Phobic Fear Research Articles

Altered Functional Coupling of the Bed Nucleus of the Stria Terminalis and Amygdala in Spider Phobic Fear.

Background: Individuals with spider phobic (SP) fear show hypervigilance and amygdala hyperactivity toward fear-associated stimuli, which may promote the development of other anxiety disorders. The amygdala is a key region within the fear network, which is connected to the anxiety system, where the bed nucleus of the stria terminalis (BNST) plays a crucial role. However, the BNST's involvement in phobic fear is unknown. Therefore, this study investigated the association of phobic fear and anxiety on these regions' functional connectivity (FC) in SP compared to healthy controls (HC). Methods: 7T-functional MRI resting-state FC of 30 individuals with SP and 45 HC was assessed to detect network differences between these groups. The association of phobic fear severity, trait anxiety, and social anxiety on FC was explored using linear regressions combined with seed-to-voxel analyses with amygdala and BNST as primary seeds, corrected for age and sex. Results: In SP, phobic fear was associated with reduced FC between the left amygdala and the right supramarginal gyrus. In contrast, anxiety severity was related to increased FC between the right BNST and the left inferior frontal gyrus. Moreover, social anxiety was related to decreased FC between bilateral BNST and left precuneus. Conclusions: These findings show changes in FC in SP, connecting fear with altered activity in the BNST and amygdala. The results suggest that persistent anxiety in phobic fear is associated with abnormal brain function in these regions, potentially explaining susceptibility to anxiety disorders and processes involved in phobic fear, such as threat perception, avoidance, and salience. Impact statement This is the first study to report altered FC mechanisms of BNST and amygdala in individuals with SP using 7T ultra-high field resting-state data. So far, only distinct characterization of brain regions, especially of BNST and amygdala, involved in those disorders exists. Our results contribute to closing this knowledge gap by providing the first evidence that deviant BNST and amygdala function in SP might elucidate the susceptibility to other anxiety disorders.

Extensive functional connectivity between brain areas implicated in mental imagery production and phobic fear during both emotional and neutral mental imagery

Mental imagery is used by most people in their day-to-day cognition, for example, in planning, daydreaming, or remembering. Importantly, mental imagery has a powerful influence on emotion and is critically involved in many mental disorders. Thus, understanding the link between mental imagery and emotion is of clinical interest. For example, exposure therapy can be successfully conducted using mental imagery of fear-provoking stimuli, i.e., imaginal exposure. In this vein, accumulating evidence shows that mental imagery of a fearful stimulus produces a similar physiological and neural response as actual perception of the stimulus. Alas, knowledge of the neural processes underlying the link between mental imagery and emotion is limited. Functional magnetic resonance imaging data from a previous study on imaginal exposure (N = 30) was used to examine the functional connectivity during the production of phobic and neutral mental imagery. Regions of interest were selected from meta-analyses on brain regions consistently recruited during mental imagery production and phobic fear, respectively. Results showed that these regions were positively correlated during both phobic and neutral mental imagery production. Very few differences in functional connectivity between phobic and neutral imagery were found. Specifically, weaker functional connectivity between the supplemental motor area and a region including parts of the left insula and inferior frontal gyrus was observed during phobic (vs neutral) imagery. In conclusion, our findings suggest that brain regions previously implicated in mental imagery production and phobic fear are highly interconnected during the production of both phobic and neutral imagery.

DNA methylation levels of the serotonin transporter gene are not associated with the outcome of highly standardized one-session exposure-based fear treatment

