Showing papers in "Psychiatry Research-neuroimaging in 2007"

An abbreviated version of the Connor-Davidson Resilience Scale (CD-RISC), the CD-RISC2: Psychometric properties and applications in psychopharmacological trials

Abstract: Resilience may be an important component of the prevention of neuropsychiatric disease. Resilience has proved to be quantifiable by scales such as the Connor-Davidson Resilience Scale (CD-RISC). Here, we introduce a two-item version of this scale, the CD-RISC2. We hypothesize that this shortened version of the scale has internal consistency, test-retest reliability, convergent validity, and divergent validity as well as significant correlation with the full scale. Additionally, we hypothesize that the CD-RISC2 can be used to assess pharmacological modification of resilience. We test these hypotheses by utilizing data from treatment trials of post-traumatic stress disorder, major depression, and generalized anxiety disorder with setraline, mirtazapine, fluoxetine, paroxetine, venlafaxine XR, and kava as well as data from the general population, psychiatric outpatients, and family medicine clinic patients.

Dissociation of cognitive from affective components of theory of mind in schizophrenia

Abstract: Patients suffering from schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of theory of mind. However, there is conflicting evidence regarding their ability to perform on theory of mind tasks. Based on previous findings with patients suffering from prefrontal damage, the present study suggests that the behavioral deficit of schizophrenic patients may be due to impaired 'affective theory of mind' abilities, rather than to a general impairment in theory of mind. To test this hypothesis we assessed the ability of 22 schizophrenic patients and 55 age-matched healthy controls, to judge first and second order affective vs. cognitive mental state attribution, based on eye gaze. The relationships between negative and positive symptoms of schizophrenia, and affective and cognitive theory of mind were also assessed. Results indicated that while healthy controls made fewer errors on affective as compared to cognitive theory of mind conditions, schizophrenic patients showed a less prominent trend. Although the pattern of reaction time did not differ significantly between groups, the patients made significantly more errors in the affective conditions, as compared to controls. Furthermore, correlation analysis indicated that impaired affective theory of mind in these patients correlated with their level of negative symptoms. These results indicate that individuals with high level of negative symptoms of schizophrenia may demonstrate selective impairment in their ability to attribute affective mental states. These findings offer new insight into the affective facets of social behavior that may underlie the profound behavioral disturbances observed in schizophrenia.

Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study.

Abstract: Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of fronto-limbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.

Self-efficacy and empowerment as outcomes of self-stigmatizing and coping in schizophrenia

Abstract: The concept of internalized stigma or self-stigma is central to the understanding of the psychological harm caused by stigma. In this study, we aim to demonstrate how the evaluative dimension of self-concept (self-efficacy and empowerment) mediates the psychological effects of self-stigmatizing and coping with stigma. As important examples of psychological effects, depression and quality of life were focussed on. In 172 outpatients with DSM-IV schizophrenia, measures of self-stigma and devaluation, coping with stigma, self-efficacy, empowerment, quality of life and depression were assessed. It was hypothesized that withdrawal and secrecy as important coping strategies yielded to higher levels of anticipatory anxiety of future stigmatizing. Higher levels of perceived discrimination and devaluation were hypothesised to undermine self-efficacy and illness-related empowerment. Lowering of empowerment was supposed to enhance depression and reduce quality of life. This hypothesis was tested by Structural Equation Modeling as a method of data analysis. The results supported the hypothesized model; i.e., 46% of depression and 58% of quality of life reduction could be explained by eroded empowerment. Moreover, 51% of the empowerment reduction was explained by reduction in self-efficacy at a more general level by dysfunctional coping and higher levels of anticipated stigma. Taken together, our data suggest an avoidant coping style as a risk factor for anticipatory stigma, which erodes self-efficacy and empowerment. These data have implications for cognitive behavioral approaches, which should focus on anticipated stigma to improve recovery in schizophrenia.

