Canine intrahepatic portosystemic shunts: Interlobar and intralobar classifications.

This two-part study design showed that a canine congenital intrahepatic portosystemic shunt (IPSS) may be classified by its location within a liver fissure (interlobar) or lobe (intralobar). A prospective anatomic study reviewed normal canine liver morphology and showed the CT angiography (CTA) appearance of the normal canine ductus venosus (DV), which was confirmed via dissection and literature review to be between the papillary process and left-lateral liver lobe (in the fissure for ligamentum venosum). A retrospective multi-institutional case series documented the frequency of imaging findings in 56 dogs with a single IPSS that underwent portal CTA at Cornell University or the Schwarzman Animal Medical Center between June 2008 and August 2022. An interlobar IPSS was seen in 24 of 56 (43%) dogs, all arose from the left portal branch except one. These shunts were typically near the median plane, remained interlobar throughout the course, and were nearly always (96%) craniodorsal to the porta hepatis. Four types were distinguished: patent DV (11 dogs), left interlobar (11 dogs), right interlobar (1 dog), and ventral interlobar (1 dog). Only about half (46%) were in the fissure for ligamentum venosum and therefore classified as a patent DV. An intralobar IPSS was seen in 32 of 56 (57%) dogs, most (88%) originated from the right portal branch and were in the right-lateral liver lobe (21 dogs) or caudate process (7 dogs). During canine portal CTA, documenting the interlobar or intralobar location of an IPSS might increase the consistency and validity of IPSS description.

Mood and neural responses to social rejection do not seem to be altered in resilient adolescents with a history of adversity.

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered "resilient"), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Brain structure abnormalities in adolescent girls with conduct disorder.

BACKGROUND: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for sex differences in the relationship between CD and brain structure. METHODS: Female adolescents with CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20) underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were performed using voxel-based morphometry. We also tested for sex differences using archive data obtained from male CD and control participants. RESULTS: Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls. Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume, whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume. The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis interactions in bilateral anterior insula. CONCLUSIONS: We observed structural abnormalities in brain regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly overlap with those reported in previous studies of CD in male adolescents.

5-HTTLPR-environment interplay and its effects on neural reactivity in adolescents.

It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11 years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity.

Interacting outcome retrieval, anticipation, and feedback processes in the human brain.

Cognitive control is an inherently multivariate phenomenon, and its neural basis is currently unclear. Here we examined using functional magnetic resonance imaging how participants retrieve prelearnt information from memory, use this information to guide responses for an impending decision, and adjust their responses based on outcome feedback. We developed a behavioral task designed to manipulate memory outcome-retrieval load, outcome-anticipation interval, and outcome-feedback processes. This allowed us to understand the neural basis of these cognitive processes in isolation and how they interact. Extending previous work, we found a retrieval-load by outcome-feedback interaction in the left globus pallidus; an outcome-feedback by anticipation-interval interaction in the inferior prefrontal cortex; a retrieval-load by anticipation-interval interaction in the midcingulate gyrus and a load by interval by outcome interaction in the right frontal pole. These results further advance our knowledge of how fundamental cognitive processes interact physiologically to give rise to higher-level behavioral control.

Investigating the effects of cerebellar transcranial direct current stimulation on saccadic adaptation and cortisol response.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) over the prefrontal cortex has been shown to modulate subjective, neuronal and neuroendocrine responses, particularly in the context of stress processing. However, it is currently unknown whether tDCS stimulation over other brain regions, such as the cerebellum, can similarly affect the stress response. Despite increasing evidence linking the cerebellum to stress-related processing, no studies have investigated the hormonal and behavioural effects of cerebellar tDCS. METHODS: This study tested the hypothesis of a cerebellar tDCS effect on mood, behaviour and cortisol. To do this we employed a single-blind, sham-controlled design to measure performance on a cerebellar-dependent saccadic adaptation task, together with changes in cortisol output and mood, during online anodal and cathodal stimulation. Forty-five participants were included in the analysis. Stimulation groups were matched on demographic variables, potential confounding factors known to affect cortisol levels, mood and a number of personality characteristics. RESULTS: Results showed that tDCS polarity did not affect cortisol levels or subjective mood, but did affect behaviour. Participants receiving anodal stimulation showed an 8.4% increase in saccadic adaptation, which was significantly larger compared to the cathodal group (1.6%). CONCLUSION: The stimulation effect on saccadic adaptation contributes to the current body of literature examining the mechanisms of cerebellar stimulation on associated function. We conclude that further studies are needed to understand whether and how cerebellar tDCS may module stress reactivity under challenge conditions.