Epigenetic alterations are regarded as a potential mechanism mediating the effects of environmental risk factors on vulnerability for a range of mental health problems. Recent studies have addressed the question whether DNA methylation patterns predict the outcome of psychological interventions and whether treatment effects might be associated with changes of DNA methylation. We assessed phobic fear symptoms, treatment-relevant traits and treatment response in 308 adults free of psychotropic medication - highly fearful of either spiders, blood-injury-injections, dental-treatments or heights - all subjected to highly standardized exposure-based one-session fear treatment. DNA methylation level of the promotor region of the serotonin transporter gene (SLC6A4) was assessed in either saliva samples (spider and dental treatment fear cohorts) or oral mucosa (BII, heights) to check whether possible effects are independent of the surrogate tissue examined. Moreover, in order to examine possible DNA methylation by genotype effects, patients were assessed for genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR). DNA methylation levels were neither associated with pre-treatment fear levels, treatment relevant traits or treatment outcome data even when allelic variation of the 5HTTLPR was considered. Overall DNA methylation levels were higher in saliva samples compared to buccal samples. In saliva samples there was a small pre- to post-treatment increase in DNA methylation, which, however, was also not associated with the investigated phenotypes. We conclude that DNA methylation of SLC6A4 is no suitable biomarker for response efficacy to highly standardized one-session exposure-based fear treatments.

Guided reactivation of personal phobic memories prior to exposure exercises prevents the renewal of fear responses in subjects with claustrophobic fears

Background and objectivesBasic research suggest behavioral strategies for interferencing the reconsolidation of fear memories to be a promising approach in reducing clinical fears. However, first clinical studies revealed mixed results highlighting the need to identify boundary conditions. We experimentally tested the specific hypothesis that post-retrieval threat exposure prevents context renewal usually observed in protocols without fear memory reactivation. MethodsIn a preliminary investigation forty-three individuals with claustrophobic fears reactivated the individual phobic memory or not during a guided emotional imagery task and then performed standardized threat exposure to provide new information for updating the original memory. During retests seven and 28 days later, the context was different from that during treatment in half of the subjects. ResultsIn those who were guided, the fear memory was successfully reactivated as indexed by increased skin conductance level (SCL) during the imagery of personal scenes relative to neutral scenes. During retests the subjects of the memory non-activation group showed a return of reported fear after context change that, however, was not observed after post-retrieval exposure. In line, autonomic arousal (SCL) decreased over time in the memory reactivation group only if the context changed during retest. LimitationsLimited sample size and the inclusion of an analog sample reduce the generalizability of the results. ConclusionsThe reactivation of fear memory prior to treatment through guided imagery of past personal phobic situations prevented contextual renewal of phobic fears which was observed in those subjects without reactivation of memory.

Children’s perception of phobogenic stimuli in virtual reality

There has been a growing interest in treatments involving exposure in virtual reality (VR) for a number of anxiety disorders and phobias. Contrary to expectations, this technique has proven less popular with phobic children and is less appealing to them than to adults. The hypothesis is that children may be more apprehensive about virtual aversive stimuli than adults. In Study 1, the perception of virtual phobogenic stimuli was assessed in 523 participants between the ages of 7 and 60. To analyze to what extent anxiety and phobic fear predict apprehension, 38 school-aged children took part in Study 2. The results show that children apprehend phobic virtual stimulus more than adults and that apprehension is associated with specific phobic fear rather than a general anxiety state. Results are discussed in terms of clinical interest, children’s cognitive development, and a priori fear of virtual reality stimuli. • Virtual reality to treat phobias is not always attracting for children. • Children and adolescents showed more apprehension than adults toward virtual spiders. • Apprehension is specifically associated with the intensity of phobic fears. • It is important to address people’s apprehension when proposing to use VR in therapy.

Treating specific phobia fear of injury through narrative therapy post-release: A clinical case study

ABSTRACT There are an estimated 2.2 million people incarcerated in the United States and many suffer from mental illness. Specific phobia, fear of injury affects 7–9% of adults and 75% of those with specific phobia fear more than one situation or object. Specific phobia consists of fear and anxiety or frequent avoidance of an item or situation that leads to significant distress or impairment. Narrative therapy allows individuals to deconstruct their problematic stories and create a more preferred narrative. Narrative concepts of empowerment and resilience enable clients to change their lives. A case study displayed potential efficacy in utilizing narrative therapy with an individual post-release living with a fear of injury. Clinical implications and future directions are provided to expand on this necessary work.

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry.

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency, while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: (a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders and (b) previously underreported behavioral traits.

