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Raben Rosenberg

Publications and source records attributed to Raben Rosenberg.

At least 19 recordsLinked to original sources
PubMed2007

Testing the self-medication hypothesis of depression and aggression in cannabis-dependent subjects.

BACKGROUND: A self-medication hypothesis has been proposed to explain the association between cannabis use and psychiatric and behavioral problems. However, little is known about the reasons for use and reactions while intoxicated in cannabis users who suffer from depression or problems controlling violent behavior. METHOD: We assessed 119 cannabis-dependent subjects using the Schedules of Clinical Assessment in Neuropsychiatry (SCAN), parts of the Addiction Severity Index (ASI), and questionnaires on reasons for cannabis use and reactions to cannabis use while intoxicated. Participants with lifetime depression and problems controlling violent behavior were compared to subjects without such problems. Validity of the groupings was corroborated by use of a psychiatric treatment register, previous use of psychotropic medication and convictions for violence. RESULTS: Subjects with lifetime depression used cannabis for the same reasons as others. While under the influence of cannabis, they more often experienced depression, sadness, anxiety and paranoia, and they were less likely to report happiness or euphoria. Participants reporting problems controlling violent behavior more often used cannabis to decrease aggression, decrease suspiciousness, and for relaxation; while intoxicated they more often reacted with aggression. CONCLUSIONS: Subjects with prior depression do not use cannabis as a mean of self-medication. They are more likely to experience specific increases of adverse symptoms while under the influence of cannabis, and are less likely to experience specific symptom relief. There is some evidence that cannabis is used as a means of self-medication for problems controlling aggression.

Adolescent↗
PubMed2006

[Pain and depression].

Pain and depression are often associated. The frequency of pain complaints in depressed patients is 13-100%. In general, depressed patients have a higher pain threshold than do controls, but lower and unchanged thresholds have also been observed. The frequency of depression in chronic pain patients is 1.5-100%. Pain etiology, short education, marital status, gender, psychiatric family history and unemployment are risk factors for depression. Possible mechanisms underlying the pathophysiology of depression and pain could be involvement of the monoamines (5-HT and NA) and the HPA axis.

Central Nervous System↗
PubMed2006

Electroconvulsive therapy: predictors and trends in utilization from 1976 to 2000.

BACKGROUND: Use of electroconvulsive therapy (ECT) may have changed during the last decades due to advances in psychopharmacology and organizational changes of psychiatric care. OBJECTIVES: To identify predictors for receiving ECT for the first time and to describe temporal trends in ECT utilization. METHODS: A register-based case-control study. The sample included 2010 cases treated with ECT between 1976 and 2000 and 148,284 controls. RESULTS: Predictors for receiving first ECT were unipolar affective disorders, long admissions, and no previous admissions. Significantly fewer patients with bipolar and schizoaffective disorders received the treatment in 2000 compared with 1976. CONCLUSIONS: Unipolar affective disorders, long duration of admissions, and no history of previous admissions are strong predictors of receiving first ECT. Despite a decrease in available inpatient beds, the treatment is used in 5.5% of admissions, and during the last 15 years of the study period, ECT utilization has been remarkably stable.

Adolescent↗
PubMed2005

Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans.

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) or clomipramine on cerebral blood flow (CBF) were evaluated. CBF was measured with positron emission tomography (PET) in 27 normal subjects scanned under baseline conditions and, on the same day, after an intravenous (IV) infusion of placebo, citalopram, or clomipramine using a randomized, double-blind design. The main effects of the drugs on blood flow occurred in the thalamus, hypothalamus, and cingulate cortex. Compared to placebo, clomipramine reduced blood flow in the mediodorsal and ventral lateral nuclei of the thalamus, whereas citalopram reduced blood flow in the pulvinar nucleus and the hypothalamus. Compared to clomipramine, citalopram decreased blood flow in the cingulate cortex. The findings support previous reports showing acute central effects of citalopram and clomipramine on regional serotonergic functions measured by PET. Acute side effects may, however, require that care is taken in the selection of experimental designs for future PET studies using IV administration of these antidepressants.

Adult↗
PubMed2005

Cognitive neuropsychiatry: conceptual, methodological and philosophical perspectives.

Cognitive neuropsychiatry attempts to understand psychiatric disorders as disturbances to the normal function of human cognitive organisation, and it attempts to link this functional framework to relevant brain structures and their pathology. This recent scientific discipline is the natural extension of cognitive neuroscience into the domain of psychiatry. We present two examples of recent research in cognitive neuropsychiatry: delusions of control in schizophrenia, and affective disorders. The examples demonstrate how the cognitive approach is a fruitful and necessary supplement to the otherwise successful biological psychiatry paradigm, which tend to bypass the cognitive level. Philosophy concerns some of the core concepts involved in psychiatric illness, particularly concerning rationality, thought and action, reality testing, and the self. We present concrete examples that illustrate how philosophical conceptual tools can be particularly important for the construction and interpretation of the cognitive models relevant to the understanding of psychiatric illness. We conclude that cognitive neuropsychiatry is a fruitful and necessary supplement to biological psychiatry. Furthermore, cognitive neuropsychiatry itself may benefit significantly from employing philosophical conceptual tools in the interpretation and construction of its cognitive models. The cognitive and philosophical approaches may thus be further steps towards a scientific psychopathology.