How biopsychosocial depressive risk shapes behavioral and neural responses to social evaluation in adolescence.

INTRODUCTION: Understanding the emotional responsivity style and neurocognitive profiles of depression-related processes in at-risk youth may be helpful in revealing those most likely to develop affective disorders. However, the multiplicity of biopsychosocial risk factors makes it difficult to disentangle unique and combined effects at a neurobiological level. METHODS: In a population-derived sample of 56 older adolescents (aged 17-20), we adopted partial least squares regression and correlation models to explore the relationships between multivariate biopsychosocial risks for later depression, emotional response style, and fMRI activity, to rejecting and inclusive social feedback. RESULTS: Behaviorally, higher depressive risk was associated with both reduced negative affect following negative social feedback and reduced positive affect following positive social feedback. In response to both cues of rejection and inclusion, we observed a general neural pattern of increased cingulate, temporal, and striatal activity in the brain. Secondly, in response to rejection only, we observed a pattern of activity in ostensibly executive control- and emotion regulation-related brain regions encompassing fronto-parietal brain networks including the angular gyrus. CONCLUSION: The results suggest that risk for depression is associated with a pervasive emotional insensitivity in the face of positive and negative social feedback.

An investigation of cognitive 'branching' processes in major depression.

BACKGROUND: Patients with depression demonstrate cognitive impairment on a wide range of cognitive tasks, particularly putative tasks of frontal lobe function. Recent models of frontal lobe function have argued that the frontal pole region is involved in cognitive branching, a process requiring holding in mind one goal while performing sub-goal processes. Evidence for this model comes from functional neuroimaging and frontal-pole lesion patients. We have utilised these new concepts to investigate the possibility that patients with depression are impaired at cognitive 'branching'. METHODS: 11 non-medicated patients with major depression were compared to 11 matched controls in a behavioural study on a task of cognitive 'branching'. In the version employed here, we recorded participant's performance as they learnt to perform the task. This involved participants completing a control condition, followed by a working memory condition, a dual-task condition and finally the branching condition, which integrates processes in the working memory and dual-task conditions. We also measured participants on a number of other cognitive tasks as well as mood-state before and after the branching experiment. RESULTS: Patients took longer to learn the first condition, but performed comparably to controls after six runs of the task. Overall, reaction times decreased with repeated exposure on the task conditions in controls, with this effect attenuated in patients. Importantly, no differences were found between patients and controls on the branching condition. There was, however, a significant change in mood-state with patients increasing in positive affect and decreasing in negative affect after the experiment. CONCLUSION: We found no clear evidence of a fundamental impairment in anterior prefrontal 'branching processes' in patients with depression. Rather our data argue for a contextual learning impairment underlying cognitive dysfunction in this disorder. Our data suggest that MDD patients are able to perform high-level cognitive control tasks comparably to controls provided they are well trained. Future work should replicate these preliminary findings in a larger sample of MDD patients.

Functional coupling of the amygdala in depressed patients treated with antidepressant medication.

