Papers by Daniel Van Kammen
New Directions in Tardive Dyskinesia Research
Journal of Clinical Psychopharmacology, 1984
European Neuropsychopharmacology, Jun 1, 1996
NAAG is an acidic dipeptide found in mM concentrations in the brain and is co-localized to a numb... more NAAG is an acidic dipeptide found in mM concentrations in the brain and is co-localized to a number of putative glutamatergic neuronal systems as well as selected aminergic pathways. Endogenous NAAO is released by a Ca 2 + dependent process upon neuronal depolarization. NAAG antagonizes the action of glutamate at NMDA receptors and is an agonist at mOlu R3 receptor. NAALAD ase is a membrane bound peptidase with sub 11M affinity for NAAG. yielding Nsacetylaspartare and glutamate. EM immunocytochemistry reveals an extracellular orientation of the catalytic site of NAALADase, consistent with the predicted structure from the cDNA sequence of a short intracellular domain, a single transmembrane element and a large globular extracellular domain. NAALADase activity appears to be pivotal in determining whether NAAG will act as an NMDA receptor antagonist or a source for synaptic glutamate. Consistent with this role, NAAG levels and NAALADase activity are altered in pathologic conditions including Huntington's Disease, amyotrophic lateral sclerosis. epilepsy and schizophrenia.
Psychiatry Research-neuroimaging, Sep 1, 1992
It has been proposed that the autonomic nervous system is dysregulated in schizophrenia. We hypot... more It has been proposed that the autonomic nervous system is dysregulated in schizophrenia. We hypothesized that measures of autonomic function, even during neuroleptic stabilization, might predict relapse following withdrawal of medication. Previously, shorter latencies to maximum pupillary constriction have been reported to differentiate acutely hospitalized schizophrenic patients from control subjects. Pupillary light reactions were recorded weekly from 19 chronic schizophrenic inpatients who were initially maintained on haloperidol and subsequently were withdrawn from medication under double-blind, placebo-controlled conditions. Patients were then classified as either relapsed or nonrelapsed (clinically stable) during the drug-free period. During the treatment phase, a shorter latency to maximum pupillary constriction significantly distinguished patients who were later to relapse from the nonrelapsers. The potential use of autonomic activity as an indicator of prodromal sensitivity was supported. In addition, these findings emphasize the need for classification of drug-free patients according to clinical status.
Schizophrenia Research, Apr 1, 1993
Explorations of Dopamine and Noradrenaline Activity and Negative Symptoms in Schizophrenia: Concepts and Controversies
Springer eBooks, 1991
Attempts to understand the pathophysiology of negative symptoms took off when Crow (1980a, b) des... more Attempts to understand the pathophysiology of negative symptoms took off when Crow (1980a, b) described the Type I and II syndromes of schizophrenia. He proposed that the Type II form was irreversible and nondopaminergic, consisting of negative symptoms, brain atrophy, poor drug response, and outcome; Type I was the reverse, i.e., positive symptoms, absence of brain atrophy (normal ventricle brain ratio, VBR), and excellent antipsychotic drug response, and consisted of a hyperdopaminergic disorder. Mackay (1980) challenged this concept and hypothesized that Type II schizophrenia was a hypodopaminergic, Kraepelinian form of schizophrenia.
Sleep, Nov 1, 1992
Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with insomnia... more Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with insomnia. The authors studied cerebrospinal fluid (CSF) DSIP-like immunoreactivity (DSIP-Ll) in IS drug-free male subjects with a DSM-IIIR diagnosis of schizophrenia. The subjects underwent a lumbar puncture and three nights of polysomnography. CSF DSIP-LI was significantly correlated with polysomnography the night before the LP: with stage 3 sleep (p = 0.05), stage 3 and delta (stages 3 + 4) sleep during the first nonrapid eye movement NREM period (p = 0.02 and p = 0.05, respectively) and the ratio of the first and second NREM period (p < 0.05), and negatively with stage 2 % sleep (p < 0.05). Whether this first report of a potential relationship between CSF DSIP-LI and slow-wave sleep in man might be generalized to sleep in nonpsychiatric subjects awaits further study.
Relapse Prediction in Schizophrenia: From Monoamines to Cytokines
KARGER eBooks, 1997
... Given the episodic nature of viral reactiva-tion, autoimmune relapse, and exposure to stress,... more ... Given the episodic nature of viral reactiva-tion, autoimmune relapse, and exposure to stress, these factors could periodi-cally occur and thereby ... Van Kammen DP, Peters JL, Yao JK, van Kammen WB, Neylan T, Shaw D, Linnoila M: Norepinephrine in acute exacerbations of ...
Relationship between immune and behavioral measures in schizophrenia
Key topics in brain research, 1997
Schizophrenia, which is a chronic but episodic disorder of unknown etiology, shares immunological... more Schizophrenia, which is a chronic but episodic disorder of unknown etiology, shares immunological features with organ specific autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis and insulin-dependent diabetes mellitus. However, recent studies have raised the issue as to whether the reported immune disturbances in schizophrenia may be the result of a stress-induced dysregulation of CNS cytokine production, rather than a permanent immunological disorder, i.e., autoimmunity.
