Biomedical subjects

Johan A den Boer

Publications and source records attributed to Johan A den Boer.

18 recordsLinked to original sources

PubMed2007

Methylphenidate-induced activation of the anterior cingulate but not the striatum: a [15O]H2O PET study in healthy volunteers.

The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal poles, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal pole, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders.

Adult↗

PubMed2006

Psychobiological characteristics of dissociative identity disorder: a symptom provocation study.

BACKGROUND: Dissociative identity disorder (DID) patients function as two or more identities or dissociative identity states (DIS), categorized as 'neutral identity states' (NIS) and 'traumatic identity states' (TIS). NIS inhibit access to traumatic memories thereby enabling daily life functioning. TIS have access and responses to these memories. We tested whether these DIS show different psychobiological reactions to trauma-related memory. METHODS: A symptom provocation paradigm with 11 DID patients was used in a two-by-two factorial design setting. Both NIS and TIS were exposed to a neutral and a trauma-related memory script. Three psychobiological parameters were tested: subjective ratings (emotional and sensori-motor), cardiovascular responses (heart rate, blood pressure, heart rate variability) and regional cerebral blood flow as determined with H(2)(15)O positron emission tomography. RESULTS: Psychobiological differences were found for the different DIS. Subjective and cardiovascular reactions revealed significant main and interactions effects. Regional cerebral blood flow data revealed different neural networks to be associated with different processing of the neutral and trauma-related memory script by NIS and TIS. CONCLUSIONS: Patients with DID encompass at least two different DIS. These identities involve different subjective reactions, cardiovascular responses and cerebral activation patterns to a trauma-related memory script.

Adult↗

PubMed2006

Ketamine administration disturbs behavioural and distributed neural correlates of fear conditioning in the rat.

The neurotransmitter glutamate and its associated receptors perform an important role in the brain circuitry underlying normal fear processing. The glutamate NMDA receptor, in particular, is necessary for the acquisition and recollection of conditioned-fear responses. Here the authors examine how acute blockage of the NMDA receptor with sub-anaesthetic doses of ketamine affects behavioural assays of fear-conditioned stress (e.g. freezing) and cFos expression in a network of brain areas that have previously been implicated in fear processing. Fear-conditioned rats displayed significantly more freezing behaviour than non-conditioned controls. In fear-conditioned rats that also received ketamine, this conditioning effect was largely neutralised. Fear conditioning also led to increased cFos expression in various areas central to fear processing, including the basolateral nucleus of the amygdala, the paraventricular nucleus of the hypothalamus and the anterior cingulate. Ketamine abolished such increases in cFos expression in most brain areas investigated. The present study therefore demonstrates that systemic ketamine administration in rats interferes with fear conditioning on a behavioural level and in a network of brain regions associated with fear and anxiety. The combination of ketamine and fear conditioning may therefore provide a useful model of abnormal fear processing, as observed in certain psychiatric conditions.

Analysis of Variance↗

PubMed2005

Chronic psychosocial stress in tree shrews: effect of the substance P (NK1 receptor) antagonist L-760735 and clomipramine on endocrine and behavioral parameters.

RATIONALE: Substance P and its preferred receptor, the neurokinin 1 receptor (NK(1)R), have been proposed as possible targets for new antidepressant therapies, although results of a recently completed phase III trial failed to demonstrate that the NK(1)R antagonist MK-869 is more effective than placebo in the treatment of depression. METHODS: In the present study, we compared the effects of the NK(1)R antagonist L-760735 with the tricyclic antidepressant clomipramine on endocrine and behavioral parameters in chronically stressed tree shrews. Animals were subjected to a 7-day period of psychosocial stress before receiving daily oral administration of L-760735 (10 mg/kg/day) or clomipramine (50 mg/kg/day). The psychosocial stress continued throughout the treatment period of 21 days. Daily morning urine was collected to measure cortisol and norepinephrine levels. All animals were videotaped daily and three types of behavior were analyzed. RESULTS: Chronic psychosocial stress resulted in a significant increase of urinary cortisol and norepinephrine concentrations. Moreover, stressed animals displayed decreased marking behavior and locomotor activity, while grooming remained unaffected. Neither treatment with clomipramine nor L-760735 was able to normalize the stress-induced elevation of cortisol or norepinephrine. On the behavioral parameters, L-760735 had a time-dependent restorative influence on marking behavior close to normal levels, without affecting locomotor activity. Grooming behavior was significantly increased by the 3 weeks of drug treatment. CONCLUSIONS: These results suggest that L-760735 was able to counteract certain stress-induced behavioral alterations in an animal model of depression.

