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Based on promising results with adults, Acceptance and Commitment Therapy (ACT) presents as a treatment opportunity for depressed adolescents. We present a pilot study that compares ACT with treatment as usual (TAU), using random allocation of participants who were clinically referred to a psychiatric outpatient service. Participants were 30 adolescents, aged M = 14.9 (SD = 2.55), with 73.6% in the clinical range for depression. At posttreatment on measures of depression participants in the ACT condition showed significantly greater improvement statistically (d = 0.38), and 58% showed clinically reliable change with a response ratio of 1.59 in favor of ACT. Outcomes from 3-month follow-up data are tentative due to small numbers but suggest that improvement increased in magnitude. Measures of global functioning showed statistically significant improvement for both conditions, although clinical change measures favored only the ACT condition. The results support conducting a larger trial of ACT for the treatment of adolescent depression.
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Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
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The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.
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This article presents an overview of the author's recent electrophysiological studies of anterior cerebral asymmetries related to emotion and affective style. A theoretical account is provided of the role of the two hemispheres in emotional processing. This account assigns a major role in approach- and withdrawal-related behavior to the left and right frontal and anterior temporal regions of two hemispheres, respectively. Individual differences in approach- and withdrawal-related emotional reactivity and temperament are associated with stable differences in baseline measures of activation asymmetry in these anterior regions. Phasic state changes in emotion result in shifts in anterior activation asymmetry which are superimposed upon these stable baseline differences. Future directions for research in this area are discussed.
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OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.
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Two reports in the last issue of this journal attempted to replicate aspects of our previous studies on anterior electroencephalogram (EEG) asymmetry, affective style, and depression. In this commentary, an overview is provided of our model of anterior asymmetries, affective style, and psychopathology. Emphasis is placed on conceptualizing the prefrontal and anterior temporal activation patterns within a circuit that includes cortical and subcortical structures. The causal status of individual differences in asymmetric activation in the production of affective style and psychopathology is considered. Major emphasis is placed on EEG methods, particularly the need for multiple assessments to obtain estimates of asymmetric activation that better reflect an individual's true score. Issues specific to each of the two articles are also considered. Each of the articles has more consistency with our previously published data than the authors themselves suggest. Recommendations are made for future research to resolve some of the outstanding issues.
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BACKGROUND: Studies using electroencephalogram (EEG) measures of activation asymmetry have reported differences in anterior asymmetry between depressed and nondepressed subjects. Several studies have suggested reciprocal relations between measures of anterior and posterior activation asymmetries. We hypothesized that depressed subjects would fail to show the normal activation of posterior right hemisphere regions in response to an appropriate cognitive challenge. METHODS: EEG activity was recorded from 11 depressed and 19 nondepressed subjects during the performance of psychometrically matched verbal (word finding) and spatial (dot localization) tasks. Band power was extracted from all epochs of artifact-free data and averaged within each condition. Task performance was also assessed. RESULTS: Depressed subjects showed a specific deficit in the performance of the spatial task, whereas no group differences were evident on verbal performance. In posterior scalp regions, nondepressed controls had a pattern of relative left-sided activation during the verbal task and relative right-sided activation during the spatial task. In contrast, depressed subjects failed to show activation in posterior right hemisphere regions during spatial task performance. CONCLUSIONS: These findings suggest that deficits in right posterior functioning underlie the observed impairments in spatial functioning among depressed subjects.
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BACKGROUND: The frontal lobe has been crucially involved in the neurobiology of major depression, but inconsistencies among studies exist, in part due to a failure of considering modulatory variables such as symptom severity, comorbidity with anxiety, and distinct subtypes, as codeterminants for patterns of brain activation in depression. METHODS: Resting electroencephalogram was recorded in 38 unmedicated subjects with major depressive disorder and 18 normal comparison subjects, and analyzed with a tomographic source localization method that computes the cortical three-dimensional distribution of current density for standard electroencephalogram frequency bands. Symptom severity and anxiety were measured via self-report and melancholic features via clinical interview. RESULTS: Depressed subjects showed more excitatory (beta3, 21.5-30.0 Hz) activity in the right superior and inferior frontal lobe (Brodmann's area 9/10/11) than comparison subjects. In melancholic subjects, this effect was particularly pronounced for severe depression, and right frontal activity correlated positively with anxiety. Depressed subjects showed posterior cingulate and precuneus hypoactivity. CONCLUSIONS: While confirming prior results implicating right frontal and posterior cingulate regions, this study highlights the importance of depression severity, anxiety, and melancholic features in patterns of brain activity accompanying depression.
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We evaluated the efficacy of a mindful parenting program for changing parents’ mindfulness, child management practices, and relationships with their early adolescent youth and tested whether changes in parents’ mindfulness mediated changes in other domains. We conducted a pilot randomized trial with 65 families and tested an adapted version of the Strengthening Families Program: For Parent and Youth 10–14 that infused mindfulness principles and practices against the original program and a delayed intervention control group. Results of pre-post analyses of mother and youth-report data showed that the mindful parenting program generally demonstrated comparable effects to the original program on measures of child management practices and stronger effects on measures of mindful parenting and parent–youth relationship qualities. Moreover, mediation analyses indicated that the mindful parenting program operated indirectly on the quality of parent–youth relationships through changes in mindful parenting. Overall, the findings suggest that infusing mindful parenting activities into existing empirically validated parenting programs can enhance their effects on family risk and protection during the transition to adolescence.

