Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect

Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18–40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.     

Sexually dimorphic distribution of orbitofrontal sulcogyral pattern in schizophrenia

Aim: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by a remarkable inter‐individual variability that likely reflects neurobehavioral traits and genetic aspects of neurodevelopment. The aim of the present study was to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and healthy controls (HC) to determine group differences in OFC sulcogyral pattern as well as gender differences between groups. Methods: Forty‐seven SZ patients (M/F, 23/24) and forty‐seven HC (M/F, 17/30), matched on age and gender, were analyzed using magnetic resonance imaging. The sulcogyral pattern was classified into type I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous paper. Chi‐squared analysis was used to investigate group and gender differences in the sulcogyral pattern distribution, and categorical regression was used to explore clinical correlations. Results: The distribution of OFC sulcogyral pattern in HC replicated the results found in the previous study (left, χ² = 0.02, P = 0.989; right, χ² = 0.97, P = 0.616), in that there were no gender differences. Moreover, the distribution in SZ‐M was in accordance with that in the previous study (left, χ² = 1.59, P = 0.451; right, χ² = 0.14, P = 0.933). Additionally, within SZ‐M, patients with the type III pattern had a higher total positive and negative syndrome scale score (β = 0.902, F = 14.75, P = 0.001). In contrast, the distribution in the right hemisphere in the SZ‐F group differed significantly from that observed in SZ‐M (χ² = 6.017, P = 0.046), but did not differ from HC (χ² = 2.557, P = 0.110). Conclusion: OFC sulcogyral pattern is altered in SZ‐M but not in SZ‐F, possibly reflecting gender differences in early neurodevelopment.     

Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study.

BACKGROUND: Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition. METHODS: Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor. RESULTS: Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann's area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects. CONCLUSIONS: Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.     

Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder

Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3‐D high‐spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age‐ and gender‐matched healthy controls. Optimized voxel‐based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism‐Extraversion‐Openness Personality Inventory scores. Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait‐Anxiety (β = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait‐Anxiety (β = ?0.394, F = 5.341, P = 0.032) and Neuroticism trait (β = ?0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.     

Parcellation of the human orbitofrontal cortex based on gray matter volume covariance

The human orbitofrontal cortex (OFC) is an enigmatic brain region that cannot be parcellated reliably using diffusional and functional magnetic resonance imaging (fMRI) because there is signal dropout that results from an inherent defect in imaging techniques. We hypothesise that the OFC can be reliably parcellated into subregions based on gray matter volume (GMV) covariance patterns that are derived from artefact‐free structural images. A total of 321 healthy young subjects were examined by high‐resolution structural MRI. The OFC was parcellated into subregions‐based GMV covariance patterns; and then sex and laterality differences in GMV covariance pattern of each OFC subregion were compared. The human OFC was parcellated into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. This parcellation scheme was validated by the same analyses of the left OFC and the bilateral OFCs in male and female subjects. Both visual observation and quantitative comparisons indicated a unique GMV covariance pattern for each OFC subregion. These OFC subregions mainly covaried with the prefrontal and temporal cortices, cingulate cortex and amygdala. In addition, GMV correlations of most OFC subregions were similar across sex and laterality except for significant laterality difference in the OFCl. The right OFCl had stronger GMV correlation with the right inferior frontal cortex. Using high‐resolution structural images, we established a reliable parcellation scheme for the human OFC, which may provide an in vivo guide for subregion‐level studies of this region and improve our understanding of the human OFC at subregional levels. Hum Brain Mapp 36:538–548, 2015. © 2014 Wiley Periodicals, Inc.     

Neocortical modulation of the amygdala response to fearful stimuli.

