Probable Case of Neuroleptic Malignant Syndrome Following Administration of Antituberculotic Drugs in a Chlorpromazine-Treated Patient

Neuroleptic malignant syndrome (NMS), a potentially fatal adverse reaction to neuroleptics, is known to occur more often in the initial stage of antipsychotic treatment. We describe a patient with chronic schizophrenia who, in a few days after the addition of antituberculotic drugs to his antipsychotic regimen, developed probable NMS without pyrexia. We reasoned that rifampin, a strong hepatic enzyme inducer, decreased the plasma chlorpromazine concentration of the patient, with the result of cholinergic hyperactivity and finally, the symptoms of NMS. Therefore, physicians should be aware of drug interactions and the likelihood of NMS, and consider antipsychotic dose adjustment when prescribing drugs that may influence pharmacokinetic properties of antipsychotics in a patient with schizophrenia receiving long-term antipsychotic treatment

Altered resting-state connectivity in subjects at ultra-high risk for psychosis: an fMRI study

<p>Abstract</p> <p>Background</p> <p>Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects.</p> <p>Methods</p> <p>This study utilized functional magnetic resonance imaging (fMRI) to investigate resting-state DMN and task-related network (TRN) functional connectivity in 19 UHR subjects and 20 matched healthy controls. The bilateral posterior cingulate cortex was selected as a seed region, and the intrinsic organization for all subjects was reconstructed on the basis of fMRI time series correlation.</p> <p>Results</p> <p>Default mode areas included the posterior/anterior cingulate cortices, the medial prefrontal cortex, the lateral parietal cortex, and the inferior temporal region. Task-related network areas included the dorsolateral prefrontal cortex, supplementary motor area, the inferior parietal lobule, and middle temporal cortex. Compared to healthy controls, UHR subjects exhibit hyperconnectivity within the default network regions and reduced anti-correlations (or negative correlations nearer to zero) between the posterior cingulate cortex and task-related areas.</p> <p>Conclusions</p> <p>These findings suggest that abnormal resting-state network activity may be related with the clinical features of UHR subjects. Neurodevelopmental and anatomical alterations of cortical midline structure might underlie altered intrinsic networks in UHR subjects.</p

Reduced cortical folding of the anterior cingulate cortex in obsessive-compulsive disorder

Background: Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. Methods: We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupted" or "continuous" according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology. Results: Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a "prominent" or "present" paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls. Limitations: Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates. Conclusion: Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.This work was supported by Cognitive Neuroscience Program of the Korean Ministry of Science and Technology (M10644020003-08N4402-00310).Jung MH, 2009, PROG NEURO-PSYCHOPH, V33, P605, DOI 10.1016/j.pnpbp.2009.02.017Whittle S, 2009, PSYCHIAT RES-NEUROIM, V172, P68, DOI 10.1016/j.pscychresns.2008.06.005Gu BM, 2008, BRAIN, V131, P155, DOI 10.1093/brain/awm277Fornito A, 2007, ACTA PSYCHIAT SCAND, V116, P467, DOI 10.1111/j.1600-0447.2007.01069.xShin YW, 2007, HUM BRAIN MAPP, V28, P1128, DOI 10.1002/hbm.20338Huster RJ, 2007, NEUROIMAGE, V34, P888, DOI 10.1016/j.neuroimage.2006.10.023De Geus F, 2007, PSYCHIAT CLIN NEUROS, V61, P45, DOI 10.1111/j.1440-1819.2007.01609.xFornito A, 2006, SCHIZOPHR RES, V88, P192, DOI 10.1016/j.schres.2006.06.034Jang JH, 2006, AM J PSYCHIAT, V163, P1202Kim YY, 2006, BRAIN TOPOGR, V18, P201, DOI 10.1007/s10548-006-0269-2Klimkeit EI, 2006, CORTEX, V42, P113Valente AA, 2005, BIOL PSYCHIAT, V58, P479, DOI 10.1016/j.biopsych.2005.04.021Rosenberg DR, 2004, J AM ACAD CHILD PSY, V43, P1146, DOI 10.1097/01.chi.0000132812.44664.2dFornito A, 2004, CEREB CORTEX, V14, P424, DOI 10.1093/cercor/bhh004Shin YW, 2004, PSYCHIAT CLIN NEUROS, V58, P16Yucel M, 2003, BRIT J PSYCHIAT, V182, P518Yucel M, 2002, BIOL PSYCHIAT, V52, P15Lyoo IK, 2001, J CLIN PSYCHIAT, V62, P637Allman JM, 2001, ANN NY ACAD SCI, V935, P107Yucel M, 2001, CEREB CORTEX, V11, P17Bradshaw JL, 2000, BRAIN LANG, V73, P297Bush G, 2000, TRENDS COGN SCI, V4, P215Penalva J, 2000, BIOSENS BIOELECTRON, V15, P99Lohmann G, 1999, CEREB CORTEX, V9, P754Magnotta VA, 1999, CEREB CORTEX, V9, P151Tibbo P, 1999, J PSYCHIATR NEUROSCI, V24, P15Rosenberg DR, 1998, BIOL PSYCHIAT, V43, P623Purcell R, 1998, BIOL PSYCHIAT, V43, P348SAXENA S, 1998, BRIT J PSYCHIAT S, V35, P26FIRST MB, 1998, STRUCTURED CLIN INTESIEGEL S, 1998, NONPARAMETRIC STAT BRauch SL, 1997, J NEUROPSYCH CLIN N, V9, P568Bartley AJ, 1997, BRAIN, V120, P257VanEssen DC, 1997, NATURE, V385, P313Paus T, 1996, CEREB CORTEX, V6, P207FIRST MB, 1996, STRUCTURED CLIN INTEVOGT BA, 1995, J COMP NEUROL, V359, P490DEVINSKY O, 1995, BRAIN, V118, P279ARMSTRONG E, 1995, CEREB CORTEX, V5, P56PAULS DL, 1995, AM J PSYCHIAT, V152, P76KIM JS, 1995, KOREAN J CLIN PSYCHO, V14, P111*AM PSYCH ASS, 1994, DIAGN STAT MAN MENTBAXTER LR, 1992, ARCH GEN PSYCHIAT, V49, P681HUANG CC, 1991, BRAIN DEV-JPN, V13, P27WELKER W, 1990, CEREBRAL CORTEX B, V8, P3DIXON WJ, 1990, BMDP STAT SOFTWARE MHOLLANDER E, 1990, ARCH GEN PSYCHIAT, V47, P27CROW TJ, 1989, ARCH GEN PSYCHIAT, V46, P1145GOODMAN WK, 1989, ARCH GEN PSYCHIAT, V46, P1006GOODMAN WK, 1989, ARCH GEN PSYCHIAT, V46, P1012SWEDO SE, 1989, ARCH GEN PSYCHIAT, V46, P518RAKIC P, 1988, SCIENCE, V241, P170BEAR D, 1986, ARCH NEUROL-CHICAGO, V43, P598GESCHWIND N, 1985, ARCH NEUROL-CHICAGO, V42, P521FLORHENRY P, 1983, CEREBRAL BASIS PSYCH, P301CHI JG, 1977, ANN NEUROL, V1, P86ANNETT M, 1970, BRIT J PSYCHOL, V61, P303CRICHTONBROWNE J, 1879, BRAIN, V2, P42

