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ABSTRACT: Torrisi S, Moody TD, Vizueta N, Thomason ME, Monti MM, Townsend JD, Bookheimer SY, Altshuler LL. Differences in resting corticolimbic functional connectivity in bipolar I euthymia. Bipolar Disord 2013: 00: 000-000. © 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objective: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. Methods: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low-frequency fluctuations in blood oxygen level-dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed-to-voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. Results: The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). Conclusions: Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait-related and clinically important imaging biomarker.
Bipolar Disorders 01/2013; · 5.29 Impact Factor
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Robert M Post, Lori L Altshuler,
Gabriele S Leverich,
Mark A Frye,
Trisha Suppes,
Susan L McElroy,
Paul E Keck,
Willem A Nolen,
Ralph W Kupka,
Heinz Grunze,
Mike Rowe
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ABSTRACT: OBJECTIVE: A role for childhood adversity in the development of numerous medical conditions in adults has been described in the general population, but has not been examined in patients with bipolar disorder who have multiple medical comorbidities which contribute to their premature mortality. METHODS: More than 900 outpatients (average age 41) with bipolar disorder completed questionnaires that included information about the occurrence of verbal, physical, or sexual abuse in childhood and whether their parents had a mood or substance abuse disorder, or a history of suicidality. These factors were combined to form a total childhood adversity score, which was then related to one or more of 30 medical conditions patients rated as present or absent. RESULTS: The child adversity score was significantly related to the total number of medical comorbidities a patient had (p<.001), as well as to 11 specific medical conditions that could be modeled in a logistic regression (p<.03). These included: asthma, arthritis, allergies, chronic fatigue syndrome, chronic menstrual irregularities, fibromyalgia, head injury (without loss of consciousness), hypertension, hypotension, irritable bowel syndrome, and migraine headaches. LIMITATIONS: The contribution of parental diagnosis to childhood adversity is highly inferential. CONCLUSIONS: These data link childhood adversity to the later occurrence of multiple medical conditions in adult outpatients with bipolar disorder. Recognition of these relationships and early treatment intervention may help avert a more severe course of not only bipolar disorder but also of its prominent medical comorbidities and their combined adverse effects on patients'health, wellbeing, and longevity.
Journal of affective disorders 01/2013; · 3.76 Impact Factor
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ABSTRACT: Hegarty CE, Foland-Ross LC, Narr KL, Sugar CA, McGough JJ, Thompson PM, Altshuler LL. ADHD comorbidity can matter when assessing cortical thickness abnormalities in patients with bipolar disorder. Bipolar Disord 2012: 14: 843-855. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Attention-deficit hyperactivity disorder (ADHD) is prevalent in patients with bipolar disorder (BP), but very few studies consider this when interpreting magnetic resonance imaging findings. No studies, to our knowledge, have screened for or controlled for the presence of ADHD when examining cortical thickness in patients with BP. We used a 2 × 2 design to evaluate the joint effects of BP and ADHD on cortical thickness and uncover the importance of ADHD comorbidity in BP subjects. Methods: The study included 85 subjects: 31 healthy controls, 17 BP-only, 19 ADHD-only, and 18 BP/ADHD. All patients with BP were subtype I, euthymic, and not taking lithium. Groups did not differ significantly in age or gender distribution. We used cortical thickness measuring tools combined with cortical pattern matching methods to align sulcal/gyral anatomy across participants. Significance maps were used to check for both main effects of BP and ADHD and their interaction. Post-hoc comparisons assessed how the effects of BP on cortical thickness varied as a function of the presence or absence of ADHD. Results: Interactions of BP and ADHD diagnoses were found in the left subgenual cingulate and right orbitofrontal cortex, demonstrating that the effect of BP on cortical thickness depends on ADHD status. Conclusions: Some brain abnormalities attributed to BP may result from the presence of ADHD. Diagnostic interactions were found in regions previously implicated in the pathophysiology of BP, making it vital to control for an ADHD comorbid diagnosis when attempting to isolate neural or genetic abnormalities specific to BP.