Adrenal Glands↗

PubMed2005

Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed. However, multivariate analysis of continuous autism-related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid-compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12-repeat allele with rigid-compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.

Adolescent↗

PubMed2005

The effect of chronic selective serotonin reuptake inhibitor treatment on serotonin 1B receptor sensitivity and HPA axis activity.

The authors have investigated 5-HT 1B receptor function in prefrontal cortex and dorsal hippocampus as well as the HPA axis response after subchronic (24 h) and chronic (15 days) treatment with the SSRI citalopram. All experiments were carried out in presence of citalopram to prevent rapid resensitization of the 5-HT(1B) receptors. Moreover, this more closely resembles the clinical situation. The concentration of citalopram was measured in both brain areas to ensure comparable levels in the different treatment groups. Using microdialysis, the authors found that under those conditions the effect of the 5-HT 1B receptor antagonists SB 224289 and the mixed 5-HT 1B/1D receptor antagonist GR 127935 on extracellular levels of 5-HT was unaltered by duration of treatment. Basal levels of 5-HT, however, were increased in the dorsal hippocampus following chronic treatment. In addition, plasma levels of the catecholamines adrenaline and noradrenaline and the HPA axis hormones ACTH and corticosterone were all decreased after chronic treatment.

Adrenocorticotropic Hormone↗

PubMed2005

Effect of increased serotonin levels on [18F]MPPF binding in rat brain: fenfluramine vs the combination of citalopram and ketanserin.

[18F]MPPF is a selective serotonin-1A (5-HT1A) receptor antagonist and may be used to measure changes in the functional levels of serotonin (5-HT). The technique is based on the assumption that the injected radiolabeled ligand competes for the same receptor as the endogenous transmitter. Results from studies using serotonergic ligands are not always consistent. The aim of the present study was to investigate if [18F]MPPF binding is decreased after an increase in 5-HT levels. [18F]MPPF binding was assessed in conscious rats using ex vivo autoradiography. We studied the effect of the 5-HT-releasing agent and reuptake inhibitor fenfluramine (10 mg/kg i.p.) and of a combination of the selective serotonin reuptake inhibitor (SSRI) citalopram (10 micromol/kg, s.c.) with the 5-HT2C antagonist ketanserin (100 nmol/kg, s.c). The effect of both treatments on extracellular 5-HT levels was determined using microdialysis. Fenfluramine treatment resulted in a 30-fold increase in extracellular 5-HT levels in the ventral hippocampus and induced a significant reduction of [18F]MPPF binding in the frontal cortex, hypothalamus, amygdala, and hippocampus. The microdialysis results showed a 10-fold 5-HT increase in the ventral hippocampus after combined administration of ketanserin and citalopram. The combination, however, did not affect [18F]MPPF binding. Our data show that [18F]MPPF binding in conscious rats is only reduced after substantial and therefore nonphysiological increases in 5-HT levels. These results may imply that the majority of 5-HT1A receptors is in the low-affinity state, in vivo.

Animals↗

PubMed2004

Gender differences in the relation between social support, problems in parent-offspring communication, and depression and anxiety.

