Cortical thickness and oscillatory phase resetting: A proposed mechanism of salience network dysfunction in schizophrenia
Lena Palaniyappan MRCPsych, Kathrin Doege PhD, Pavan Mallikarjun MRCPsych, Elizabeth Liddle PhD, Peter Francis Liddle PhD MRCPsych.
Psychiatriki, 2012 (in press)
Abstract:
Background: Schizophrenia is characterised by both electrophysiological abnormalities and consistent... more
Abstract:
Background: Schizophrenia is characterised by both electrophysiological abnormalities and consistent changes in the structure of cortical grey matter. But the relationship between these two observations is largely unknown. Structural changes reported in schizophrenia include reduced grey matter volume, thickness and surface area in several cortical regions, but most frequently in the insula and anterior cingulate cortex. These two regions together constitute an intrinsic brain circuit known as the ‘Salience Network’, which has a key role in stimulus processing. During stimulus processing tasks, evoked activity is noted using electroencephalography (EEG). Phase resetting of ongoing oscillations contributes to this evoked activity.
Methods: In this study, we investigated the relationship between the cortical thickness in the Salience Network (measured using MRI) and the degree of phase resetting observed during an oddball task (measured using EEG) in 18 patients with schizophrenia and 20 healthy controls.
Results: In patients with schizophrenia the reduced thickness in the Salience Network was associated with the inefficient phase resetting of theta oscillations.
Conclusions: Our findings suggest that the grey matter reduction seen in the Salience Network in patients with schizophrenia has substantial functional consequences. In particular, the structural defect of the insula that is seen in schizophrenia is likely to be associated with less efficient recruitment of brain circuits for processing information. This implies a possible mechanism by which disruptions in the intrinsic Salience Network can result in a general disturbance in salience detection seen in schizophrenia.
From the Problem of the Nature of Psychosis to the Phenomenological Reform of Psychiatry. Historical and Epistemological Remarks on Ludwig Binswanger’s Psychiatric Project, Medicine Studies, 2012 (DOI) 10.1007/s12376-012-0076-x
This paper focuses on one of the original moments of the development of the “phenomenological” current of psychiatry,... more This paper focuses on one of the original moments of the development of the “phenomenological” current of psychiatry, namely, the psychopathological research of Ludwig Binswanger. By means of the clinical and conceptual problem of schizophrenia as it was conceived and developed at the beginning of the twentieth century, I will try to outline and analyze Binswanger’s perspective from a both historical and epistemological point of view. Binswanger’s own way means of approaching and conceiving schizophrenia within the scientific, medical, and psychiatric context of that time will lead us to grasp the epistemological stakes at the origins of his project of reforming psychiatry by means of phenomenology. I will finally attempt to upgrade and update Binswanger’s project in light of the current reappraisal of phenomenology within the ongoing debate on psychopathology engaged by studies in the field of science and philosophy of mind.
Download (.pdf) Modafinil-induced psychosis
Wu, P., S. G. Jones, C. J. Ryan, D. Michail, and T. Robinson. 2008. Modafinil-induced psychosis. Internal Medicine Journal 38 (8): 677-678.
Modafinil is a relatively new wakefulness-promoting agent used for the treatment of excessive sleepiness due to... more Modafinil is a relatively new wakefulness-promoting agent used for the treatment of excessive sleepiness due to narcolepsy and other sleep disorders. We report on a man who had an acute psychotic episode after ingesting too much modafinil.
Brain vs Behavior: An Effect Size Comparison of Neuroimaging and Cognitive Studies of Genetic Risk for Schizophrenia
Emma Jane Rose and Gary Donohoe. Schizophrenia Bulletin (in press)
Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be more penetrant at the... more Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be more penetrant at the level of brain structure and function than at the level of behavior. However, to date the relative sensitivity of imaging vs cognitive measures of these variants has not been quantified. We considered effect sizes associated with cognitive and imaging studies of 9 robust SZ risk genes (DAOA, DISC1, DTNBP1, NRG1, RGS4, NRGN, CACNA1C, TCF4, and ZNF804A) published between January 2005–November 2011. Summary data was used to calculate estimates of effect size for each significant finding. The mean effect size for each study was categorized as small, medium, or large and the relative frequency of each category was compared between modalities and across genes. Random effects meta-analysis was used to consider the impact of experimental methodology on effect size. Imaging studies reported mostly medium or large effects, whereas cognitive investigations commonly reported small effects. Meta-analysis confirmed that imaging studies were associated with larger effects. Effect size estimates were negatively correlated with sample size but did not differ as a function of gene nor imaging modality. These observations support the notion that SZ risk variants show larger effects, and hence greater penetrance, when characterized using indices of brain structure and function than when indexed by cognitive measures. However, it remains to be established whether this holds true for individual risk variants, imaging modalities, or cognitive functions, and how such effects may be mediated by a relationship with sample size and other aspects of experimental variability.