Genes in treatment: Polygenic risk scores for different psychopathologies, neuroticism, educational attainment and IQ and the outcome of two different exposure-based fear treatments

Objectives Evidence for a genetic influence on psychological treatment outcome so far has been inconsistent, likely due to the focus on candidate genes and the heterogeneity of the disorders treated. Using polygenic risk scores (PRS) in homogenous patient samples may increase the chance of detecting genetic influences. Methods A sample of 342 phobic patients treated either for clinically relevant dental fear (n = 189) or other (mixed) phobic fears (n = 153) underwent highly standardised exposure-based CBT. A brief five-session format was used to treat dental fear, whereas longer multi-session treatments were used with the mixed-fear cohort. PRS were calculated based on large genetic studies of Neuroticism, Educational Attainment (EA), Intelligence, and four psychopathology domains. We compared PRS of post-treatment and follow-up remitters and non-remitters and regressed PRS on fear reduction percentages. Results In the dental fear cohort, EA PRS were associated with treatment outcomes, i.e. drop-out, short- and long-term remission state, fear reduction, and attendance of subsequent dental appointments. In the mixed fear treatment cohort, no gene effects were observable. Conclusions Results indicate the importance of EA-related traits for outcomes following brief, but not long, standardised exposure-based CBT. Such use of PRS may help inform selection and tailoring of treatments.

КЛИНИЧЕСКАЯ ВАЛИДИЗАЦИЯ ШКАЛ ЭКСПАНСИВНОСТИ,ОГРАНИЧИТЕЛЬНОГО КОНТРОЛЯ, КОРРЕКЦИИ, ФОБИЧЕСКИХСТРАХОВ МОДИФИЦИРОВАННОГО ВАРИАНТА ОПРОСНИКАНЕВРОТИЧЕСКИХ РАССТРОЙСТВ

Background. On the basis of the statements of the questionnaire of neurotic disorders within the framework of the Rush model, which is a kind of modern test theory, 13 scales with proven psychometric properties were formed. This article evaluates the clinical effectiveness of four of them. Purpose of the study. To carry out clinical validation of scales of expansiveness, restrictive control, correction and phobic fears of the modified version of the neurotic disorders questionnaire. Material and methods. A total of 296 people were examined, among them 167 women and 129 men. Statistical methods of research included factor analysis of standardized residuals, ROC-analysis, and correlation analysis. Results. The scales under study have a homogeneous structure. With the help of ROC-analysis, moderate differentiating properties of the scales were revealed, and cutoff values were calculated, which were the criteria for interpretation. Correlation analysis of the total indicator revealed statistically significant correlations between the studied scales and the MMPI scores, the QIDS-SR16 questionnaire and the Hamilton Anxiety Rating Scale (HADS). Conclusions. The scales of expansiveness, restrictive control, correction and phobic fears of the modified version of the neurotic disorders questionnaire are clinically valid and can be used to solve various practical problems.

Exploring the neural basis of fear produced by mental imagery: imaginal exposure in individuals fearful of spiders.

Imaginal exposure, i.e. reducing fear using exposure to mental imagery, is a widely used psychological treatment technique for dysfunctional fears. Yet, little is known about its underlying neural mechanisms. The present study examines the neural basis of imaginal exposure using a novel experimental procedure consisting of repeated exposure to flashpoint mental imagery of phobic (spiders) and neutral (gloves) stimuli. Whether the 10 min long imaginal exposure procedure could reduce fear responses was examined one week later. Thirty participants fearful of spiders underwent the experimental procedure. Neural activity was assessed using functional magnetic resonance imaging (session 1). Subjective fear and skin conductance responses were measured throughout the study (sessions 1 and 2). Imaginal exposure evoked intense fear and heightened skin conductance responses, and indicated robust activation in several brain regions, including amygdala, midcingulate cortex and insula. Findings demonstrate that neural activity in fear-processing brain areas can be elicited solely by generating a mental image of a phobic stimulus, that is, in the absence of the percept. Relevant for treatment development, results reveal that a single 10 min session of brief exposures to flashpoint mental imagery can lead to lasting reductions in phobic fear at both the subjective and physiological levels. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.

