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Previous research has demonstrated that individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test (WCST) than those who are heterozygous. This study sought to determine whether variation in the rs2067477 genotype was associated with differential changes in brain structure. Data from 227 patients with established schizophrenia or schizoaffective disorder were obtained from the Australian Schizophrenia Research Bank. Whole-brain voxel-based morphometry was performed to compare regional grey matter volume (GMV) between the 267C/C (N=191) and 267C/A (N=36) groups. Secondary analyses tested for an effect of genotype on cognition (the WCST was not available). Individuals who were homozygous (267C/C) demonstrated significantly reduced GMV in the right precentral gyrus compared to those who were heterozygous (267C/A). These preliminary results suggest that the rs2067477 genotype is associated with brain structure in the right precentral gyrus in individuals with schizophrenia/schizoaffective disorder. Future studies are required to replicate these results and directly link the volumetric reductions with specific cognitive processes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Stress and abnormal hypothalamic-pituitary-adrenal axis functioning have been implicated in the early phase of psychosis and may partly explain reported changes in brain structure. This study used magnetic resonance imaging to investigate whether biological measures of stress were related to brain structure at baseline and to structural changes over the first 12 weeks of treatment in first episode patients (n=22) compared with matched healthy controls (n=22). At baseline, no significant group differences in biological measures of stress, cortical thickness or hippocampal volume were observed, but a significantly stronger relationship between baseline levels of cortisol and smaller white matter volumes of the cuneus and anterior cingulate was found in patients compared with controls. Over the first 12 weeks of treatment, patients showed a significant reduction in thickness of the posterior cingulate compared with controls. Patients also showed a significant positive relationship between baseline cortisol and increases in hippocampal volume over time, suggestive of brain swelling in association with psychotic exacerbation, while no such relationship was observed in controls. The current findings provide some support for the involvement of stress mechanisms in the pathophysiology of early psychosis, but the changes are subtle and warrant further investigation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Amygdala volume has been proposed as a neural risk biomarker for psychotic illness, but findings in the ultra-high risk for psychosis (UHR) population have been somewhat inconsistent, which may be related to underlying social cognitive abilities. The current study investigated whether amygdala volumes were related to emotion-recognition impairments in UHR individuals, and whether volumes differed by sex. Secondary aims were to assess whether (a) emotion-recognition performance was associated with interhemispheric amygdala volume asymmetry and (b) amgydala volume and volume asymmetry acted as a mediator between emotion-recognition and outcome measures. The amygdala was manually delineated from magnetic resonance images for 39 UHR individuals who had also completed facial and prosody emotion-recognition tasks. Partial correlations were conducted to examine associations between amydgala volume/asymmetry and recognition of negative emotions. Mediation analyses were conducted using regression and bootstrapping techniques. Amygdala volume was positively correlated with sadness emotion recognition, in particular prosody, for females only. Left amygdala volume mediated the effect of sadness recognition on depressive symptoms, negative symptoms, overall psychopathology, and global functioning in females. Findings suggest a complex relationship between emotion recognition, the structure of the amygdala and illness outcome, where recognition of sadness appears to be the precipitator of this relationship in UHR females. Further research is needed to determine illness specificity and to confirm our sex- and emotion-specific results., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This MRI study examined the morphology of the olfactory sulcus, a potential marker of early neurodevelopment in 26 patients with bipolar I disorder and 24 matched controls. Bipolar patients had significantly shallower olfactory sulci bilaterally compared to controls, suggesting that neurodevelopmental abnormalities contribute to the neurobiology of bipolar disorder., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Previous studies have demonstrated alterations to fronto-limbic circuitry and callosal structure in borderline personality disorder (BPD). We predicted that a first-presentation BPD cohort who demonstrated orbitofrontal cortex (OFC) reductions would show regional reductions in the anterior corpus callosum., Method: Twenty teenage first-presentation BPD patients and twenty matched healthy controls underwent Magnetic resonance imaging (MRI) was performed in 20 teenaged first-presentation BPD patients and 20 matched healthy controls. Corpus callosum size and shape and ventricular volume were estimated using established methods and compared between the two groups. The relationship between illness variables and callosal morphology was also examined. OFC volume was correlated with callosal and ventricular variables., Results: BPD participants and controls did not differ on measures of callosal size or shape, or ventricular size. BPD participants showed an alteration to the pattern of age-related expansions seen in the callosum. BPD participants with a history of trauma did not demonstrate significant neuroanatomical differences from those without. OFC volumes did not correlate with the thickness of the anterior corpus callosum., Conclusion: Gross neuroanatomical changes are not present at the level of the callosum in teenagers with first-presentation BPD. Changes seen in other studies might reflect factors associated with the duration of BPD, such as recurrent comorbidity with axis I disorders, or treatment., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present study was to investigate whether volumetric abnormalities of the caudate nuclei predate the onset of psychotic illness. Caudate nuclei volume (CNVs), excluding the tail, were measured using region-of-interest (ROI) tracing of magnetic resonance imaging (MRI) scans acquired on a 1.5T scanner. Subjects included 39 individuals deemed at ultra-high risk of psychosis who converted to psychosis (UHR-P) after initial MRI scanning; 39 matched individuals at ultra-high risk who did not convert to psychosis (UHR-NP); and 39 matched healthy controls. All subjects were neuroleptic-naïve. After adjusting CNVs for intracranial volume (ICV), univariate analyses of variance and repeated measures analyses of variance were undertaken to examine the relationship of CNVs to psychosis transition and to family history of psychosis. Pearson's correlations were used to investigate the relationship of psychopathological scores to CNVs. CNVs did not differ significantly between UHR individuals and healthy controls, and there was no significant difference between converters and non-converters to psychosis. In the UHR group, presence of family history of psychosis was not related to CNVs. There was no correlation between CNVs and either positive or negative symptoms of schizophrenia. Significant associations were found between larger CNV and increased errors on a spatial working memory task but better verbal fluency performance. These data suggest that the caudate is macroscopically normal prior to illness onset, while the relationship to tasks of executive function may implicate the caudate together with its connections to prefrontal regions. Future research should examine changes longitudinally together with analysis of shape to assess subregions of the caudate that connect with prefrontal cortex.

