Table 2.

Summary of studies examining affect-modulated startle reactivity in PTSD.

Category	Study	Experimental Paradigm	Diagnostic Instrument	Subjects	Comorbid Diagnosis?	Medication*	Key result(s)
Studies investigating general startle	Butler et al. (1990)	Startle probe alone	DSM-IIIR	13 PTSD; 12 combat controls	No comorbid diagnosis	A	Higher startle in PTSD for 95 and 100 dB probes, but not other probes
	Shalev et al. (1992)	Startle probe alone	SCID-R	14 PTSD; 14 other anxiety disorders (7 PD; 3 GAD; 4 OCD); 15 subjects with trauma exposure, but no psychopathology; 19 with no trauma exposure or psychopathology	PTSD: 2 AA; 1 MD	C	Trend toward larger general startle in PTSD
	Morgan, Grillon, Southwick, Nagy, et al. (1995)	Startle probe alone	SCID-R	18 PTSD; 11 combat controls	5 past and current PD; 15 past MD	B	- General startle greater in PTSD - No difference in results due to PD diagnosis
	Orr et al. (1995)	Startle probe alone	SCID-R	37 PTSD; 19 combat controls	PTSD: 1 BP II; 14 MD; 7 DYS; 1 psychotic disorder not otherwise specified; 6 AA; 7 SA; 6 PD w/o AGO; 7 SO; 2 SP; 3 OCD; 2 GAD; 6 borderline personality; 2 ASPD Combat controls: 1 MD; 2 DYS; 2 AA; 1 PD w/o AGO; 2 SO; 1 GAD; 1 borderline personality	D	- General startle greater in PTSD than combat controls - No differences due to comorbid disorder - Medication use had no effect on results
	Morgan et al. (1996)	Startle probe alone	SCID-R	10 PTSD; 7 combat controls; 15 civilian controls	2 AA	B	- General startle greater in PTSD than civilian and combat controls - Civilian and combat controls not different from each other
	Morgan et al. (1997)	Startle probe alone	SCID-R	13 PTSD; 16 controls	6 PD w/o AGO; 11 MD	B	- General startle greater in PTSD group greater than controls for left eye, but not right eye - This effect more driven by recent-PTSD group and not long-standing PTSD group - No difference in results due to comorbid PD or MD
	Shalev et al. (1997)	Startle probe alone	SCID-R	Patients referred for trauma-related distress: 30 with PTSD; 28 without PTSD	PTSD: 12 MD; 4 PD; 1 dissociative disorder Without PTSD: 18 past PTSD; 5 MD; 2 adjustment disorder	B	General startle greater in PTSD than non PTSD
	Ladwig et al. (2002)	Startle probe alone	Diagnostic checklist recommended by World Health Organization	11 PTSD; 19 controls; all subjects had peritraumatic dissociation	None noted	A	General startle greater in PTSD than controls
	Ross et al. (1989)	Startle probe alone	DSM-IIIR	9 PTSD; 9 controls	4 MD; 3 GAD; 2 DYS; 2 ASPD	B	No differences between groups
	Grillon et al. (1996)	Startle probe alone	SCID-R	19 PTSD; 10 combat controls; 16 civilian controls	MD and OCD exclusionary criteria; 4 PD; 10 AA	B	No differences among groups
	Orr, Lasko, et al. (1997)	Non-startling probes alone	SCID-R	20 PTSD; 19 combat controls	None noted, apart from past AA or SA	B	No differences between groups
	Orr, Solomon, et al. (1997)	Startle probe alone	SCID-R	19 current PTSD; 74 combat controls	PTSD: 5 GAD; 6 current MD	C	No differences between groups
					Combat controls: 2 GAD; 2 current MD
	Metzger et al. (1999)	Startle probe alone	SCID-R	57 women with history of child sexual abuse: 21 current PTSD; 23 lifetime, but not current PTSD; 13 never PTSD	Current PTSD: 2 BP; 5 MD; 5 DYS; 5 PD; 3 AGO; 7 SO; 8 SP; 3 GAD; 1 somatoform; 3 eating disorder; 1 SA Lifetime PTSD: 1 MD; 1 DYS; 1 PD; 1 SP; 2 eating disorder	D	- No differences among groups - Medication use had no effect on results
					Never PTSD: 1 PD; 1 SO; 1 SP; 2 SA; 1 AA
	Orr et al. (2003)	Startle probe alone	CAPS	MZ twins discordant for combat exposure and PTS: 50 PTSD; 53 control twin	Comorbidity noted, though details not provided	C	No differences between groups
	Karl et al. (2004)	Startle probe alone with neutral, startle and trauma-related sounds; pre- and post-treatment assessment	CAPS	17 motor vehicle accident survivors - 10 PTSD; 3 subsyndrome; 4 non PTSD	None noted	A	- No differences among groups at pre-treatment - No differences between startle and trauma-related sounds in groups - Decreased general startle in treatment group as compared to waitlist controls
				- Subjects randomly assigned to treatment or control waitlist
	Guthrie and Bryant (2005)	Startle probe alone; EMG activity assessed pre- and post-trauma	CAPS	35 trauma-exposed firefighters; 36 non-trauma exposed controls	None noted	B	- No differences between groups - In both groups, mean pre-trauma startle activity predictive of mean post-trauma startle activity
	Carson et al. (2007)	Startle probe alone	CAPS and SCID	Nurses with Vietnam War-related PTSD: 39 current PTSD; 40 past PTSD; 49 exposed but no PTSD	Current group: 2 other BP; 16 MD; 4 DYS; 7 PD; 1 AGO; 6 SO; 5 SP; 1 OCD; 1 undifferentiated somatoform; 4 binge-eating; 2 AA	D	- No differences among groups - Medication use had no effect on results
					Past group: 2 PD; 1 SP; 1 body dysmorphic disorder
					No PTSD: 2 MD; 2 DYS; 4 SP; 1 binge eating disorder
	Jovanovic, Norrholm, Sakoman, et al. (2009)	Startle probe alone	CAPS	45 PTSD; 33 controls	Exclusionary criteria included SA or BP	A	- No differences between groups - Some evidence for impaired habituation across trials in PTSD
	Shalev et al. (2000)	Startle probe alone; EMG activity assessed 1 week, 1 month and 4 months post-trauma	CAPS and SCID-R	21 PTSD alone; 15 PTSD and MD; 16 MD alone; 166 neither PTSD nor MD	None noted except for MD	A	- No difference among groups at 1 week post-trauma - At 1- and 4-month post-trauma, PTSD took longer to habituate to startle - No difference among groups because of MD