Disproportionate Alterations in the Anterior and Posterior Insular Cortices in Obsessive–Compulsive Disorder

Recent studies have reported that the insular cortex is involved in the pathophysiology of obsessive–compulsive disorder (OCD). However, specific morphometric abnormalities of the insular subregions remain unclear. In this study, we examined insular cortical volume to determine whether the volume of the anterior and posterior insular cortices of unmedicated OCD patients differed according to different symptom dimensions.Using magnetic resonance imaging, we measured the gray matter volumes of the insular cortex and its subregions (anterior and posterior divisions) in 41 patients with OCD (31 drug-naïve and 10 non-medicated) and 53 healthy controls. Volumetric measures of the insular cortex were compared according to different OC symptoms. Enlarged anterior and reduced posterior insular cortices were observed in OCD patients. The insular volumetric alterations were more significant in OCD patients with predominant checking rather than cleaning symptoms when compared with healthy controls.Our results suggest the presence of unbalanced anterior and posterior insular volumetric abnormalities in unmedicated OCD patients and emphasize the distinct role of the insular cortex in different OC symptoms. We propose that the insular morphometric alterations may influence the modulation of interoceptive processing, the insular functional role, in OCD patients with different symptoms

The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder

Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) while performing the ToL task at baseline and again after 16 weeks of SSRI treatment. Internetwork connectivity was compared across the groups and treatment statuses (pretreatment versus posttreatment). At baseline, compared with the HCs, the OCD patients showed lower internetwork connectivity between the dorsal attention network and the default-mode network during the ToL planning task. After 16 weeks of SSRI treatment, the OCD patients showed improved clinical symptoms accompanied by normalized network connectivity, although their improved behavioral performance in the ToL task did not reach that of the HCs. Our findings support the conceptualization of OCD as a network disease characterized by an imbalance between brain networks during goal-directed planning and suggest that internetwork connectivity may serve as an early biomarker of the effects of SSRIs on goal-directed planning.Y

Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.Y

Reduced cortical folding of the anterior cingulate cortex in obsessive–compulsive disorder