BACKGROUND: The cortical circuitry involved in conscious cognitive processes and the subcortical circuitry involved in fear responses have been extensively studied with neuroimaging, but their interactions remain largely unexplored. A recent functional magnetic resonance imaging (fMRI) study demonstrated that the engagement of the right prefrontal cortex during the cognitive evaluation of angry and fearful facial expressions is associated with an attenuation of the response of the amygdala to these same stimuli, providing evidence for a functional neural network for emotional regulation. METHODS: In the current study, we have explored the generalizability of this functional network by using threatening and fearful non-face stimuli derived from the International Affective Picture System (IAPS), as well as the influence of this network on peripheral autonomic responses. RESULTS: Similar to the earlier findings with facial expressions, blood oxygen level dependent fMRI revealed that whereas perceptual processing of IAPS stimuli was associated with a bilateral amygdala response, cognitive evaluation of these same stimuli was associated with attenuation of this amygdala response and a correlated increase in response of the right prefrontal cortex and the anterior cingulate cortex. Moreover, this pattern was reflected in changes in skin conductance. CONCLUSIONS: The current results further implicate the importance of neocortical regions, including the prefrontal and anterior cingulate cortices, in regulating emotional responses mediated by the amygdala through conscious evaluation and appraisal.     

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.     

Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a fMRI study.

BACKGROUND: Significant differences between individual responses to emotional stimuli can be important for the study of emotion. We investigated whether incorporating individual ratings of emotional arousal in the analysis of functional magnetic resonance imaging (fMRI) data improves the detection of activation in the medial prefrontal cortex (MPFC) and sublenticular extended amygdala (SLEA), areas implicated in the processing of emotional salience. METHODS: Healthy subjects viewed counterbalanced blocks of aversive, nonaversive, and blank images. Outside the scanner, they rated the intensity of emotional arousal (salience) of each presented picture. RESULTS: Incorporating the subject's response to each stimulus by using individualized regressors produced more robust activations within MPFC and SLEA compared with a simple boxcar regressor, identical for all subjects. CONCLUSIONS: Our findings demonstrate that individual behavioral data are useful in improving detection of activation in block-design functional imaging studies.     

Altered orbitofrontal sulcogyral patterns in adult males with high-functioning autism spectrum disorders

Functions of the orbitofrontal cortex include diverse social, cognitive and affective processes, many of which are abnormal in autism spectrum disorders (ASDs). Recently, altered orbitofrontal sulcogyral patterns have been revealed in several psychiatric conditions, such as schizophrenia, indicating a possibility that altered orbitofrontal sulcogyral morphology reflects abnormal neurodevelopment. However, the presence of sulcal alterations in ASD remains unexplored. Using structural magnetic resonance imaging, subtypes of the ‘H-shaped’ sulcus (Type I, II and III, in order of frequency), posterior orbital sulcus (POS) and intermediate orbital sulcus were identified in each hemisphere of adult males with ASD (n = 51) and matched normal controls (n = 55) based on the study by Chiavaras and Petrides. ASD showed a significantly altered distribution of H-shaped sulcal subtypes in both hemispheres, with a significant increase of Type III. A significant alteration in the distribution of sulcal subtypes was also identified in the right hemisphere POS of ASD. Categorical regression analysis revealed that Type I and II expressions predicted a reduced total Autism-Spectrum Quotient score. Furthermore, Type I expression was associated with a reduced ‘attention to detail’ subscale score. The results demonstrate that altered sulcogyral morphology can be a marker for abnormal neurodevelopment leading to the increased risk of developing autism.     

Oxytocin, sexually dimorphic features of the social brain, and autism

The common features of autism spectrum disorder, a highly heritable representative pervasive developmental disorder with significant heterogeneity and multiple-genetic factors, are severe dysfunction in social reciprocity, abnormalities in social brain regions, and disproportionately low probability in the female gender. Concomitantly, certain domains of mental function, such as emotional memory and social reciprocity, show a significant sex difference. In addition, recent neuroimaging studies have shown significant sexual dimorphisms in neuroanatomical correlates of social cognition. Recently, some sexually dimorphic factors, including oxytocin, vasopressin, and genes linked with the x-chromosome, have received attention because of their possible contribution to mental development especially in the social cognitive domain. Taking this evidence together, it is hypothesized that a sexually dimorphic factor associated with social reciprocity could affect characteristics of autism spectrum disorder including dysfunction in social reciprocity, abnormalities in social brain regions, and disproportionately low probability in female gender. This review article overviews sexual dimorphisms in clinical features of autism spectrum disorder, in normal social cognition, and in social brain function and structure. The association of oxytocin with sexual dimorphisms, social reciprocity, neural correlates of social cognition, and the pathogenesis of autism spectrum disorder were further summarized. Recent studies have suggested that oxytocin plays a role in social attachment in experimental animals, in enhancing social interactive ability in human adults, and in the pathogenesis of autism spectrum disorder. Thus, the ongoing accumulated evidence suggests that oxytocin deserves to be examined as a candidate that causes the sexually dimorphic aspect of human social reciprocity, social brain development and the pathogenesis of autism spectrum disorder.     

