While much research has focused on the role of severe life events as risk factors for depression onset, less is known about the relationship between nonsevere life events and depression recurrence. The current study examined the cumulative effects of nonsevere and positive life events on depression recurrence in an outpatient sample of recurrently depressed women treated to remission with interpersonal psychotherapy (IPT). A Cox proportional hazards model was used to test this relationship in 124 adult women who entered into the maintenance phase of IPT treatment (IPT-M) and completed at least one Life Events and Difficulties Schedule (LEDS) interview. The cumulative experience of nonsevere life events that were subject- or joint-focused and non-independent was significantly related to depression recurrence during the maintenance treatment phase. None of the other event categories were significantly related to depression recurrence. These findings may help to clarify the mechanisms by which life events contribute to depression recurrence and to guide the development of more efficacious maintenance treatments.
Major Depressive Disorder; Life Events and Difficulties Schedule; Interpersonal Psychotherapy; stress sensitization; stress generation
The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression.
We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration.
There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F ≥ 9.8; p ≤ .05, corrected). Whole brain post hoc analyses (all t ≥ 4.2; p ≤ .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC.
White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.
Depression; diffusion tensor imaging; inferior longitudinal fasciculus; mood disorders; superior longitudinal fasciculus; uncinate fasciculus
This study is a retrospective chart review comparing rural-dwelling Caucasian and Hispanic outpatients' attribution of depressive symptoms. Based on the data gathered at intake, Hispanics were more likely to attribute depression to curse/spell and supernatural causes, while Caucasians were more likely to attribute symptoms to hereditary factors or job stress. Among both groups, higher CESD score was associated with problems with significant others or how they got along with others. Among Hispanics, depression severity was additionally associated with problems related to job or finances. Our findings point to a consequential role for clinical inquiry into attributed causes of depressive symptoms.
Resilience is proposed as a significant component of successful aging. Young adult carriers of the Serotonin Transporter Polymorphism (5HTTLPR) short(s) allele appear to have reduced resilience to stress. We examined if presence of the short allele was associated with poorer emotional resilience in older adults.
In a cross-sectional study of 99 healthy, community-dwelling, older adults we determined 5HTTLPR genotype status and administered the Connor-Davidson Resilience Scale and self-reported measures of successful aging, cognition and health.
There was no significant association between the 5HTTLPR s allele and resilience. S allele carriers had worse cognition and self-report ratings of successful aging.
These findings suggest that the impact of the 5HTTLPR s allele on stress-related outcomes may attenuate with older age. However, s allele status appears to be a biomarker of poorer self-rated successful aging, and cognitive performance in older adults.
5-HTT; Serotonin transporter polymorphism; Resilience; Stress; Successful Aging; Cognition
Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q–Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders.
Genome-wide association studies (GWAS) have thus far identified only a small fraction of the heritability of common complex disorders, such as severe mental disorders. We used a conditional false discovery rate approach for analysis of GWAS data, exploiting “genetic pleiotropy” to increase discovery of common gene variants associated with schizophrenia and bipolar disorders. Leveraging the increased power from combining GWAS of two associated phenotypes, we found a striking overlap in polygenic signals, allowing for the discovery of several new common gene variants associated with bipolar disorder and schizophrenia that were not identified in the original analysis using traditional GWAS methods. Some of the gene variants have been identified in other studies with large targeted replication samples, validating the present findings. Our pleiotropy-informed method may be of significant importance for detecting effects that are below the traditional genome-wide significance level in GWAS, particularly in highly polygenic, complex phenotypes, such as schizophrenia and bipolar disorder, where most of the genetic signal is missing (i.e., “missing heritability”). The findings also offer insights into mechanistic relationships between bipolar disorder and schizophrenia pathogenesis.
Schizophrenia is associated with executive dysfunction. Yet, the degree to which executive functions are impaired differentially, or above and beyond underlying basic cognitive processes is less clear. Participants included 145 matched pairs of individuals with schizophrenia (SCs) and normal comparison subjects (NCs). Executive functions were assessed with 10 tasks of the Delis-Kaplan Executive Function System (D-KEFS), in terms of “achievement scores” reflecting overall performance on the task. Five of these tasks (all measuring executive control) were further examined in terms of their basic component (e.g., processing speed) scores and contrast scores (reflecting residual higher order skills adjusted for basic component skills). Group differences were examined via multivariate analysis of variance. SCs had worse performance than NCs on all achievement scores, but the greatest SC-NC difference was that for the Trails Switching task. SCs also had worse performance than NCs on all basic component skills. Of the executive control tasks, only Trails Switching continued to be impaired after accounting for impairments in underlying basic component skills. Much of the impairment in executive functions in schizophrenia may reflect the underlying component skills rather than higher-order functions. However, the results from one task suggest that there might be additional impairment in some aspects of executive control.