Biological Psychiatry↗
PubMed2005

Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases.

BACKGROUND: Few studies have examined samples of people with cannabis-induced psychotic symptoms. AIMS: To establish whether cannabis-induced psychotic disorders are followed by development of persistent psychotic conditions, and the timing of their onset. METHOD: Data on patients treated for cannabis-induced psychotic symptoms between 1994 and 1999 were extracted from the Danish Psychiatric Central Register. Those previously treated for any psychotic symptoms were excluded. The remaining 535 patients were followed for at least 3 years. In a separate analysis, the sample was compared with people referred for schizophrenia-spectrum disorders for the first time, but who had no history of cannabis-induced psychosis. RESULTS: Schizophrenia-spectrum disorders were diagnosed in 44.5% of the sample. New psychotic episodes of any type were diagnosed in 77.2%. Male gender and young age were associated with increased risk. Development of schizophrenia-spectrum disorders was often delayed, and 47.1% of patients received a diagnosis more than a year after seeking treatment for a cannabis-induced psychosis. The patients developed schizophrenia at an earlier age than people in the comparison group (males, 24.6 v. 30.7 years, females, 28.9 v. 33.1 years). CONCLUSIONS: Cannabis-induced psychotic disorders are of great clinical and prognostic importance.

Adult↗
PubMed2004

The Danish PET/depression project: performance on Stroop's test linked to white matter lesions in the brain.

The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.

Adult↗
PubMed2004

[N-methyl-11C]Mirtazapine for positron emission tomography neuroimaging of antidepressant actions in humans.

RATIONALE: Many actions of antidepressant drugs cannot yet be studied using positron emission tomography (PET) neuroimaging due to lack of suitable radioligands. We believe that mirtazapine, radiolabeled with C-11, might be suitable for PET neuroimaging of alpha2-adrenoceptors in selected regions of the living human brain. OBJECTIVE: To determine the regional central biodistribution and pharmacokinetics of [N-methyl-11C]mirtazapine in humans. METHODS: Five healthy volunteers received an intravenous injection of [N-methyl-11C]mirtazapine for evaluating its metabolism, biodistribution and pharmacokinetics. RESULTS: [N-methyl-11C]Mirtazapine entered the brain readily, with initial clearance from blood to tissue (K1) ranging from 0.31 ml/ml/min in amygdala to 0.54 ml/ml/min in thalamus. The rate of metabolism of [N-methyl-11C]mirtazapine in the bloodstream was relatively slow, with 20-40% of [11C]-derived radioactivity still present as parent compound at 60 min post-injection. The clearance of [N-methyl-11C]mirtazapine from the tissue compartment (k2') ranged from a low of 0.03 min(-1) in amygdala to a high of 0.06-0.07 min(-1) in thalamus and cerebellum. The volume of distribution (Ve') of [N-methyl-11C]mirtazapine was markedly greater in hippocampus and amygdala (11.3-12.0) than in cerebellum (6.7), with intermediate levels in the thalamus (9.4). CONCLUSIONS: [N-methyl-11C]Mirtazapine has suitable properties for PET neuroimaging. We envision [N-methyl-11C]mirtazapine as a molecular probe for PET imaging of antidepressant actions at sites such as alpha2-adrenoceptors in the living human brain.

Adrenergic alpha-Agonists↗
PubMed2004

Pain thresholds during and after treatment of severe depression with electroconvulsive therapy.

Pain and depression are often associated suggesting that both conditions share a common neurobiological mechanism, which modulate emotional function and processing of noxious information. Pain thresholds are hypothesized to be altered in depressed patients and normalized with the amelioration of depression. The purpose of this study was therefore to determine pain thresholds in patients during and after treatment with electroconvulsive therapy (ECT) of severe depression and in healthy controls. Seventeen depressed patients (Hamilton depression score > 18) and an age and gender matched control group of same size participated in the study. Pain detection and tolerance thresholds to pressure and pain tolerance thresholds to the Cold Pressor Test by exposure to ice-water was measured twice in depressed patients during and after ECT and twice in controls with a similar time interval. While ECT significantly improved Hamilton depression score (from mean 23.9 (SD:5) to mean 12.5 (SD:5.7)) there was no significant change in pain thresholds during and after ECT in the patient group. However, depressed patients had significantly lower pain tolerance in the Cold Pressor Test on both examinations and on pressure pain tolerance on the second examination day than their corresponding control subjects. The differential effect of ECT on depression score and pain processing indicate that mood and noxious processing are not medicated directly by the same systems but that a complex relationship between pain and depression exists.

Adolescent↗
PubMed2003

The Danish PET/depression project: poor verbal fluency performance despite normal prefrontal activation in patients with major depression.

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.

