Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia

Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long‐term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3R) blockade by antipsychotics.

[1]  G. Remington,et al.  Achievement motivation in early schizophrenia: Relationship with symptoms, cognition and functional outcome , 2018, Early intervention in psychiatry.

[2]  M. Husain,et al.  The anatomy of apathy: A neurocognitive framework for amotivated behaviour , 2017, Neuropsychologia.

[3]  J. Rhodes,et al.  Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise , 2017, Neuroscience.

[4]  Shenmin Zhang,et al.  Hemispheric lateralization of resting-state functional connectivity of the ventral striatum: an exploratory study , 2017, Brain Structure and Function.

[5]  A. Aleman,et al.  Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders , 2016, Neuroscience & Biobehavioral Reviews.

[6]  I. Weiner,et al.  Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia , 2016, Experimental Neurology.

[7]  B. Pollock,et al.  Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study , 2016, Psychopharmacology.

[8]  M. Chakravarty,et al.  Glutamatergic Metabolites, Volume and Cortical Thickness in Antipsychotic-Naive Patients with First-Episode Psychosis: Implications for Excitotoxicity , 2016, Neuropsychopharmacology.

[9]  Min Tae M Park,et al.  Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder , 2016, Neuropsychopharmacology.

[10]  G. Remington,et al.  Treating Negative Symptoms in Schizophrenia: an Update , 2016, Current Treatment Options in Psychiatry.

[11]  P. Tobler,et al.  Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia. , 2016, Journal of psychiatry & neuroscience : JPN.

[12]  James C. Ford,et al.  Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder. , 2016, The Journal of neuropsychiatry and clinical neurosciences.

[13]  I. Agartz,et al.  First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia , 2016, European Archives of Psychiatry and Clinical Neuroscience.

[14]  Nur Amirah Abdul Rashid,et al.  Baseline social amotivation predicts 1-year functioning in UHR subjects: A validation and prospective investigation , 2015, European Neuropsychopharmacology.

[15]  B. Ardekani,et al.  Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder. , 2015, Alcohol.

[16]  B. Pollock,et al.  Evaluation of Antipsychotic Dose Reduction in Late-Life Schizophrenia: A Prospective Dopamine D2/3 Receptor Occupancy Study. , 2015, JAMA psychiatry.

[17]  M. J. Nirenberg,et al.  Preoperative factors of apathy in subthalamic stimulated Parkinson disease: A PET study , 2015, Neurology.

[18]  G. Remington,et al.  Motivational deficits in early schizophrenia: Prevalent, persistent, and key determinants of functional outcome , 2015, Schizophrenia Research.

[19]  G. Remington,et al.  Motivation and Social Cognition in Patients with Schizophrenia , 2015, Journal of the International Neuropsychological Society.

[20]  Alan A. Wilson,et al.  Dopamine D2/3 receptor availability in the striatum of antipsychotic-free older patients with schizophrenia—A [11C]-raclopride PET study , 2015, Schizophrenia Research.

[21]  P. Fletcher,et al.  Antipsychotics and Amotivation , 2015, Neuropsychopharmacology.

[22]  I. Melle,et al.  Brain structure abnormalities in first-episode psychosis patients with persistent apathy , 2015, Schizophrenia Research.

[23]  Thomas E. Nichols,et al.  Common genetic variants influence human subcortical brain structures , 2015, Nature.

[24]  C. Svarer,et al.  Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome , 2015, Schizophrenia bulletin.

[25]  M. Mallar Chakravarty,et al.  Multi-atlas segmentation of the whole hippocampus and subfields using multiple automatically generated templates , 2014, NeuroImage.

[26]  D. Wolf,et al.  Amotivation in schizophrenia: integrated assessment with behavioral, clinical, and imaging measures. , 2014, Schizophrenia bulletin.

[27]  G. Remington,et al.  Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia , 2014, Acta psychiatrica Scandinavica.

[28]  G. Remington,et al.  Motivational deficits and cognitive test performance in schizophrenia. , 2014, JAMA psychiatry.

[29]  L. Stan Leung,et al.  Deep brain stimulation of the medial septum or nucleus accumbens alleviates psychosis-relevant behavior in ketamine-treated rats , 2014, Behavioural Brain Research.

[30]  T. A. Carpenter,et al.  Gamma Aminobutyric Acidergic and Neuronal Structural Markers in the Nucleus Accumbens Core Underlie Trait-like Impulsive Behavior , 2014, Biological Psychiatry.

[31]  G. Remington,et al.  Neural substrates underlying effort computation in schizophrenia , 2013, Neuroscience & Biobehavioral Reviews.

