Psychomotor slowing, negative symptoms and dopamine receptor availability—an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients

Heinz, Andreas; Knable, Michael B.; Coppola, Richard; Gorey, Julia G.; Jones, Douglas W.; Lee, Kan Sam; Weinberger, Daniel R.

doi:10.1016/s0920-9964(98)00003-6

Cited by 123 publications

(83 citation statements)

References 18 publications

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“…This observation is in accordance with previous studies, which showed that the degree of dopamine D2 receptor blocked in the striatum is directly correlated both with psychomotor slowing and with the negative symptom ''apathy,'' reflecting a motivational deficit associated with dysfunction of striatal dopaminergic neurotransmission. 59 However, the process of learning, which occurred before previously neutral cues are attributed with incentive salience in the above-mentioned studies, occurred ''before'' subjects entered the scanner. They were trained for about 15 min and learned that an abstract cue, such as a circle, for the rest of the task will represent a conditioned stimulus that predicts reward.…”

Section: Stress-induced Dopamine Firing: Animal Findings and Human Obmentioning

confidence: 97%

Dopaminergic Dysfunction in Schizophrenia: Salience Attribution Revisited

Heinz¹,

Schlagenhauf²

2010

Schizophrenia Bulletin

365

271

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A dysregulation of the mesolimbic dopamine system in schizophrenia patients may lead to aberrant attribution of incentive salience and contribute to the emergence of psychopathological symptoms like delusions. The dopaminergic signal has been conceptualized to represent a prediction error that indicates the difference between received and predicted reward. The incentive salience hypothesis states that dopamine mediates the attribution of ''incentive salience'' to conditioned cues that predict reward. This hypothesis was initially applied in the context of drug addiction and then transferred to schizophrenic psychosis. It was hypothesized that increased firing (chaotic or stress associated) of dopaminergic neurons in the striatum of schizophrenia patients attributes incentive salience to otherwise irrelevant stimuli. Here, we review recent neuroimaging studies directly addressing this hypothesis. They suggest that neuronal functions associated with dopaminergic signaling, such as the attribution of salience to reward-predicting stimuli and the computation of prediction errors, are indeed altered in schizophrenia patients and that this impairment appears to contribute to delusion formation.Key words: psychosis/delusion/reward/ventral striatum/ fMRI/FDOPA It has long been suggested that dopamine dysfunction plays a major role in the pathogenesis of schizophrenic psychosis.1 First studies with positron emission tomography (PET) suggested that dopamine D2 receptors are indeed upregulated in schizophrenia patients 2 ; however, this finding was not confirmed in further studies.3 Also, studies on dopamine D2 receptor genotype failed to find an association between functional variance and schizophrenia. 4 It was not until 1996 that in vivo imaging studies first found convincing evidence of dopamine dysregulation in acute psychosis: Laruelle et al 5 and Breier et al 6 used the fact that radioligands, such as raclopride, are displaced by endogenous dopamine due to competition for binding at dopamine D2 receptors ( figure 1 and figure 2). They applied psychostimulants to release dopamine and observed increased displacement of dopamine D2 receptor ligands in unmedicated schizophrenia patients compared with healthy controls, suggesting that the pool of releasable dopamine is increased in patients suffering from schizophrenic psychosis. This hypothesis was further supported by studies using the radioligand [ 18 F]fluoro-3,4-dihydroxyphenyl-Lalanine (FDOPA), which is absorbed by dopaminergic neurons and metabolized into dopamine and subsequently stored in the presynaptic terminal. Studies with this radioligand suggested increased striatal dopamine synthesis capacity in unmedicated schizophrenia patients [8][9][10] ; a recent study by Kumakura et al 11 used a refined technology that takes into account that presynaptical dopamine is not simply trapped but instead released into the extracellular space in association with neuronal activation. This study found considerable differences in dopamine storage capacity between schizophreni...