Working memory capacity predicts language comprehension in schizophrenic patients
Schizophrenia Research, May 1, 1996
The association between language comprehension and working memory capacity was evaluated in 25 ma... more The association between language comprehension and working memory capacity was evaluated in 25 male DSM-III-R schizophrenic patients (14 inpatients; 11 outpatients), and in 11 male normal controls (no lifetime DSM-III-R disorder). Patients and controls did not differ significantly on age and education. Language comprehension was examined as a function of two types of processing demand: grammatical complexity (complex versus simple sentences) and presentation rate (accelerated versus conversational). Schizophrenic patients showed significantly reduced language comprehension and decreased working memory capacity for language, compared with controls. Patients showed general difficulty in comprehending accurately, rather than exhibiting problems with specific grammatical structures. Subject groups were highly accurate and did not differ in their ability to perceive the individual words in sentences presented at the accelerated rate (intelligibility). Presentation rate and grammatical complexity affected comprehension accuracy in all groups, however, with increases in rate and complexity producing decreases in understanding. Of most importance, theoretically, is the finding that working memory capacity predicted language comprehension accuracy in both schizophrenic patients and normal controls. Results suggest that language comprehension deficits in schizophrenic patients may involve a general dysfunction that is associated with working memory capacity for language.
Biological Psychiatry, Jun 1, 1993
EEG sleep studies in schizophrenic patients are influenced by alterations in clinical state and m... more EEG sleep studies in schizophrenic patients are influenced by alterations in clinical state and medication status. The current study defines longitudinal alterations in electroencephalographic (EEG) sleep for 10 healthy men who were schizophrenic patients who remained relatively clinically stable during a double-blind neuroleptic withdrawal study. Clinical a,:sessments and EEG sleep studies were performed at baseline on haloperidol, and then at 2week and 6-week drug-free periods. Sleep continuity and rapid eye movement (REAl) sleep measures declined not only between the haloperidol baseline and 2-week drug-free conditions, but continued to decline from 2-week to 6-weeks neuroleptic-free. Alterations in EEG sleep from the 2-week to 6-week haloperidol-free assessments did not correlate with changes in clinical symptoms suggesting effects related to drug-withdrawal or subclinical state changes. These results show that despite relative clinical stability over time, the EEG sleep of schizophrenic patients continues to change following withdrawal of a neuroleptic and is dependent on the duration of the drug-free interval.
Schizophrenia Research, Apr 1, 1993
Cerebrospinal Fluid Studies in Schizophrenia
Springer eBooks, 1980
The group of disorders known collectively as schizophrenia15 continues to be a critical problem f... more The group of disorders known collectively as schizophrenia15 continues to be a critical problem for modern psychiatry and accounts for large expenditures for the community (estimated at $19.6 billion annually)66 and tragedy for many families. The chance that a person will be treated for schizophrenia in his lifetime has been reported to be about 2% (4 million people in the United States). Schizophrenia accounts for about 50% of the available mental hospital beds, or about 25% of all available hospital beds in the United States.86 The disorder is equally common in males and females.
British Journal of Psychiatry, May 1, 1980
Sleep Medicine, Feb 1, 2011
Objective-Determine the effects of pimavanserin tartrate [ACP-103; N-(4-flurophenylmethyl)-N-(1-m... more Objective-Determine the effects of pimavanserin tartrate [ACP-103; N-(4-flurophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide], a selective serotonin 5-HT 2A receptor inverse agonist, on slow wave sleep (SWS), other sleep parameters, and attention/vigilance. Methods-Forty-five healthy adults were randomized to pimavanserin (1, 2.5, 5, or 20 mg) or placebo in a double-blind fashion (n = 9/group). Pimavanserin or placebo was administered once daily, in the morning, for 13 consecutive days. The effects of pimavanserin were measured after the first dose and again after 13 days. Sleep parameters were measured by polysomnography. Effects on attention/vigilance were measured by a continuous performance task. Results-Compared to placebo, pimavanserin significantly increased SWS following single and multiple dose administration. Pimavanserin also decreased number of awakenings. PSG variables not affected by pimavanserin included sleep period time, total sleep time, sleep onset latency, number of stage shifts, total time awake, early morning wake, and microarousal index. Changes in sleep architecture parameters, sleep profile parameters, and spectral power density parameters were consistent with a selective increase in SWS. Pimavanserin did not adversely affect performance on the continuous performance test measured on the evening before or morning after polysomnography. Conclusions-These data suggest that pimavanserin selectively increases slow wave sleep and decreases awakenings, an effect that does not diminish with repeated administration.