Validity of the mental health component scale of the 12-item Short-Form Health Survey (MCS-12) as measure of common mental disorders in the general population

Abstract: This study assessed the screening utility of the 12-item Short-Form Health Survey's (SF-12) mental health component scale (MCS-12) for diagnosable depression and anxiety disorders in a general population sample, and thus, the validity of this scale as a measure of mental health in epidemiological research. Data were from the Australian National Survey of Mental Health and Wellbeing ( N =10,504). Diagnoses were made using the Composite International Diagnostic Interview. The MCS-12 was compared to other brief scales: the RAND Mental Health Component scale (RAND MHC-12, an alternative scoring method for the MCS-12), the 12-item General Health Questionnaire (GHQ-12), the Kessler Psychological Distress Scale (K10 and K6), and an estimate of the Mental Health Inventory (MHI-5). The MCS-12 and RAND MHC-12 were equally able to discriminate respondents with the target diagnoses. The MCS-12 performed better than the GHQ-12, and equally to the K6 for diagnoses of depression, though not anxiety disorders, where the K6 showed greater utility. The K10 out-performed the MCS-12 for all diagnoses. Areas under receiver operating characteristics curves (AUC) indicated that the MCS-12 is valid measure of mental health in epidemiological research, and a useful screening tool for both depression (AUC=0.92) and anxiety disorders (AUC=0.83).

Stigma, social function and symptoms in schizophrenia and schizoaffective disorder: associations across 6 months

Abstract: Research suggests stigma is a barrier to self-esteem and the attainment of resources in schizophrenia. Less clear is the association of stigma experiences with symptoms and social function both concurrently and prospectively. To assess this, symptoms were measured using the Positive and Negative Syndrome Scale, social function was measured using the Quality of Life Scale and stigma experience was assessed using the Internalized Stigma of Mental Illness Scale among 36 persons with schizophrenia at two points, 6 months apart. Correlations found stigma was associated with concurrent levels of positive and emotional discomfort symptoms and degree of social contact. When initial stigma levels were controlled for, stigma at 6 months was predicted by baseline levels of positive symptoms. Greater initial stigma predicted greater emotional discomfort at follow-up. Results suggest internalized stigma is linked with social function and symptoms. Positive symptoms may make some persons with schizophrenia more vulnerable to ongoing stigma experience.

Adaptive control deficits in attention-deficit/hyperactivity disorder (ADHD): The role of error processing

Abstract: Cognitive performance of children with attention-deficit hyperactivity disorder (ADHD) is characterized by large moment-to-moment fluctuations in cognitive control reflected by a highly inconsistent and inaccurate response style. It has been suggested that abnormal error processing underlies this failure to implement adequate control. We investigated the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) time-locked to erroneous responses in 16 rigorously screened ADHD boys aged 8-12 years and 16 age-matched normal control boys during a modified Eriksen flanker paradigm with two levels of time pressure. Children with ADHD responded as fast and regularly as controls, but committed significantly more errors, particularly when facing time pressure and response conflict. ADHD children produced shorter runs of correct responses than controls. In addition, with high time pressure, error runs were prolonged relative to control children, suggesting an increase in both frequency and magnitude of temporary lapses of control. ERP amplitude differences between correct and incorrect responses were diminished in ADHD children, whereas post-error slowing remained unaffected. This pattern of results indicates that a specific deficit in monitoring ongoing behaviour, rather than insufficient strategic adjustments, gave rise to performance limitations in ADHD. Findings are discussed in terms of anterior cingulate cortex (ACC) dysfunction, leading to a failure to predict the likelihood that an error occurs in a given context.

Psychophysiological ambulatory assessment of affective dysregulation in borderline personality disorder.

Abstract: Many experts now believe that pervasive problems in affect regulation constitute the central area of dysfunction in borderline personality disorder (BPD). However, data is sparse and inconclusive. We hypothesized that patients with BPD, in contrast to healthy gender and nationality-matched controls, show a higher frequency and intensity of self-reported emotions, altered physiological indices of emotions, more complex emotions and greater problems in identifying specific emotions. We took a 24-hour psychophysiological ambulatory monitoring approach to investigate affect regulation during everyday life in 50 patients with BPD and in 50 healthy controls. To provide a typical and unmanipulated sample, we included only patients who were currently in treatment and did not alter their medication schedule. BPD patients reported more negative emotions, fewer positive emotions, and a greater intensity of negative emotions. A subgroup of non-medicated BPD patients manifested higher values of additional heart rate. Additional heart rate is that part of a heart rate increase that does not directly result from metabolic activity, and is used as an indicator of emotional reactivity. Borderline participants were more likely to report the concurrent presence of more than one emotion, and those patients who just started treatment in particular had greater problems in identifying specific emotions. Our findings during naturalistic ambulatory assessment support emotional dysregulation in BPD as defined by the biosocial theory of [Linehan, M.M., 1993. Cognitive-Behavioral Treatment of Borderline Personality Disorder. The Guildford Press, New York.] and suggest the potential utility for evaluating treatment outcome.

Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder--a postmortem study.

Abstract: Prefrontal cortical (PFC) and hippocampal (HI) volume reductions have been consistently found in patients with recurrent depressive disorder (DD). Here we examine the possibility that oxidative stress, widely implicated in neuronal cell damage, may contribute to these brain structural changes. We compared manganese (Mn) and copper/zinc (Cu/Zn) superoxide dismutase (SOD) coenzyme concentrations in postmortem PFC and hippocampal brain tissue from 7 patients with DD and 7 neuropsychiatrically healthy controls using sandwich-type enzyme-linked immunosorbent assay (ELISA) technique. The concentration of Cu/Zn-SOD was significantly increased in the PFC but not in the hippocampus of patients. There was no significant change in Mn-SOD enzyme concentration in either region. Our findings contribute to the growing body of evidence implicating oxidative stress in the pathophysiology of depressive disorder.

Prevalence of dissociative disorders among women in the general population

Abstract: This study sought to determine the prevalence of dissociative disorders among women in the general population, as assessed in a representative sample of a city in central Turkey. The Dissociative Disorders Interview Schedule (DDIS), the Borderline Personality Disorder section of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II), and the PTSD-Module of the Structured Clinical Interview for DSM-III-R (SCID) were administered to 628 women in 500 homes. The mean age of participants was 34.8 (S.D.=11.5, range: 18-65); 18.3% of participants (n=115) had a lifetime diagnosis of a dissociative disorder. Dissociative disorder not otherwise specified (DDNOS) was the most prevalent diagnosis (8.3%); 1.1% of the population was diagnosed as having dissociative identity disorder (DID). Participants with a dissociative disorder had borderline personality disorder, somatization disorder, major depression, PTSD, and history of suicide attempt more frequently than did participants without a dissociative disorder. Childhood sexual abuse, physical neglect, and emotional abuse were significant predictors of a dissociative disorder diagnosis. Only 28.7% of the dissociative participants had received psychiatric treatment previously. Because dissociative disorders are trauma-related, significant part of the adult clinical consequences of childhood trauma remains obscure in the minds of mental health professionals and of the overall community. Revisions in diagnostic criteria of dissociative disorders in the DSM-IV are recommended.

The five-factor gambling motivation model.

Abstract: Pathological gambling is a serious social issue, but the underlying psychological motivations are poorly understood. This study developed a five-factor gambling motivation model. The five factors that motivate gambling (socialization, amusement, avoidance, excitement, and monetary motives) were derived from study data obtained from 240 college students. The structure of the five-factor model was confirmed by factor analysis of responses from 234 frequent gamblers. We then compared the "monetary motive version" of this model with the "parallel version" to determine which model more accurately describes how the five factors influence gambling. The monetary motive model holds that amusement, excitement, and avoidance motives influence gambling severity only through mediation of the monetary motive. The parallel model proposes that the five motives all independently influence gambling severity. We found that the avoidance and excitement motives did not have direct effects on gambling severity, but the monetary motive showed a direct positive influence. Thus the monetary motive model was more effective than the parallel model in explaining the influence of specific gambling motives on gambling severity. These findings may help in the improvement of therapy for pathological gambling.

DNA damage in bipolar disorder.

Abstract: Bipolar disorder (BD) is a prevalent, chronic, severe, and highly disabling psychiatric disorder that is associated with increased morbidity and mortality due to general medical conditions. There is an emerging body of evidence correlating chronic medical conditions with DNA damage. The present study was designed to assess DNA damage in BD patients using the comet assay (CA). Thirty-two bipolar-I outpatients diagnosed using the Structured Clinical Interview for DSM-IV were matched with 32 healthy volunteers. Manic and depressive symptoms were assessed using the Young Mania Rating Scale and the Hamilton Depression Rating Scale, respectively. Peripheral blood samples were collected and a standard protocol for CA preparation and analysis was performed. The present study showed that BD outpatients present an increased frequency of DNA damage relative to controls. The frequency of DNA damage correlated with the severity of symptoms of depression and mania.

HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions.