	Griffin (2008)	Startle probe alone; EMG activity assessed 1-month and 6-months following trauma	CAPS and SCID	40 rape or trauma survivors; PTSD classification based on diagnosis at 6-month followup	At 1-month post-trauma: 26 women with PTSD symptom diagnosis; 12 PTSD symptom and MD; 1 MD only At 6-month post-trauma: 16 women with PTSD; 5 PTSD and MD; 4 MD	B	- No differences in startle at 1-month post-trauma assessment - PTSD group had larger startle at 6-month followup than non-PTSD - This was due to increase in startle for PTSD group
	Ornitz and Pynoos (1989)	Startle probe alone	DSM-III	6 PTSD; 6 controls	None noted	B	General startle in PTSD less than controls
	Medina et al. (2001)	Startle probe alone	LASC	46 women exposed to high levels of childhood corporal punishment and high levels of partner aggression	None noted	A	PTSD symptom score negatively correlated with general startle
Studies investigating context-potentiated, fear potentiated, and/or general startle	Morgan, Grillon, Southwick, Davis, et al. (1995)	Startle probes presented alone, and during anticipation of aversive stimuli and recovery phases	SCID-R	9 PTSD; 10 controls	4 PD; 5 AA	A	- Greater general startle in PTSD during probes alone and anticipation phases, but not recovery phase - Evidence regarding FPS unclear as significantly greater FPS in PTSD driven by one subject
	Grillon et al. (1998a)	Startle probes during adaptation phase, and light and darkness conditions	SCID-R	19 PTSD; 13 combat controls; 20 civilian controls	BP and SA exclusionary criteria	B	- No differences among groups during adaptation - Startle during darkness and light conditions greater in PTSD than combat and civilian controls
							- No differences in context-potentiated startle (startle during darkness – light) between PTSD and combat controls
							- However, PTSD showed greater context-potentiated startle than civilian controls
							- 6 additional subjects eliminated due to being “nonresponders”
	Grillon et al. (1998b)	Startle probe in non-stressful and stressful experimental contexts; subjects tested twice; session 1 involved probe alone; session 2 involved probes under safety and threat of shock conditions	SCID-R	34 PTSD; 17 combat controls; 14 civilian controls	1 BP; 17 MD; 4 SA; 6 PD w/ AGO; 4 PD w/o AGO; 8 SO; 1 OCD; 1 antisocial behavior/borderline personality disorder	B	- No differences in session 1 (i.e., general startle) - No differences in FPS among groups in session 2 - Greater general startle in PTSD in second session - Comorbid MD did not affect results
	Grillon and Morgan (1999)	Startle in conditioning paradigm using safe and threat cues in 2 separate sessions	SCID-R	12 PTSD; 12 combat controls	1 AA; no other psychiatric disorder	B	- PTSD showed increased startle from the first session to session two in habituation and pre-conditioning phases; controls showed decreased startle for the same comparison
							- No differences between startle to safe and threat cues in first session in PTSD
	Pole et al. (2003)	Startle during threat of shock	SCID, CAPS, and MS-PV	55 police officers endorsing range of PTSD symptoms; 6 full PTSD	Full PTSD: MD; DYS; AA; SA; SO; SP and/or GAD Remaining subjects: SP; AA; SA	D	- Startle reactivity during threat of shock with electrodes attached, but no imminent shock (i.e., medium threat), positively related to greater PTSD symptoms - Medication use had no effect on results
	Pole et al. (2009)	Startle during threat of shock; EMG activity assessed only prior to trauma exposure	SCID and PTSDCL	138 police academy cadets; PTSD symptoms assessed after 1 year of exposure to police trauma	No mental health disorder during initial assessment	B	- No differences in resting (i.e., general) startle - After accounting for age, general psychiatric distress, and prior trauma exposure, startle reactivity during threat of shock with electrodes attached, but no imminent shock (i.e., medium threat), was a significant predictor of PTSD symptoms
	Jovanovic, Norrholm, Fennell, et al. (2009)	Startle in conditioning paradigm using safe and threat cues	CAPS and SCID	27 PTSD - subjects divided into high and low PTSD symptom groups; 28 controls	Comorbid MD and SA present but details not noted; BP excluded	D	- No differences in FPS among groups - High symptom PTSD group did not show fear inhibition to threat cue when paired with safe cue like low symptom PTSD group and controls
							- This effect mostly due to re-experiencing and avoidance symptoms, but not hyperarousal symptoms
							- Medication use had no effect on results
	Grillon et al. (in press)	Startle during anticipation of aversive stimuli	SCID and for PTSD patients, CAPS	16 PTSD; 18 GAD; 34 controls	PTSD patients: 4 current MD; 2 past MD; 2 past SA GAD patients: 3 SO; 1 current MD; 1 past SA; 1 SP	B	- No differences in FPS (i.e., startle during cue – cue-free periods) among groups - Context-potentiated startle greater in PTSD (i.e., startle during unpredictable periods > predictable > neutral)
							Controls and GAD: - Context-potentiated startle during predictable periods > unpredictable & > neutral
Studies using affect-modulated startle paradigms	Cuthbert et al. (2003)	Startle during imagery	ADIS-R	28 SP; 30 SO; 26 PD w/ AGO; 22 PTSD; 24 controls	26% SO; 17% SP; 27% GAD; comorbid mood disorder (MD or DYS) lowest for SP (11%) and highest for PD (42%) and PTSD (55%)	D	- General startle (startle during inter-trial intervals) in PTSD > SP, SO, and controls - Lack of FPS (startle during imagery) in PTSD - Startle pattern similar to PD - Medication use had no effect on results
	Miller and Litz (2004)	Affect picture-startle paradigm interspersed with shock stressor and trauma stressor	CAPS	35 veterans with PTSD; 24 combat controls	None noted	C	- No differences in resting (i.e., general) startle - Startle before trauma stressor similar in all groups - However, after trauma stressor, greater startle to unpleasant pictures for PTSD group

