Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder

BACKGROUND: The purported functions of medial temporal lobe structures suggest their involvement in the pathophysiology of bipolar disorder (BD). Previous reports of abnormalities in the volume of the amygdala and hippocampus in patients with BD have been inconsistent in their findings and limited to adult samples. Appreciation of whether volumetric abnormalities are early features of BD or whether the abnormalities represent neurodegenerative changes associated with illness duration is limited by the paucity of data in juvenile samples. OBJECTIVE: To investigate amygdala and hippocampal volume in adults and adolescents with BD.Setting and PARTICIPANTS: Subjects included 36 individuals (14 adolescents and 22 adults) in outpatient treatment for BD type I at a university hospital or Veterans Affairs medical center or in the surrounding community, and 56 healthy comparison subjects (23 adolescents and 33 adults).Design and MAIN OUTCOME MEASURES: Amygdala and hippocampal volumes were defined and measured on high-resolution anatomic magnetic resonance imaging scans. We used a mixed-model, repeated-measures statistical analysis to compare amygdala and hippocampal volumes across groups while covarying for total brain volume, age, and sex. Potential effects of illness features were explored, including rapid cycling, medication, alcohol or other substance dependence, duration, and mood state. RESULTS: For both the amygdala and hippocampal regions, we found an overall significant volume reduction in the BD compared with the control group (P<.0001). Amygdala volume reductions (15.6%) were highly significant (P<.0001). We observed a nonsignificant trend (P =.054) toward reductions in hippocampal volumes of lesser magnitude (5.3%). Effects of illness features were not detected. CONCLUSIONS: These results suggest that BD is associated with decreased volumes of medial temporal lobe structures, with greater effect sizes in the amygdala than in the hippocampus. These abnormalities are likely manifested early in the course of illness, as they affected adolescent and adult subjects similarly in this sample.     

Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.

BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. RESULTS: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.     

Reduced amygdalar gray matter volume in familial pediatric bipolar disorder

OBJECTIVE: Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls. METHOD: Twenty children and adolescents with BD I (mean age = 4.6 years, four females) and 20 healthy age, gender, and IQ-matched controls underwent high-resolution magnetic resonance imaging at 3 T. Patients were mostly euthymic and most were taking medications. Amygdala, hippocampus, thalamus, and caudate volumes were determined by manual tracings from researchers blinded to diagnosis. Analyses of covariance were performed, with total brain volume, age, and gender as covariates. RESULTS:No differences were found in the volumes of hippocampus, caudate, and thalamus between subjects with BD and controls. Subjects with BD had smaller volumes in the left and right amygdala, driven by reductions in gray matter volume. Exploratory analyses revealed that subjects with BD with past lithium or valproate exposure tended to have greater amygdalar gray matter volume than subjects with BD without such exposure. CONCLUSIONS: Children and adolescents with early-onset BD may have reduced amygdalar volumes, consistent with other studies in this population. Prolonged medication exposure to lithium or valproate may account for findings in adults with BD of increased amygdalar volume relative to controls.     

Progressive grey matter alterations in bipolar disorder across the life span – A systematic review

Objectives

To elucidate the relationship between the course of bipolar disorder (BD) and structural brain changes across the life span, we conducted a systematic review of longitudinal imaging studies in adolescent and adult BD patients.

Methods

Eleven studies with 329 BD patients and 277 controls met our PICOS criteria (participants, intervention, comparison, outcome and study design): BD diagnosis based on DSM criteria, natural course of disease, comparison of grey matter changes in BD individuals over ≥1-year interval between scans.

Results

The selected studies yielded heterogeneous findings, partly due to varying patient characteristics, data acquisition and statistical models. Mood episodes were associated with greater grey matter loss in frontal brain regions over time. Brain volume decreased or remained stable in adolescent patients, whereas it increased in healthy adolescents. Adult BD patients showed increased cortical thinning and brain structural decline. In particular, disease onset in adolescence was associated with amygdala volume reduction, which was not reported in adult BD.

Conclusions

The evidence collected suggests that the progression of BD impairs adolescent brain development and accelerates structural brain decline across the lifespan. Age-specific changes in amygdala volume in adolescent BD suggest that reduced amygdala volume is a correlate of early onset BD. Clarifying the role of BD in brain development across the lifespan promises a deeper understanding of the progression of BD patients through different developmental episodes.     

MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults

OBJECTIVE: To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. BACKGROUND: Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. METHODS: Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. RESULTS: Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects. CONCLUSIONS: There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.     

Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism.

Background: Neurobiological factors have been implicated in the increased susceptibility for developing alcohol dependence that offspring from alcoholic families exhibit. The P300 component of the event-related potential shows developmental changes during childhood and adolescence that appear to be related to risk status. The underlying structural changes that accompany these neurophysiological changes are not well understood.Methods: Magnetic resonance imaging was used to measure cerebral, amygdala, and hippocampal volumes in 17 high-risk adolescent and young adult offspring from multiplex alcoholism families and 17 age-, gender-, and IQ-matched control subjects without a family history for alcoholism or other substance dependence. Twenty-two of the subjects are part of a longitudinal prospective study and have been followed an average of 7.3 years, making it possible to relate P300 developmental trajectories to structural volumes.Results: High-risk adolescents and young adults showed reduced right amygdala volume in comparison with control subjects. Right amygdala volume was significantly correlated with visual P300 amplitude.Conclusions: Offspring from families having a high density of alcoholism differ in both neurophysiological and neuroanatomical characteristics that could not be explained by personal drinking history or particular childhood and adolescent psychopathology. Because the amygdala tends to increase in volume during childhood and adolescence, smaller volumes in high-risk children may indicate a developmental delay that parallels delays seen in visual P300 amplitude.     

Relation Between Amygdala Structure and Function in Adolescents With Bipolar Disorder

ObjectivePrevious study supports the presence of reduced volume and elevated response to emotional stimuli in amygdala in adolescents with bipolar disorder (BD). In the present study, structural and functional magnetic resonance imaging scans were obtained during the same neuroimaging session to examine amygdala structure-function relations in adolescents with BD. We hypothesized that amygdala volume would be inversely associated with amygdala response to emotional stimuli, such that BD participants with the smallest amygdala volumes would exhibit the highest amygdala response.MethodFifty-one adolescents (21 with BD I and 30 control adolescents, ages 10-18 years) underwent structural and functional magnetic resonance imaging scans. Amygdala volume (n = 49) and signal change (n = 44) during emotional face processing were compared between groups, and structure-function correlations were examined within the BD group (n = 16).ResultsAdolescents with BD showed decreased amygdala volume (p = .009) and increased amygdala response to emotional faces (p = .043). There was no significant interaction between diagnosis and emotion type. A significant inverse association between amygdala volume and activation during emotional face processing was observed (r = ?0.54, p = .029).ConclusionsDecreased volume and increased response to emotional stimuli in the amygdala in adolescents with BD are consistent with previous reports. This study represents the first report, to our knowledge, of the two findings in the same adolescent BD sample and supports an amygdala structure-function relation characterized by an inverse association between volume and response to emotional stimuli. This preliminary finding requires replication and suggests a possible pathophysiological link between abnormalities in amygdala structure and response to emotional stimuli in BD. J. Am. Acad. Child Adolesc. Psychiatry,2009;48(6):636-642.     

Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis

Little work has directly examined the course of hippocampal volume in children and adults with childhood maltreatment-related posttraumatic stress disorder (PTSD). Data from adults suggest that hippocampal volume deficits are associated with PTSD, whereas findings from children with PTSD generally show no hippocampal volume deficits in PTSD. Additionally, the role of the amygdala in emotional response makes it a possible region for investigation in children and adults with childhood maltreatment-related PTSD. The objectives of this study were 2-fold: (1) to meta-analytically determine whether hippocampal and amygdala volumes in children and adults with PTSD from childhood maltreatment differ from those in healthy controls, and (2) to use cross-sectional findings performed with meta-analyses as a proxy for longitudinal studies to estimate the course of hippocampal and amygdala volumes in child and adult subjects with PTSD from childhood maltreatment. Using electronic databases, we identified articles containing hippocampal and amygdala data for children with PTSD and adults with PTSD from childhood maltreatment. Data were extracted and effect sizes were calculated using Comprehensive Meta-Analysis Version 2.0. Reduced bilateral hippocampal volume was found in adults with childhood maltreatment-related PTSD compared with healthy controls, but this deficit was not seen in children with maltreatment-related PTSD, suggesting hippocampal volume deficits from childhood maltreatment may not be apparent until adulthood. Greater left than right hippocampal volume was found in the adult healthy control group but not in the PTSD group. Amygdala volume in children with maltreatment-related PTSD did not differ from that in healthy controls. Hippocampal volume is normal in children with maltreatment-related PTSD but not in adults with PTSD from childhood maltreatment, suggesting an initially volumetrically normal hippocampus with subsequent abnormal volumetric development occurring after trauma exposure. However, longitudinal studies are needed to support these preliminary findings.     