We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid (E-EPA) on hippocampal T(2) relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up. There was an increase in T(2) in the placebo group but not in the E-EPA group, suggesting a neuroprotective effect of E-EPA treatment. In addition, the smaller the increase in T(2), the greater the improvement in negative symptoms., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

This structural magnetic resonance imaging study investigated insular cortex volume in 26 patients with bipolar I disorder and 24 matched controls. While insular volume did not differ between these groups, exploratory analyses demonstrated that the number of depressive episodes correlated negatively with the anterior insular volume in the patients, suggesting it may have a role in the pathophysiology of bipolar disorder., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

This magnetic resonance imaging study investigated the superior temporal gyrus (STG) subregion volumes in 20 teenagers with first-presentation borderline personality disorder (BPD) and 20 healthy controls. While the STG volume early in the course of BPD did not differ from that of healthy controls, the BPD participants with violent episodes had a smaller left caudal STG volume compared with those without such episodes during the previous 6 months. Our preliminary findings might reflect the neurobiological heterogeneity of the disorder., (Copyright @ 2009 Elsevier Ireland Ltd. All rights reserved.)

Reductions in the size of the anterior callosum have been described for both first-episode and established schizophrenia and bipolar affective disorder, but never in individuals with psychotic bipolar disorder. We recruited 110 first-episode psychosis subjects (74 schizophrenia spectrum and 36 affective psychosis) and 36 age- and gender-matched controls. The callosum was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images, and total area, length and curvature of the callosum were compared. The schizophrenia-spectrum group showed reductions in thickness of the genu across schizophreniform and schizoaffective disorder and schizophrenia, and the schizoaffective disorder group also showed an increase in thickness in the splenium and isthmus. None of these changes were seen in the affective disorder group, although a non-significant increase in the region of the isthmus and splenium was seen, particularly in the depressed group. Psychotic affective disorders do not show the anterior callosal reductions that are seen in the schizophrenia-spectrum group at first episode. The schizoaffective patients show additional posterior callosal expansions that may be a marker of an affective diathesis. This suggests that schizoaffective disorder may represent two interacting illness processes or be mid-way along a continuum of these two broad categories of illness at first psychosis.

Reports of volumetric abnormalities in the anterior cingulate cortex (ACC) in adults with established borderline personality disorder (BPD) are inconsistent, and it is not known whether such abnormalities are present early in the disorder. We aimed to investigate ACC volume in a first-presentation teenage BPD sample with minimal exposure to treatment. Fifteen female BPD patients and 15 healthy female control participants underwent magnetic resonance imaging (MRI) scanning. ACC volumes were estimated using a reliable method that accounts for inter-individual variation in sulcal morphology, and measurements were compared between the two groups. Analysis of variance revealed a decrease in volume of the left ACC in BPD patients compared with control participants. This volumetric change was correlated with parasuicidal behavior and impulsivity. A measure of ACC volume asymmetry was also correlated with fear of abandonment symptoms. Our results suggest that ACC volumetric abnormalities early in the course of BPD might be related to clinical correlates of the disorder. Longitudinal studies are needed to examine the nature of this abnormality over the course of the disorder.

The passivity phenomenon is a distressing Schneiderian first rank symptom in patients with schizophrenia. Based on extant data of functional and structural cerebral changes underlying passivity, we sought to examine cerebral white matter integrity in our subjects. We hypothesised that the passivity phenomenon would be associated with white matter changes in specific cortical (frontal, parietal cortices, and cingulate gyrus) and subcortical regions (thalamus and basal ganglia) and correlated with relevant neurocognitive deficits, compared with characteristics in those without the passivity phenomenon. Thirty-six subjects (11 with passivity and 25 without passivity) with schizophrenia were compared with 32 age-, gender- and handedness-matched healthy controls using diffusion tensor imaging. Neuropsychological testing was administered. Patients with passivity were associated with increased fractional anisotropy within the frontal cortex, cingulate gyrus, and basal ganglia and decreased fractional anisotropy within the thalamus when compared with patients without passivity. Within patients with passivity, fractional anisotropy in the frontal cortex correlated with the age of onset of illness and neurocognitive deficits related to attention and executive functioning. The findings suggest distributed involvement of cortical and subcortical regions underlying passivity and support the notion of neural network models underlying specific psychiatric symptoms such as passivity.