Gender differences in the buffer-effect of social support in the relation between stressful circumstances and the development of depression and anxiety disorders are widely assumed, but few studies address this three-way interaction between gender, stress, and support. Data in the present study came from the baseline assessment of the Adolescents at Risk for Anxiety and Depression (ARIADNE) study in 502 adolescent and young-adult children of 356 parents in the Netherlands with a depression, panic disorder and/or obsessive-compulsive disorder. Results indicate that the daughters benefit more from social support than the sons when problems in parent-offspring communication are high, but that this effect holds only for depression symptoms and particularly in relation to problems in father-offspring communication. Social support does not seem to play a role in the development of anxiety.

Adolescent↗

PubMed2004

Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates.

OBJECTIVE: To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). METHOD: Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined. RESULTS: Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels. CONCLUSIONS: The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.

Adolescent↗

PubMed2004

Future antidepressants: what is in the pipeline and what is missing?

Monoamine reuptake inhibitors still reign in the treatment of major depression, but possibly not for long. While medicinal chemists have been able to reduce the side effects of these drugs, their delayed onset of action and considerable non-response rate remain problematic. Of late, serious questions have been raised regarding the efficacy of monoamine reuptake inhibitors. The present review presents an inventory of what is (and until recently was) in the antidepressant pipeline of pharmaceutical companies. Novel antidepressant compounds can be categorised into four groups depending on their target(s): (i) monoamine receptors; (ii) non-monoamine receptors; (iii) neuropeptide receptors; and (iv) hormone receptors. Other possible targets include components of post-receptor intracellular processes and elements of the immune system; to date, however, compounds specifically aimed at these targets have not been the subject of clinical trials. Development of several compounds targeted at monoamine receptors has recently been discontinued. At least five neurokinin-1 (NK(1)) receptor antagonists were until recently in phase II of clinical testing. However, the apparent interest in the NK(1) receptor should not be interpreted as representing a departure from the monoamine hypothesis since neurokinins also modulate monoaminergic systems. In the authors' view, development of future antidepressants will continue to rely on the serendipity-based monoamine hypothesis. However, an alternative approach, based on the hypothesis that chronic stress precipitates depressive symptoms, might be more productive. Unfortunately, clinical results using drugs targeted at components of the HPA axis have not been very encouraging to date. In the short run, the authors believe that augmentation strategies offer the best hope for improving the efficacy of antidepressant treatment. Several approaches to improve the efficacy of SSRIs are conceivable, such as concurrent blockade of monoamine autoreceptors and the addition of antipsychotics, neuromodulators or hormones (HPA axis and gender related). In the long-term, however, construction of a scientifically verified conceptual framework will be needed before more effective antidepressants can be developed. It can be argued that it is not depression itself that should be treated, but rather that its duration should be reduced by pharmacological means. Animal models that take this concept into consideration and identify mechanisms for acceleration of recovery from the effects of stress need to be developed.

Animals↗

PubMed2003

Mood regulation in seasonal affective disorder patients and healthy controls studied in forced desynchrony.

In healthy subjects, both the duration of wakefulness and the circadian pacemaker have been demonstrated to be involved in the regulation of mood. Some features of affective disorders suggest that these two factors also play a role in the dysregulation of mood. In particular, disturbances of the circadian pacemaker have been proposed to be a pathogenetic factor in Seasonal Affective Disorder, winter type (SAD). This report presents a test of this proposition. To this end seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which they were exposed to six 20-h days. This protocol enables us to discriminate the extent to which the course of mood is determined by the imposed 20-h sleep-wake cycle from the influence of the circadian pacemaker on that course. Patients participated during a depressive episode, after recovery upon light therapy and in summer. Controls were studied in winter and in summer. Between SAD patients and controls no significant differences were observed in the period length nor in the timing of the endogenous circadian temperature minimum. In both groups, sleep-wake cycle- and pacemaker-related components were observed in the variations of mood, which were not significantly different between conditions.