Bipolar Disorders 12/2012; 14(8):843-855. · 5.29 Impact Factor
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Lara C Foland-Ross,
Paul M Thompson,
Catherine A Sugar,
Katherine L Narr,
Conor Penfold,
Roxanne E Vasquez,
Jennifer Townsend,
Jeffrey Fischer,
Priya Saharan,
Carrie E Bearden, Lori L Altshuler
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ABSTRACT: Structural neuroimaging studies of the amygdala and hippocampus in bipolar disorder have been largely inconsistent. This may be due in part to differences in the proportion of subjects taking lithium or experiencing an acute mood state, as both factors have recently been shown to influence gray matter structure. To avoid these problems, we evaluated euthymic subjects not currently taking lithium. Thirty-two subjects with bipolar type I disorder and 32 healthy subjects were scanned using magnetic resonance imaging. Subcortical regions were manually traced, and converted to three-dimensional meshes to evaluate the main effect of bipolar illness on radial distance. Statistical analyses found no evidence for a main effect of bipolar illness in either region, although exploratory analyses found a significant age by diagnosis interaction in the right amygdala, as well as positive associations between radial distance of the left amygdala and both prior hospitalizations for mania and current medication status. These findings suggest that, when not treated with lithium or in an acute mood state, patients with bipolar disorder exhibit no structural abnormalities of the amygdala or hippocampus. Future studies, nevertheless, that further elucidate the impact of age, course of illness, and medication on amygdala structure in bipolar disorder are warranted.
Psychiatry research. 11/2012;
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ABSTRACT: With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed.
Brain Imaging and Behavior 10/2012; · 1.66 Impact Factor
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ABSTRACT: BACKGROUND: The inferior frontal cortical (IFC)-striatal network plays an integral role in response inhibition and is compromised in patients with Bipolar Disorder (BP) or Attention-Deficit/Hyperactivity Disorder (ADHD). Prior BP functional neuroimaging studies have not accounted for ADHD comorbidity despite its high prevalence. METHODS: The authors conducted an fMRI study using a response inhibition task (Go-NoGo) in 32 euthymic adults with BP, half with comorbid ADHD (BP/ADHD); 16 adults with ADHD alone; and 30 healthy controls. Within- and between-group whole-brain analyses were performed to assess for significant neural function differences. RESULTS: All groups activated frontal and striatal regions involved in response inhibition. ANOVA results demonstrated significant interaction effects of BP and ADHD in the anterior and posterior cingulate, left superior and middle frontal gyri and left inferior parietal lobule. Follow-up comparisons showed significant differences between BP subjects with and without ADHD. Other regions demonstrated main effects of BP (left inferior frontal gyrus, left middle frontal gyrus, right superior frontal gyrus and left insula) and ADHD (left inferior frontal gyrus, left precentral gyrus and right anterior cingulate). LIMITATIONS: This study, as the first of its kind, requires replication using large sample sizes and controlling for potential effects of medication. CONCLUSIONS: Euthymic bipolar adults with comorbid ADHD have significantly different neural activation patterns from BP patients without this comorbidity. If understanding of the neurobiology of bipolar disorder is to be achieved, it is critical to control for this potential confound, something not done by most prior fMRI studies of adults with BP.
Journal of affective disorders 10/2012; · 3.76 Impact Factor
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George Bartzokis,
Po H Lu,
Panthea Heydari,
Alexander Couvrette,
Grace J Lee,
Greta Kalashyan,
Frank Freeman,
John W Grinstead,
Pablo Villablanca,
J Paul Finn,
Jim Mintz,
Jeffry R Alger, Lori L Altshuler
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ABSTRACT: BACKGROUND: Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. METHODS: Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R(2)) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). RESULTS: Only R(2) reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R(2) < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R(2) and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. CONCLUSIONS: The R(2) and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.
Biological psychiatry 09/2012; · 8.93 Impact Factor
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ABSTRACT: BACKGROUND: The symptoms of bipolar disorder suggest dysfunction of emotion regulatory networks. In healthy control populations, downregulation of emotional responses activates the ventral lateral prefrontal cortex (vlPFC) and dampens amygdala activation. This study investigated frontal and limbic function and connectivity during emotion downregulation in euthymic subjects with bipolar I disorder (BPI) and healthy control subjects. METHODS: Thirty BPI and 26 control subjects underwent functional magnetic resonance imaging scanning while performing an emotion processing task with passive viewing and emotion downregulation conditions. Contrasts were made for each group comparing the downregulation and passive viewing conditions, and these were entered into a between-group random effects analysis to assess group differences in activation. Psychophysiological interaction analyses were conducted to test for significant group differences in functional connectivity between the amygdala and inhibitory frontal regions (i.e., vlPFC). RESULTS: Control subjects showed the expected robust bilateral activation of frontal and limbic regions during passive viewing and emotion downregulation tasks. Between-group analyses revealed similar activation of BPI and control subjects during passive viewing but significantly decreased activation in bilateral vlPFC, bilateral anterior and posterior cingulate, medial frontal gyrus, and bilateral dorsal lateral prefrontal cortex during emotion downregulation in subjects with BPI. Connectivity analysis demonstrated that control subjects had significantly greater negative functional connectivity between the left amygdala and bilateral vlPFC compared with subjects with BPI. CONCLUSIONS: This study provides evidence that dysfunction in the neural networks responsible for emotion regulation, including the prefrontal cortex, cingulate, and subcortical structures, are present in BPI subjects, even while euthymic.