The amygdala plays a central role in various aspects of affect processing and mood regulation by its rich anatomical connections to other limbic and cortical regions. It is plausible that depressive disorders, and response to antidepressant drugs, may reflect changes in the physiological coupling between the amygdala and other components of affect-related large-scale brain systems. We explored this hypothesis by mapping the functional coupling of right and left amygdalae in functional magnetic resonance imaging data acquired from 19 patients with major depressive disorder and 19 healthy volunteers, each scanned twice (at baseline and 8 weeks later) during performance of an implicit facial affect processing task. Between scanning sessions, the patients received treatment with an antidepressant drug, fluoxetine 20 mg/day. We found that the amygdala was positively coupled bilaterally with medial temporal and ventral occipital regions, and negatively coupled with the anterior cingulate cortex. Antidepressant treatment was associated with significantly increased coupling between the amygdala and right frontal and cingulate cortex, striatum, and thalamus. Treatment-related increases in functional coupling to frontal and other regions were greater for the left amygdala than for the right amygdala. These results indicate that antidepressant drug effects can be measured in terms of altered coupling between components of cortico-limbic systems and that these effects were most clearly demonstrated by enhanced functional coupling of the left amygdala.

Psychosocial stress affects the acquisition of cerebellar-dependent sensorimotor adaptation.

Despite being overlooked in theoretical models of stress-related disorders, differences in cerebellar structure and function are consistently reported in studies of individuals exposed to current and early-life stressors. However, the mediating processes through which stress impacts upon cerebellar function are currently unknown. The aim of the current experiment was to test the effects of experimentally-induced acute stress on cerebellar functioning, using a classic, forward saccadic adaptation paradigm in healthy, young men and women. Stress induction was achieved by employing the Montreal Imaging Stress Task (MIST), a task employing mental arithmetic and negative social feedback to generate significant physiological and endocrine stress responses. Saccadic adaptation was elicited using the double-step target paradigm. In the experiment, 48 participants matched for gender and age were exposed to either a stress (n = 25) or a control (n = 23) condition. Saliva for cortisol analysis was collected before, immediately after, and 10, and 30 min after the MIST. Saccadic adaptation was assessed approximately 10 min after stress induction, when cortisol levels peaked. Participants in the stress group reported significantly more stress symptoms and exhibited greater total cortisol output compared to controls. The stress manipulation was associated with slower learning rates in the stress group, while control participants acquired adaptation faster. Learning rates were negatively associated with cortisol output and mood disturbance. Results suggest that experimentally-induced stress slowed acquisition of cerebellar-dependent saccadic adaptation, related to increases in cortisol output. These 'proof-of-principle' data demonstrate that stress modulates cerebellar-related functions.

A longitudinal functional magnetic resonance imaging study of verbal working memory in depression after antidepressant therapy.

BACKGROUND: Impairments in the neural circuitry of verbal working memory are evident in depression. Factors of task demand and depressive state might have significant effects on its functional neuroanatomy. METHODS: Two groups underwent functional magnetic resonance imaging while performing a verbal working memory task of varying cognitive load (n-back). The patient group comprised 20 medication-free individuals in an acute episode of unipolar major depression and the control group comprised 20 healthy individuals. Scans were acquired at weeks 0 (baseline), 2, and 8. Patients received treatment with fluoxetine after the baseline scan. Cerebral activations were measured for mean overall activation as well as the linear and quadratic load-response activity with increasing task demand (1-, 2-, 3-back). RESULTS: There were no significant differences in performance accuracy between groups. However, a main effect of group was observed in the load-response activity in frontal and posterior cortical regions within the verbal working memory network in which patients showed a greater load-response relative to control subjects. Group by time effects were revealed in the load-response activity in the caudate and thalamus. As a marker of treatment response, a lower linear load-response at baseline in the dorsal anterior cingulate, left middle frontal, and lateral temporal cortices was associated with an improved clinical outcome. CONCLUSIONS: Maintenance of performance accuracy in patients was accompanied by a significant increase in the load-response activity in frontal and posterior cortical regions within the verbal working memory network. These data also provide further support for resilience of activity in the anterior cingulate as a predictor of treatment response in depression.

Neural responses to happy facial expressions in major depression following antidepressant treatment.

