Yoichiro Takayanagi

Accuracy of Reports of Lifetime Mental and Physical Disorders: Results From the Baltimore Epidemiological Catchment Area Study

IMPORTANCE Our understanding of how mental and physical disorders are associated and contribute to health outcomes in populations depends on accurate ascertainment of the history of these disorders. Recent studies have identified substantial discrepancies in the prevalence of mental disorders among adolescents and young adults depending on whether the estimates are based on retrospective reports or multiple assessments over time. It is unknown whether such discrepancies are also seen in midlife to late life. Furthermore, no previous studies have compared lifetime prevalence estimates of common physical disorders such as diabetes mellitus and hypertension ascertained by prospective cumulative estimates vs retrospective estimates. OBJECTIVE To examine the lifetime prevalence estimates of mental and physical disorders during midlife to late life using both retrospective and cumulative evaluations. DESIGN, SETTING, AND PARTICIPANTS Prospective population-based survey (Baltimore Epidemiologic Catchment Area Survey) with 4 waves of interviews of 1071 community residents in Baltimore, Maryland, between 1981 and 2005. MAIN OUTCOMES AND MEASURES Lifetime prevalence of selected mental and physical disorders at wave 4 (2004-2005), according to both retrospective data and cumulative evaluations based on 4 interviews from wave 1 to wave 4. RESULTS Retrospective evaluations substantially underestimated the lifetime prevalence of mental disorders as compared with cumulative evaluations. The respective lifetime prevalence estimates ascertained by retrospective and cumulative evaluations were 4.5% vs. 13.1% for major depressive disorder, 0.6% vs. 7.1% for obsessive-compulsive disorder, 2.5% vs. 6.7% for panic disorder, 12.6% vs. 25.3% for social phobia, 9.1% vs. 25.9% for alcohol abuse or dependence, and 6.7% vs. 17.6% for drug abuse or dependence. In contrast, retrospective lifetime prevalence estimates of physical disorders ascertained at wave 4 were much closer to those based on cumulative data from all 4 waves. The respective prevalence estimates ascertained by the 2 methods were 18.2% vs. 20.2% for diabetes, 48.4% vs. 55.4% for hypertension, 45.8% vs. 54.0% for arthritis, 5.5% vs. 7.2% for stroke, and 8.4% vs. 10.5% for cancer. CONCLUSIONS AND RELEVANCE One-time, cross-sectional population surveys may consistently underestimate the lifetime prevalence of mental disorders. The population burden of mental disorders may therefore be substantially higher than previously appreciated.

Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness

Background Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls. Method Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis. Results Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%. Conclusion Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia.

Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia

BACKGROUND Although clinical and neuropsychological findings have implicated functional deficits of the orbitofrontal cortex (OFC) in schizophrenia, structural magnetic resonance imaging (MRI) studies of this region have yielded inconsistent findings. In addition, it remains elusive whether the OFC morphology in first-episode patients is related to their clinical features. METHOD MR images were acquired from 42 (24 males, 18 females) first-episode schizophrenia patients and 35 (20 males, 15 females) age-, gender-, and parental socio-economic status (SES)-matched healthy subjects. The OFC sub-regions (orbital gyrus and straight gyrus) were measured on contiguous 1-mm-thick coronal slices. The OFC sulco-gyral pattern was also evaluated for each subject. Furthermore, the relationships between OFC morphology and clinical measures were examined. RESULTS The volumes of the bilateral orbital gyri were significantly reduced in schizophrenia patients compared with healthy subjects, whereas the volumes of the straight gyri did not show differences between the groups. Among the schizophrenia patients, the volume of the left orbital gyrus was inversely correlated with their SES and illness duration. The OFC sulco-gyral patterns were significantly different between the patients and controls in the right hemisphere. CONCLUSION This study demonstrated morphologic abnormalities of the OFC in first-episode schizophrenia patients, which may have reflected neurodevelopmental aberrations and neurodegenerative changes during the first episode of the illness. Our findings also suggest that such brain structural changes are related to the social dysfunction observed in schizophrenia.