Fronto-limbic brain abnormalities in juvenile onset bipolar disorder.

BACKGROUND: Advances in brain imaging techniques and cognitive neuropsychology have brought new possibilities for the in vivo study of the pathophysiology of neuropsychiatric disorders, including bipolar disorder (BD). Recently, such studies have been extended to the pediatric age range. Here we review the neuroimaging and neuropsychological studies conducted in BD children and adolescents. METHODS: A review of the peer-reviewed published literature was conducted in Medline for the period of 1966 to April 2005. RESULTS: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies suggest abnormalities in fronto-limbic structures in pediatric BD patients, similar to those found in adults. A notable exception in pediatric BD patients is smaller amygdala volumes compared to healthy controls, contrary to what has been reported in most adult studies. CONCLUSIONS: Further research evaluating children and adolescents is needed to study the normal neurodevelopmental process and to answer how and when the illness processes that result in bipolar disorder exert their effects on the developing brain.     

Longitudinal changes in amygdala,hippocampus and cortisol development following early caregiving adversity

Although decades of research have shown associations between early caregiving adversity, stress physiology and limbic brain volume (e.g., amygdala, hippocampus), the developmental trajectories of these phenotypes are not well characterized. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4–20 years old) completed 1–3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239) and structural MRI (N = 156). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth rate of the amygdala, resulting in smaller volumes by adolescence. Amygdala and hippocampal volumes were also prospectively associated with future morning cortisol in both groups. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood.     

Sexually dimorphic changes in the amygdala in relation to delusional beliefs in first episode psychosis

BACKGROUND: Few attempts have been made to examine the relationship between amygdala abnormalities and specific symptoms in psychosis. The present study explored the relationship between amygdala morphology and mood congruent and mood incongruent delusional beliefs. METHODS: Amygdala volumes were measured in 43 patients presenting with delusional beliefs in the context of their first episode of psychosis and 43 healthy volunteers matched for age and gender. RESULTS: Left-greater-than-right-asymmetry of the amygdala varied as a function of gender and mood congruence of delusional beliefs, due to asymmetrical enlargement of the left amygdala in women presenting with predominantly mood incongruent delusions. However, there was no difference in amygdala volumes across groups. CONCLUSIONS: Amygdala abnormalities in women may be associated with aberrant emotional processing that could contribute to the development of mood incongruent delusional beliefs. Sexually dimorphic changes in the amygdala may contribute to differential phenotypic illness expression in men and women.     

Amygdala Functional Connectivity Features in Grief: A Pilot Longitudinal Study

ObjectiveAcute grief, in an important minority of older adults, can become protracted, intense, and debilitating, leading to the development of complicated grief (CG). However, the neurobiologic mechanisms underlying a maladaptive grief response after an attachment loss are unknown. The current study aimed to examine the amygdala brain network features that cross-sectionally explain the symptom variance and longitudinally relate to grief symptom trajectories after an attachment loss.MethodsBaseline amygdala functional connectivity (Fc) was assessed using a seed-based resting-state functional magnetic resonance imaging method in 35 adults who were within 1-year after death of a loved one and 21 healthy comparison (HC) participants. Magnetic resonance imaging scans were obtained at baseline, and clinical assessments, including the inventory of complicated grief (ICG) were completed at weeks 0, 8, 16, and 26 (endpoint).ResultsRelative to HC participants, grief participants showed increased amygdala Fc in the posterior default mode (bilateral medial temporal lobes and left precuneus) and thalamus. Amygdala Fc in the default mode and ventral affective regions positively correlated with ICG scores at baseline. Furthermore, increased baseline amygdala functional connections with the dorsal frontal executive control and salience network regions correlated with worsening ICG scores over time. These longitudinal findings persisted after controlling for covariates, including baseline depressive and anxiety symptoms.ConclusionThese results provide novel preliminary evidence suggesting amygdala-based brain network measures to cross-sectionally explain symptom variance and longitudinally correlate with grief symptom trajectories in grievers. Amygdala brain network function measures may have the potential to serve as biomarkers of CG.     