Carbon dioxide induction of panic anxiety in schizophrenia with auditory hallucinations
Psychiatry Res. 2011 Aug 30;189(1):38-42. Epub 2011 Jun 29.
Carbon dioxide induction of panic anxiety in... more
Psychiatry Res. 2011 Aug 30;189(1):38-42. Epub 2011 Jun 29.
Carbon dioxide induction of panic anxiety in schizophrenia with auditory hallucinations.
Savitz AJ, Kahn TA, McGovern KE, Kahn JP.
Source
Department of Psychiarty, Weill Cornell Medical College, White Plains, NY 10605, USA.
Abstract
Panic is commonly co-morbid with schizophrenia. Panic may emerge prodromally, contribute to specific psychotic symptoms, and predict medication response. Panic is often missed due to agitation, impaired cognition, psychotic symptom overlap and limited clinician awareness. Carbon dioxide exposure has been used reliably to induce panic in non-psychotic panic subjects, but has not been systematically studied in schizophrenia. Eight inpatients with schizophrenia, recent auditory hallucinations, none preselected for panic, all on antipsychotic medication, received a structured Panic and Schizophrenia Interview (PaSI), assessing DSM-IV panic symptoms concurrent with paroxysmal auditory hallucinations. On that interview, all eight subjects reported panic concurrent with auditory hallucinations. At one sitting, subjects were exposed, in random order, to 35% carbon dioxide and to placebo room air, blinded to condition. All subjects experienced panic to carbon dioxide, one with limited symptoms. Only one subject panicked to placebo. One subject (one of only two without antipanic medication) had paroxysmal voices concurrent with induced panic. With added adjunctive clonazepam, that patient had marked clinical improvement and no response to carbon dioxide re-challenge. This first systematic examination offers preliminary evidence that carbon dioxide safely induces panic symptoms in schizophrenia. Panic may be prevalent and pathophysiologically significant in schizophrenia with auditory hallucinations.
Adjunctive alprazolam for schizophrenia with panic anxiety: Clinical observation and pathogenetic implications.
Am J Psychiatry. 1988 Jun;145(6):742-4. Adjunctive alprazolam for schizophrenia with panic anxiety: clinical observation and pathogenetic implications. Kahn JP, Puertollano MA, Schane MD, Klein DF. Source: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Abstract
Seven patients with schizophrenia and panic attacks all showed marked improvement of positive... more
Abstract
Seven patients with schizophrenia and panic attacks all showed marked improvement of positive and negative schizophrenic symptoms when alprazolam was openly added to antipsychotic medication. Panic attacks may identify alprazolam-responsive schizophrenic patients and may define a distinct pathophysiologic subgroup.
Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia
Sugranyes G, Kyriakopoulos M, Dima D, O'Muircheartaigh J, Corrigall R, Pendelbury G, Hayes D, Calhoun VD, Frangou S
Schizophr
BACKGROUND: Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise... more
BACKGROUND: Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity.
METHODS: We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted "features" [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources.
RESULTS: Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum.
CONCLUSIONS: This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder.
The Threat of Givenness in Jean-Luc Marion: Toward a New Phenomenology of Psychosis
by Joseph Carew
Symposium: Canadian Journal of Continental Philosophy. Vol 13.2 (Fall 2009): 97-115.