Biological psychiatry 07/2012; · 8.93 Impact Factor
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ABSTRACT: Although the amygdala and ventrolateral prefrontal cortex have been implicated in the pathophysiology of bipolar I disorder, the neural mechanisms underlying bipolar II disorder remain unknown. The authors examined neural activity in response to negative emotional faces during an emotion perception task that reliably activates emotion regulatory regions.
Twenty-one nonmedicated depressed bipolar II patients and 21 healthy comparison subjects underwent functional MRI (fMRI) while performing an emotional face-matching task. Within- and between-group whole-brain fMRI activation and seed-based connectivity analyses were conducted.
In depressed bipolar II patients, random-effects between-group fMRI analyses revealed a significant reduction in activation in several regions, including the left and right ventrolateral prefrontal cortices (Brodmann's area [BA] 47) and the right amygdala, a priori regions of interest. Additionally, bipolar patients exhibited significantly reduced negative functional connectivity between the right amygdala and the right orbitofrontal cortex (BA 10) as well as the right dorsolateral prefrontal cortex (BA 46) relative to healthy comparison subjects.
These findings suggest that bipolar II depression is characterized by reduced regional orbitofrontal and limbic activation and altered connectivity in a fronto-temporal circuit implicated in working memory and emotional learning. While the amygdala hypoactivation observed in bipolar II depression is opposite to the direction seen in bipolar I mania and may therefore be state dependent, the observed orbitofrontal cortex hypoactivation is consistent with findings in bipolar I depression, mania, and euthymia, suggesting a physiologic trait marker of the disorder.
American Journal of Psychiatry 07/2012; 169(8):831-40. · 12.54 Impact Factor
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ABSTRACT: Bipolar disorder (BP) is characterized by a dysfunction of mood, alternating between states of mania/hypomania and depression. Thus, the primary abnormality appears to be an inability to regulate emotion, the result of which is emotional extremes. The purpose of this paper is to review the current functional magnetic resonance imaging (fMRI) literature on adult patients with BP using emotion processing or regulation paradigms.
A search was conducted on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression, bipolar euthymia, emotion, and amygdala. Only those studies that were conducted in adult patients using an emotion activation task were included in the final review.
Using tasks that assess neural functioning during emotion processing and emotion regulation, many fMRI studies have examined BP subjects during mania and euthymia. Fewer fMRI studies have been conducted during depression, and fewer still have included the same subjects in multiple mood states. Despite these limitations, these studies have demonstrated specific abnormalities in frontal-limbic regions. Using a variety of paradigms, investigators have specifically evaluated the amygdala (a structure within the limbic system known to be critical for emotion) and the prefrontal cortex (PFC) (a region known to have a regulatory function over the limbic system).
These investigations reveal that amygdala activation varies as a function of mood state, while the PFC remains persistently hypoactivated across mood states. Emotional dysregulation and lability in mania and depression may reflect disruption of a frontal-limbic functional neuroanatomical network.
Bipolar Disorders 06/2012; 14(4):326-39. · 5.29 Impact Factor
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ABSTRACT: The inferior frontal cortical-striatal network plays an integral role in response inhibition in normal populations. While inferior frontal cortex (IFC) impairment has been reported in mania, this study explored whether this dysfunction persists in euthymia.
Functional magnetic resonance imaging (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder and 30 healthy subjects while performing the Go/NoGo response inhibition task. Behavioral data were collected to evaluate accuracy and response time. Within-group and between-group comparisons of activation were conducted using whole-brain analyses to probe significant group differences in neural function.
Both groups activated bilateral IFC. However, between-group comparisons showed a significantly reduced activation in this brain region in euthymic patients with bipolar disorder compared to healthy subjects. Other frontal and basal ganglia regions involved in response inhibition were additionally significantly reduced in bipolar disorder patients, in both the medicated and the unmedicated subgroups. No areas of greater activation were observed in bipolar disorder patients versus healthy subjects.
Bipolar disorder patients, even during euthymia, have a persistent reduction in activation of brain regions involved in response inhibition, suggesting that reduced activation in the orbitofrontal cortex and striatum is not solely related to the state of mania. These findings may represent underlying trait abnormalities in bipolar disorder.