Cognition; Executive function; Schizoaffective disorder; Psychotic disorders; Trail Making Test; D-KEFS
The reasons for the reportedly high use of TV watching among older adults despite its potential negative health consequences are not known.
To investigate age differences in time use and affective experience in TV use in a nationally representative sample
Using an innovative assessment of affective experience in a nationally representative sample, several putative reasons were examined for age-related increases in TV use. A sample of 3982 Americans aged 15–98 years who were assessed using a variant of the Day Reconstruction Method, a survey method for measuring how people experience their lives, was analyzed. To understand age increases in TV use, analyses examined whether older people (1) enjoy TV more, (2) watch TV because it is less stressful than alternatives, or whether (3) TV use related to age differences in demographics, being alone, or life satisfaction. Data were collected in 2006 and analyzed in 2008–2009.
Adults aged >65 years spent threefold more waking time watching TV than young adults. Despite this trend, older people enjoyed TV less, in contrast to stable enjoyment with other leisure activities. Older adults did not seem to experience the same stress buffering effects of watching TV as did young and middle-aged adults. This negative age-associated trend in how TV was experienced was not accounted for by demographic factors or in time spent alone. Greater TV use, but not time spent in other leisure activities, was related to lower life satisfaction.
Older adults watch more TV but enjoy it less than younger people. Awareness of this discrepancy could be useful for those developing interventions to promote reduced sedentary behaviors in older adults.
Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps < .05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps > .34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.
Alcohol; Functional connectivity; Adolescence; Frontoparietal; At-risk
This study examined differences in the frequency of leisure activity participation and relationships to depressive symptom burden and cognition in Latino and Caucasian women. Cross-sectional data were obtained from a demographically matched subsample of Latino and Caucasian (n = 113 each) post-menopausal women (age ≥60), interviewed in 2004–06 for a multi-ethnic cohort study of successful aging in San Diego County. Frequencies of engagement in 16 leisure activities and associations between objective cognitive performance and depressive symptom burden by ethnicity were identified using bivariate and linear regression, adjusted for physical functioning and demographic covariates. Compared to Caucasian women, Latinas were significantly more likely to be caregivers and used computers less often. Engaging in organized social activity was associated with fewer depressive symptoms in both groups. Listening to the radio was positively correlated with lower depressive symptom burden for Latinas, and better cognitive functioning in Caucasians. Cognitive functioning was better in Latinas who read and did puzzles. Housework was negatively associated with Latinas’ emotional health and Caucasians’ cognitive functioning. Latino and Caucasian women participate in different patterns of leisure activities. Additionally, ethnicity significantly affects the relationship between leisure activities and both emotional and cognitive health.
A series of reports have recently appeared using tensor based morphometry statistically-defined regions of interest, Stat-ROIs, to quantify longitudinal atrophy in structural MRIs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This commentary focuses on one of these reports, Hua et al. (2010), but the issues raised here are relevant to the others as well. Specifically, we point out a temporal pattern of atrophy in subjects with Alzheimer’s disease and mild cognitive impairment whereby the majority of atrophy in two years occurs within the first 6 months, resulting in overall elevated estimated rates of change. Using publicly-available ADNI data, this temporal pattern is also found in a group of identically-processed healthy controls, strongly suggesting that methodological bias is corrupting the measures. The resulting bias seriously impacts the validity of conclusions reached using these measures; for example, sample size estimates reported by Hua et al. (2010) may be underestimated by a factor of five to sixteen.