Amygdala reduction in patients with ADHD compared with major depression and healthy volunteers

Frodl T, Stauber J, Schaaff N, Koutsouleris N, Scheuerecker J, Ewers M, Omerovic M, Opgen‐Rhein M, Hampel H, Reiser M, Möller H.‐J, Meisenzahl E. Amygdala reduction in patients with ADHD compared with major depression and healthy volunteers. Objective: Results in adult attention deficit hyperactivity disorder (ADHD) on structural brain changes and the clinical relevance are contradictory. The aim of this study was to investigate whether in adult patients with ADHD hippocampal or amygdala volumes differs from that in healthy controls and patients with major depression (MD). Method: Twenty patients with ADHD, 20 matched patients with MD and 20 healthy controls were studied with high resolution magnetic resonance imaging. Results: Amygdala volumes in patients with ADHD were bilaterally smaller than in patients with MD and healthy controls. In ADHD, more hyperactivity and less inattention were associated with smaller right amygdala volumes, and more symptoms of depression with larger amygdala volumes. Conclusion: This study supports findings that the amygdala plays an important role in the systemic brain pathophysiology of ADHD. Whether patients with ADHD and larger amygdala volumes are more vulnerable to affective disorders needs further investigation.     

Amygdala and hippocampus volumes in pediatric major depression.

BACKGROUND: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. METHODS: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. RESULTS: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. CONCLUSIONS: Smaller amygdalas are present early in the course of pediatric depression and may predispose to the development of this disorder or perhaps more generally of childhood mood disorders. Future research should examine the longitudinal course and functional correlates of amygdala volume abnormalities in childhood-onset depression, including their possible moderation by gender.     

Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder

Perlman SB, Almeida JRC, Kronhaus DM, Versace A, LaBarbara EJ, Klein CR, Phillips ML. Amygdala activity and prefrontal cortex–amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder. Bipolar Disord 2012: 14: 162–174. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Methods: Thirty‐one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block‐design emotion processing task requiring color‐labeling of a color flash superimposed on a task‐irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top‐down) and following (bottom‐up) activity between the PFC and the left and right amygdalae. Results: Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted‐BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed‐BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted‐BD and depressed‐BD subjects. Discussion: EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala–PFC circuitry, supporting implicit emotion processing between remitted‐BD and depressed‐BD subjects, which may underlie changes from remission to depression in BD.     

Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder.

BACKGROUND: In vivo imaging studies in adult bipolar patients have suggested enlargement of the amygdala. It is not known whether this abnormality is already present early in the illness course or whether it develops later in life. We conducted a morphometric MRI study to examine the size of specific temporal lobe structures in adolescents and young adults with bipolar disorder and healthy control subjects, as well as their relationship with age, to examine possible neurodevelopmental abnormalities. METHODS: Subjects included 16 DSM-IV bipolar patients (16 +/- 3 years) and 21 healthy controls (mean age +/- SD = 17 +/- 4 years). Measures of amygdala, hippocampus, temporal gray matter, temporal lobe, and intracranial volumes (ICV) were obtained. RESULTS: There was a trend to smaller left amygdala volumes in patients (mean volumes +/- SD = 1.58 +/- .42 mL) versus control subjects (1.83 +/- .4 mL; F = 3.87, df = 1,32, p = .06). Bipolar patients did not show significant differences in right or left hippocampus, temporal lobe gray matter, temporal lobe, or right amygdala volumes (analysis of covariance, age, gender, and ICV as covariates, p > .05) compared with healthy control subjects. Furthermore, there was a direct correlation between left amygdala volumes and age (r =. 50, p = .047) in patients, whereas in healthy controls there was an inverse correlation (r = -.48, p = .03). CONCLUSIONS: The direct correlation between left amygdala volumes and age in bipolar patients, not present in healthy control subjects, may reflect abnormal developmental mechanisms in bipolar disorder.     

A developmental examination of amygdala response to facial expressions

Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala-hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions.     

Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment

Hajek T, Cullis J, Novak T, Kopecek M, Höschl C, Blagdon R, O’Donovan C, Bauer M, Young L T, MacQueen G, Alda M. Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.
Bipolar Disord 2012: 14: 261–270. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). Methods: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non‐Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li‐naïve, young BD participants (15–30 years of age) and 18 sex‐ and age‐matched healthy controls. We compared hippocampal volumes obtained from 1.5‐T magnetic resonance imaging (MRI) scans using optimized voxel‐based morphometry with small volume correction. Results: The non‐Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li‐naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. Conclusions: Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li‐naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.     

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy.

BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.     

Amygdala and insula volumes prior to illness onset in bipolar disorder: a magnetic resonance imaging study

There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328 days - UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12 months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippocampus, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippocampal volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched samples.