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Section: Stress-induced Dopamine Firing: Animal Findings and Human Obmentioning

confidence: 97%

Dopaminergic Dysfunction in Schizophrenia: Salience Attribution Revisited

Heinz¹,

Schlagenhauf²

2010

Schizophrenia Bulletin

365

271

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“…In addition to deficits in motivation, psychomotor slowing is a prominent feature of both mood disorders and schizophrenia, and has been shown to correlate with symptoms of anhedonia and amotivation (Heinz et al, 1998;Lemke et al, 1999;Stein, 2008). Motor retardation can be assessed in psychiatric patients using objective measures of psychomotor processing or reaction time and tests of fine motor speed, which have been shown to be more sensitive than self-reported symptoms and clinician ratings (Bennabi et al, 2013;Caligiuri and Ellwanger, 2000;Morrens et al, 2007).…”

Section: Reduced Motivation and Psychomotor Function In Psychiatric Dmentioning

confidence: 99%

“…Motor retardation can be assessed in psychiatric patients using objective measures of psychomotor processing or reaction time and tests of fine motor speed, which have been shown to be more sensitive than self-reported symptoms and clinician ratings (Bennabi et al, 2013;Caligiuri and Ellwanger, 2000;Morrens et al, 2007). In schizophrenia, psychomotor symptoms have been shown to correlate with negative symptoms, such as apathy and amotivation, as well as with depressive symptoms, and confer significant impairments in function and increased patient burden (Ananth et al, 1991;Heinz et al, 1998;Morrens et al, 2007). Motor deficits are also observed in patients with bipolar II, as well as in bipolar I during the depressed phase (Bennabi et al, 2013;Mitchell et al, 2001).…”

Section: Reduced Motivation and Psychomotor Function In Psychiatric Dmentioning

confidence: 99%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

319

237

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Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

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“…Troisi and coworkers observed that unmedicated young male schizophrenic patients could be distinguished from normal controls on the basis of their behavioral repertoire during interviews, including the use of "prosocial" behaviors such as yes-nodding and smiling, the use of gestures, and the amount of so-called "displacement activities" as nonverbal signals of motivational conflict (Troisi et al, 1998). Facial and bodily expressivity of patients with schizophrenia may, however, be influenced by a number of factors: It may correlate inversely with neuroleptic dosage (Schneider et al, 1992), be reduced by the presence of negative symptoms (Trémeau et al, 2005), or altered by a combination of both, because it has repeatedly been pointed out that classic antipsychotic medications may worsen existing negative symptoms (Heinz et al, 1998).…”

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confidence: 99%

Nonverbal Behavior During Standardized Interviews in Patients With Schizophrenia Spectrum Disorders

Brüne¹,

Sonntag²,

Abdel‐Hamid³

et al. 2008

Journal of Nervous &Amp; Mental Disease

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Several studies have consistently shown that patients with schizophrenia or schizophrenia spectrum disorders (SSD) can be distinguished from normal controls on the basis of their nonverbal behavior during standardized interviews, with considerable interactions between negative symptoms and poor facial expressivity. However, most studies have examined unmedicated patients, and gender of both interviewer and interviewee has not been taken into account. In this study we assessed the nonverbal behavior of male and female patients with SSD who were receiving second-generation antipsychotic medication (SGA) using the Ethological Coding System for Interviews (Troisi, 1998). In addition, we used a novel 5-factor model of the Positive and Negative Symptom Scale (PANSS, van der Gaag et al., 2006) to correlate nonverbal behavior with standard psychopathology ratings. Our findings strongly resembled results of previous studies into nonverbal behavior of patients with SSD, despite differences in cultural backgrounds and gender of the interviewer. Negative symptoms were inversely correlated with several of the nonverbal behavioral dimensions. Medication dose did not correlate with any one of the behavioral or psychopathological measures. Patients with SSD make less use of their nonverbal behavioral repertoire compared with controls, independent of antipsychotic treatment. Culture-specific nonverbal expressivity seems to play an additional (minor) role in distinguishing patients from healthy controls.

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Psychomotor slowing, negative symptoms and dopamine receptor availability—an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients

Cited by 123 publications

References 18 publications

Dopaminergic Dysfunction in Schizophrenia: Salience Attribution Revisited

Dopaminergic Dysfunction in Schizophrenia: Salience Attribution Revisited

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Nonverbal Behavior During Standardized Interviews in Patients With Schizophrenia Spectrum Disorders

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