Abstract: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the most prominent neurobiological findings in major depressive disorder (MDD). The relationship of regional brain metabolism to HPA axis dysfunction in depressed patients, however, is still unclear. In this study, to examine the clinical pharmacotherapeutic effects on HPA axis function and brain metabolism in MDD patients, we performed the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test on 24 antidepressant-free patients with MDD a few days after positron emission tomography (PET) with a radiotracer, [(18)F]-fluorodeoxyglucose (FDG). Moreover, 10 patients who responded to pharmacotherapy were re-tested. 75% of unmedicated MDD patients exhibited a heightened cortisol response to the DEX/CRH test, and thus were defined as non-suppressors. Non-suppressors showed a marked hypometabolism in the medial prefrontal cortex as compared with suppressors. After successful pharmacotherapy, enhanced cortisol responsiveness normalized. Prior to treatment of the unmedicated MDD, a significant hypometabolism in various frontal regions and a significant hypermetabolism in the right hippocampus and parahippocampal gyrus were observed compared with controls. Metabolic activity in treatment responders showed a normalizing pattern in almost all the areas that had been characterized by metabolic abnormality at baseline except for the medial prefrontal cortex. These results indicate that depressed patients remitted with antidepressant treatment were accompanied by resolution of HPA dysregulation and alteration of regional glucose metabolism in the prefrontal cortical, limbic and paralimbic regions.

White matter abnormalities associated with auditory hallucinations in schizophrenia: a combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging.

Abstract: White matter (WM) abnormalities in schizophrenia may offer important clues to a better understanding of the disconnectivity associated with the disorder. The aim of this study was to elucidate a WM basis of auditory hallucinations in schizophrenia through the simultaneous investigation of WM tract integrity and WM density. Diffusion tensor images (DTIs) and structural T1 magnetic resonance images (MRIs) were taken from 15 hallucinating schizophrenic patients, 15 non-hallucinating schizophrenic patients and 22 normal controls. Voxel-based analyses and post-hoc region of interest analyses were obtained to compare the three groups on fractional anisotropy (FA) derived from DTI as well as WM density derived from structural MRIs. In both the hallucinating and non-hallucinating groups, FA of the WM regions was significantly decreased in the left superior longitudinal fasciculus (SLF), whereas WM density was significantly increased in the left inferior longitudinal fasciculus (ILF). The mean FA value of the left frontal part of the SLF was positively correlated with the severity score of auditory hallucinations in the hallucinating patient group. Our findings show that WM changes were mainly observed in the frontal and temporal areas, suggesting that disconnectivity in the left fronto-temporal area may contribute to the pathophysiology of schizophrenia. In addition, pathologic WM changes in this region may be an important step in the development of auditory hallucinations in schizophrenia.

Myelin staining of deep white matter in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and unipolar major depression

Abstract: Neuroimaging and postmortem studies suggest the involvement of white matter disease in schizophrenia, bipolar disorder, and unipolar major depression. To date there is no published, collective study of myelin staining in these three psychiatric disorders. Deep white matter lesions, potentially affecting corticolimbic circuits, have been particularly implicated in late life depression and poor outcome bipolar disorder. We hypothesized that individuals with these disorders would manifest reduced deep white matter myelin staining compared to normal controls. Sixty transverse sections of fixed dorsolateral prefrontal cortex - 15 from individuals with each psychiatric disorder and 15 from normal controls - were stained according to the method of Kluver and Barrera. Myelin staining intensity was quantified by digital image analysis and expressed as a percent of grey matter staining for a given section. Mean deep (but not gyral) white matter myelin staining was less intense in all three psychiatric groups compared to control. This difference was statistically significant for the bipolar and unipolar groups, with a strong trend toward attenuated staining in the schizophrenic group. Our findings are consistent with postmortem and neuroimaging studies of affective disorders that indicate an increased prevalence of deep white matter lesions in unipolar and bipolar affective disorders.

Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva

Abstract: Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress.

Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes

Abstract: Schizophrenia patients show a disconnection in amygdala-medial prefrontal cortex and autonomic arousal systems for processing fear. Concurrent functional magnetic resonance imaging [fMRI] and skin conductance recording were used to determine whether these disturbances are specific to fear, or present in response to other signals of danger. We also examined whether these disturbances distinguish a specific symptom profile. During scanning, 27 schizophrenia (13 paranoid, 14 nonparanoid) and 22 matched healthy control subjects viewed standardized facial expressions of fear, anger and disgust (versus neutral). Skin conductance responses [SCRs]were acquired simultaneously to assess phasic increases in arousal. 'With-arousal' versus 'without-arousal' responses were analysed using non-parametric methods. For controls, 'with-arousal' responses were associated with emotion-specific activity for fear (amygdala), disgust (insula) and anger (anterior cingulate), together with common medial prefrontal cortex [MPFC] engagement, as predicted. Schizophrenia patients displayed abnormally increased phasic arousal, with concomitant reductions in emotion-specific regions and MPFC. These findings may reflect a general disconnection between central and autonomic systems for processing signals of danger. This disjunction was most apparent in patients with a profile of paranoia, coupled with poor social function and insight. Heightened autonomic sensitivity to signals of fear, threat or contamination, without effective neural mechanisms for appraisal, may underlie paranoid delusions which concern threat and contamination, and associated social and interpersonal difficulties.

Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia

Abstract: The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP

Social anhedonia and schizotypy: The contribution of individual differences in affective traits, stress, and coping.

Abstract: While social anhedonia is a promising indicator of vulnerability to schizophrenia, it remains uncertain whether anhedonia is a core feature of schizotypy or merely a secondary associated characteristic. This issue was examined by comparing dimensional scores on schizophrenia spectrum personality disorder symptoms derived from clinical interviews among three groups: a) "pure" social anhedonics with high scores on the Revised Social Anhedonia Scale (SAS; [Eckblad, M.L., Chapman, L.J., Chapman, J.P., Mishlove, M., 1982. The Revised Social Anhedonia Scale. Unpublished test, University of Wisconsin, Madison.]) and low scores on the Magical Ideation Scale (MIS, [Eckblad, M.L., Chapman, L.J., 1983. Magical ideation as an indicator of schizotypy. Journal of Consulting and Clinical Psychology, 51, 215-225.]), b) subjects with high MIS and low SAS scores, and c) controls with low scores on both scales. This study also sought to identify individual differences in stress reactivity, personality, coping style, and social support that might be related to severity of clinical symptoms among at-risk subjects. Compared to controls, the SAS group had higher levels of schizotypal, schizoid, and paranoid symptoms and the MIS group had higher schizotypal symptoms. Among social anhedonics, individual differences in perceived stress, trait negative affectivity, and coping style accounted for over 40% of the variance in schizotypal and paranoid symptoms. This cross-sectional study bolsters support for the validity of social anhedonia as a primary feature of schizotypy. Longitudinal studies are required to determine whether these individual differences potentiate clinical outcomes among social anhedonics.

Atypical involvement of frontostriatal systems during sensorimotor control in autism

Abstract: Autism is a neurodevelopmental disorder involving dysmaturation of widely distributed brain systems. Accordingly, behaviors that depend on distributed systems, such as higher level cognition and sensorimotor control, are compromised in the disorder. The current study investigated alterations in neural systems underlying sensorimotor disturbances in autism. An fMRI investigation was conducted using saccadic and pursuit eye movement paradigms with 13 high functioning individuals with autism and 14 age- and IQ-matched typically developing individuals. Individuals with autism had reduced activation in cortical eye fields and cerebellar hemispheres during both eye movement tasks. When executing visually guided saccades, individuals with autism had greater activation bilaterally in a frontostriatal circuit including dorsolateral prefrontal cortex, caudate nucleus, medial thalamus, anterior and posterior cingulate cortex, and right dentate nucleus. The increased activation in prefrontal–striatal–thalamocortical circuitry during visually guided saccades indicates that systems typically dedicated to cognitive control may need to compensate for disturbances in lower-level sensorimotor systems. Reduced activation throughout visual sensorimotor systems may contribute to saccadic and pursuit disturbances that have been reported in autism. These findings document that neurodevelopmental disturbances in autism affect widely distributed brain systems beyond those mediating language and social cognition. © 2007 Elsevier Ireland Ltd. All rights reserved.

Progressive changes of white matter integrity in schizophrenia revealed by diffusion tensor imaging.

