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Etiological beliefs of depression have differing impacts on motivation, hope, and treatment expectations. However, it is unclear where people are exposed to these beliefs.

Cortical-subcortical hyperconnectivity related to affective-behavioral integration and cortical network hypoconnectivity related to cognitive control have been demonstrated in obsessive-compulsive disorder (OCD); the study objective was to examine whether these connectivity patterns predict treatment response.Adolescents (ages 12-17) and adults (ages 24-45) were randomly assigned to 12 sessions of exposure and response prevention (ERP) or stress management therapy (SMT), an active control. Before treatment, resting-state connectivity of ventromedial prefrontal cortical (vmPFC), cingulo-opercular, frontoparietal, and subcortical regions was assessed with functional MRI. OCD severity was assessed with the Yale-Brown Obsessive Compulsive Scale before, during, and after treatment. Usable fMRI and longitudinal symptom data were obtained from 116 patients (68 female; 54 adolescents; 60 medicated).ERP produced greater decreases in symptom scores than SMT. ERP was selectively associated with less vmPFC-subcortical (caudate and thalamus) connectivity in both age groups and primarily in unmedicated participants. Greater symptom improvement with both ERP and SMT was associated with greater cognitive-control (cingulo-opercular and frontoparietal) and subcortical (putamen) connectivity across age groups. Developmental specificity was observed across ERP and SMT treatments, such that greater improvements with ERP than SMT were associated with greater frontoparietal-subcortical (nucleus accumbens) connectivity in adolescents but greater connectivity between frontoparietal regions in adults. Comparison of response-predictive connections revealed no significant differences compared with a matched healthy control group.The results suggest that less vmPFC-subcortical connectivity related to affect-influenced behavior may be important for ERP engagement, whereas greater cognitive-control and motor circuit connectivity may generally facilitate response to psychotherapy. Finally, neural predictors of treatment response may differ by age.

Anxiety has been studied using EEG/ERP approaches for many years, and substantive effects have been observed across the frequency spectrum. This chapter introduces the reader to the wide variety of work that has been done examining associations between anxiety and oscillatory measures. It focuses particularly on the nature of the relationship between anxiety and oscillatory metrics reflecting motivational/emotional and cognitive control dynamics involved in balancing bottom-up and top-down influences on behavior. The chapter discusses these findings in the context of cognitive, affective, and motivational models of anxiety. Furthermore, it covers the approaches to indexing the processes relevant to those models.

Particular phases of the menstrual cycle may exacerbate affective symptoms for females with a diagnosed mental health disorder. However, there are mixed findings regarding whether affective symptoms change across the menstrual cycle in females without a clinical diagnosis. The window of vulnerability model proposes that natural increases in ovarian hormones in the mid-luteal phase of the menstrual cycle lead to systematic changes in brain networks associated with affective processing. Consequently, the model posits that females may experience stress more intensely and remember negative events more readily in the mid-luteal phase, increasing their risk for higher affective symptoms. Using a 35-day longitudinal study design, we tested the window of vulnerability model in a non-clinical sample. We tracked naturally cycling females' daily stress and three types of affective symptoms: anxious apprehension, anxious arousal, and anhedonic depression. Using multilevel modeling, we simultaneously modeled within- and between-person associations among stress and menstrual phase for each affective symptom. We found increased anhedonic depression in the mid-luteal phase but not anxious apprehension or anxious arousal. Moreover, we detected a positive association between within- and between-person stress and anxious apprehension and anhedonic depression, but not anxious arousal. These associations were not stronger in the mid-luteal phase. Overall, we provide weak evidence for a window of vulnerability for affective symptoms in the mid-luteal phase of the menstrual cycle. Our findings suggest that stress is a better predictor of fluctuations in affective symptoms than the menstrual cycle. Moreover, our findings highlight the importance of measuring multiple negative affective symptoms because they may be differentially related to stress and the menstrual cycle.

Background Obsessive compulsive disorder (OCD) is associated with elevated suicide risk, but the directionality of the association between OCD severity and suicidal ideation has not been established, which was the goal of this study. Methods Participants (n = 325) were adults with either a current or past diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) OCD who were assessed annually for suicidal ideation and OCD symptom severity for six years. Cross-lagged panel analyses statistically compared unidirectional and bidirectional models over time. Serious suicide-related adverse events were reported. Results The best-fitting and most parsimonious model included paths predicting suicidal ideation from OCD symptom severity, but not vice versa. These results were confirmed by comparing a model with cross-lagged paths constrained equal to a freely estimated model. Higher OCD symptom severity in a given year was associated with a higher suicidal ideation severity in the subsequent year. Five suicide-related adverse events were reported throughout the duration of the study, including two suicide deaths and three suicide attempts. Limitations The study relied on a single-item, annual measure of suicidal ideation in adults, with substantial variability in severity of suicide risk, and missing data increased with later observations in the study. Discussion OCD symptom severity predicted next year suicidal ideation severity. In contrast, suicidal ideation severity in a given year did not predict next-year OCD symptom severity in this OCD sample. Thus, rather than waiting for suicidal ideation to resolve, clinicians should consider providing empirically supported treatments for OCD.