Perigenual cingulate gyrus volume in patients with schizophrenia: a magnetic resonance imaging study.

BACKGROUND: Anterior cingulate gyrus abnormalities have been suggested to be involved in the pathophysiology of schizophrenia; however, little is known about morphologic changes in the perigenual cingulate gyrus in schizophrenia patients. METHODS: We investigated perigenual cingulate gyrus volume in 40 schizophrenia patients (20 men, 20 women) and 40 age- and gender-matched normal controls using magnetic resonance imaging. Volume of both gray and white matter of the perigenual cingulate gyrus was measured on consecutive axial 1-mm slices. RESULTS: Total (left and right) perigenual cingulate gray matter volume was significantly reduced in female schizophrenia patients compared with female controls. There was no significant difference in the gray matter volume of the perigenual cingulate gyrus between male patients and male controls. Left perigenual cingulate white matter volume was significantly reduced in the patient compared with the control group. Furthermore, significant gender differences were found in the total gray and white matter volume of the perigenual cingulate gyrus in control subjects (women > men), although these gender differences were not significant in the patient group. CONCLUSIONS: Our findings suggests volume reduction of the perigenual cingulate gyrus in schizophrenia patients, especially women and that gender differences in perigenual cingulate morphology among normal subjects are, as has been suggested for other parts of the brain, reduced in schizophrenia patients.     

Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinson's disease

Decision-making and recognition of emotions are often impaired in patients with Parkinson's disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected ( P  < 0.05 FEW-small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.     

Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression.

BACKGROUND: Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression. METHODS: Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior. RESULTS: Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces. CONCLUSIONS: These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.     

Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression.

Previous studies have shown a reduction of orbital frontal cortex volume and an increase in magnetic resonance imaging signal hyperintensities in geriatric depression. We aimed to assess the relationship between subcortical gray- and deep white-matter lesions and orbital frontal cortex volume in elderly depressives and controls.The study included 41 elderly depressed patients and 41 age-matched control subjects. The orbital frontal cortex volume was measured in both hemispheres using a standardized MRI procedure. Signal hyperintensities were rated on (T2)-weighted MRI with qualitative lesion analyses performed according to an established hyperintensity classification system.After controlling for total cerebral hemisphere, age and sex, the geriatric depressed subjects had significant reduction in orbital frontal cortex volume and compared with the control group. Multiple linear regression modeling indicated that reduced orbital frontal cortex volumes were significantly associated with increased subcortical gray-matter lesions.Our study confirmed the reduction of OFC volume in geriatric depressed subjects. We also suggest that subcortical lesions may decrease OFC volume. Further studies are needed to understand how subcortical lesions may be related to OFC volume changes.     

Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study

Objective:  To investigate neural activity in prefrontal cortex and amygdala during bipolar depression.
Methods:  Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis.
Results:  Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant.
Conclusions:  Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder.     

