De Novo Fear Conditioning Across Diagnostic Groups in the Affective Disorders: Evidence for Learning Impairments

doi:10.1016/j.beth.2013.12.012

Behavior Therapy

Volume 45, Issue 5, September 2014, Pages 619-629

https://doi.org/10.1016/j.beth.2013.12.012 Get rights and content

Highlights

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We assess fear conditioning in controls and patients with depression, PTSD, or panic
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Fear conditioning was attenuated in those with PTSD or depression
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Effect sizes suggest slower extinction among patients, particularly those with panic
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We discuss results in context of cognitive deficits common to anxiety and mood disorders

Abstract

De novo fear conditioning paradigms have served as a model for how clinical anxiety may be acquired and maintained. To further examine variable findings in the acquisition and extinction of fear responses between clinical and nonclinical samples, we assessed de novo fear conditioning outcomes in outpatients with either anxiety disorders or depression and healthy subjects recruited from the community. Overall, we found evidence for attenuated fear conditioning, as measured by skin conductance, among the patient sample, with significantly lower fear acquisition among patients with depression and posttraumatic stress disorder. These acquisition deficits were evident in both the simple (considering the CS+ only) and differential (evaluating the CS+ in relation to the CS-) paradigms. Examination of extinction outcomes were hampered by the low numbers of patients who achieved adequate conditioning, but the available data indicated slower extinction among the patient, primarily panic disorder, sample. Results are interpreted in the context of the cognitive deficits that are common to the anxiety and mood disorders, with attention to a range of potential factors, including mood comorbidity, higher-and lower-order cognitive processes and deficits, and medication use, that may modulate outcomes in fear conditioning studies, and, potentially, in exposure-based cognitive behavioral therapy.

Section snippets

Participants

A total of 168 participants (88 females), ages 18 to 64 years, were enrolled in the study. The sample included 102 healthy controls (HC) with no history of mood disorder, and 66 treatment-seeking participants with anxiety and mood disorders. In the clinical sample, participants met DSM-IV criteria as determined by the Structured Clinical Interview for DSM-IV (SCID-IV; First, Spitzer, Gibbon, & Williams, 1995) for a current primary diagnosis of either (a) posttraumatic stress disorder (PTSD; n =

Preliminary analyses

Demographic information is presented in Table 1. We examined potential differences among groups for relevant demographic characteristics, including age, sex, ethnicity, and race. A significant difference emerged for age, F(3, 140) = 8.23, p = .00, with post-hoc Tukey’s tests showing that the depression and PTSD groups had a significantly higher mean age than controls (p < .01). In addition, the groups differed significantly in sex distribution, χ² (3, n = 146) = 8.36, p = .04, with a higher proportion of

Discussion

The current study offers two particular contributions to the de novo fear conditioning literature. First, this was a particularly large study, with statistical analysis of 96 healthy controls and 55 treatment-seeking patients with anxiety and mood disorders. This compares well to the average total sample size of 47 in the fear acquisition studies reviewed by Lissek et al. (2005). Second, in the current study, we provide the first published data, to our knowledge, on simple and differential

Conflict of Interest Statement

The authors are aware of no conflicts with the content of this manuscript; nonetheless, in the past 2 years, Dr. Otto has received consulting income from MicroTransponder Inc., ProPhase, and Concert Pharmaceuticals, as well as royalties for the use of the SIGH-A from ProPhase. Dr. Simon reports past 2 years research support from American Foundation for Suicide Prevention, Forest Laboratories, NIMH, DOD, honoraria from the MGH Psychiatry Academy and spousal equity in Elan, Dandreon, G Zero and