[32]  D. Collins,et al.  Performing label‐fusion‐based segmentation using multiple automatically generated templates , 2013, Human brain mapping.

[33]  A. Aleman,et al.  Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts. , 2013, Journal of psychiatric research.

[34]  Dopamine D2/3 occupancy of ziprasidone across a day: a within-subject PET study , 2013, Psychopharmacology.

[35]  S. Borgwardt,et al.  Volumetric Changes in the Basal Ganglia After Antipsychotic Monotherapy: A Systematic Review , 2013, Current medicinal chemistry.

[36]  J. Salamone,et al.  The Mysterious Motivational Functions of Mesolimbic Dopamine , 2012, Neuron.

[37]  Y. Melamed,et al.  Evaluation of the capacity of inpatients with chronic schizophrenia to provide informed consent for participation in clinical trials; use of the Hebrew version of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). , 2012, The Israel Medical Association journal : IMAJ.

[38]  D. R. Weinberger,et al.  Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia , 2012, Schizophrenia Research.

[39]  V. Sturm,et al.  Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy , 2012, Neuropsychopharmacology.

[40]  D. Louis Collins,et al.  BEaST: Brain extraction based on nonlocal segmentation technique , 2012, NeuroImage.

[41]  A. Graff-Guerrero,et al.  Dopamine D2 Receptor Occupancy and Clinical Effects: A Systematic Review and Pooled Analysis , 2011, Journal of clinical psychopharmacology.

[42]  Richard E Carson,et al.  Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum , 2011, The European journal of neuroscience.

[43]  Daniel Antonius,et al.  Avolition and expressive deficits capture negative symptom phenomenology: implications for DSM-5 and schizophrenia research. , 2011, Clinical psychology review.

[44]  D. Zald,et al.  Reconsidering anhedonia in depression: Lessons from translational neuroscience , 2011, Neuroscience & Biobehavioral Reviews.

[45]  E. Procyk,et al.  Neuroanatomical Basis of Motivational and Cognitive Control: A Focus on the Medial and Lateral Prefrontal Cortex. , 2011 .

[46]  Paul Cumming,et al.  Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas. , 2010, The international journal of neuropsychopharmacology.

[47]  M. Weisbrod,et al.  Neural correlates of reward processing in schizophrenia — Relationship to apathy and depression , 2010, Schizophrenia Research.

[48]  S. Haber,et al.  Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. , 2010, Archives of general psychiatry.

[49]  S. Haber,et al.  The Reward Circuit: Linking Primate Anatomy and Human Imaging , 2010, Neuropsychopharmacology.

[50]  Guy M. McKhann,et al.  The Hippocampus and Nucleus Accumbens as Potential Therapeutic Targets for Neurosurgical Intervention in Schizophrenia , 2009, Stereotactic and Functional Neurosurgery.

[51]  Alan A. Wilson,et al.  The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO. , 2009, Archives of general psychiatry.

[52]  Mark Slifstein,et al.  Dose–Occupancy Study of Striatal and Extrastriatal Dopamine D2 Receptors by Aripiprazole in Schizophrenia with PET and [18F]Fallypride , 2008, Neuropsychopharmacology.

[53]  Shitij Kapur,et al.  Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study. , 2007, The American journal of psychiatry.

[54]  Alan A. Wilson,et al.  Striatal Vs Extrastriatal Dopamine D2 Receptors in Antipsychotic Response—A Double-Blind PET Study in Schizophrenia , 2007, Neuropsychopharmacology.

[55]  R. P. Maguire,et al.  Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[56]  D. Collins,et al.  The creation of a brain atlas for image guided neurosurgery using serial histological data , 2003, NeuroImage.

[57]  Andrew J Saykin,et al.  Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits. , 2004, The American journal of psychiatry.

[58]  Thomas Grisso,et al.  MacArthur Competence Assessment Tool for Clinical Research(maccat-Cr) , 2001 .

[59]  S. Kapur,et al.  Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. , 2000, The American journal of psychiatry.

[60]  C. Randolph,et al.  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. , 1998, Journal of clinical and experimental neuropsychology.

[61]  Vincent J. Cunningham,et al.  Parametric Imaging of Ligand-Receptor Binding in PET Using a Simplified Reference Region Model , 1997, NeuroImage.

[62]  Christer Halldin,et al.  A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients , 1997, Psychopharmacology.

[63]  D L Hill,et al.  Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. , 1997, Medical physics.

[64]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[65]  G. Sedvall,et al.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. , 1992, Archives of general psychiatry.

[66]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.