Background Survival requires effective shifting of attention from one stimulus to another as goals change. It has been consistently demonstrated that posttraumatic stress disorder (PTSD) is associated with both faster orienting of attention toward and slower disengagement of attention from affective stimuli. Prior work, however, suggests that attention abnormalities in PTSD may extend beyond the affective domain. Methods We used the Attention Network Test—modified to include invalid spatial cues—in conjunction with functional magnetic resonance imaging to examine the neurocognitive underpinnings of visuospatial attention in participants with PTSD (n = 31) and control participants who were (n = 20) and were not (n = 21) exposed to trauma. Results We observed deficits in the utilization of spatial information in the group with PTSD. Specifically, compared with the non-trauma-exposed group, participants with PTSD showed a smaller reaction time difference between invalidly and validly cued targets, demonstrating that they were less likely to use spatial cues to inform subsequent behavior. We also found that in both the PTSD and trauma-exposed control groups, utilization of spatial information was positively associated with activation of attentional control regions (e.g., right precentral gyrus, inferior and middle frontal gyri) and negatively associated with activation in salience processing regions (e.g., right insula). Conclusions This pattern suggests that both trauma exposure and psychopathology may be associated with alterations of spatial attention. Overall, our findings suggest that both attention- and salience-network abnormalities may be related to altered attention in trauma-exposed populations. Treatments that target these neural networks could therefore be a new avenue for PTSD research.

Posttraumatic Stress Disorder (PTSD) is associated with alterations in attention at the behavioral and neural levels. However, there are conflicting findings regarding the specific type of attention impairments present in PTSD, as the commonly used tests of attention do not isolate the mechanisms behind attention abnormalities, and the constructs measured do not map onto the neurocircuits governing attention. Here, we review the literature on attention processing in PTSD and offer directions for future research to clarify these unanswered questions. First, using instruments that allow assessment of behavioral and neurophysiological attention components will be necessary to understand attention deficits in PTSD. Second, focus on intra-individual variability in addition to assessment of central tendency may help clarify some of the mixed findings. Third, longitudinal studies on attentional processes are warranted to determine how attention contributes to the development and maintenance of PTSD. Integration of behavioral and neural measures of attention will be useful in understanding the pathophysiology of PTSD.

Social anxiety disorder (SAD) is characterized by exaggerated reactivity to social threat, often documented by biased attention to threatening information, and increased activation in brain regions involved in salience/threat processing. Attention training has been developed to ameliorate the attention bias documented in individuals with SAD, with mixed results. We investigated patterns of brain activation underlying acute attention modulation in 41 participants (29 with SAD and 12 health controls). We then investigated how brain activation changed over time in both groups in response to a 4-session attention training protocol (toward threat, away from threat, no-training control). Results revealed diminished pre-training deactivation in the insula in SAD participants during attention modulation. SAD participants also demonstrated an increase in insula deactivation over time, suggestive of an improvement in attention modulation of emotion, and this was associated with a decrease in symptom severity. Attention training did not, itself, lead to clinical improvement, though there was a trend level effect of training toward threat on increased insula deactivation over time. While deficits in attentional control and emotion modulation are documented in individuals with SAD, current attention training protocols are not robustly effective in ameliorating aberrant functioning. Pursuit of training protocols that have more robust impacts on the relevant neural circuitry may have some value.

Background: Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide, possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that carbon dioxide–mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid-sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods: We conducted a case-control analysis (n ¼ 414 PD cases and 846 healthy controls) of ACCN2 single nucleotide polymorphisms and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n ¼ 1048) or task-evoked reactivity to emotional stimuli (n ¼ 103) in healthy individuals. Results: Two single nucleotide polymorphisms at the ACCN2 locus showed evidence of association with PD: rs685012 (odds ratio ¼ 1.32, gene-wise corrected p ¼ .011) and rs10875995 (odds ratio ¼ 1.26, gene-wise corrected p ¼ .046). The association appeared to be stronger when early-onset (age # 20 years) PD cases and when PD cases with prominent respiratory symptoms were compared with controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p ¼ .035) as well as task-evoked amygdala reactivity to fearful and angry faces (p ¼ .0048). Conclusions: Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to proneness to anxiety. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD.

Prior work has revealed that posttraumatic stress disorder (PTSD) is associated with altered (a) attentional performance and (b) resting-state functional connectivity (rsFC) in brain networks linked to attention. Here, we sought to characterize and link these behavioral and brain-based alterations in the context of Posner and Peterson's tripartite model of attention. Male military veterans with PTSD (N = 49; all deployed to Iraq or Afghanistan) and healthy age-and-gender-matched community controls (N = 26) completed the Attention Network Task. A subset of these individuals (36 PTSD and 21 controls) also underwent functional magnetic resonance imaging (fMRI) to assess rsFC. The behavioral measures revealed that the PTSD group was impaired at disengaging spatial attention, relative to the control group. FMRI measures further revealed that, relative to the control group, the PTSD group exhibited greater rsFC between the salience network and (a) the default mode network, (b) the dorsal attention network, and (c) the ventral attention network. Moreover, problems with disengaging spatial attention increased the rsFC between the networks above in the control group, but not in the PTSD group. The present findings link PTSD to both altered orienting of spatial attention and altered relationships between spatial orienting and functional connectivity involving the salience network. Interventions that target orienting and disengaging spatial attention may be a new avenue for PTSD research.

Anxiety disorders are among the most common psychiatric disorders, affecting one in four individuals over a lifetime. Although our understanding of the etiology of these disorders is incomplete, familial and genetic factors are established risk factors. However, identifying the specific casual genes has been difficult. Within the past several years, advances in molecular and statistical genetic methods have made the genetic dissection of complex disorders a feasible project. Here we provide an overview of these developments, with a focus on their implications for genetic studies of anxiety disorders. Although the genetic and phenotypic complexity of the anxiety disorders present formidable challenges, advances in neuroimaging and experimental animal models of anxiety and fear offer important opportunities for discovery. Real progress in identifying the genetic basis of anxiety disorders will require integrative approaches that make use of these biologic tools as well as larger-scale genomic studies. If successful, such efforts may yield novel and more effective approaches for the prevention and treatment of these common and costly disorders. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc.