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. Author manuscript; available in PMC: 2018 May 24.
Published in final edited form as: Expert Rev Neurother. 2016 Jun 27;16(10):1155–1174. doi: 10.1080/14737175.2016.1199276

Table 2. Summary of Threat Conditioning and Extinction Studies in Youth with Anxiety Disorders.

Study Diagnosis N Age CS US DV Phases Conditioning and Extinction Results Additional Comparisons
Pliszka et al. [71] ANX, ADHD, HC 56 (11 ANX, 23 ADHD, 22 HC) 6-12 2 squares paired with a different loud tone (500-1000 Hz) for 4 s White notes for 200 ms at 110 dB SCR, HR PRE-CON: N/A
CON: 8 CS+, 8 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 4 CS+, 4 CS-
ER: N/A
CON: Differential CON (CS+ > CS-) observed in SCR and HR across participants. No group differences.
EXT: EXT observed in HR across groups, with no difference between CS+ and CS-. However, differential CON still present in SCR across groups (CS+ > CS-).
N/A.
Liberman et al. [78] ANX (SoP, GAD, SP, SAD), HC 83 (53 ANX, 30 HC) 7-14 4 neutral cartoons for 5 s US 105 dB tone (1000 Hz) for 500 ms
Startle 105 dB white noise for 50 ms
SCR, FPS, SR PRE-CON: 4 stimuli
CON: 6 CS+, 6 CS-, 6 US
GEN: N/A
CXT: N/A
EXT: 8 CS+, 8 CS-
ER: N/A
PRE-CON: No sig differencesbetween groups in FPS, SCR, or SR.
CON: Differential CON observed in HC group using SR arousal' rating, but not ANX group. No differential CON in FPS or SCR. No group differences.
EXT: Differential CON observed in ANX group using SR fear' rating and FPS, but not in HC group.
Gender: (only in ANX group). Latency of FPS was greater in boys than girls during PRE-CON. During EXT, shorter FPS latency in girls than boys.
Craske et al. [72] ANX (SoP, GAD, SP, PD, SAD), ANX-AR, HC 49 (23 ANX, 15 ANX-AR, 11 HC) 7-12 4 shapes for 8 s 107 dB tone (1000 Hz) for 1 s SCR, SR PRE-CON: 4 shapes
CON: 8 CS+, 8 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 4 CS+, 4 CS-
ER: 4 CS+, 4 CS-
CON: Differential CON observed across all groups on SCR. ANX exhibited greater anticipatory SCR relative to HC and AR groups across stimuli.
EXT: ANX exhibited greater anticipatory SCR relative to HC group across stimuli. ANX reported lower valence toward CS+ post CON compared to HC. No differencesin EXT between ANX and AR groups.
ER: Average 12 days ER. ANX and AR exhibited greater anticipatory SCR relative to HC group across stimuli.
N/A.
Lau et al. [73] ANX (SoP, GAD, SAD), HC 54 (16 ANX, 38 HC) Mn = 13.5 2 neutral female faces for 8 s Fearful face + 95 dB scream for 3 s SR PRE-CON: 4 CS+, 4 CS-
CON: 16 CS+, 16 CS-, 12 US
GEN: N/A
CXT: N/A
EXT: 3 CS+, 3 CS-
ER: 12 CS+, 12 CS-
CON: Differential CON exhibited across groups (CS+ > CS-), however ANX group had higher ratings to the CS+ (but not the CS-) compared to HC group. Anxiety symptoms associated with fear ratings of CS+ across groups.
EXT: Differential CON exhibited across groups (CS+ > CS-).
ER: Average 16 days ER. Attrition at ER associated with males and higher levels of fear to CS+ following EXT. Both groups continued to rate CS+ > CS-.
Stability: Magnitude of correlations within stimulus time across EXT to ER demonstrated strong stability for CS+ (r=.57) and CS= (r=.55). Additionally strong association of differential fear CON across visits (r=.51).
Waters et al. [74] ANX (SoP, GAD, SP), HC 35 (17 ANX, 18 HC) 8-12 4 shapes for 8 s 10 dB tone (1000 Hz) for 1 s SCR, SR PRE-CON: 4 shapes
CON: 8 CS+, 8 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 4 CS+, 4 CS-
ER: N/A
PRE-CON: No group or stimuli difference.
CON: ANX group exhibited differential CON (CS+>CS-) on self-report arousal and SCR, but HC group only on SCR. ANX group also had larger SCR to CS, compared to HC group during orienting response.
EXT: No group difference on self-report, but ANX group exhibited greater SCR to both stimuli compared to HC group. Differential CON in ANX group observed in SCR orienting response, but not other aspects or in HC group.
N/A.
Britton et al. [41] ANX (SoP, GAD), HC 65 (23 ANX, 42 HC) 8-19 CS 2 neutral female faces for 7-8 s
GS 9 blended images for 7-8 s
US Fearful face + 95 dB scream for 1 s
Startle 10 psi air puff for 40 ms
FPS, SCR, SR, fMRI PRE-CON: 4 CS+, 4 CS-
CON: 10 CS+, 10 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 8 CS+, 8 CS-
GEN ER: 3 CS+, 3 CS-, 27 GS
PRE-CON: No difference in SCR or FPS.
CON: ANX group more likely to discontinue participation. Differential CON observed (CS+ > CS-) across groups for FPS, SCR, and SR. ANX group had greater SR to stimuli compared to HC group.
EXT: ANX group had impaired EXT to CS+ compared to HC group. Additionally, ANX group had similarly high SR ratings of CSs compared to HC group.