Bipolar Disorders 06/2012; 14(4):442-50. · 5.29 Impact Factor
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ABSTRACT: Bipolar disorder and schizophrenia share common pathophysiological processes and may have similar perceptual abnormalities. Mismatch negativity (MMN) and P3a - event-related potentials associated with auditory preattentional processing - have been extensively studied in schizophrenia, but rarely in bipolar disorder. Furthermore, MMN and P3a have not been examined between diagnostic subgroups of patients with bipolar disorder. We evaluated MMN and P3a in patients with bipolar disorder compared to patients with schizophrenia and healthy controls.
MMN and P3a were assessed in 52 bipolar disorder patients, 30 schizophrenia patients, and 27 healthy control subjects during a duration-deviant auditory oddball paradigm.
Significant MMN and P3a amplitude reductions were present in patients with bipolar disorder and schizophrenia relative to controls. The MMN reduction was more prominent in patients with schizophrenia than bipolar disorder, at a trend level. P3a did not differ significantly between patient groups. There were no MMN or P3a differences between patients with bipolar I (n = 34) and bipolar II (n = 18) disorder. Patients with bipolar I disorder failed to show lateralized MMN, in contrast to the other groups. No MMN or P3a differences were found between patients with bipolar disorder taking (n = 12) and not taking (n = 40) lithium, as well as between those taking (n = 30) and not taking (n = 22) antipsychotic medications.
Patients with bipolar disorder showed deficits in preattentive auditory processing, including MMN deficits that are less severe and P3a deficits that are slightly more pronounced, than those seen in schizophrenia.
Bipolar Disorders 05/2012; 14(3):239-48. · 5.29 Impact Factor
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ABSTRACT: Prior structural neuroimaging studies of the amygdala in patients with bipolar disorder have reported higher or lower volumes, or no difference relative to healthy controls. These inconsistent findings may have resulted from combining subjects in different mood states. The prefrontal cortex has recently been reported to have a lower volume in depressed versus euthymic bipolar patients. Here we examined whether similar mood state-dependent volumetric differences are detectable in the amygdala.
Forty subjects, including 28 with bipolar disorder type I (12 depressed and 16 euthymic), and 12 healthy comparison subjects were scanned on a 3T magnetic resonance image (MRI) scanner. Amygdala volumes were manually traced and compared across subject groups, adjusting for sex and total brain volume.
Statistical analyses found a significant effect of mood state and hemisphere on amygdala volume. Subsequent comparisons revealed that amygdala volumes were significantly lower in the depressed bipolar group compared to both the euthymic bipolar (p=0.005) and healthy control (p=0.043) groups.
Our study was cross-sectional and some patients were medicated.
Our results suggest that mood state influences amygdala volume in subjects with bipolar disorder. Future studies that replicate these findings in unmedicated patient samples scanned longitudinally are needed.
Journal of affective disorders 04/2012; 139(3):298-301. · 3.76 Impact Factor
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Robert M Post,
Gabriele S Leverich, Lori L Altshuler,
Mark A Frye,
Trisha Suppes,
Susan L McElroy,
Paul E Keck,
Willem A Nolen,
Mike Rowe,
Ralph W Kupka,
Heinz Grunze,
Frederick K Goodwin
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ABSTRACT: The long-term impact of prior antidepressant exposure on the subsequent course of bipolar illness remains controversial.
139 outpatients (mean age, 42 years) with bipolar I disorder diagnosed by DSM-IV criteria had a detailed retrospective examination of their prior course of illness on the National Institute of Mental Health Life Chart Method. Number of prior antidepressant trials and total duration of antidepressant exposure were assessed. Prospective long-term response (for at least 6 months) to naturalistic treatment in the network from 1996 through 2002 was the primary outcome measure as it related to prior antidepressant exposure (and other illness variables) by logistic regression, with P < .05 used for statistical significance in this post hoc analysis.
Greater number of antidepressant trials, but not duration of antidepressant exposure, was related to prospective nonresponse (P = .0051) whether or not antidepressants were covered by concurrent treatment with a mood stabilizer or atypical antipsychotic. Poor prospective response was also independently related to having had an anxiety disorder and 20 or more prior affective episodes.
That the number of antidepressant trials, but not duration of antidepressant treatment, was associated with prospective nonresponse suggests that it is the repeated use of antidepressants to treat episodes of depression that is related to poor prospective response to naturalistic treatment. The direction of causality is unclear as to whether more antidepressant trials led to this increased treatment resistance or whether a difficult course of illness with more episodes and anxiety comorbidity engendered more attempts at antidepressant treatment.