Background: Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. Methods: We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupted" or "continuous" according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology. Results: Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a "prominent" or "present" paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls. Limitations: Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates. Conclusion: Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.This work was supported by Cognitive Neuroscience Program of the Korean Ministry of Science and Technology (M10644020003-08N4402-00310).Jung MH, 2009, PROG NEURO-PSYCHOPH, V33, P605, DOI 10.1016/j.pnpbp.2009.02.017Whittle S, 2009, PSYCHIAT RES-NEUROIM, V172, P68, DOI 10.1016/j.pscychresns.2008.06.005Gu BM, 2008, BRAIN, V131, P155, DOI 10.1093/brain/awm277Fornito A, 2007, ACTA PSYCHIAT SCAND, V116, P467, DOI 10.1111/j.1600-0447.2007.01069.xShin YW, 2007, HUM BRAIN MAPP, V28, P1128, DOI 10.1002/hbm.20338Huster RJ, 2007, NEUROIMAGE, V34, P888, DOI 10.1016/j.neuroimage.2006.10.023De Geus F, 2007, PSYCHIAT CLIN NEUROS, V61, P45, DOI 10.1111/j.1440-1819.2007.01609.xFornito A, 2006, SCHIZOPHR RES, V88, P192, DOI 10.1016/j.schres.2006.06.034Jang JH, 2006, AM J PSYCHIAT, V163, P1202Kim YY, 2006, BRAIN TOPOGR, V18, P201, DOI 10.1007/s10548-006-0269-2Klimkeit EI, 2006, CORTEX, V42, P113Valente AA, 2005, BIOL PSYCHIAT, V58, P479, DOI 10.1016/j.biopsych.2005.04.021Rosenberg DR, 2004, J AM ACAD CHILD PSY, V43, P1146, DOI 10.1097/01.chi.0000132812.44664.2dFornito A, 2004, CEREB CORTEX, V14, P424, DOI 10.1093/cercor/bhh004Shin YW, 2004, PSYCHIAT CLIN NEUROS, V58, P16Yucel M, 2003, BRIT J PSYCHIAT, V182, P518Yucel M, 2002, BIOL PSYCHIAT, V52, P15Lyoo IK, 2001, J CLIN PSYCHIAT, V62, P637Allman JM, 2001, ANN NY ACAD SCI, V935, P107Yucel M, 2001, CEREB CORTEX, V11, P17Bradshaw JL, 2000, BRAIN LANG, V73, P297Bush G, 2000, TRENDS COGN SCI, V4, P215Penalva J, 2000, BIOSENS BIOELECTRON, V15, P99Lohmann G, 1999, CEREB CORTEX, V9, P754Magnotta VA, 1999, CEREB CORTEX, V9, P151Tibbo P, 1999, J PSYCHIATR NEUROSCI, V24, P15Rosenberg DR, 1998, BIOL PSYCHIAT, V43, P623Purcell R, 1998, BIOL PSYCHIAT, V43, P348SAXENA S, 1998, BRIT J PSYCHIAT S, V35, P26FIRST MB, 1998, STRUCTURED CLIN INTESIEGEL S, 1998, NONPARAMETRIC STAT BRauch SL, 1997, J NEUROPSYCH CLIN N, V9, P568Bartley AJ, 1997, BRAIN, V120, P257VanEssen DC, 1997, NATURE, V385, P313Paus T, 1996, CEREB CORTEX, V6, P207FIRST MB, 1996, STRUCTURED CLIN INTEVOGT BA, 1995, J COMP NEUROL, V359, P490DEVINSKY O, 1995, BRAIN, V118, P279ARMSTRONG E, 1995, CEREB CORTEX, V5, P56PAULS DL, 1995, AM J PSYCHIAT, V152, P76KIM JS, 1995, KOREAN J CLIN PSYCHO, V14, P111*AM PSYCH ASS, 1994, DIAGN STAT MAN MENTBAXTER LR, 1992, ARCH GEN PSYCHIAT, V49, P681HUANG CC, 1991, BRAIN DEV-JPN, V13, P27WELKER W, 1990, CEREBRAL CORTEX B, V8, P3DIXON WJ, 1990, BMDP STAT SOFTWARE MHOLLANDER E, 1990, ARCH GEN PSYCHIAT, V47, P27CROW TJ, 1989, ARCH GEN PSYCHIAT, V46, P1145GOODMAN WK, 1989, ARCH GEN PSYCHIAT, V46, P1006GOODMAN WK, 1989, ARCH GEN PSYCHIAT, V46, P1012SWEDO SE, 1989, ARCH GEN PSYCHIAT, V46, P518RAKIC P, 1988, SCIENCE, V241, P170BEAR D, 1986, ARCH NEUROL-CHICAGO, V43, P598GESCHWIND N, 1985, ARCH NEUROL-CHICAGO, V42, P521FLORHENRY P, 1983, CEREBRAL BASIS PSYCH, P301CHI JG, 1977, ANN NEUROL, V1, P86ANNETT M, 1970, BRIT J PSYCHOL, V61, P303CRICHTONBROWNE J, 1879, BRAIN, V2, P42