Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical ...structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, ); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT.
To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (
= 58) before and after CBT as well as never-depressed controls (
= 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT.
Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions.
Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.
Depressed patients show abnormalities in brain connectivity at rest, including hyperconnectivity within the default mode network (DMN). However, there is well-known heterogeneity in the clinical ...presentation of depression that is overlooked when averaging connectivity data. We used data-driven parsing of neural connectivity to reveal subgroups among 80 depressed patients completing resting state fMRI. Directed functional connectivity paths (eg, region A influences region B) within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation, a method shown to accurately recover the direction and presence of connectivity paths in individual participants. Individuals were clustered using community detection on neural connectivity estimates. Subgroups were compared on network features and on clinical and biological/demographic characteristics that influence depression prognosis. Two subgroups emerged. Subgroup A, containing 71% of the patients, showed a typical pattern of connectivity across DMN nodes, as previously reported in depressed patients on average. Subgroup B exhibited an atypical connectivity profile lacking DMN connectivity, with increased dorsal anterior cingulate-driven connectivity paths. Subgroup B members had an over-representation of females (87% of Subgroup B vs 65% of Subgroup A; χ
=3.89, p=0.049), comorbid anxiety diagnoses (42.9% of Subgroup B vs 17.5% of Subgroup A; χ
=5.34, p=.02), and highly recurrent depression (63.2% of Subgroup B vs 31.8% of Subgroup A; χ
=5.38, p=.02). Neural connectivity-based categorization revealed an atypical pattern of connectivity in a depressed patient subset that would be overlooked in group comparisons of depressed and healthy participants, and tracks with clinically relevant phenotypes including anxious depression and episodic recurrence. Data-driven parsing suggests heterogeneous substrates of depression; ideally, future work building on these findings will inform personalized treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Theta burst stimulation (TBS) is thought to affect reward processing mechanisms, which may increase and decrease reward sensitivity. To test the ability of TBS to modulate response to strong primary ...rewards, participants hypersensitive to primary rewards were recruited. Twenty men and women with at least two opposite-sex, sexual partners in the last year received two forms of TBS. Stimulations were randomized to avoid order effects and separated by 2 hours to reduce carryover. The two TBS forms have been demonstrated to inhibit (continuous) or excite (intermittent) the left dorsolateral prefrontal cortex using different pulse patterns, which links to brain areas associated with reward conditioning. After each TBS, participants completed tasks assessing their reward responsiveness to monetary and sexual rewards. Electroencephalography (EEG) was recorded. They also reported their number of orgasms in the weekend following stimulation. This signal was malleable by TBS, where excitatory TBS resulted in lower EEG alpha relative to inhibitory TBS to primary rewards. EEG responses to sexual rewards in the lab (following both forms of TBS) predicted the number of orgasms experienced over the forthcoming weekend. TBS may be useful in modifying hypersensitivity or hyposensitivity to primary rewards that predict sexual behaviors. Since TBS altered the anticipation of a sexual reward, TBS may offer a novel treatment for sexual desire problems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The promise of a new generation of therapies targeted to address neurobiological mechanisms thought to underlie psychological disorders, particularly depression, using cognitive and behavioral ...techniques is discussed. Relationships between such neurobehaviorally focused therapies and other psychological and rehabilitative interventions are also discussed. Their potential utility as adjuncts to conventional treatment, and the importance of multi-method assessment in their evaluation are emphasized. Finally, initial data from a neurobehavioral "cognitive control training" (CCT) adjunctive intervention for severe unipolar depression is presented as an extended example. These data suggest that CCT aids in reducing both physiological mechanisms underlying depression as well as depressive symptomatology.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
This pilot study examined the relationships between the effects of sleep deprivation on subjective and objective measures of sleepiness and affect, and psychomotor vigilance performance. ...Following an adaptation night in the laboratory, healthy young adults were randomly assigned to either a night of total sleep deprivation (SD group; n = 15) or to a night of normal sleep (non‐SD group; n = 14) under controlled laboratory conditions. The following day, subjective reports of mood and sleepiness, objective sleepiness (Multiple Sleep Latency Test and spontaneous oscillations in pupil diameter, PUI), affective reactivity/regulation (pupil dilation responses to emotional pictures), and psychomotor vigilance performance (PVT) were measured. Sleep deprivation had a significant impact on all three domains (affect, sleepiness, and vigilance), with significant group differences for eight of the nine outcome measures. Exploratory factor analyses performed across the entire sample and within the SD group alone revealed that the outcomes clustered on three orthogonal dimensions reflecting the method of measurement: physiological measures of sleepiness and affective reactivity/regulation, subjective measures of sleepiness and mood, and vigilance performance. Sleepiness and affective responses to sleep deprivation were associated (although separately for objective and subjective measures). PVT performance was also independent of the sleepiness and affect outcomes. These findings suggest that objective and subjective measures represent distinct entities that should not be assumed to be equivalent. By including affective outcomes in experimental sleep deprivation research, the impact of sleep loss on affective function and their relationship to other neurobehavioral domains can be assessed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in ...postmenopausal women.