The authors examined the time course of affective responding associated with different affective dimensions--anxious apprehension, anxious arousal, and anhedonic depression--using an emotion-modulated startle paradigm. Participants high on 1 of these 3 dimensions and nonsymptomatic control participants viewed a series of affective pictures with acoustic startle probes presented before, during, and after the stimuli. All groups exhibited startle potentiation during unpleasant pictures and in anticipation of both pleasant and unpleasant pictures. Compared with control participants, symptomatic participants exhibited sustained potentiation following the offset of unpleasant stimuli and a lack of blink attenuation during and following pleasant stimuli. Common and unique patterns of affective responses in the 3 types of mood symptoms are discussed.
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The heart rate, breathing rate, and skin resistance were recorded for 20 community home girls (Home group) and for 20 age-matched girls from a regular school (School group). The former group had a significantly higher rate of breathing and a more irregular breath pattern known to correlate with high fear and anxiety, than the School group. Skin resistance was significantly lower in the School group, which may suggest greater arousal, 28 girls of the Home group formed 14 pairs, matched for age and duration of stay in the home. Subjects of a pair were randomly assigned to either yoga or games groups. For the former emphasis was on relaxation and awareness, whereas for the latter increasing physical activity was emphasized. At the end of an hour daily for six months both groups showed a significant decrease in the resting heart rate relative to initial values (Wilcoxon paired-sample rest), and the yoga group showed a significant decrease in breath rate, which appeared more regular but no significant increase in the skin resistance. These results suggest that a yoga program which includes relaxation, awareness, and graded physical activity is a useful addition to the routine of community home children.
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The effects of Zen breath meditation were compared with those of relaxation on college adjustment. 75 undergraduates (aged 17–40 yrs) were divided into 3 groups using randomized matching on the basis of initial anxiety scores of the College Adjustment Scales. Ss also completed the Taylor Manifest Anxiety Scale. The 3 groups included, meditation, relaxation, and control. Training for the meditation and relaxation groups took place during a 1-hr instructional session with written instructions being distributed. After 6 wks anxiety and depression scored significantly decreased for the meditation and relaxation groups. Interpersonal problem scores also significantly decreased for the meditation group.