Nonlinear image registration; Regional change quantification; MRI biomarkers; Clinical trials; Bias; Alzheimer’s disease
This study utilized a new cellular phone ecological momentary assessment approach to investigate daily emotional dynamics in 47 youth with Major Depressive Disorder (MDD) and 32 no psychopathology controls (CON), ages 7 – 17. Information about emotional experience in the natural environment was obtained using answer-only cellular phones while MDD youth received an 8 week course of cognitive behavioral therapy and/or psychopharmacological treatment. Compared to CON youth, MDD youth reported more intense and labile global negative affect, greater sadness, anger, and nervousness, and a lower ratio of positive to negative affect. These differences increased with pubertal maturation. MDD youth spent more time alone and less time with their families than CON youth. Although differences in emotional experiences were found across social contexts, MDD youth were more negative than CON youth in all contexts examined. As the MDD participants progressed through treatment, diagnostic group differences in the intensity and lability of negative affect decreased, but there were no changes in the ratio of positive to negative affect or measures of social context. We discuss methodological innovations and advantages of this approach, including improved ecological validity and access to information about variability in emotions, change in emotions over time, the balance of positive and negative emotions, and the social context of emotional experience.
ecological momentary assessment; experience sampling; depression; emotionality; emotion regulation; social context; psychotherapy
To elucidate the relationship between the two hallmark proteins of Alzheimer's disease (AD), amyloid-β (Aβ) and tau, and clinical decline over time among cognitively normal older individuals.
A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.
Research centers across the United States and Canada.
We examined one hundred seven participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.
Main Outcome Measures
Using linear mixed effects models, we investigated the relationship between CSF p-tau181p, CSF Aβ1-42 and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes (CDR-SB), and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog).
We found a significant relationship between decreased CSF Aβ1-42 and longitudinal change in global CDR, CDR-SB, and ADAS-cog in individuals with elevated CSF p-tau181p. In the absence of CSF p-tau181p, the effect of CSF Aβ1-42 on longitudinal clinical decline was not significantly different from zero.
In cognitively normal older individuals, Aβ-associated clinical decline over a mean of three years may occur only in the presence of ongoing, “downstream” neurodegeneration.
To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication.
This report describes how those challenges were met in the study “Depression: The Search for Treatment Relevant Phenotypes”, being carried out at the University of Pittsburgh and the University of Pisa, Italy.
Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems.
By having bilingual investigators and staff members who spent time at one another’s sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year.
This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings.
The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them.
Intense efforts are underway to evaluate neuroimaging measures as biomarkers for neurodegeneration in premanifest Huntington’s disease (preHD). We used a completely automated longitudinal analysis method to compare structural scans in preHD and controls.
Using a one-year longitudinal design, we analyzedT1-weighted structural scans in 35 preHD individuals and 22 age-matched controls. We used the SIENA software tool (Structural Image Evaluation, using Normalization, of Atrophy) to yield overall Percentage Brain Volume Change (PBVC) and voxel-level changes in atrophy. We calculated sample sizes for a hypothetical disease modifying (neuroprotection) study.
We found significantly greater yearly atrophy in preHD vs. controls (Mean PBVC controls = −0.149%; preHD = −0.388%; p=.031, Cohen’s d=.617). For a preHD subgroup closest to disease onset, yearly atrophy was over three times that of controls (Mean PBVC close-to-onset preHD = −0.510%; p=.019, Cohen’s d=.920). This atrophy was evident at the voxel level in periventricular regions – consistent with well-established preHD basal ganglia atrophy. We estimated that a neuroprotection study using SIENA would only need 74close-to-onset individuals in each arm (treatment vs. placebo) to detect a 50% slowing in yearly atrophy with80% power.
Automated whole-brain analysis of structural MRI can reliably detect preHD disease progression over one year. These results were attained with a readily available imaging analysis tool – SIENA – which is observer-independent, automated, and robust with respect to image quality, slice thickness, and different pulse sequences. This MRI biomarker approach could be used to evaluate neuroprotection in preHD.
MRI biomarker; Premanifest HD; Longitudinal atrophy
To explore factors associated with the provision of diabetes-monitoring practices among older Latinos with type 2 diabetes.
Data from 547 Latinos (≥55 years) were analyzed from the 2007 California Health Interview Survey. Multivariate logistic regression modeled the relationship between health status and sociodemographic factors and the receipt of semiannual HbA1c tests, annual foot exams, and annual retinal exams.
The majority of older Latino diabetics received foot exams (87%) and retinal exams (77%), but the provision of semiannual HbA1c tests (30%) was low. Higher English-language proficiency and health insurance coverage were associated with the provision of HbA1c tests and foot exams, but not retinal exams. Insulin therapy was positively associated with semiannual HbA1c testing, but negatively associated with foot exams.