Absent within Jean-Luc Marion’s theory of selfhood is an account of psychosis that displaces standard phenomenological... more Absent within Jean-Luc Marion’s theory of selfhood is an account of psychosis that displaces standard phenomenological and psychoanalytic models. Working primarily with Book V of Being Given, my paper sketches the formal possibilities exhibited in a self who cannot manage the superabundance of the given and, swept away by an uncontrollable flood of givenness, thereby falls into a hysteria of self-experience and loses its ipseity. Then, contrasting psychosis with positive figures of the self, I explore the dynamic relationship between givenness and the gifted highlighted by the phenomenological diremption and effacement of selfhood displayed in both.
Treatment of Comorbid Panic Disorder and Schizophrenia: Evidence for a Panic Psychosis
Treatment of Comorbid Panic Disorder and Schizophrenia:
Evidence for a Panic Psychosis
Jeffrey P. Kahn, MD; and John R. Meyers, MD
Why is it important to consider comorbid
panic disorder in schizophrenia?
After all, schizophrenia wreaks... more
Why is it important to consider comorbid
panic disorder in schizophrenia?
After all, schizophrenia wreaks such
devastation on patients' lives that panic disorder
would seem trivial in comparison. However, clinical
experience and a growing literature suggest
that comorbid panic disorder may be a major
determinant of distress and dysfunction across
many psychiatric disorders, including schizophrenia.
The recognition of panic disorder in
patients with schizophrenia is crucial for designing
effective treatment. In addition, panic disorder
may play a significant pathogenetic role in
some schizophrenic illness.
During the past 30 years, the diagnosis of psychotic
disorders has become increasingly precise.
Symptoms that were once lumped together under
one diagnosis are now accurately distinguished
from one another, with disorders such as psychotic
mania, delusional depression, and paranoid
delusional disorder being properly differentiated.
These more specific diagnoses came into common
use as psychiatry better understood their symptom
clusters, natural history, and treatment
response. For example, the discovery of lithium
made the distinction between psychotic mania and
schizophrenia far more clinically pressing.
As a result of recent interest in psychiatric
comorbidity, illnesses once thought to be distinct
from one another, such as obsessive-compulsive
disorder and schizophrenia, are now known to
have important areas of overlap. Some clinicians
use the term "schizo-obsessive disorder" to
describe this condition. Similarly, social phobia
has been suggested as an etiologic factor for
schizophrenia. This article considers the treatment
of comorbid panic disorder and schizophrenia
and, in light of these new perspectives, the
possibility of a distinct "panic psychosis."
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The impact of familial risk for schizophrenia or bipolar disorder on cognitive control during episodic memory retrieval.
Christodoulou T, Messinis L, Papathanasopoulos P, Frangou S
Psychiatry Research 2012. doi:10.1016/j.psychres.2011.12.028
BACKGROUND: Episodic memory impairment is a robust correlate of familial risk for schizophrenia (SZ) and bipolar... more
BACKGROUND: Episodic memory impairment is a robust correlate of familial risk for schizophrenia (SZ) and bipolar disorder (BD); still much is unknown about the processes that underlie this deficit and how they may be implicated in BD and SZ. We examined the possibility that (a) episodic memory impairment may arise from abnormalities in the cognitive control of interference between task-relevant and task-irrelevant memories during retrieval; inability to suppress task-irrelevant representations could give rise to intrusions of inappropriate memories and increased rate of forgetting, (b) cognitive control deficits during retrieval may be differentially affected by familial predisposition to SZ or BD.
METHODS: We examined episodic memory in relatives of patients with SZ (SZ-R) (n=15) or BD (BD-R) (n=17) compared to healthy controls (n=23) using the California Verbal Learning Test (CVLT) and the Doors and People Test (DPT). All relatives were free of any psychiatric morbidity and were matched to controls on age, sex, educational achievement and general intellectual ability.
RESULTS: During the CVLT, both relatives' groups made significantly more perseverative recall errors than controls. However, intrusion errors were significantly increased in SZ-R only. SZ-R also showed increased rate of forgetting in the DPT while BD-R were comparable to controls.
CONCLUSIONS: Familial predisposition to SZ, compared to that of BD, was associated with significantly greater impairment in cognitive control processes during episodic memory retrieval with some evidence of specificity for SZ in connection with mechanisms relating to increased forgetting.