Background: Mindfulness is the development of a nonjudgmental accepting awareness of moment-by-moment experience. Intentionally attending to one’s ongoing stream of sensations, thoughts, and emotions as they arise has a number of benefits, including the ability to react with greater flexibility to events and sustain attention. Thus the teaching of mindfulness-based skills to children and their carers is a potential means of improving family relationships and helping children achieve more positive developmental outcomes through increased ability to sustain attention and manage emotions. We provide a review of recent studies evaluating mindfulness-based interventions targeting children, adolescents, and families in educational and clinical settings.Method: Searches were conducted of several databases (including Medline, PsychINFO and Cochrane Reviews) to identify studies that have evaluated mindfulness-based interventions targeting children, adolescents or families published since 2009.Results: Twenty-four studies were identified. We conclude that mindfulness-based interventions are an important addition to the repertoire of existing therapeutic techniques. However, large-scale, methodologically rigorous studies are lacking. The interventions used in treatment evaluations vary in both content and dose, the outcomes targeted have varied, and no studies have employed methodology to investigate mechanisms of change.Conclusions: There is increasing evidence that mindfulness-based therapeutic techniques can have a positive impact on a range of outcome variables. A greater understanding of the mechanisms of change is an important future direction of research. We argue that locating mindfulness-based therapies targeting children and families within the broader child and family field has greater promise in improving child and family functioning than viewing mindful parenting as an independent endeavor.
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Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.
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In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression.
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The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.
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Objective: A strong relation between negative affect and craving has been demonstrated in laboratory and clinical studies, with depressive symptomatology showing particularly strong links to craving and substance abuse relapse. Mindfulness-based relapse prevention (MBRP), shown to be efficacious for reduction of substance use, uses mindfulness-based practices to teach alternative responses to emotional discomfort and lessen the conditioned response of craving in the presence of depressive symptoms. The goal in the current study was to examine the relation between measures of depressive symptoms, craving, and substance use following MBRP. Method: Individuals with substance use disorders (N = 168; mean age 40.45 years, SD = 10.28; 36.3% female; 46.4% non-White) were recruited after intensive stabilization, then randomly assigned to either 8 weekly sessions of MBRP or a treatment-as-usual control group. Approximately 73% of the sample was retained at the final 4-month follow-up assessment. Results: Results confirmed a moderated-mediation effect, whereby craving mediated the relation between depressive symptoms (Beck Depression Inventory) and substance use (Timeline Follow-Back) among the treatment-as-usual group but not among MBRP participants. MBRP attenuated the relation between postintervention depressive symptoms and craving (Penn Alcohol Craving Scale) 2 months following the intervention (ƒ² = .21). This moderation effect predicted substance use 4 months following the intervention (ƒ² = .18). Conclusion: MBRP appears to influence cognitive and behavioral responses to depressive symptoms, partially explaining reductions in postintervention substance use among the MBRP group. Although results are preliminary, the current study provides evidence for the value of incorporating mindfulness practice into substance abuse treatment and identifies a potential mechanism of change following MBRP.