Major depressive disorder (MDD) has been associated with increased pituitary gland volume (PGV), which is thought to reflect stress-related dysregulation related to hypothalamic-pituitary-adrenal (HPA) axis activity. However, it is unclear whether PGV alteration reflects a "dynamic" change related to current mood instability or if it is a stable marker of illness vulnerability. In this study we investigated PGV in currently depressed patients (cMDD) (n=31), remitted depressed patients (rMDD) (n=31) and healthy controls (n=33), using 1.5 Tesla magnetic resonance imaging (MRI). The groups were matched for age and gender. We found no significant PGV, intra-cranial volume (ICV) or whole brain volume (WBV) differences between cMDD patients, rMDD patients and healthy controls. Furthermore, PGV was not correlated with clinical features of depression (e.g., age of onset; number of episodes; and scores on subscales of the Beck Depression Inventory, the Positive Affect and Negative Affect Scale, and the Mood and Anxiety Symptom Questionnaire). In conclusion, PGV does not appear to be a marker of current or past MDD in adult patients.

There is evidence that anterior cingulate cortex (ACC) function is related to individual differences in temperament. An important question regards how early such brain-behavior associations emerge. We examined the relationship between cortical folding patterns of the ACC, which are functionally relevant and primarily determined by birth, and individual differences in four core temperament dimensions (Effortful Control, Negative Affectivity, Surgency, and Affiliation). Magnetic resonance imaging was used to classify 153 (81 male) early adolescents as displaying a leftward asymmetric, rightward asymmetric, or symmetric pattern of ACC folding, as indexed by the incidence and extent of the paracingulate sulcus (PCS). A leftward asymmetric pattern of ACC folding was associated with significantly higher temperamental Effortful Control and lower Negative Affectivity than a rightward asymmetric pattern. Further, this difference was significant only for males. Across males and females, a symmetric pattern was associated with higher temperamental Affiliation than was a rightward asymmetric pattern of ACC folding. These findings suggest that early neurodevelopmental processes contribute to individual differences in temperament. They also illustrate sexual dimorphisms in the neural underpinnings of temperament.

It is not known whether the fronto-limbic volume reductions found in adults with established borderline personality disorder (BPD) are present early in the disorder. The aim of the study was to investigate orbitofrontal cortex (OFC), hippocampal and amygdala volumes in a first-presentation teenage BPD sample with minimal exposure to treatment. Groups of 20 BPD patients and 20 healthy control participants underwent magnetic resonance imaging. Hippocampal, amygdala, OFC and whole brain volumes were estimated and compared between the two groups. Analysis of variance revealed reversal of the normal (right>left) asymmetry of OFC grey matter volume in the BPD group, reflecting right-sided OFC grey matter loss in the BPD group compared with control participants. No significant differences were found for amygdala or hippocampal volumes comparing BPD with control participants. We identified OFC but not hippocampal or amygdala volumetric differences early in the course of BPD. Hippocampal and amygdala volume reductions observed in adult BPD samples might develop during the course of the disorder, although longitudinal studies are needed to examine this.

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic-pituitary-adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Abnormalities of the anterior cingulate cortex (ACC) are thought to be involved in the pathophysiology of bipolar disorder, but structural Magnetic Resonance Imaging (MRI) studies have reported variable findings. Reasons for this include a failure to consider variability in regional cortical folding patterns and a reliance on relatively coarse measures (e.g., volume) to index anatomical change. We sought to overcome these limitations by combining a novel protocol for parcellating the ACC and adjacent paracingulate cortex (PaC) that accounts for inter-individual variations in sulcal and gyral morphology with a cortical surface-based approach that allowed calculation of regional grey matter volume, surface area and cortical thickness in 24 patients with bipolar I disorder and 24 matched controls. No changes in grey matter volume or surface area were identified in any region, but patients did show significant reductions in cortical thickness in the left rostral PaC and right dorsal PaC that were not attributable to group differences in cortical folding patterns. These findings suggest that bipolar disorder is associated with more pronounced changes in the PaC, and that reliance on volumetric measures alone may obscure more subtle differences.

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n=20) and the total BPD cohort (n=20). However, within the BPD cohort, those exposed to childhood trauma (n=9) tended to have smaller pituitaries (-18%) than those with no history of childhood trauma (n=10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic-pituitary-adrenal axis dysfunction.

Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-naïve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.

Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain corticostriatal networks, although functional imaging studies of OCD rarely apply network-sensitive analysis methods. In this study, we compared a univariate and a multivariate analysis of PET data in OCD patients and healthy subjects; the latter approach was considered more suitable for characterizing functional networks of brain activity. Although both methods suggested there was abnormal corticostriatal activity in OCD patients, the nature, extent and magnitude of this activity was clearly enhanced by the multivariate approach. Implications for the analysis of such studies are discussed.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.