Note:

Under Diagnostic Instruments: ADIS-R = Anxiety Disorders Interview Schedule–Revised; CAPS = Clinician Administered PTSD Scale; LASC = Los Angeles Symptom Checklist; MS-PV = Mississippi Scale – Police Version; PTSDCL = PTSD Symptom Checklist; SCID = Structured Clinical Interview for DSM-IV axis I disorders; SCID-R = Structured Clinical Interview for DSM-III-R

Under Comorbid Diagnosis: AA = Alcohol Abuse/Dependence; AGO = Agoraphobia; ASPD = Antisocial Personality Disorder; BP = Bipolar Disorder; DYS = Dysthymia = DYS; GAD = Generalized Anxiety Disorder; MD = Major depression; OCD = Obsessive Compulsive Disorder; PD = Panic Disorder; PTSD = Post-traumatic stress disorder; SA = Substance Abuse/Dependence; SO = Social Phobia; SP = Specific Phobia

Under Key Result(s): FPS = Fear-Potentiated Startle

^*

Medication use was classified as follows:

• A = None noted
• B = Medication-free
• C = Medication use specified, but effect of medication not assessed
• D = Medication use specified and effect of medication assessed

Medication usage varied widely and included multiple classes of drugs such as anti-anxiety, antidepressant, and neuroleptic medication. For the sake of simplicity, we treated all classes of drugs the same and collapsed them into a generic medication category. Additionally, some studies also noted subjects stopping medication use for some arbitrary period prior to the experiment (e.g., 2 weeks, 4 weeks, etc.). In such cases, we elected to classify these subjects as “medication-free” for the purposes of that particular study.