Depression is a disorder of the representation and regulation of mood and emotion. The circuitry underlying the representation and regulation of normal emotion and mood is reviewed, including studies at the animal level, human lesion studies, and human brain imaging studies. This corpus of data is used to construct a model of the ways in which affect can become disordered in depression. Research on the prefrontal cortex, anterior cingulate, hippocampus, and amygdala is reviewed and abnormalities in the structure and function of these different regions in depression is considered. The review concludes with proposals for the specific types of processing abnormalities that result from dysfunctions in different parts of this circuitry and offers suggestions for the major themes upon which future research in this area should be focused.
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Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.
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Converging findings suggest that depressed individuals exhibit disturbances in positive emotion. No study, however, has ascertained which specific positive emotions are implicated in depression. We report two studies that compare how depressive symptoms relate to distinct positive emotions at both trait and state levels of assessment. In Study 1 (N=185), we examined associations between depressive symptoms and three trait positive emotions (pride, happy, amusement). Study 2 compared experiential and autonomic reactivity to pride, happy, and amusement film stimuli between depressive (n=24; DS) and non-depressive (n=31; NDS) symptom groups. Results indicate that symptoms of depression were most strongly associated with decreased trait pride and decreased positive emotion experience to pride-eliciting films. Discussion focuses on the implications these findings have for understanding emotion deficits in depression as well as for the general study of positive emotion.
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The effectiveness of an 8-week mindfulness training for adolescents aged 11–15 years with ADHD and parallel Mindful Parenting training for their parents was evaluated, using questionnaires as well as computerized attention tests. Adolescents (N = 10), their parents (N = 19) and tutors (N = 7) completed measurements before, immediately after, 8 weeks after and 16 weeks after training. Adolescents reported on their attention and behavioral problems and mindful awareness, and were administered two computerized sustained attention tasks. Parents as well as tutors reported on adolescents’ attention and behavioral problems and executive functioning. Parents further reported on their own parenting, parenting stress and mindful awareness. Both the mindfulness training for the adolescents and their parents was delivered in group format. First, after mindfulness training, adolescents’ attention and behavior problems reduced, while their executive functioning improved, as indicated by self-report measures as well as by father and teacher report. Second, improvements in adolescent’ actual performance on attention tests were found after mindfulness training. Moreover, fathers, but not mothers, reported reduced parenting stress. Mothers reported reduced overreactive parenting, whereas fathers reported an increase. No effect on mindful awareness of adolescents or parents was found. Effects of mindfulness training became stronger at 8-week follow-up, but waned at 16-week follow-up. Our study adds to the emerging body of evidence indicating that mindfulness training for adolescents with ADHD (and their parents) is an effective approach, but maintenance strategies need to be developed in order for this approach to be effective in the longer term.

Losses in relationships, work, and other areas of life often accompany the physical discomfort of chronic pain. Often the depth and intensity of the grief associated with chronic pain are overlooked or possibly misdiagnosed and treated as depression. We used an 8-week mindfulness meditation program to determine its effectiveness in addressing the grieving process among 39 patients diagnosed with chronic pain. Eighteen patients volunteered to be in a comparison group. The study was conducted in a regional hospital's pain clinic and patients completed the Response to Loss Scale (measuring grief), the Beck Depression Inventory, and the State Trait Anxiety Inventory. Results indicated that the treatment group advanced significantly more quickly through the initial stages of grieving than the comparison group. In addition, the treatment group demonstrated significant reductions in depression and state anxiety, but no significant differences emerged when comparing groups on the final stages of grieving or trait anxiety.

Objective To examine the effect of parental training on disturbed behavior of early childhood cases presented to the pediatricians. Methods The patients who reported in pediatric OPD of the Himalayan Institute of Medical Sciences, Dehradun, with complaints of low learning, poor memory, vertigo, speech problem, stress, headache, depression, adjustment problems, aggression, and hostile behavior were included in the study. Children aged 3 through 6 (N = 60), were screened through PBQ (Preschool Behavior Questionnaire), DST (developmental screening Test), and Vineland Social Maturity Scale (VSMS). Children included in the study had an average range of developmental quotient 85–90 (mean DQ = 87.5). Range of social quotient was 40–45 (mean SQ = 42.5). Twenty four fortnightly sessions of ‘parental training’ using the model of ‘Mindful Parenting’ were conducted. Single group t test method was applied in order to see the difference in mean of pre and post assessment of PBQ. Results After concluding parental training (after 24 sessions), mean difference of total disturbed behavior was found to be significant (t value: 5.31 > .05) Similarly, the mean difference of hostile/aggressive behavior (t value: 10.2 > .05), anxious behavior (t value: 18.5 > .05), and hyperactive/distractible behavior (t value: 1.97 > .05) were found to be significant. Conclusions These results provide some evidence in favor of parental training in managing behavioral problems occurring in early childhood. Instead of putting the child immediately on medication, parents can get training and prepare a plan to understand and make a change in child’s behavior leading to better health.

Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother–infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial ( n = 31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p < 0.05) and negative affect (effect size, 0.83; p < 0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy.

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