Abstract: Recent magnetic resonance imaging (MRI) studies using diffusion tensor imaging (DTI) have suggested reduced fractional anisotropy (FA) in the white matter (WM) of the brain in patients with schizophrenia. We tried to examine whether such reduction in FA exists and whether such changes in FA progress in an age-dependent manner in a Japanese sample of chronic schizophrenia. FA values were compared between 42 patients with chronic schizophrenia and 42 controls matched for age and gender, by using DTI with voxel-by-voxel and region-of-interest analyses. Correlations of FA values with age and duration of illness were examined. Patients with schizophrenia showed lower FA values, compared to controls, in the widespread WM areas including the uncinate fasciculi and cingulum bundles. A significant group-by-age interaction was found for FA in the WM, i.e., age-related reduction of FA was more pronounced in schizophrenics than in controls. A significant negative correlation between FA and duration of illness was also found in the WM. Our data confirmed decreased FA in schizophrenics, compared to controls in the widespread WM areas. Such decreased FA values in schizophrenia might be attributable, at least in part, to progressive changes after the onset of the illness.

Mapping brain structure in attention deficit-hyperactivity disorder: A voxel-based MRI study of regional grey and white matter volume

Abstract: The neuroanatomical basis of attention deficit-hyperactivity disorder (ADHD) is postulated to involve brain circuitry responsible for attention and executive function. Relatively new automated methods of MRI analysis allow rapid examination of each volume element (voxel) of whole brain, therefore we planned a comprehensive quantitative examination of brain anatomy in children with ADHD using voxel-based methods. We aimed to quantify whole brain, global tissue class and regional grey and white matter volume differences in 28 male children with ADHD and 31 closely matched controls. Since ADHD is often complicated by comorbid oppositional defiant disorder (ODD) and conduct disorder (CD), we also conducted post-hoc analyses of subgroups of children with ADHD with and without these comorbidities. Significant regional deficits in ADHD were observed within a predominantly right-sided frontal-pallidal-parietal grey matter network and bilateral white matter tracts. Post-hoc comparisons suggested that comorbid ODD or CD did not greatly alter the extent of regional pathology in ADHD. The exceptions being cerebellar and striatal volume deficits which were significantly greater in children with ADHD plus comorbidities, but not those with ADHD alone, compared to controls. Overall, restricted structural brain abnormalities caused by ADHD were localized to brain systems known to be necessary for attention and executive function.

The associations among hippocampal volume, cortisol reactivity, and memory performance in healthy young men

Abstract: In aged and pathological populations, reduced hippocampal volume is frequently described in association with impairment of hippocampus-dependent cognitive processes and chronically elevated cortisol levels. Recent studies in young healthy subjects show a negative association between hippocampal volume and memory. The aim of the present study was to investigate the associations among hippocampal volume, cortisol levels and memory performance in a group of healthy young men. Hippocampal volume was determined by manual segmentation of high-resolution 3D Magnetic Resonance Images from 13 subjects. Stress-induced cortisol levels in response to the "Trier Social Stress Test" (TSST) as well as the cortisol response to awakening (CRA) over four weeks were assessed. Declarative memory performance was tested before and after exposure to the TSST. The results show that larger hippocampal volume was associated with a significantly stronger cortisol increase in response to the TSST and a significantly greater CRA. Moreover, larger hippocampal volume was associated with significantly lower memory performance before the TSST. Our results challenge the direction of the frequently observed relationships among hippocampal volume, cortisol reactivity and memory performance and question the relevance of findings in clinical and aged subjects for young healthy populations.

Elevated pain thresholds correlate with dissociation and aversive arousal in patients with borderline personality disorder

Abstract: In addition to reduced pain perception, patients with borderline personality disorder (BPD) show higher pain thresholds under subjective stress conditions as compared with non-stress conditions. However, the correlation between symptoms of stress and pain thresholds has not been investigated so far. Using a new and convenient methodology, electric stimulation, we expected higher pain and detection thresholds in patients with BPD than in to healthy controls as well as a positive correlation between pain thresholds and symptoms of stress (aversive arousal and dissociation) in BPD patients. Twelve female patients with BPD and twelve healthy controls were included in the study. Electric stimulation was applied on the right index finger, and detection and pain thresholds were assessed by gradually intensifying the stimuli. We found significantly elevated pain thresholds in patients with BPD as compared with healthy controls, but no difference between patients and controls in detection thresholds. In patients, a significant positive correlation was revealed between pain thresholds and dissociation as well as between pain thresholds and aversive arousal. Besides demonstrating a close correlation between pain thresholds and symptoms of stress in patients with BPD, this study replicated earlier findings of reduced pain perception in patients with BPD. Measuring electric pain thresholds is a valid and reasonable method for larger studies.