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Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations
by Nora S Vyas
Nora S. Vyas, Nitin Gogtay (2012)
Frontiers Psychiatry, Vol 3 (Article 29), 1-5
doi:10.3389/fpsyt2012.00029
Early onset schizophrenia (onset before adulthood) is a rare, severe and chronic form of schizophrenia. The clinical... more Early onset schizophrenia (onset before adulthood) is a rare, severe and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment refractory cses. Based on the current literature, second generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies.
The psychosis continuum in the general population: findings from the São Paulo Epidemiologic Catchment Area Study
Alexandre Andrade Loch, Yuan-Pang Wang, Wulf Rössler, Luis Fernando Tófoli, Camila Magalhães Silveira and Laura Helena Andrade
The aim of the study was to examine the psychosis continuum in a Latin-American community setting. Data were from the... more The aim of the study was to examine the psychosis continuum in a Latin-American community setting. Data were from the Brazilian São Paulo Epidemiologic Catchment Area Study, a cross-sectional survey conducted in two boroughs of the city of São Paulo. The Composite International Diagnosis Interview (version 1.1) was applied to a probabilistic sample of 1,464 adults, who were interviewed in their household, in order to identify the presence of psychotic symptoms. A subsample was assessed with Schedules for Clinical Assessment in Neuropsychiatry interview. We described the occurrence of psychotic symptoms, categorized into subgroups according to their clinical impact, disability, and help-seeking behavior. The correlation of socio-demographic variables, depressive symptoms, and alcohol and substance use disorders with those psychotic subgroups was analyzed. Polychotomic logistic regression tested the associations between subgroups of psychosis (clinical and subclinical) and the correlates. Of the total sample, 38.0% presented at least one lifetime psychotic symptom, 1.9% met the criteria for an ICD-10 diagnosis of non-affective psychosis, 5.4% presented clinically relevant psychotic symptoms, and 30.7% endorsed clinically non-relevant symptoms. The most common psychotic symptom was delusion with a plausible explanation (in 18.6%). The presence of any psychiatric diagnosis was associated with the presence of psychotic symptoms (OR range, 1.9–8.9). Subclinical psychosis subgroups were found to be associated with the 18–24 year age bracket, chronic depressive mood, and alcohol use disorder. Our results support the concept of a psychosis continuum in Latin-American populations, suggesting that different risk factors influence their manifestation across the continuum.
Dissociable Morphometric Differences of the Inferior Parietal Lobule in Schizophrenia
Lena Palaniyappan and Peter F. Liddle
European Archives of Psychiatry & Clinical Neurosciences
Abstract
Objectives: Inferior Parietal Lobule (IPL) forms an integral part of a critical frontoparietal... more
Abstract
Objectives: Inferior Parietal Lobule (IPL) forms an integral part of a critical frontoparietal network, which has been implicated in various clinical symptoms and cognitive deficits seen in schizophrenia. Despite its functional relevance, the relatively few studies that have investigated the structural changes in the IPL report inconsistent findings concerning the nature and localization of these changes.
Methods: We employed a blinded, automated labeling procedure to measure cortical thickness, surface area and the degree of cortical folding of the two distinct subregions of the IPL (Angular Gyrus and Supramarginal Gyrus) in 57 patients with schizophrenia and 41 controls using high resolution magnetic resonance imaging.
Results: Within the IPL, we observed more pronounced morphological changes in supramarginal gyrus compared to angular gyrus in schizophrenia. While supramarginal gyrus in patients showed reduced gyrification, contracted surface area and thinning, the morphometric changes in angular gyrus were largely confined to a reduction in surface area. Significant hemispheric asymmetry was observed in the gyrification of the supramarginal gyrus.
Conclusions: Our findings suggest that in addition to abnormalities in the neurodevelopmental processes that contribute to regional surface area and cortical thickness, a specific defect in cortical folding, especially affecting the left hemisphere is likely to occur in schizophrenia.