A topography of 21 phobic fears: network analysis in an epidemiological sample of adult twins.

Few factor analyses and no network analyses have examined the structure of DSM phobic fears or tested the specificity of the relationship between panic disorder and agoraphobic fears. Histories of 21 lifetime phobic fears, coded as four-level ordinal variables (no fear to fear with major interference) were assessed at personal interview in 7514 adults from the Virginia Twin Registry. We estimated Gaussian Graphical Models on individual phobic fears; compared network structures of women and men using the Network Comparison Test; used community detection to determine the number and nature of groups in which phobic fears hang together; and validated the anticipated specific relationship between panic disorder and agoraphobia. All networks were densely and positively inter-connected; networks of women and men were structurally similar. Our most frequent and stable solution identified four phobic clusters: (i) blood-injection, (ii) social-agoraphobia, (iii) situational, and (iv) animal-disease. Fear of public restrooms and of diseases clustered with animal and not, respectively, social and blood-injury phobias. When added to the network, the three strongest connections with lifetime panic disorder were all agoraphobic fears: being in crowds, going out of the house alone, and being in open spaces. Using network analyses applied to a large epidemiologic twin sample, we broadly validated the DSM-IV typography but did not entirely support the distinction of agoraphobic and social phobic fears or the DSM placements for fears of public restrooms and diseases. We found strong support for the specificity of the relationship between panic disorder and agoraphobic fears.

Large-group one-session treatment: Feasibility and efficacy in 138 individuals with phobic fear of flying

Recent research suggests that exposure-based large-group one-session treatments (LG-OSTs) may represent useful and efficient treatment options for different types of phobic fear. Although there are effective single session- and small group-interventions for the treatment of clinically relevant Fear of Flying (FoF), no LG-OST for this type of phobic fear has been realized so far. The present study aimed to investigate feasibility and efficacy of an LG-OST for the treatment of clinically relevant FoF. Two months after an initial diagnostics to assess FoF severity and confirm the underlying diagnoses (89% specific flight phobia; 10% agoraphobia), 138 patients attended the LG-OST consisting of psychoeducation, imparting of a breathing technique and a joint 2 ½ hour exposure flight in a chartered airplane (Airbus A320). FoF again was assessed at pre- and post-treatment as well as at 6-months follow-up with the latter again containing clinical diagnostics. Only a small decrease in FoF emerged in the pre-treatment interval. From pre-to post-treatment however, substantial reductions in FoF were observed with a large mean ‘intention-to-treat’ effect size of Cohen's d = 1.42 that remained stable over time (mean d = 1.44). At follow-up, 71% of the patients were rated as fully (55%) or partially remitted (16%). Also concerning the treatment of clinically relevant FoF, a LG-OST proved feasible and effective. Therefore, LG-OST can be regarded as a highly efficient and promising treatment tool which in terms of efficiency combines the advantages of one-session individual and group treatments.

Üniversite Öğrencilerinde Nomofobi ve Sosyal Anksiyete Düzeylerinin Karşılaştırılması

Objectives: The aim of this study is to determine and compare the nomophobia and social anxiety levels of university students.Method: The descriptive and cross-sectional study was carried out between April and June 2017 at Ataturk University. 703 university students who used smartphones and agreed to participate in the study were included in it. Personal Information Form, Nomophobia Scale and the Liebowitz Social Anxiety Scale were used for data collection. Before starting the study, it received the ethics committee approval and written permission in which the study was carried out. Data were analysed using SPSS 20.0 package program.Findings: 78.38% of the students were female, 21.62% were male and 54.62% were 1st-grade students. 31.86% of students reported using smartphones over 5 years and 8.25% reported using smartphones for the last one year. It was determined that students’ general weighted grade point average was 2.57±0.68 and 75.28±25.38 points from Nomophobia Scale, 50.68±12.67 scores from social phobic fear subscale of the Liebowitz Social Anxiety Scale, and 50.00±13.89 from social phobic avoidance subscale. A statistically significant positive correlation was found between the total scores of the Nomophobia Scale and the Liebowitz Social Anxiety Scale r=0.195, p

Reducing Amygdala Activity and Phobic Fear through Cognitive Top-Down Regulation.