GEN ER: Average 20 days after EXT. During threat appraisal questions, ANX group exhibited lower sub-genual anterior cingulated activation compared to HC group. Additionally, ANX group had greater activation to CSs and not gradient stimuli in vmPFC.
Compared data with 49 adults (18 ANX, 31 HC)
Age Differences: Youth have greater SCR during CON and EXT than adults. Less EXT in youth FPS compared to adults. Additionally, ANX adults had hypoactivation in vmPFC during threat appraisal compared to other groups.
Haddad et al. [75] ANX, HC 26 (15 ANX, 11 HC) 11-17 CS 2 neutral female faces for 6 s
Control cue (CC) Grey oval for 6 s
Fearful face + 95 dB scream for 1 s SR fMRI PRE-CON: 5 CS+, 5 CS-, 5 CC
CON: 30 CS+, 15 CS-, 15 CC, 15 US
GEN: N/A
CXT: N/A
EXT: NR
ER: N/A
PRE-CON: ANX group had higher nervous SR to CS+ than HC group. No within group difference to CSs.
CON: Differential CON (CS+> CS- > CC) across groups, with the ANX group reporting greater nervousness to both stimuli compared to CON group. CON group exhibited greater activation in amygdala, right hippocampus, and vmPFC compared to ANX group to threat cue (CS+ relative to CC).
AGE: Age was not associate with nervous SR ratings of stimuli during PRE-CON or CON. Age-related activation increases to CS+ relative to CC observed in the insula and DLPFC across the sample.
ANX and AGE: In HC group, greater response with to CS- > CC in DLPFC, bilateral insula and striatum, but not in ANX group.
Shechner et al. [76] ANX (SoP, GAD, SP, SAD), HC 32 (15 ANX, 17 HC) Mn = 11.5-13.0 2 neutral female faces for 7-8 s or 2 colored bells for 7-8 s US 95 dB scream + fearful face for 1s or 95 dB alarm + red bell for 1 s
Startle 10 psi air puff for 40 ms
SCR, FPS, SR PRE-CON: 4 CS+, 4 CS-
CON: 10 CS+, 10 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 8 CS+, 8 CS-
ER: N/A
PRE-CON: No stimuli or group difference in SR or SCR.
CON: 6 youth (3 ANX, 3 HC) discontinued task. Differential CON (CS+ > CS-) in SR, FPS, and SCR observed across groups.
EXT: Differential CON (CS+> CS-) observed in SR across groups, but no differences in SCR or FPS.
Task Comparison: “Screaming Lady” and Bell CON task had moderate to strong ICC for SR and SCR CON and EXT (r=.42-.65), but only modest association for FPS CON (r=.34-36). However, some task specific differences were observed.
Age: Compared data with 52 adults (22 ANX, 30 HC). Youth exhibited higher overall SCR, FPS, and differential CON compared to adults who had lower SCR and did not exhibit differential CON.
Waters & Kershaw [77] ANX (SoP, GAD, SP, SAD) 34 ANX (18 TVB, 16 TAB) 7-12 2 colored shapes for 8 s 107 dB tone (1000 Hz) for 1 s SCR, SR PRE-CON: NR
CON: 8 CS+, 8 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 4 CS+, 4 CS-
ER: N/A
CON: Greater orienting response in TAB compared to TVB in first trial block, with larger unconditioned response to US in TAB across blocks. However no group difference in anticipatory response (i.e., CON).
EXT: SR anxiety to CSs decreased across groups after EXT. However, TAB had higher SR anxiety ratings compared to TVB, with greater orienting responses across CS to the first trial block. No group differences in SR or SCR.
N/A
Waters & Pine [79] ANX (SoP, GAD, SP, SAD), HC 76 (44 ANX: 26 RESP, 18 NON-RESP; 32 HC) 7-13 2 colored shapes for 8 s 107 dB tone (1000 Hz) for 1 s SCR, SR PRE-CON: NR
CON: 8 CS+, 8 CS-, 8 US
GEN: N/A
CXT: N/A
EXT: 4 CS+, 4 CS-
ER: N/A
CON: Differential CON in SCR exhibited across groups, but no group differences. NON RESP had higher unpleasant SR of CSs after CON compared to PRE-CON or EXT. However, this was not observed in RESP or HC groups.
EXT: RESP and HC exhibited decreased SCR over trial blocks. Additionally, SCR to the CS+ during first trial block were larger than NON RESP, but neither RESP or NON RESP differed from HC group.
Change In Anxiety: Change in child-reported anxiety associated with initial EXT response to CS+ trials (r=.48)

Note: ANX = Anxious, SoP = Social Phobia, GAD = Generalized Anxiety Disorder, SP = Specific Phobia, PD = Panic Disorder, SAD = Separation Anxiety Disorder, ANX AR = Anxiety At-Risk, CON = Conditioning, CS = conditioned stimulus, CXT = Context Conditioning, dB = decibel, DEP = Depressed, DV = Dependent variable, ER = Extinction Retention, ET = Eye tracking, EXT = Extinction, fMRI = functional magnetic resonance imaging, FPS = Fear potentiated startle, GEN = Generalization, GEN ER = Generalization Extinction Retention, GS = Generalization Gradient Stimulus, HC = Healthy Controls, HR = Heart rate, Hz = hertz, Mn = Mean, ms = millisecond, N/A = Not Applicable, PRE-CON = Pre-Conditioning, psi = pounds per square inch, s = seconds, SCR = Skin conductance response, SR = Self-report, US = unconditioned stimulus, vmPFC = ventralmedial prefrontal cortex.