Adult↗

PubMed2003

Gender-specific effects of social housing in rats after chronic mild stress exposure.

UNLABELLED: Stress plays an important role in the development of affective disorders. Women show a higher prevalence for these disorders than men. The course of a depression is thought to be positively influenced by social support. The authors have used a chronic mild stress model in which rats received footshocks daily for 3 weeks. Since rats are social animals we hypothesized that "social support" might reduce the adverse effects of chronic stress. To test this hypothesis, male and female rats were housed individually or socially in unisex groups of four rats. An open field test was repeated four times during the 3 weeks of treatment. Neuronal activation in the paraventricular nucleus of the hypothalamus (PVN) and dorsal raphe nucleus (DRN) in response to stress was measured the last day with c-fos. Chronic stress exposure increased locomotor activity in the open field, especially during the first minute. This was most pronounced in the individually housed females. In females, social housing prevented the stress-induced increase of locomotor activity, while in males social housing had no effect. Fos immunoreactive (FOS-ir) in the PVN was increased in all stress-exposed groups, except for the socially housed females due to a higher FOS-ir in controls. Individually housed males and socially housed females showed increased FOS-ir in the DRN and the increase was almost significant in socially housed males. IN CONCLUSION: These results show that social housing can enhance coping with stress in female rats, whereas in male rats group housing did not have a positive influence on stress-sensitivity.

Animals↗

PubMed2002

Lithium concentrations in plasma of lithium-treated psychiatric patients in the Netherlands: commentary on Cusin et al.

Seasonal variations in 68 psychiatric patients receiving prophylactic lithium treatment in the Netherlands between 1974 and 1994 were analyzed and compared with findings from Italy. Although lithium doses remained stable, there was a significant change in plasma levels of lithium, with values in spring and summer tending to exceed those in autumn and winter. These findings are similar to those reported in Italy, although the maximal seasonal change was approximately 5% in the Netherlands compared with approximately 10% in Italy. The difference could reflect the hotter summer climate in Italy, associated with increased perspiration. Future studies should measure perspiration levels directly.

Adult↗

PubMed2002

rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest.

BACKGROUND: Our goal was to identify brain structures involved in anticipatory anxiety in panic disorder (PD) patients compared to control subjects. METHODS: Seventeen PD patients and 21 healthy control subjects were studied with H(2)(15)O positron emission tomography scan, before and after a pentagastrin challenge. RESULTS: During anticipatory anxiety we found hypoactivity in the precentral gyrus, the inferior frontal gyrus, the right amygdala, and the anterior insula in PD patients compared to control subjects. Hyperactivity in patients compared to control subjects was observed in the parahippocampal gyrus, the superior temporal lobe, the hypothalamus, the anterior cingulate gyrus, and the midbrain. After the challenge, the patients showed decreases compared to the control subjects in the precentral gyrus, the inferior frontal gyrus, and the anterior insula. Regions of increased activity in the patients compared to the control subjects were the parahippocampal gyrus, the superior temporal lobe, the anterior cingulate gyrus, and the midbrain. CONCLUSIONS: The pattern of regional cerebral blood flow activations and deactivations we observed both before and after the pentagastrin challenge was the same, although different in intensity. During anticipatory anxiety more voxels were (de)activated than during rest after the challenge.

Adult↗

PubMed2002

A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder.