OBJECTIVE: Processing affective facial expressions is an important component of interpersonal relationships. However, depressed patients show impairments in this system. The present study investigated the neural correlates of implicit processing of happy facial expressions in depression and identified regions affected by antidepressant therapy. METHOD: Two groups of subjects participated in a prospective study with functional magnetic resonance imaging (fMRI). The patients were 19 medication-free subjects (mean age, 43.2 years) with major depression, acute depressive episode, unipolar subtype. The comparison group contained 19 matched healthy volunteers (mean age, 42.8 years). Both groups underwent fMRI scans at baseline (week 0) and at 8 weeks. Following the baseline scan, the patients received treatment with fluoxetine, 20 mg daily. The fMRI task was implicit affect recognition with standard facial stimuli morphed to display varying intensities of happiness. The fMRI data were analyzed to estimate the average activation (overall capacity) and differential response to variable intensity (dynamic range) in brain systems involved in processing facial affect. RESULTS: An attenuated dynamic range of response in limbic-subcortical and extrastriate visual regions was evident in the depressed patients, relative to the comparison subjects. The attenuated extrastriate cortical activation at baseline was increased following antidepressant treatment, and symptomatic improvement was associated with greater overall capacity in the hippocampal and extrastriate regions. CONCLUSIONS: Impairments in the neural processing of happy facial expressions in depression were evident in the core regions of affective facial processing, which were reversed following treatment. These data complement the neural effects observed with negative affective stimuli.

Social pain and social gain in the adolescent brain: A common neural circuitry underlying both positive and negative social evaluation.

Social interaction inherently involves the subjective evaluation of cues salient to social inclusion and exclusion. Testifying to the importance of such social cues, parts of the neural system dedicated to the detection of physical pain, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been shown to be equally sensitive to the detection of social pain experienced after social exclusion. However, recent work suggests that this dACC-AI matrix may index any socially pertinent information. We directly tested the hypothesis that the dACC-AI would respond to cues of both inclusion and exclusion, using a novel social feedback fMRI paradigm in a population-derived sample of adolescents. We show that the dACC and left AI are commonly activated by feedback cues of inclusion and exclusion. Our findings suggest that theoretical accounts of the dACC-AI network as a neural alarm system restricted within the social domain to the processing of signals of exclusion require significant revision.

Enhanced emotion regulation capacity and its neural substrates in those exposed to moderate childhood adversity.

Individuals exposed to childhood adversities (CA) present with emotion regulation (ER) difficulties in later life, which have been identified as risk and maintenance factors for psychopathologies. However, it is unclear if CA negatively impacts on ER capacity per se or whether observed regulation difficulties are a function of the challenging circumstances in which ER is being deployed. In this longitudinal study, we aimed to clarify this association by investigating the behavioral and neural effects of exposure to common moderate CA (mCA) on a laboratory measure of ER capacity in late adolescence/young adulthood. Our population-derived samples of adolescents/young adults (N = 53) were administered a film-based ER-task during functional magnetic resonance imaging that allowed evaluation of ER across mCA-exposure. mCA-exposure was associated with enhanced ER capacity over both positive and negative affect. At the neural level, the better ER of negative material in those exposed to mCA was associated with reduced recruitment of ER-related brain regions, including the prefrontal cortex and temporal gyrus. In addition mCA-exposure was associated with a greater down-regulation of the amygdala during ER of negative material. The implications of these findings for our understanding of the effects of mCA on the emergence of resilience in adolescence are discussed.

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study.

BACKGROUND: Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. OBJECTIVES: To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. DESIGN: Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. SETTING: Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. PATIENTS AND OTHER PARTICIPANTS: We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers. Intervention After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. MAIN OUTCOME MEASURES: Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group x time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. RESULTS: Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. CONCLUSIONS: Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the dynamic range of the left prefrontal cortex. Changes in anterior cingulate function associated with symptomatic improvement indicate that fMRI may be a useful surrogate marker of antidepressant treatment response.