Reduced Ventral Anterior Cingulate and Amygdala Volumes in Medication-Naïve Females With Major Depressive Disorder: A Voxel-Based Morphometric Magnetic Resonance Imaging Study

Abstract: High resolution magnetic resonance imaging and voxel-based morphometry were used to compare regional gray matter volumes between 14 medication-naive female participants with a first episode of major depressive disorder (MDD) and 13 female healthy comparison participants (HC). Volumes of bilateral ventral anterior cingulate cortex (vACC) and right amygdala were significantly smaller in the MDD group than in the HC group. These results suggest that volume reductions in vACC and amygdala in females with MDD are present at illness onset.

Behavioural studies of spatial working memory dysfunction in schizophrenia: A quantitative literature review

Abstract: Cognitive impairments in schizophrenia have been recognized as a prominent feature of the illness. Research is now focusing on determining a relationship between neurocognitive impairments, and social and functional outcome. Despite a number of comprehensive reviews on neurocognitive measures and reports on spatial working memory abnormalities in patients with schizophrenia when compared to healthy volunteers, there have been no meta-analyses of the extent of the abnormality in this group of patients. We reviewed 33 studies (from 1992 to 2005) on spatial working memory impairment in schizophrenia with the aim of providing a quantitative assessment of the consistency and the magnitude of the deficit. From the quantitative data analysis, it is evident that patients with schizophrenia are consistently more impaired on the spatial working memory measures than healthy controls. These impairments may be related to social disability and explain some cognitive deficits that characterize the clinical presentation of schizophrenia.

Cannabis abuse and risk for psychosis in a prodromal sample

Abstract: The goal of the present study was to examine the rate of cannabis use among participants in the Cognitive Assessment and Risk Evaluation (CARE) Program, a longitudinal program for individuals who are "at risk" for developing a psychotic disorder. Cannabis abuse was assessed in 48 individuals identified as at risk for psychosis based on subsyndromal psychotic symptoms and/or family history. At 1 year follow-up, 6 of the 48 (12.5%) at risk subjects had made the transition to psychosis. Of the 32 subjects who had no use or minimal cannabis use, one subject (3.1%) converted to psychosis. Of the 16 subjects who met criteria for cannabis abuse/dependence, five (31.3%) converted to psychosis. The results show a significant association between cannabis abuse and conversion to psychosis in this sample. Nicotine use was also found to be significantly associated with later conversion. The significant associations between cannabis and nicotine abuse and conversion to psychosis in individuals at risk for schizophrenia suggest that early identification and intervention programs should screen for and provide education about the deleterious effects of these substances.

Measuring shame and guilt by self-report questionnaires : A validation study

Abstract: Quantitative assessment of shame and guilt using self-report questionnaires can help to understand the role of these emotions in various mental disorders. However, shame and guilt measures have predominantly been tested among healthy subjects that usually show low levels of guilt and shame. Thus, little is known about the comparative validity of different shame and guilt questionnaires in a population of shame- and guilt-prone persons with mental illness as compared to healthy subjects. This study used the Test of Self-Conscious Affect (TOSCA-3), the Personal Feelings Questionnaire (PFQ-2) and the Experiential Shame Scale (ESS) among 60 women with borderline personality disorder (BPD) and 60 healthy women. Intercorrelations of shame-proneness, guilt-proneness and state shame as well as their correlations with self-efficacy, empowerment, state and trait-anxiety, experiential avoidance, depression, and general psychopathology were assessed. In both groups, shame-proneness was moderately related to guilt-proneness, both as assessed by the TOSCA-3 and the PFQ-2. For the TOSCA-3, among healthy subjects shame-proneness was significantly correlated with other constructs while guilt-proneness was not. This difference turned largely insignificant among women with BPD. For the PFQ-2, shame- and guilt-proneness showed similar correlational patterns with other constructs in both groups. The guilt-proneness scale of the TOSCA-3 showed poor internal consistency. State shame (ESS) was strongly related to state anxiety in both groups, and its correlations with other constructs were similar to state anxiety. The discriminant validity of the TOSCA-3 to distinguish between shame- and guilt-proneness may be diminished in clinical samples. The measure of state shame (ESS) showed a large overlap with state anxiety.

Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease.

Abstract: While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with 18F-2-fluoro-2-deoxy- d -glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus.

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug.

Abstract: The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.