The Journal of Clinical Psychiatry 03/2012; 73(7):924-30. · 5.80 Impact Factor
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ABSTRACT: Few studies have examined the relationship between local anatomic thickness of the cortex and the activation signals arising from it. Using structural and functional MRI, we examined whether a relationship exists between cortical thickness and brain activation. Twenty-eight participants were asked to perform the Go/NoGo response inhibition task known to activate the anterior cingulate and the prefrontal cortex. Structural data of the same regions were simultaneously collected. We hypothesized that cortical thickness in these brain regions would positively correlate with brain activation. Data from the structural MRI were aligned with those of functional MRI activation. There was a positive linear correlation between cortical thickness and activation during response inhibition in the right anterior cingulate cortex (Brodmann's Area 24). No significant thickness-activation correlations were found in the prefrontal cortex. Correlations between cortical thickness and activation may occur only in certain brain regions.
Neuroreport 03/2012; 23(7):420-4. · 1.66 Impact Factor
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ABSTRACT: Iron is essential for triggering oligodendrocytes to myelinate, however, in gray matter (GM) iron increases with age and is associated with age-related degenerative brain diseases. Women have lower iron levels than men, both in the periphery and in the brain, particularly in white matter (WM), possibly due to iron loss through menstruation. We tested the hypothesis that hysterectomy could increase WM iron levels. We assessed 3 WM and 5 gray matter regions in 39 postmenopausal women, of whom 15 had premenopausal hysterectomy, utilizing a validated magnetic resonance imaging technique called field-dependent R2 increase (FDRI) that quantifies ferritin iron. A group of 54 matched male subjects was included for comparison. Amongst women, hysterectomy was associated with significantly higher frontal lobe WM iron. Men had higher iron levels than women without hysterectomy in 3 brain regions but did not differ from women with hysterectomy in any region. The results suggest that menstruation-associated blood loss is a source of gender differences in brain iron. It is possible that brain iron can be influenced by peripheral iron levels and may thus be a modifiable risk factor for age-related degenerative diseases.
Neurobiology of aging 09/2011; 33(9):1950-8. · 5.94 Impact Factor
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Lara C Foland-Ross,
Susan Y Bookheimer,
Matthew D Lieberman,
Catherine A Sugar,
Jennifer D Townsend,
Jeffrey Fischer,
Salvatore Torrisi,
Conor Penfold,
Sarah K Madsen,
Paul M Thompson, Lori L Altshuler
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ABSTRACT: Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vlPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest.
NeuroImage 08/2011; 59(1):738-44. · 5.89 Impact Factor
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ABSTRACT: A preliminary within-subjects MRI study of seven patients with a diagnosis of bipolar I disorder revealed that, compared to remission, depression was associated with gray matter density increases in subgenual prefrontal cortex, parahippocampal gyrus, and inferior temporal gyri. Decreases were observed in superior and inferior frontal gyri and anterior cingulate.
Psychiatry Research 07/2011; 193(1):53-5. · 2.52 Impact Factor
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George Bartzokis,
Po H Lu,
Chetan P Amar,
Erika P Raven,
Nicole R Detore, Lori L Altshuler,
Jim Mintz,
Joseph Ventura,
Laurie R Casaus,
John S Luo,
Kenneth L Subotnik,
Keith H Nuechterlein
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ABSTRACT: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations.
Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects.
Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study.
WM volume change scores.
WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function.
The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.
Biological Psychiatry 07/2011; 132(1):35-41. · 8.28 Impact Factor
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ABSTRACT: Many patients with bipolar disorder do not regain their premorbid level of occupational functioning even after mood episodes have resolved. The reasons for this are not well understood. We evaluated the relationship between neurocognition and occupational function in bipolar disorder patients, following symptomatic recovery.
A total of 79 previously employed adults with bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks clinically euthymic) following a manic episode underwent a neurocognitive evaluation and assessment of occupational functioning. Study participants were evaluated every three months thereafter for up to nine months. Factor analysis was applied to reduce the initial set of neurocognitive variables to five domains: episodic memory, working memory/attention, executive function, visual scanning, and speed of processing. Multiple logistic regression models were used to examine the joint predictive values of these domains for determining occupational recovery.
At the time of symptomatic recovery, four of five neurocognitive factors were significant predictors of concomitant occupational recovery and the fifth, executive function, showed a trend in the same direction. For those not occupationally recovered at baseline, longitudinal analyses revealed that changes between baseline and the three-month follow-up timepoint in most cognitive domains were robust and highly significant predictors of occupational recovery at three months.
These findings indicate that better neurocognitive function in multiple domains and improvement in these domains over time are strongly predictive of subsequent occupational recovery. Treatments that target cognitive deficit may therefore have potential for improving long-term vocational functioning in bipolar illness.
Bipolar Disorders 06/2011; 13(4):323-33. · 5.29 Impact Factor