The amygdala is critically involved in emotional processing, including fear responses, and shows hyperactivity in anxiety disorders. Previous research in healthy participants has indicated that amygdala activity is down-regulated by cognitively demanding tasks that engage the PFC. It is unknown, however, if such an acute down-regulation of amygdala activity might correlate with reduced fear in anxious participants. In an fMRI study of 43 participants (11 men) with fear of snakes, we found reduced amygdala activity when visual stimuli were processed under high cognitive load, irrespective of whether the stimuli were of neutral or phobic content. Furthermore, dynamic causal modeling revealed that this general reduction in amygdala activity was partially mediated by a load-dependent increase in dorsolateral PFC activity. Importantly, high cognitive load also resulted in an acute decrease in perceived phobic fear while viewing the fearful stimuli. In conclusion, our data indicate that a cognitively demanding task results in a top-down regulation of amygdala activity and an acute reduction of fear in phobic participants. These findings may inspire the development of novel psychological intervention approaches aimed at reducing fear in anxiety disorders.

Glucocorticoids and cortical decoding in the phobic brain

Glucocorticoids reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories and enhancing the consolidation of new corrective memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory-related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example, visual-temporal pathways; however, these analyses were limited to a-priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We reanalyzed functional magnetic resonance imaging (fMRI) data from a previously published study with spider-phobic patients and healthy controls. The patients received glucocorticoids or a placebo before the exposure to spider images. There was moderate evidence that patients with phobia had higher decoding of phobic content in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed strong evidence for correlation with experienced fear. Patients with cortisol reported a reduction of fear by 10–13%; however, there was only weak evidence for changes in neural decoding compared to placebo which was found in the precuneus, the opercular cortex, and the left cerebellum.

Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder

BackgroundIn rodents, context specificity of Pavlovian extinction is attenuated by manipulations that impair hippocampal function, including systemic administration of scopolamine, a muscarinic-cholinergic receptor antagonist. Context renewal translates into return of fear following exposure therapy to feared situations. We evaluated the effectiveness of scopolamine for attenuating context renewal of phobic fear in humans. MethodsA total of 60 participants (35 female, 22 male, 1 transgender, 2 undeclared) with social anxiety disorder and fear of public speaking were randomized to placebo, 0.5 mg scopolamine, or 0.6 mg scopolamine. They completed seven exposure sessions in an exposure context and subsequently tested in the exposure context (extinction retest) versus a different context (context renewal test), which were counterbalanced. Testing 1 month later occurred in the exposure context (long-term extinction retest). Fear measures included skin conductance and self-reported distress during speeches. Hippocampus-dependent cognitive tasks were completed as well. ResultsScopolamine augmented extinction across exposure sessions on skin conductance response and skin conductance level. Lower skin conductance response at context renewal in scopolamine groups relative to the placebo group was constrained to simple effects and complicated by unexpected outcomes within placebo and on self-reported fear. Scopolamine led to lower skin conductance response at long-term extinction retest. Scopolamine impaired performance on a cognitive task of hippocampal function. ConclusionsNoninvasive and well-tolerated scopolamine impaired hippocampal processes and augmented extinction during exposure. Drug-free effects persisted 1 month later. Findings at context renewal were limited and suggestive only. Further investigation is warranted with varying scopolamine dosages.