Participants were 97 253 women (89 259 white, 7994 black) from the Women's Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over approximately 8 years. Optimists (top versus bottom quartile "pessimists") had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent.
Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.
We review likely neurobiological substrates of cognitions related to fear and anxiety. Cognitive processes are linked to abnormal early activity reflecting hypervigilance in subcortical networks ...involving the amygdala, hippocampus, and insular cortex, and later recruitment of cortical regulatory resources, including activation of the anterior cingulate cortex and prefrontal cortex to implement avoidant response strategies. Based on this evidence, we present a cognitive-neurobiological information-processing model of fear and anxiety, linking distinct brain structures to specific stages of information processing of perceived threat.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective:In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined ...amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset.Method:Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined.Results:During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >−0.38) and percent of positive specific memories recalled (r values >0.59).Conclusions:The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments targeting amygdala hypoactivity and blunted salience during positive autobiographical recall could exert antidepressant effects.
Persistent low grade depression symptoms are common and impairing in major depressive disorder (MDD) yet rarely reported in treatment follow-up studies (Judd et al., 1998a; Kennedy et al., 2004), ...suggesting that extant sustained remission rates may not reflect this important clinical feature. Furthermore, no long-term MDD treatment follow-up study has reported on quality of life ratings across functioning levels and years throughout the follow-up period, thus the severity, breadth, and persistence of functional impairment remain unclear. Accordingly, the current study evaluated the course of MDD with consideration of low grade depressive symptomatology and holistic features (e.g., quality of life).
We report long-term (9–14 years) follow-up data from individuals with MDD (N = 37) who underwent either Cognitive Therapy (CBT) or a course of selective serotonin reuptake inhibitor (SSRI) treatment. Patients provided retrospective reports of depression symptoms and quality of life in the years following treatment.
Chronic depression symptoms (most often mild in severity) and decreased quality of life in multiple domains are frequent and suggest poorer sustained remission rates than previously observed in the literature.
Study limitations include small sample size recruited via convenience sampling methods.
Findings support a conceptualization of depression recovery that entails persistent symptoms and vulnerabilities. Clinical recommendations are provided for discussing these features of depression recovery with patients.
•Major depressive disorder involves chronic inter-episode low grade symptomatology.•Major depressive disorder involves persistent, diverse deficits in quality of life.•Vulnerabilities persist after treatment for those with major depressive disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A growing number of health-related sciences, including audiology, have increasingly recognized the importance of affective phenomena. However, in audiology, affective phenomena are mostly studied as ...a consequence of hearing status. This review first addresses anatomical and functional bidirectional connections between auditory and affective systems that support a reciprocal affect-hearing relationship. We then postulate, by focusing on four practical examples (hearing public campaigns, hearing intervention uptake, thorough hearing evaluation, and tinnitus), that some important challenges in audiology are likely affect-related and that potential solutions could be developed by inspiration from affective science advances. We continue by introducing useful resources from affective science that could help audiology professionals learn about the wide range of affective constructs and integrate them into hearing research and clinical practice in structured and applicable ways. Six important considerations for good quality affective audiology research are summarized. We conclude that it is worthwhile and feasible to explore the explanatory power of emotions, feelings, motivations, attitudes, moods, and other affective processes in depth when trying to understand and predict how people with hearing difficulties perceive, react, and adapt to their environment.
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