Evidence for altered amygdala activation in schizophrenia in an adaptive emotion recognition task

Deficits in social cognition seem to present an intermediate phenotype for schizophrenia, and are known to be associated with an altered amygdala response to faces. However, current results are heterogeneous with respect to whether this altered amygdala response in schizophrenia is hypoactive or hyperactive in nature. The present study used functional magnetic resonance imaging to investigate emotion-specific amygdala activation in schizophrenia using a novel adaptive emotion recognition paradigm. Participants comprised 11 schizophrenia outpatients and 16 healthy controls who viewed face stimuli expressing emotions of anger, fear, happiness, and disgust, as well as neutral expressions. The adaptive emotion recognition approach allows the assessment of group differences in both emotion recognition performance and associated neuronal activity while also ensuring a comparable number of correctly recognized emotions between groups. Schizophrenia participants were slower and had a negative bias in emotion recognition. In addition, they showed reduced differential activation during recognition of emotional compared with neutral expressions. Correlation analyses revealed an association of a negative bias with amygdala activation for neutral facial expressions that was specific to the patient group. We replicated previous findings of affected emotion recognition in schizophrenia. Furthermore, we demonstrated that altered amygdala activation in the patient group was associated with the occurrence of a negative bias. These results provide further evidence for impaired social cognition in schizophrenia and point to a central role of the amygdala in negative misperceptions of facial stimuli in schizophrenia.     

Smaller amygdala is associated with anxiety in patients with panic disorder

Aims:  Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety.
Methods:  Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State–Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety.
Results:  Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = −2.248, d.f. = 55, P  = 0.029; right: t = −2.892, d.f. = 55, P  = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,−6,−16], Z score = 3.92, family-wise error-corrected P  = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = −0.545, P  = 0.016).
Conclusions:  These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack.     

Abnormally persistent latent inhibition induced by lesions to the nucleus accumbens core, basolateral amygdala and orbitofrontal cortex is reversed by clozapine but not by haloperidol

Latent inhibition (LI) is the proactive interference of inconsequential preexposure to a stimulus with its ability to signal significant events, and disrupted LI is considered to model positive symptoms of schizophrenia. We have recently shown that lesions of the nucleus accumbens core (NACc), basolateral amygdala (BLA) and orbitofrontal cortex (OFC) produce abnormally persistent LI, and suggested that this phenomenon may model negative symptoms. Here we tested whether NACc, BLA and OFC lesion-induced persistent LI would be reversed by the atypical antipsychotic drug (APD) clozapine but not by the typical APD haloperidol. Because clozapine's action is likely reflecting its 5HT2A receptor antagonism, we also tested whether NACc lesion-induced persistent LI would be reversed by the selective 5HT2A antagonist M100907. LI was measured in a conditioned emotional response procedure by comparing suppression of drinking in response to a tone in rats receiving 0 (non-preexposed) or 40 tone presentations (preexposed) followed by five tone-shock pairings. Under these conditions, control rats did not show LI but all lesioned rats persisted in exhibiting LI, and this was reversed by clozapine but not by haloperidol. In addition, M100907 reversed NACc lesion-induced persistent LI. These two novel phenomena, abnormally persistent LI and its selective reversal by an atypical APD, suggest a novel index of schizophrenia relevant behavioral abnormality and of atypical antipsychotic activity in the LI model. The identification of brain regions whose damage leads to persistent LI in the rat may provide valuable cues on dysfunctional brain circuits involved in negative symptoms and in the action of atypical APDs.     

Brain morphological abnormality in schizophrenia is independent of country of origin

OBJECTIVE: The disorder schizophrenia has a worldwide prevalence of 1% and is generally associated with lateral cerebral ventricular enlargement. Whether there is a relationship between these two findings is unclear but has aetiological relevance. METHOD: Consecutively admitted Chinese patients (n = 19) with first episode of schizophrenia and healthy community volunteers (n = 29) underwent magnetic resonance imaging brain scan. The groups were balanced for age, sex, best social class and handedness. These patients were similar on clinical and socio-demographic indices to those who declined participation (n = 15). Semi-automated volumetric analysis of whole brain volume, cortical grey matter, cerebrospinal fluid, sulci and lateral ventricles was performed. RESULTS: Chinese patients in their first episode of schizophrenia have significant enlargement of lateral ventricles. CONCLUSION: Brain morphological abnormality in schizophrenia is present regardless of the country of origin. The importance of genes in driving normal brain development and stable prevalence suggests that aetiology may favour genes over environment.     

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.