PLOS Currents, Aug 30, 2011
It is generally believed that treatments are available to manage irritability in Huntington's dis... more It is generally believed that treatments are available to manage irritability in Huntington's disease (HD). However, lack of an evidence base prevents the establishment of treatment guidelines for this symptom. The research literature fails to address behavioral intervention strategies, drug selection, drug dosing, management of inadequate response to a single drug, or preferred drugs when additional behavioral symptoms comorbid to irritability are present. In an effort to inform clinical decisionmaking we surveyed an international group of experts to address these points. The experts consistently endorsed an antipsychotic drug (APD) as first choice for treatment of urgent and aggressive irritability behaviors. However, there was variation in practice patterns for treating less severe symptoms. Serotonin reuptake inhibitors (SSRIs) were first choice drug treatments by most respondents across all geographic regions. However, APDs were also endorsed as first choice for mild or moderate irritability, more frequently in Europe than in North America and Australia. Antiepileptic mood stabilizers (AEDs) were used by fewer respondents as first choice drug. Perceived efficacy for control of mild or moderate irritability was judged somewhat higher for APDs than SSRIs or AEDs. Benzodiazepines were not used as monotherapy, but frequently as an adjunctive drug in the setting of comorbid anxiety. Though many cited lack of experience with mirtazapine, others familiar with its use in HD chose it as an alternative monotherapy, or as adjunctive therapy if insomnia was a comorbid factor. This report presents survey results, reviews available irritability studies, and lastly proposes an algorithm for the treatment of irritability in HD derived from expert preferences obtained through this survey. Irritability is a frequently reported neuropsychiatric disorder in HD, in addition to depression, anxiety, apathy, and obsessivecompulsive behaviors [2]. HD irritability has been defined as a temporary psychologic state characterized by impatience, intolerance, and reduced control over temper, which can progress to angry and aggressive verbal or behavioral outbursts [3]. Estimates of irritability vary from 31% to 65% according to studies using different methods of sampling and measurement [4] [5]. A study comparing self and care-partner assessment shows a higher reported incidence for irritability when information is obtained from care-partners [6], suggesting a component of lack of awareness in patients. However, many are aware and recognize that they are too easily provoked, and take more time to calm down after provocation [7]. Irritability can precede the onset of motor symptoms of HD [8] and it occurs over all stages of disease. However, measures of irritability do not track with disease progression [7] [9]. Further, patients differ in the degree to which they experience irritability: some "feel" irritable, some exhibit mild irritability without further behavioral manifestations, while the behavior of others can escalate to physical aggression. At all levels of severity, it is vital to recognize irritability as part of the disease process, and not to mischaracterize patients as difficult, stubborn, or "character disordered" which adds to strain experienced by patients and families. Early recognition and treatment of this symptom is important because irritability behaviors that escalate can be a tipping point in terms of care partner burnout and subsequent need to institutionalize HD patients.
American Journal of Psychiatry, Nov 1, 1981
Archives of General Psychiatry, Feb 1, 1990
Fluoxetine Fluoxetine Striatum 77.8±6.8f 70.5±2.6f Accumbens 70.6 ±9.9*1 85.0 ±5.7 Hippocampus 88... more Fluoxetine Fluoxetine Striatum 77.8±6.8f 70.5±2.6f Accumbens 70.6 ±9.9*1 85.0 ±5.7 Hippocampus 88.1 ±7.0 74.8±6.0f Frontal cortex 61.0±5.1f 78.6±1.7f "Control values (saline-placebo pretreated, and then treated with NSD-1015) averaged 2.02±0.10, 2.35±0.12, 0.082±0.011,and0.194±0.015ngof dopa per milligram of wet brain tissue for striatum, accumbens, hippocampus, and frontal cortex, re¬ spectively. fThere was a significant difference from matched controls by f test at P<.05 or less (n = 10 rats per condition). were no significant effects in occipital
Schizophrenia Research, 1992
CPs (p < 0. IO). Although the SPs spent less time in REM sleep (p<O.O5), further REM sleep parame... more CPs (p < 0. IO). Although the SPs spent less time in REM sleep (p<O.O5), further REM sleep parameters, including REM latency and REM density, were not altered. In conclusion, our findings in drug-naive patients with a first episode of a schizophrenic disorder are in favour of an arousal linked disturbance at the beginning of the night sleep resulting in a delayed sleep onset and a disturbed build-up of SWS. On the other hand, we did not observe changes in REM latency or REM density in these patients.
Longitudinal assessment of deficit syndrome characteristics
Schizophrenia Research, Apr 1, 1993
Delta sleep inducing peptide-like immunoreactivity and sleep EEG results in schizophrenia
Schizophrenia Research, May 1, 1991
ABSTRACT Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with... more ABSTRACT Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with insomnia. The authors studied cerebrospinal fluid (CSF) DSIP-like immunoreactivity (DSIP-LI) in 15 drug-free male subjects with a DSM-IIIR diagnosis of schizophrenia. The subjects underwent a lumbar puncture and three nights of polysomnography. CSF DSIP-LI was significantly correlated with polysomnography the night before the LP: with stage 3 sleep (p = 0.05), stage 3 and delta (stages 3 + 4) sleep during the first nonrapid eye movement NREM period (p = 0.02 and p = 0.05, respectively) and the ratio of the first and second NREM period (p &lt; 0.05), and negatively with stage 2% sleep (p &lt; 0.05). Whether this first report of a potential relationship between CSF DSIP-LI and slow-wave sleep in man might be generalized to sleep in nonpsychiatric subjects awaits further study.
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Papers by Daniel Van Kammen