11 long+	?	29.7	Post	SCR	• No differences during acquisition • CS discrimination during extinction long allele <short/short
Garpenstrand et al.²⁷	MAO-A VNTR	Swedish Caucasian	No	E	40°	14/26	15 low/25 high	?	29.7	Post	SCR	• Differences during either acquisition or extinction
Huertas et al.⁷⁹	DRD2 C957T	Spanish Caucasian	No	E	63	31/32	51T+/9CC	?	19–27	Post	SCR	• Differential conditioning during acquisition CC>T-carriers • NS for extinction
Huertas et al.⁷⁹	DRD2 Taq1A/ANKK1 Taq1A	Spanish Caucasian	No	E	63	31/32	18A1−/42A1+	?	19–27	Post	SCR	• Differences during either acquisition or extinction
Domschke et al.⁸³	NPSR1 A/T	German Caucasian	?	E/C	205	151/54	25AA/150T+	?	35.4	Post	Subjective anxiety	• Symptom reports during exposure (but not anticipation and recovery) T-carrier>AA
Raczka et al.⁷⁵	NPSR1 A/T	German Caucasian	Yes^k^,^l	E	66	0/66	28AA/38T+ (13TT)	?	27.8	Post	SCR, fear ratings, fMRI	• Fear ratings to the CSs T-carrier>AA • CS− evoked brain activity in the rdmPFC T-carrier>AA
Ressler et al.⁸⁷	ADCYAP1R1 rs2267735	?	?	E	?	?	?	?	?	?	FPS	• CS+/CS− discrimination in female CC<G-carriers • No differences in men

Abbreviations: ADCYAP1R1, pituitary adenylate cyclase 1 receptor; ANKK1, ankyrin repeat and kinase domain containing; BDNF, brain-derived neurotrophic factor; CAPS, Clinician-Administered PTSD Scale; COMT, catechol-o-methyltransferase; CS, conditioned stimulus; FPS, fear-potentiated startle; fMRI, functional magnetic resonance imaging, 5-HTTLPR, 5-HTT linked polymorphic region; HWE, Hardy–Weinberg equilibrium; ITI, Inter-trial interval; MAO-A, monoamine oxidase A; NPS, neuropeptide S; SCR, skin conductance response; UCS, unconditioned stimulus; VNTR, variable number of tandem repeat region.
?, Not specified in the respective publication.
+, Mean carriers, for example, s+=carriers of the s-allele.
Note: For some studies HWE was not applicable (N/A) as individuals were selected or partly selected based on their respective genotype group.
^aScreening based on a questionnaire, telephone interview or interview, but not a clinical diagnostic interview.
^bTriallelic classification.
^cN=42 for the follow-up analyses that yielded genotype-specific findings, but N=45 in total, number of females and males is given for the post-treatment sample.
Drug screening using urine toxicological test.
^eGenotypes defined by the triallelic method (5-HTTLPR/rs25531). ‘High expression’=L_A/L_A; ‘low expression’=all other genotypes.
PTSD patients: The presence of lifetime history of bipolar disorder, psychotic disorders and the presence of substance dependence or abuse disorders (excluding nicotine and caffeine) in the previous 6 months were exclusion criteria. Community sample: Past history of drug abuse, use of an illegal drug, lifetime history of a psychiatric disorder or suffering from a psychiatric condition at the time of the evaluation was excluded. The presence of previous traumatic experiences was not evaluated in this group.
^gCommunity sample.
^hHWE PTSD+: yes; HWE PTSD−: no.
ⁱN=70 for the fMRI sample and N=72 for the SCR sample.
^jAlthough the genotype distributions suggest an a priori selection, as they do not reflect population allele frequencies, no information about participant selection is given, leaving open the possibility of a selective drop out, particularly in the light of the high drop-out rates reported.
Clinical diagnostic interview, for example, MINI.
^lUnclear as to how screening was performed.

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Table 3 Overview of important specifications of the sample for the experimental and clinical studies

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