There are considerable missed opportunities in the provision of diabetes monitoring for older Latinos, particularly those with limited English proficiency, less comprehensive insurance, and noninsulin therapy.
type 2 diabetes; health services; Mexican American
We developed models of Specialized Care for Bipolar Disorder (SCBD) and a psychosocial treatment [Enhanced Clinical Intervention (ECI)] that is delivered in combination with SCBD. We investigated whether SCBD and ECI + SCBD are able to improve outcomes and reduce health disparities for young and elderly individuals, African Americans, and rural residents with bipolar disorder.
Subjects were 463 individuals with bipolar disorder, type I, II, or not otherwise specified, or schizoaffective disorder, bipolar type, randomly assigned to SCBD or ECI + SCBD and followed longitudinally for a period of one to three years at four clinical sites.
Both treatment groups significantly improved over time, with no significant differences based on age, race, or place of residence, except for significantly greater improvement among elderly versus adult subjects. Improvement in quality of life was greater in the ECI + SCBD group. Of the 299 participants who were symptomatic at study entry, 213 achieved recovery within 24 months, during which 86 of the 213 subjects developed a new episode. No significant difference was found for race, place of residence, or age between the participants who experienced a recurrence and those who did not. However, the adolescent patients were less likely than the adult and elderly patients to experience a recurrence.
This study demonstrated the effectiveness of SCBD and the additional benefit of ECI independent of age, race, or place of residence. It also demonstrated that new mood episodes are frequent in individuals with bipolar disorder who achieve recovery and are likely to occur in spite of specialized, guideline-based treatments.
bipolar disorder; health disparities; outcomes; randomized trial
Attitudes toward own aging (ATOA) refers to expectations about the personal experience of aging. As of now, there is limited literature that addresses the impact of ATOA on indicators of psychological, physical, and social health. In this study, we examine associations between ATOA and several measures associated with successful aging.
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women enrolled in the San Diego site of the Women's Health Initiative study. ATOA was measured using the Philadelphia Geriatric Morale Scale (PGMS)
The final sample consisted of 1151 women. The mean ATOA score was 3.8 indicating generally positive ATOA. Positive ATOA score was significantly associated with younger age, lower income, being married, higher SF-36 Physical Composite scores, higher SF-36 Mental composite scores, lower depression scores, and higher resilience scores. Approximately 40% of variance in ATOA scores was explained by successful aging-related domain scores.
Better physical and emotional functioning, greater resilience and lower depression are associated with more positive ATOA. Associations with sociodemographic traits are complex. Modifying ATOA may have potential to impact a broad range of health and successful aging related outcomes.
Attitude toward aging; Depression; Health; Social status; Spirituality; Personal mastery; Optimism
Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy vs. depression-specific psychotherapy.
318 adult outpatients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. The outcomes of primary interest were predictors and moderators time to remission on monotherapy at 12 weeks.
Participants with higher scores on the need for medical reassurance factor of the PAS-SR had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the MOODS-SR experienced more rapid remission with SSRI. Nonspecific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the social phobia spectrum total score. Higher baseline HRSD-17 and-25, and Work and Social Adjustment Scale scores also predicted longer time to remission, while being married predicted shorter time to remission.
This exploratory study identified several nonspecific predictors, but few moderators of psychotherapy vs. pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.
The term “functional connectivity” is used to denote correlations in activation among spatially-distinct brain regions, either in a resting state or when processing external stimuli. Functional connectivity has been extensively evaluated with several functional neuroimaging methods, particularly PET and fMRI. Yet these relationships have been quantified using very different measures and the extent to which they index the same constructs is unclear. We have implemented a variety of these functional connectivity measures in a new freely-available MATLAB toolbox. These measures are categorized into two groups: whole time-series and trial-based approaches. We evaluate these measures via simulations with different patterns of functional connectivity and provide recommendations for their use. We also apply these measures to a previously published fMRI data set (Siegle et al. 2003; 2007) in which activity in dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (DLPFC) was evaluated in 32 control subjects during a digit sorting task. Though all implemented measures demonstrate functional connectivity between dACC and DLPFC activity during event-related tasks, different participants appeared to display qualitatively different relationships.
