Table 1.

Summary of studies examining affect-modulated startle reactivity in various internalizing disorders except PTSD.

Category	Study	Experimental Paradigm	Diagnostic Instrument	Subjects	Comorbid Diagnosis?	Medication*	Key result(s)
Phobias	Vrana et al. (1992)	Startle during imagery; pre- and post-treatment assessments	DSM-IIIR	2 SP	None noted	A	Reduced FPS after treatment
	de Jong et al. (1991)	Startle during live exposure; pre- and post-treatment assessments	Spider Questionnaire	41 SP	None noted	A	Reduced FPS after treatment
	de Jong et al. (1996)	Startle during live exposure; pre- and post-treatment assessments	DSM-IV	20 SP	None noted	A	Reduced FPS after treatment
	Hamm et al. (1997)	Affective-picture startle paradigm	Snake, Spider, and Mutilation Questionnaire	48 SP 16 controls	None noted	A	FPS for phobic scenes: SP > Controls
	Globisch et al. (1999)	Affective-picture startle paradigm	Snake and Spider Questionnaire	38 SP; 48 controls	None noted	A	FPS for phobic scenes: SP > Controls
	McTeague et al. (2009)	Startle during imagery	ADIS-IV	75 SO; 75 controls	25 circumscribed SO; 50 generalized SO; 27 generalized SO with mood disorder; 4 circumscribed SO with mood disorder	D	- General startle reactivity greater for all patients than controls - Generalized SO group showed potentiation across all scenes - However, generalized SO and MD showed potentiation only for personalized fear scenes - Medication use had no effect on results
	de Jong et al. (1993)	Startle during live exposure; pre- and post-treatment assessments	Spider Questionnaire	37 SP	None noted	A	SP did not show valence-modulated startle
	Merckelbach et al. (1995)	Startle during backward-masked 30 ms slides	DSM-IIIR	17 SP; 12 controls	None noted	A	No differences in FPS between groups
Panic Disorder with or without Agoraphobia	Melzig et al. (2007)	Startle under adaptation, threat of shock, darkness and safe conditions	ADIS-IV	26 outpatients with PD; 22 controls	17 AGO; 11 MD; 3 SP; 1 SO; 1 somatoform	D	- PD with MD did not show threat-potentiated startle while PD alone did - Trend toward greater startle in PD alone than controls (p = .08) - PD using SSRIs showed greater startle during adaptation than all other subjects
	Cuthbert et al. (2003)	Startle during imagery	ADIS-R	28 SP; 30 SO; 26 PD w/ AGO; 22 PTSD; 24 controls; 3 past BP	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	- Startle potentiation in SP, SO and controls, but not in PD - PD trend toward larger general startle (startle during inter-trial intervals) than SP, SO and controls - Medication use had no effect on results
	Lang et al. (2007)	Startle during imagery	ADIS-IV	30 SP; 36 SO; 27 PD w/ AGO; 26 GAD; 40 controls	52% MD	D	- FPS: SP > SO > PD w/ AGO > GAD - Trait anxiety inversely related to FPS - Medication use had no effect on results
	Grillon et al. (2008)	Startle during anticipation of aversive stimuli	SCID-I	24 PD; 24 controls	5 SO; MD excluded	B	PD patients showed greater startle reactivity to intertrial interval probes in unpredictable aversive condition than neutral condition; Controls showed no such effect
	Grillon et al. (1994)	Startle during threat of shock	ADIS-R	34 PD; 49 controls	5 PD w/o AGO; 26 PD w/ AGO; 1 SO; 2 GAD	A	Younger patients (< 40 y.o.) with PD showed larger startle during threat periods; Older patients did not
Depression	Allen et al. (1999)	Affect-picture startle	SCID-R	14 inpatient with current MD; 14 nondepressed	Details not noted though article mentions subjects had other diagnoses	C	- General startle reactivity for MD less than controls - Severely MD subjects showed startle potentiation during pleasant pictures
	Dichter et al. (2004)	Affect-picture startle; assessed effect of Bupropion on startle	DSM-IV and Hamilton Rating Scale for Depression	14 outpatient MD; 16 nondepressed	3 with some anxiety disorder	D	- Valence-modulated startle absent in MD - Medication use had no effect on results
	Forbes et al. (2005)	Affect-picture startle	A variety of instruments using DSM-III, DSM-III-R, or DSM-IV criteria	38 MD; 38 BP; both groups had childhood-onset depression; 60 controls	68.4% (76.3% MD) with lifetime history of anxiety disorder, and 12.3% (5.6% MD) with ASPD	D	- MD showed blink inhibition during pleasant scenes relative to neutral, and no potentiation for unpleasant versus neutral scenes - Lack of startle modulation associated with history of repeated depressive episodes - Medication use had no effect on results
	Kaviani et al. (2004)	Affect-movie clips startle	DSM-IV	22 inpatients with MD; 22 controls	None noted	C	- Controls and low MD showed valence-modulated startle; high MD did not - Effect related to anhedonia scores
	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	- No differences in FPS for subjects with and without comorbid MD - However, greater general startle (startle during inter-trial intervals) for comorbid MD than without - Medication use had no effect on results
	Lang et al. (2007)	Startle during imagery	ADIS-IV	30 SP; 36 SO; 27 PD w/ AGO; 26 GAD; 40 controls	52% MD	D	- FPS in those with comorbid MD less than those without comorbid MD - Medication use had no effect on results
Other anxiety disorders	Kumari et al. (2001)	Affect-movie clips startle	DSM-IV	10 inpatient OCD; 10 controls	None noted	C	Increased general startle reactivity in OCD
	Buhlman et al. (2007)	Startle probe alone	SCID	20 outpatient OCD; 21 controls	4 SO; 3 body dysmorphic disorder; 2 MD; 2 DYS; 2 SP; 1 GAD; 1 PD w/ AGO; 1 trichotillomania	D	- Trend toward higher general startle reactivity in OCD (p = .07) - Unmedicated participants did not differ from controls
	Lang et al. (2007)	Startle during imagery	ADIS-IV	30 SP; 36 SO; 27 PD w/ AGO; 26 GAD; 40 controls	52% MD	D	- FPS: SP > SO > PD w/ AGO > GAD - Trait anxiety inversely related to FPS - Medication use had no effect on results
	Ray et al. (2009)	Startle probes during probes alone, tasks engaging ANS and attention, and relaxation and rumination/worr y periods	ADIS-IV	9 GAD; 9 controls	None noted	B	GAD showing greater general startle than controls across entire task except for probe alone period at beginning of task
	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 among groups PTSD patients: -Context-potentiated startle during unpredictable periods > predictable > neutral Controls and GAD: -Context-potentiated startle during predictable periods > unpredictable & > neutral

Note:

Under Diagnostic Instruments: ADIS-IV = Anxiety Disorder Interview Schedule for DSM-IV; ADIS-R = Anxiety Disorders Interview Schedule–Revised; 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.