Adult↗
PubMed2003

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat.

RATIONALE: A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. However, the neurochemical rationale behind this strategy needs to be further clarified. OBJECTIVES: We examined the effect of chronic citalopram and subchronic lithium, alone or in combination, on (a) serum levels of citalopram and lithium, (b) animal behaviour and (c) hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. Furthermore, we examined the serum level of citalopram and hippocampal 5-HT following one acute citalopram injection. METHODS: Microdialysis in the freely moving animals was used to determine hippocampal 5-HT and 5-HIAA. The animal behaviour was examined in the open field and forced swim test. RESULTS. We found that chronic administration of citalopram (20 mg/kg/24 h s.c.) significantly increased the 5-HT baseline relative to vehicle-treated rats. Addition of subchronic lithium (60 mmol/kg chow pellet p.o.) to chronic citalopram therapy further elevated the 5-HT levels. Moreover, we found acute citalopram (5 mg/kg s.c.) to increase the 5-HT level. The immobility time in the FST and the locomotion in the OF were unaffected by any treatments. CONCLUSIONS: The present results support the assumption that increases in hippocampal 5-HT neurotransmission may be important in the augmentatory effect of lithium.

Animals↗
PubMed2003

[Which are the elements of an international evaluation of research? Experiences from an evaluation of Swedish psychiatric research].

INTRODUCTION: In order to ensure the quality of research, it is necessary to perform an external evaluation of the quality and structure of the research environments on a regular basis and consider them in a national and international perspective. MATERIAL AND METHODS: There are several ways of evaluating research. The author mentions an audit-like expert evaluation based on his own experience from an evaluation of Swedish psychiatric research in 2000. RESULTS AND DISCUSSION: A short comparison with Danish psychiatric research is made. One of the advantages of this method is that the research evaluation can be carried out by the members of the research teams in an open dialogue among peers. This procedure makes it possible to focus on weaknesses and strengths with the purpose of planning future strategies and organisation in the most appropriate way. An obvious limitation, however, is the competence assigned to the expert group whose composition is important for the result.

Biomedical Research↗
PubMed2003

Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity.

Nitric oxide (NO) is an unconventional transmitter molecule in the nervous system, synthesized by nitric oxide synthase (NOS) following activation of the N-methyl-D-aspartate (NMDA) receptor. Several in vivo studies have demonstrated that NO modulates the extracellular levels of various neurotransmitters in the central nervous system, while serotonin (5-HT) re-uptake may be influenced by the NO pathway. Moreover, inhibitors of NOS exhibit antidepressant-like and anxiolytic-like properties in various animal models. Therefore, the aims of the present study were to clarify the involvement of distinct antidepressants acting on the serotonin re-uptake site in the regulation of the activity of hippocampal NOS in vitro, in vivo and ex vivo. We found that citalopram, paroxetine, imipramine and N(G)-nitro-L-arginine dose dependently decreased the hippocampal NOS activity in vitro. Moreover, local administration of citalopram, paroxetine, tianeptine, imipramine and N(G)-nitro-L-arginine significantly decreased the hippocampal NOS activity in vivo at a concentration significantly lower than in vitro. No effect on NOS activity following retrodialysis with 5-HT was observed. Acute (5 mg/kg, s.c.) and chronic (3 weeks, 20 mg/kg/24 h) systemic administration of citalopram did not influence NOS activity ex vivo. The effects on NOS represent a response to structurally dissimilar serotonergic antidepressants. However, since these data reflect effects on basal NOS activity, we believe that serotonergic antidepressants do not directly affect NOS at dosages used clinically, but the findings may reflect a secondary action of antidepressants on the glutamate NMDA receptor following their primary inhibitory action at the 5-HT transporter.

Animals↗
PubMed2002

Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats.

The forced swimming test (FST) has been extensively used as a screening model for new antidepressant agents. It has been shown that drugs which reduce the amount of nitric oxide (NO) have the same outcome in this model as classic antidepressants. In addition, previous studies have shown that methylene blue, which acts as a direct inhibitor of both NOS and soluble guanylate cyclase (sGC), mimics the effect of clinically effective antidepressants in patients and in the FST. The present study examined the effects of the specific inhibitor of the NO-sGC pathway, [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) and of the neuronal NOS inhibitor 7-nitroindazole (7-NI) in the FST. We found that ODQ (10 and 20 mg/kg) significantly decreased the immobility time in the FST compared to the control. Similarly, injections of 7-NI (30 or 60 mg/kg) reduced immobility time as well as Imipramine (IMI, 30 mg/kg). Interestingly, L-Arginine (250 mg/kg) administered in combination with ODQ reversed the effect of ODQ but displayed no effect when administered alone. Locomotion activity was significantly decreased following administration of IMI (30 mg/kg) and 7-NI (30 and 60 mg/kg) but was unaffected after administration of ODQ (10 and 20 mg/kg). These findings suggest that the NO-sGC-cGMP pathway may play an important role in the mediation of the behavioural effect in the FST without influence on motor activity.

Animals↗