Aberrant Cortical Gyrification in Schizophrenia: A Surface Based Morphometry Study
Palaniyappan, L & Liddle PF
Journal of Psychiatry and Neuroscience. In press
Abstract
Background: Schizophrenia is considered to be a disorder of cerebral connectivity associated with... more
Abstract
Background: Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in cortical connectivity at an early period of cortical maturation can result in widespread defects in cortical gyrification. Investigating the anatomical distribution of gyrification defects can provide important information about neurodevelopment in schizophrenia.
Methods: We undertook an automated surface based morphometric assessment of gyrification on 3-dimensionally reconstructed cortical surfaces across multiple vertices that cover the entire cortex. We studied 57 patients (50 males) with schizophrenia and 41 healthy controls in whom we have previously tested a specific hypothesis regarding presence of both hypo- and hypergyria in prefrontal cortex using a frontal region-of-interest approach.
Results: Regions with significant reductions in gyrification (hypogyria) were seen predominantly in the left hemisphere, involving the insula and several regions of the multimodal association cortex. Although the prefrontal hypergyria documented earlier did not survive the statistical correction required for a whole brain search (cluster inclusion at p=0.0001), significant hypergyric frontal clusters emerged when the threshold was lowered (cluster inclusion at p=0.05). In insula, a reduction in gyrification was related to reduced cortical thickness in patients.
Limitations: We studied a sample of patients taking antipsychotics, which could have confounded the results. Our sample was predominantly male, limiting the generalisability.
Conclusions: Our observations suggest that the disturbances in cortical gyrification seen in schizophrenia might be related to a disrupted interaction between the paralimbic and the multimodal association cortex and thus contribute to the pathogenesis of the illness.
The effects of psychosis risk variants on brain connectivity: a meta-analysis
Omar Mothersill, Sinead Kelly, Emma Jane Rose, & Gary Donohoe (2012). Frontiers in Psychiatry. 3 (18).
In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural... more In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e. functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e. Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d=0.76) and structural connectivity (mean d=1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q=2.17, p>0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q=6.928, p=0.008).Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation.
Can Genetics Inform the Management of Cognitive Deficits in Schizophrenia?
by Nora S Vyas
Vyas NS, Shamsi SA, Malhotra AK, Aitchison KJ, Kumari V (2012)
There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been... more There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.
Distress or Disability?
Proceedings of a symposium held at Lancaster University, 15-16 November 2011.
This symposium was organised jointly by Mental Health in Higher Education, the Centre for Disability Research at... more
This symposium was organised jointly by Mental Health in Higher Education, the Centre for Disability Research at Lancaster University and the School of Social Work at the University of Central Lancashire. The symposium was by invitation only and brought together scholars (including
academics, activists and research students) from the north-west of England to explore the issues that arise from trying to situate mental distress or ’madness’ within the social model of disability. We specifically focussed on psychosis, hearing voices and other extra-ordinary experiences, as these raise particular issues and challenges.
Structural Correlates of Auditory Hallucinations in Schizophrenia: A Meta-analysis
Lena Palaniyappan, Vijender Balain, Joaquim Radua, Peter F Liddle
Schizophrenia Research, In Press
Background: Despite being one of the most common symptoms of schizophrenia, determining the neural correlates of... more
Background: Despite being one of the most common symptoms of schizophrenia, determining the neural correlates of auditory hallucinations still remains elusive with various studies providing inconsistent results.
Methods: We conducted a voxel-based meta-analysis of studies investigating the structural correlates of auditory hallucinations in schizophrenia.
Results: 7 datasets including 350 patients were identified. There was a significant negative correlation between the severity of hallucinations and grey matter volume in the left insula and right superior temporal gyrus.
Conclusion: With its key role in stimulus evaluation and optimizing prediction (proximal salience), the insula is likely to be a cardinal region along with superior temporal gyrus in the mechanism of auditory hallucinations in schizophrenia.
Rationale of Combining More than One Antipsychotic in a LTC/Nursing Home Patient at Same Time
Lamoure J. Rationale of Combining More than One Antipsychotic in a LTC/Nursing Home Patient at Same Time .... more Lamoure J. Rationale of Combining More than One Antipsychotic in a LTC/Nursing Home Patient at Same Time . Canadian Healthcare Network ATE Panel. October, 2011. http://www.canadianhealthcarenetwork.ca/pharmacists/discussions/the-experts/mental-health