Reduced amygdala and hippocampal volumes in patients with methamphetamine psychosis

The similarity between psychotic symptoms in patients with schizophrenia such as hallucinations and delusions and those caused by administration of methamphetamine has been accepted. While the etiology of schizophrenia remains unclear, methamphetamine induced psychosis, which is obviously occurred by methamphetamine administration, had been widely considered as a human pharmaceutical model of exogenous psychosis. Although volume reductions in medial temporal lobe structure in patients with schizophrenia have repeatedly been reported, those in patients with methamphetamine psychosis have not yet been clarified. Magnetic resonance images (MRI) were obtained from 20 patients with methamphetamine psychosis and 20 age, sex, parental socio-economic background, and IQ matched healthy controls. A reliable manual tracing methodology was employed to measure the gray matter volume of the amygdala and the hippocampus from MRIs. Significant gray matter volume reductions of both the amygdala and hippocampus were found bilaterally in the subjects with methamphetamine psychosis compared with the controls. The degree of volume reduction was significantly greater in the amygdala than in hippocampus. While the total gray, white matter and intracranial volumes were also significantly smaller-than-normal in the patients; the regional gray matter volume reductions in these medial temporal structures remained statistically significant even after these global brain volumes being controlled. The prominent volume reduction in amygdala rather than that in hippocampus could be relatively specific characteristics of methamphetamine psychosis, since previous studies have shown significant volume reductions less frequently in amygdala than in hippocampus of the other psychosis such as schizophrenia.

Different hemodynamic response patterns in the prefrontal cortical sub-regions according to the clinical stages of psychosis.

BACKGROUND Symptomatic and functional outcomes in schizophrenia are associated with the duration of untreated psychosis. However, no candidate biomarkers have been adopted in clinical settings. Multichannel near-infrared spectroscopy (NIRS), which can easily and noninvasively measure hemodynamics over the prefrontal cortex, is a candidate instrument for clinical use. AIMS We intended to explore prefrontal dysfunction among individuals at different clinical stages, including ultra-high-risk (UHR), first-episode psychosis (FEP), and chronic schizophrenia (ChSZ), compared to healthy subjects. METHOD Twenty-two UHR subjects, 27 patients with FEP, 38 patients with ChSZ, and 30 healthy subjects participated. We measured hemodynamic changes during a block-designed letter fluency task using multichannel NIRS instruments. RESULTS We found that the activations of the bilateral ventrolateral prefrontal cortex, and the fronto-polar and anterior parts of the temporal cortical regions in the UHR group were lower than those of the controls, but similar to those of the FEP and ChSZ groups. However, the activations in the bilateral dorsolateral prefrontal cortex regions decrease with advancing clinical stage. CONCLUSIONS To the best of our knowledge, this is the first study directly comparing differences in hemodynamic changes with respect to the 3 clinical stages of psychosis. Furthermore, this study also demonstrates different patterns of impairment according to the progression of clinical stages using NIRS instruments. NIRS measurements for UHR and FEP individuals may be candidate biomarkers for the early detection of the clinical stages of psychosis.

Differentiation of first-episode schizophrenia patients from healthy controls using ROI-based multiple structural brain variables

BACKGROUND Brain morphometric measures from magnetic resonance imaging (MRI) have not been used to discriminate between first-episode patients with schizophrenia and healthy subjects. METHODS Magnetic resonance images were acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and 48 (24 males, 24 females) age- and parental socio-economic status-matched healthy subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick coronal slices from the prefrontal and central parts of the brain. Linear discriminant function analysis was conducted using standardized z scores of the volumes of each ROI. RESULTS Discriminant function analysis with cross-validation procedures revealed that brain anatomical variables correctly classified 75.6% of male subjects and 82.9% of female subjects, respectively. The results of the volumetric comparisons of each ROI between patients and controls were generally consistent with those of the previous literature. CONCLUSIONS To our knowledge, this study provides the first evidence of MRI-based successful classification between first-episode patients with schizophrenia and healthy controls. The potential of these methods for early detection of schizophrenia should be further explored.

Reduced anterior cingulate gray matter volume and thickness in subjects with deficit schizophrenia

BACKGROUND Patients with deficit schizophrenia (D-SZ) differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects such as risk factors, neurobiological correlates, treatment response and clinical outcome. It has been debated if brain morphology could differentiate D-SZ from ND-SZ. Anterior cingulate gyrus (ACG) region regulates cognitive and emotional processing and past studies reported structural changes in this region in patients with SZ. METHODS 1.5-T 3D MRI scans were obtained from 18 D-SZ patients, 30 ND-SZ patients and 82 healthy controls (HCs). We used FreeSurfer-initalized labeled cortical distance mapping (FSLCDM) to measure ACG gray matter volume, cortical thickness, and area of the gray/white interface. Furthermore, cortical thickness was compared among the 3 groups using the pooled labeled cortical distance mapping (LCDM) method. RESULTS The ACG cortex of the D-SZ group was thinner than the ND-SZ group. Pooled LCDM demonstrated that the ACG cortex was bilaterally thinner in both the ND-SZ group and the D-SZ group compared with the control group. The right ACG gray matter volume was significantly reduced in D-SZ patients as compared with healthy controls (p=0.005 CONCLUSION: Our data suggest that qualitative, categorical differences in neuroanatomy may distinguish between deficit and non-deficit subtypes of schizophrenia.