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That is, supporting differences in affective processing, and in direct contrast to anxiety, research so far has shown that patients suffering from depression show enhanced extinction learning as compared to healthy controls (Kuhn et al., 2014), as well as better differential acquisition of fear responses towards the CS+ (Nissen et al., 2010), probably mediated by less pronounced deficits in safety learning (i.e.,less pronounced fear responses toward the CS- see Jovanovic et al., 2010). Notably, there are also reports showing contrary (Otto et al., 2014), or null findings (Dibbets, van den Broek, & Evers, 2015). Furthermore, previous studies mostly rely on comparably small sample sizes (i.e. ranging from n = 13 to n = 37 patients per diagnostic group).
In the current study, we test for the specificity of deficits in fear acquisition and extinction for the anxiety disorders spectrum. We compared fear acquisition and fear extinction learning between a group of patients with either an anxiety disorder (n = 93) or depression (n = 103) attending for treatment in our outpatient center and a sample of healthy control participants (n = 60). To assess the specificity of the predictive validity of extinction learning and safety learning for the outcome of exposure-based treatments, patients additionally underwent disorder-specific cognitive behavior therapy (CBT). We found only very little evidence for differences in safety or extinction learning between healthy controls and patients with anxiety-disorders or depression using both a group-based categorical analytic approach, as well as a trans-diagnostic, dimensional analytic approach. On the contrary, for anxiety patients only, more favorable extinction learning and more favorable safety learning was associated with more favorable treatment outcome. In sum, this specific prediction of treatment outcome in anxiety patients confirms and extends current theoretical models of exposure-based treatments for anxiety disorders, but does not support the notion of general extinction learning deficits in the anxiety disorders spectrum.
Skin conductance levels and responses in Asian and White participants during fear conditioning<sup>✰</sup>
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Fear conditioning paradigms are frequently used in the translational study of anxiety and fear-related disorders. Accordingly, it is important to understand whether the measurement of fear conditioning responses is systematically influenced by an individual's race. Studies have found increased pain sensitivity and smaller physiological startle responses in Asian individuals, compared to White individuals; to our knowledge, no studies have evaluated whether skin conductance response (SCR) outcomes differ between Asian and White individuals. In a series of secondary data analyses, we investigated potential differences in skin conductance level (SCL), orienting SCR, unconditioned SCR, SCR to CS+ and CS-, differential SCR, and differential SCR non-responder status. In sample 1, Asian participants (n = 97) demonstrated a significantly smaller mean differential SCR compared to White participants (n = 86). No other between group differences were observed. In sample 2, there was no difference in mean differential SCR between Asian (n = 52) and White (n = 62) participants, although more Asian participants failed to show adequate skin conductance levels for study entry. To our knowledge, this is the first study to evaluate differences between Asian and White samples using skin conductance outcomes in a fear conditioning paradigm. We detected only subtle evidence for SCR differences between Asian and White samples, unlikely to reach significance outside large studies.
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Therefore, based on the extant evidence from neuroimaging studies, the role of amygdala in human fear learning remains uncertain. Dysfunction in fear learning is considered to contribute to the development and maintenance of numerous psychiatric disorders, including not only anxiety disorders and posttraumatic stress disorder (Otto et al., 2014; Milad et al., 2014; Duits et al., 2015; Wicking et al., 2016), but also depression (Jovanovic et al., 2010; Sandi and Richter-Levin, 2009), borderline personality disorder (Krause-Utz et al., 2016), schizophrenia (Holt et al., 2012), and bipolar disorder (Acheson et al., 2015). Therefore, assessment of fear learning has become a pertinent approach to assessment and treatment of transdiagnostic psychopathology.
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Laboratory experiments using fear conditioning and extinction protocols help lay the groundwork for designing, testing, and optimizing innovative treatments for anxiety-related disorders. Yet, there is limited basic research on fear conditioning and extinction in obsessive-compulsive disorder (OCD). This is surprising because exposure-based treatments based on associative learning principles are among the most popular and effective treatment options for OCD. Here, we systematically review and critically assess existing aversive conditioning and extinction studies of OCD. Across 12 studies, there was moderate evidence that OCD is associated with abnormal acquisition of conditioned responses that differ from comparison groups. There was relatively stronger evidence of OCD’s association with impaired extinction processes. This included multiple studies finding elevated conditioned responses during extinction learning and poorer threat/safety discrimination during recall, although a minority of studies yielded results inconsistent with this conclusion. Overall, the conditioning model holds value for OCD research, but more work is necessary to clarify emerging patterns of results and increase clinical translational utility to the level seen in other anxiety-related disorders. We detail limitations in the literature and suggest next steps, including modeling OCD with more complex conditioning methodology (e.g., semantic/conceptual generalization, avoidance) and improving individual-differences assessment with dimensional techniques.
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^☆: This research was supported by a NIMH translational research grant (MH072165) to the first author. The funding source had no other role other than financial support.

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De Novo Fear Conditioning Across Diagnostic Groups in the Affective Disorders: Evidence for Learning Impairments☆

Highlights

Abstract

Section snippets

Participants

Preliminary analyses

Discussion

Conflict of Interest Statement

Journal of Psychiatric Research

Behaviour Research & Therapy

Journal of Affective Disorders

Biological Psychiatry

American Journal of Geriatric Psychiatry

Journal of Affective Disorders

Journal of Affective Disorders

Biological Psychiatry

Biological Psychiatry

Biological Psychiatry

Biological Psychiatry

Journal of Psychiatric Research

European Psychiatry

Behavioural Brain Research

Journal of Affective Disorders

Behavour Research and Therapy

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Biological Psychiatry

Personality and Individual Differences

Journal of Affective Disorders