Table 2 Overview of important design specifications of the experimental studies

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

Author ^ref.	Polymorphism	Stimuli	UCS	Number of trials	Reinforcement ratio (%)	EXT ^a	CS duration	ITI duration	Peak detection window	Data processing	Instructed acquisition	Awareness reported	Time taken into account ^b
Garpenstrand et al.²⁷	5-HTTLPR MAO-A DRD4	Circle, triangle	Shock	H: 8 each A: 8 each E: 8 each	100	I	8 s	20–40 s	1–4 s post-onset	Range correction (X/max. response) SCRs summarized over stimuli and trials	?	No	No
Lonsdorf et al.^{36, 37}	5-HTTLPR COMTv158m BDNFv66m	KDEF faces (angry male) 95 dB startle probe	Shock	H: 6 whereof 1 each to be CS A: 9 each E: 18 each	100	D	6 s	10–18 s	SCR: 0.9–4 s post-onset FPS: 20–100 ms post-onset with peak within 150 ms	SCR: Log and range correction (1+(X/max. response)) FPS: rectified, z-scores to T-scores	No	Yes^c	No (2009) Yes (2010)
Crisan et al.²⁹	5-HTTLPR	Two colored squares (movie)	Shock	Obs.: 5 each Test: 5 each	60	—	10 s	10–14 s	0.5–4.5 s post-onset	Area under the curve extracted	No	No	No
Hajcak et al.⁷²	BDNF val66met	Rectangles differing in size	Shock	H: 4 trials A: 12 CS+ 8 each CS−	100	—	8 s	10–12 s	150 ms window relative to average of 50 ms pre-probe	Rectified in a 200 ms window starting 50 ms before startle probe, smoothed using six-point running average Amplitude converted to T-scores	Yes	N/A (instructed)	No
Soliman et al.⁷⁴	BDNF val66met	Two colored squares	95 dB aversive sound	A: 24 each^d Rev: 24 each^d E: 24 each	50	I	3 s	13 s	1–8 s post-onset	Smoothed (kernel ?) square root transformed		No	No
Huertas et al.⁷⁹	DRD2 C957T	Eckman faces (neutral male, neutral female)	Shock A: 200 ms AP: 180 ms	H: 10 faces A: 11 each^e E: 2 each^f	72.7	I	H: 8 s A: 8 s E: max 3 s	H: 4 s A: 16–20 s E: 19–21 s	1–4 s post-onset minimum amplitude: 0.01 μS	Range correction ((X/mean of the three max) × 100) Square-root transform (1+range corrected SCR)	Yes^g	No	No
Raczka et al.⁷⁵	NPSR1 A¹⁰⁷T	Circle, triangle	Shock	H: 4 each A: 18 each E: 18 each Re-A: 18 each	80	I	5 s	9–14 s	0–5 s post-onset	Peak SCR–SCL at the time of CS onset	No	No	Yes
Ressler et al.⁸⁷	ADCYAP1R1 rs2267735	Two different colored shapes 108 dB startle probe	250 ms air blast (intensity 140 psi)	H: 6 startle alone A: 12 each	100	—	C: 6 s	9–22 s	20–200 ms post-onset (startle probe)	Filtered, rectified, smoothed	?	No	Yes/no

Abbreviations: A, acquisition; ADCYAP1R1, pituitary adenylate cyclase 1 receptor; AP, aversive priming; BDNF, brain-derived neurotrophic factor; CS, conditioned stimulus; E, extinction; FPS, fear potentiated startle; 5-HTTLPR, 5-HTT linked polymorphic region; H, habituation; ITI, Inter-trial interval; KDEF, Karolinska directed emotional faces; NPS, neuropeptide; Obs, observation; Re-A, reacquisition; Rev, reversal; S; SCR, skin conductance response; UCS, unconditioned stimulus.
?, Not specified in the respective publication.
^aExtinction timing: I=immediate extinction; D=delayed extinction.
^bTime taken into account by providing additional analyses, for example, by comparing first and second half of the experiment or by providing learning rates to quantify response changes over time.
^cParticipants classified as unaware were excluded from primary analyses in both publications. Of note, BDNF met-carriers failed more often to report correctly the conditioning contingencies as compared with homozygote val-carriers, as assessed by a standardized interview performed right after the acquisition.⁹⁹
^dReinforced CS+ trials were analyzed separately; thus, in principle 24 CS− and 12 CS+ trials.
^ePlus 4 presentations of two additional faces (data not reported); during conditioning, the CS+ was paired with an aversive shock, whereas the CS− was paired with a neutral tone (both events occurring 3 s after picture onset). Although SCRs to eight paired trials each were not analyzed, only SCRs to three presentations each, which were not paired with either shock or tone respectively, were used for statistical analyses. In addition, two additional faces were each presented four times, but SCRs to these faces were not reported.
^fBoth the CS+ and CS− were presented two times in total, with the last presentation of each of them (which was used for statistical analyses) not being preceded by either a tone or a shock. During the phase preceding the two extinction test trials (the aversive priming experiment), there was one presentation of each CS+ and CS− (possibly preceded by a shock), seven presentations of the additional faces from the acquisition, 10 presentations of distracters (these were the 10 faces presented during habituation). During the AP phase, participants were presented with a set of new and old faces and had to indicate by button presses, whether the face presented was one of the four faces presented during conditioning or not. Reactions had to be made within 3 s and the face disappeared after the reactions. Any of the faces could during this AP phase been preceded by the shock or the tone.
^gParticipants were informed that one of the faces would be paired with the shock and the other one with a tone.

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Table 2 Overview of important design specifications of the experimental studies

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