Volume reductions in frontopolar and left perisylvian cortices in methamphetamine induced psychosis

Consumption of methamphetamine disturbs dopaminergic transmission and sometimes provokes schizophrenia-like-psychosis, named methamphetamine-associated psychosis (MAP). While previous studies have repeatedly reported regional volume reductions in the frontal and temporal areas as neuroanatomical substrates for psychotic symptoms, no study has examined whether such neuroanatomical substrates exist or not in patients with MAP. Magnetic resonance images obtained from twenty patients with MAP and 20 demographically-matched healthy controls (HC) were processed for voxel-based morphometry (VBM) using Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra. An analysis of covariance model was adopted to identify volume differences between subjects with MAP and HC, treating intracranial volume as a confounding covariate. The VBM analyses showed significant gray matter volume reductions in the left perisylvian structures, such as the posterior inferior frontal gyrus and the anterior superior temporal gyrus, and the frontopolar cortices, including its dorsomedial, ventromedial, dorsolateral, and ventrolateral portions, and white matter volume reduction in the orbitofrontal area in the patients with MAP compared with the HC subjects. The smaller regional gray matter volume in the medial portion of the frontopolar cortex was significantly correlated with the severe positive symptoms in the individuals with MAP. The volume reductions in the left perisylvian structure suggest that patients with MAP have a similar pathophysiology to schizophrenia, whereas those in the frontopolar cortices and orbitofrontal area suggest an association with antisocial traits or vulnerability to substance dependence.

Diabetes is associated with lower global cognitive function in schizophrenia

BACKGROUND Co-morbidity of schizophrenia (SZ) and metabolic problems such as diabetes mellitus (DM) has been suggested by many studies. Nonetheless, it is still debated whether DM affects cognitive dysfunction associated with SZ and how much treatment for DM is beneficial for cognitive functions in SZ. We addressed these questions by re-assessing the cognitive dataset from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. METHODS We identified 1289 SZ patients in which scores for several cognitive domains of verbal memory, vigilance, processing speed, reasoning, and working memory together with the composite score and metabolic characteristics (body mass index, dyslipidemia, hypertension, and DM) were available at baseline of the trial. We performed multiple linear regression analyses to assess the impact of DM on cognitive performance of SZ patients, controlling for a number of other confounding factors including obesity, hypertension, and dyslipidemia. We also conducted analyses of covariance to compare cognitive performance among SZ patients without DM and diabetic SZ sub-groups based on anti-diabetic drugs they were receiving at baseline of the trial. RESULTS Co-morbid DM with SZ predicted worse overall cognitive performance and lower scores for three cognitive domains (vigilance, processing speed, and reasoning), but none of the other metabolic factors (i.e., obesity, hypertension and dyslipidemia) correlated with cognitive function in SZ. Furthermore, SZ patients with untreated DM showed poorer overall cognitive performance and a significantly lower score in the domain of vigilance compared with SZ patients without DM. CONCLUSION Our data suggest that DM negatively affects the overall cognitive function of SZ patients.

Antidepressant use and lifetime history of mental disorders in a community sample: results from the Baltimore Epidemiologic Catchment Area Study.

OBJECTIVE Past studies have shown that many individuals who use antidepressants have no current or lifetime history of mental disorders. However, recent studies suggest that the one-time retrospective evaluation of mental disorders commonly used in such studies may substantially underestimate the true lifetime prevalence of mental disorders. We examined the prevalence of mental disorders, assessed prospectively over multiple interviews, among individuals currently using antidepressants in a community sample. METHOD Using data from the Baltimore Epidemiologic Catchment Area (ECA) Study Wave 1 (1981) through Wave 4 (2004-2005) (N = 1,071), we assessed lifetime prevalence of common mood and anxiety disorders according to DSM-III and DSM-III-R criteria, based on 4 interviews, among participants who reported current antidepressant use. Furthermore, we examined factors associated with current antidepressant use. RESULTS Thirteen percent of participants at Wave 4 reported currently using antidepressant medications. Among antidepressant users, 69% never met criteria for major depressive disorder (MDD); and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime. Female gender, Caucasian ethnicity, recent or current physical problems (eg, loss of bladder control, hypertension, and back pain), and recent mental health facility visits were associated with antidepressant use in addition to mental disorders. CONCLUSIONS Many individuals who are prescribed and use antidepressant medications may not have met criteria for mental disorders. Our data indicate that antidepressants are commonly used in the absence of clear evidence-based indications.