Subscales of the Fear Survey Schedule-III in Community Dwelling Older Adults – Relations to Clinical and Cognitive Measures

ABSTRACTObjectives: One major obstacle to the diagnosis and treatment of specific phobias in later life is the lack of assessment tools that are relevant to the fears of older adults. This study investigated the utility of five reliable subscales (Blood/Injury, Agoraphobia, Aggression, Animal/Insect, Social Fears) derived from the Fear Survey Schedule-III, a popular measure of phobic fear, in discriminating older from younger participants.Method: The sample was comprised of 81 younger and 61 older adults who completed self-report measures of anxiety and depression and neuropsychological tests.Results: Older adults scored significantly higher than their younger counterparts only on the Aggression subscale of the FSS-III; whereas younger adults scored significantly higher than the older group only on the Social Fears subscale. These subscales showed slightly different associations with other measures of anxiety, depression, and intelligence across age groups. Within the older sample, scores on the Aggression subscale were significantly higher than all other subscales except for Social Fears.Conclusions: It is recommended that clinicians and researchers use subscale scores derived from the FSS-III, rather than total scores, when treating and studying fears of later life.Clinical Implications: Use of FSS-III subscales in assessment could result in improved detection and treatment of phobias in later life, and thus raise quality of life among the elderly. Older adults’ fears of victimization should be prioritized as a possible treatment target in clinical settings.

Height Simulation in a Virtual Reality CAVE System: Validity of Fear Responses and Effects of an Immersion Manipulation.

Acrophobia is characterized by intense fear in height situations. Virtual reality (VR) can be used to trigger such phobic fear, and VR exposure therapy (VRET) has proven effective for treatment of phobias, although it remains important to further elucidate factors that modulate and mediate the fear responses triggered in VR. The present study assessed verbal and behavioral fear responses triggered by a height simulation in a 5-sided cave automatic virtual environment (CAVE) with visual and acoustic simulation and further investigated how fear responses are modulated by immersion, i.e., an additional wind simulation, and presence, i.e., the feeling to be present in the VE. Results revealed a high validity for the CAVE and VE in provoking height related self-reported fear and avoidance behavior in accordance with a trait measure of acrophobic fear. Increasing immersion significantly increased fear responses in high height anxious (HHA) participants, but did not affect presence. Nevertheless, presence was found to be an important predictor of fear responses. We conclude that a CAVE system can be used to elicit valid fear responses, which might be further enhanced by immersion manipulations independent from presence. These results may help to improve VRET efficacy and its transfer to real situations.

Glucocorticoid administration restores salience network activity in patients with spider phobia.

Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls. Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.

Mechanisms, genes and treatment: Experimental fear conditioning, the serotonin transporter gene, and the outcome of a highly standardized exposure-based fear treatment

There is considerable interindividual variation in response to psychotherapeutical intervention. In order to realize the long-term goal of personalised treatment approaches, it is important to identify behavioural and biological moderators and mediators of treatment responses. Here, we tested the predictive value of experimental fear extinction efficacy as well as the role of genetic variation of the serotonin transporter gene for the outcome of a fear-exposure treatment. A discriminative fear conditioning paradigm was conducted in 159 adults highly fearful of spiders, dental surgeries or blood, injuries and injections. Participants were genotyped for the long (L) and short (S) allelic variant of the serotonin transporter gene linked polymorphic region (5HTTLPR) and treated with a highly standardized exposure-based one-session treatment. Participants' subjective fear was assessed during experimental fear conditioning and extinction. Furthermore, subjective phobic fear was assessed at pre-, post and at 7 months follow-up treatment assessment. A threat-biased contingency learning pattern characterized by exaggerated fear responses to the CS− was associated with larger initial subjective fear reduction immediately following the large-group treatment, p = .03. There were no learning pattern-associated differences in subjective fear at 7-month follow-up. The odds of homozygous s-allele carriers to display a threat-biased contingency learning pattern were 3.85 times larger compared to l-allele carriers, p = .01. Fear-recovery in homozygous S-allele carriers at follow-up assessment, p = .01, emerged regardless of the experimental fear acquisition pattern. Our results suggest the homozygous S-allele carriers are biologically biased towards ignoring safety signals in threat-related situations. Short-term, this response pattern might be positively related to the outcome of exposure treatments, potentially due to increased responding to safe context conditions or a stronger violation of threat expectancies. However, alterations in inhibiting the response to cues formerly signalling threat evidenced for S-allele carriers can have negative impact on exposure success.