The circadian pacemaker is an endogenous clock that regulates oscillations in most physiological and psychological processes with a near 24-h period. In many species, this pacemaker triggers seasonal changes in behavior. The seasonality of symptoms and the efficacy of light therapy suggest involvement of the circadian pacemaker in seasonal affective disorder (SAD), winter type. In this study, circadian pacemaker characteristics of SAD patients were compared with those of controls. Seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which core body temperature and melatonin secretion profiles were measured for the characterization of circadian pacemaker parameters. During this protocol, which enables the study of unmasked circadian pacemaker characteristics, subjects were exposed to six 20-h days in time isolation. Patients participated twice in winter (while depressed and while remitted after light therapy) and once in summer. Controls participated once in winter and once in summer. Between the SAD patients and controls, no significant differences were observed in the melatonin-derived period or in the phase of the endogenous circadian temperature rhythm. The amplitude of this rhythm was significantly smaller in depressed and remitted SAD patients than in controls. No abnormalities of the circadian pacemaker were observed in SAD patients. A disturbance in thermoregulatory processes might explain the smaller circadian temperature amplitude in SAD patients during winter.

Adult↗

PubMed2002

Unraveling the diagnostic clues of depression and GAD: the primary care challenge.

Anxiety and depression are commonly encountered in primary care, with a prevalence ranging from 5% to 10%. These disorders are associated with significant and persistent impairment in functioning, risk of suicide, and substantial economic cost. Comorbidity of depression and anxiety is frequent and intensifies the burden of illness. However, patients with anxiety and depression often present to primary care physicians (PCPs) with ill-defined somatic symptoms, and both disorders are under-recognized and under-treated. PCPs should be aware that the typical presentation of anxiety and depression may not be with classical psychological symptoms, but rather with vague somatic symptoms that are often hard to treat and result in frequent repeat visits. Once anxiety and depression are accurately recognized, most patients can successfully be managed in primary care. A wide range of effective drugs is available, allowing selection of an optimal treatment for each patient. Antidepressants are effective as monotherapy in comorbid patients, and newer agents such as selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors have been shown to be effective in the treatment of anxiety and depression. Adherence to medication can be improved if drug treatment is integrated into a package of patient education and support. PCPs have a vital role to play in identifying anxiety and depression amongst their patients, and building a therapeutic partnership to achieve successful treatment.

Adolescent↗

PubMedDate not supplied

Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation.

OBJECTIVE: Carcinoid tumors can produce excessive amounts of biogenic amines, notably serotonin. We assessed psychiatric symptoms in carcinoid patients and peripheral metabolism of tryptophan, the precursor of serotonin. METHODS: Twenty consecutive patients with carcinoid syndrome underwent a structured psychiatric interview applying DSM-IV (Diagnostical Statistical Manual) criteria. Tumor activity was measured by determination of 24-hour urine excretion of 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin levels. Plasma tryptophan levels were measured and compared with sex- and age-matched references. RESULTS: Fifteen patients (75%) fulfilled diagnostic DSM-IV criteria for a disorder of impulse control. Tryptophan plasma levels were lower in patients compared with controls (p =.031) and were correlated negatively with urinary 5-HIAA excretion (p =.001). CONCLUSIONS: Impulse control disorders are prevalent in patients with carcinoid syndrome. The serotonin production by the tumor possibly decreases the tryptophan pool in the cerebrospinal fluid, which is the essential substrate for the production of brain serotonin as a pivotal neurotransmitter.

Aged↗

PubMedDate not supplied

Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism.

OBJECTIVE: Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients undergoing combination treatment with interferon-alpha and ribavirin. PATIENTS AND METHODS: Eighteen patients with viral hepatitis C who received interferon were included. A psychiatrist screened patients before and while on interferon-alpha treatment for 2 months, using a structured diagnostic interview. Fasting plasma tryptophan and platelet serotonin levels were measured at each visit. RESULTS: At baseline no evident psychopathology was observed. After 2 months of interferon treatment, 10 patients experienced increased irritability. No other structural psychopathology was observed. Decreased plasma tryptophan level correlated with the presence of irritability (p = .047). Platelet serotonin levels were found to be decreased during treatment (p = .002). CONCLUSIONS: Aggressive impulse dysregulation is highly prevalent in patients receiving interferon treatment. This is associated with decreased plasma tryptophan levels which may lead to attenuated peripheral and central serotonergic neurotransmission.

Adult↗