Neuroscientists have become increasingly interested in exploring dynamic relationships among brain regions. Such a relationship, when directed from one region toward another, is denoted by “effective connectivity.” An fMRI experimental paradigm which is well-suited for examination of effective connectivity is the slow event-related design. This design presents stimuli at sufficient temporal spacing for determining within-trial trajectories of BOLD activation, allowing for the analysis of stimulus-locked temporal covariation of brain responses in multiple regions. This may be especially important for emotional stimuli processing, which can evolve over the course of several seconds, if not longer. However, while several methods have been devised for determining fMRI effective connectivity, few are adapted to event-related designs, which include non-stationary BOLD responses and multiple levels of nesting. We propose a model tailored for exploring effective connectivity of multiple brain regions in event-related fMRI designs - a semi-parametric adaptation of vector autoregressive (VAR) models, termed “stimulus-locked VAR” (SloVAR). Connectivity coefficients vary as a function of time relative to stimulus onset, are regularized via basis expansions, and vary randomly across subjects. SloVAR obtains flexible, data-driven estimates of effective connectivity and hence is useful for building connectivity models when prior information on dynamic regional relationships is sparse. Indices derived from the coefficient estimates can also be used to relate effective connectivity estimates to behavioral or clinical measures. We demonstrate the SloVAR model on a sample of clinically depressed and normal controls, showing that early but not late cortico-amygdala connectivity appears crucial to emotional control and early but not late cortico-cortico connectivity predicts depression severity in the depressed group, relationships that would have been missed in a more traditional VAR analysis.
Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD).
Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined.
The BD versus HC showed significantly greater right amygdala-OFC FC (p ≤ .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001).
In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC–FA relationships in BD and HC require further study.
Amygdala; bipolar disorder; emotional processing; functional connectivity; neuroimaging; OFC
A laboratory study of sleep and circadian rhythms was undertaken in 28 spousally bereaved seniors (≥60 yrs) at least four months after the loss event. Measures taken included two nights of polysomnography (second night used), ∼36 h of continuous core body temperature monitoring, and four assessments of mood and alertness throughout a day. Preceding the laboratory study, two-week diaries were completed, allowing the assessment of lifestyle regularity using the 17-item Social Rhythm Metric (SRM) and the timing of sleep using the Pittsburgh Sleep Diary (PghSD). Also completed were questionnaires assessing level of grief (Texas Revised Inventory of Grief [TRIG] and Index of Complicated Grief [ICG]), subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]), morningness-eveningness (Composite Scale of Morningness [CSM]), and clinical interview yielding a Hamilton Depression Rating Scale (HDRS) score. Grief was still present, as indicated by an average TRIG score of about 60. On average, the bereaved seniors habitually slept between ∼23:00 and ∼06:40 h, achieving ∼6 h of sleep with a sleep efficiency of ∼80%. They took about 30 min to fall asleep, and had their first REM episode after 75 min. About 20% of their sleep was in Stage REM, and about 3% in Stages 3 or 4 (slow wave sleep). Their mean PSQI score was 6.4. Their circadian temperature rhythms showed the usual classic shape with a trough at ∼01:00 h, a fairly steep rise through the morning hours, and a more gradual rise to mid-evening, with an amplitude of ∼0.8°C. In terms of lifestyle regularity, the mean regularity (SRM) score was 3.65 (slightly lower than that usually seen in seniors). Mood and alertness showed time-of-day variation with peak alertness in the late morning and peak mood in the afternoon. Correlations between outcome sleep/circadian variables and level of grief (TRIG score) were calculated; there was a slight trend for higher grief to be associated with less time spent asleep (p = 0.07) and reduced alertness at 20:00 h (p = 0.05). Depression score was not correlated with TRIG score (p > 0.20). When subjects were divided into groups by the nature of their late spouse's death (expected/after a long-term chronic illness [n = 18] versus unexpected [n = 10]), no differences emerged in any of the variables. In conclusion, when studied at least four months after the loss event, there appears to be some sleep disruption in spousally bereaved seniors. However, this disruption does not appear to be due to bereavement-related disruptions in the circadian system.
Bereavement; Widow; Sleep; Circadian rhythms
genetic association study; disease genetics; immunogenetics; liver
Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.
cortex; cortical thickness; heritability
Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level dependent (BOLD) signal across four 3T magnets in voxelwise and region of interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control.