Atypical neural responses during face processing in female adolescents with conduct disorder.

OBJECTIVE: Conduct disorder (CD) in females is associated with negative adult outcomes including mental health problems and personality disorders. Although recent neuroimaging studies have reported changes in neural activity during facial emotion processing in males with CD or callous-unemotional (CU) traits, there have been no neuroimaging studies specifically assessing females with CD. We addressed this gap by investigating whether female adolescents with CD show atypical neural activation when processing emotional or neutral faces. METHOD: We acquired functional magnetic resonance imaging (fMRI) data from 20 female adolescents with CD and 20 female control participants while they viewed angry, sad, and neutral faces. RESULTS: An omnibus group (CD, control) by facial emotion (angry, sad, neutral) analysis of variance (ANOVA) revealed main effects of facial emotion in superior temporal cortex, fusiform gyrus, ventrolateral prefrontal cortex and insula, and main effects of group in medial orbitofrontal cortex (OFC) and right anterior insula. Female participants with CD showed reduced medial OFC and increased anterior insula responses relative to healthy controls. There were no significant group × facial emotion interactions. Lifetime CD symptoms were negatively correlated with amygdala, superior temporal cortex, fusiform gyrus, and dorsolateral prefrontal cortex activity for the contrast "all-faces versus fixation." CU traits were negatively correlated with fusiform gyrus activity for the contrast sad versus neutral faces. CONCLUSION: Females with CD showed atypical neural activation during the processing of all facial expressions, irrespective of valence. Our results demonstrate that severity of CD symptoms and CU traits is important in explaining abnormal patterns of neural activity.

General and specific effects of early-life psychosocial adversities on adolescent grey matter volume.

Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life.

5-HTTLPR and early childhood adversities moderate cognitive and emotional processing in adolescence.

BACKGROUND: Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) and exposure to early childhood adversities (CA) are independently associated with individual differences in cognitive and emotional processing. Whether these two factors interact to influence cognitive and emotional processing is not known. METHODOLOGY AND PRINCIPAL FINDINGS: We used a sample of 238 adolescents from a community study characterised by the presence of the short allele of 5-HTTLPR (LL, LS, SS) and the presence or absence of exposure to CA before 6 years of age. We measured cognitive and emotional processing using a set of neuropsychological tasks selected predominantly from the CANTAB® battery. We found that adolescents homozygous for the short allele (SS) of 5-HTTLPR and exposed to CA were worse at classifying negative and neutral stimuli and made more errors in response to ambiguous negative feedback. In addition, cognitive and emotional processing deficits were associated with diagnoses of anxiety and/or depressions. CONCLUSION AND SIGNIFICANCE: Cognitive and emotional processing deficits may act as a transdiagnostic intermediate marker for anxiety and depressive disorders in genetically susceptible individuals exposed to CA.

Subregional hippocampal deformations in major depressive disorder.

BACKGROUND: Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity. METHODS: Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42 years) and 37 age, gender and IQ-matched healthy individuals. Hippocampal volume and subregional structural differences were measured by manual tracings and identification of homologous surface points to the central core of each hippocampus. RESULTS: Both right (P=0.001) and left (P=0.005) hippocampal volumes were reduced in patients relative to healthy controls (n=37 patients and n=37 controls), while only the right hippocampus (P=0.016) showed a reduced volume in a subgroup of first-episode depression patients (n=13) relative to healthy controls. Shape analysis localised the subregional deformations to the subiculum and CA1 subfield extending into the CA2-3 subfields predominantly in the tail regions in the right (P=0.017) and left (P=0.011) hippocampi. LIMITATIONS: As all patients were in an acute depressive episode, effects associated with depressive state cannot be distinguished from trait effects. CONCLUSIONS: Subregional hippocampal deficits are present early in the course of major depression. The deformations may reflect structural correlates underlying functional memory impairments and distinguish depression from other psychiatric disorders.