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Biomedical subjects

M O Krebs

Publications and source records attributed to M O Krebs.

At least 19 recordsLinked to original sources
PubMed2001

Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1.

Abuse of cannabis is frequent among the young and is suspected to precipitate schizophrenia in vulnerable subjects. Cannabinoid receptor (CB1) is particularly concentrated in dopamine-modulated areas of the nervous system. An association between an AAT polymorphism of the CB1 gene and intravenous drug abuse has been previously reported, but not with schizophrenia. In a French Caucasian population, we compared the distribution of a single-base polymorphism revealed by MspI within the first exon of the CB1 gene in patients with schizophrenia (n = 102) and ethnic- and gender-matched controls (n = 63). No significant difference was seen in the allele or genotype distribution between the whole sample of schizophrenic patients and controls. However, we found a borderline lack of allele g and a significant lack of gg genotype in the non-substance-abusing patients compared to substance-abusing patients, the latter being similar to the controls. These results are the first report of an significant association between CB1 receptor and a subtype of schizophrenia. Studies are needed to confirm and further explore the precise role of the cannabinoid system in schizophrenia.

Adult↗
PubMed2001

Substance abuse and suicidality in schizophrenia: a common risk factor linked to impulsivity.

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.

Adult↗
PubMed2001

Impairment of predictive saccades in schizophrenia.

Using infrared oculography, we compared saccades toward predictable and pseudo-random visual targets in 19 neuroleptic-free patients with schizophrenia (including 13 neuroleptic-naïve patients) and in 29 age- and gender-matched healthy volunteers. Externally driven saccades were not different between patients and controls, whether or not the target was predictable. Anticipated saccades were specifically less accurate in the patients compared to the controls. The difference between primary gain of anticipated and non-anticipated saccades was markedly higher in the patients compared to controls (p=0.003). These results point to a deficit in the early step of internally driven oculomotor planning in schizophrenia.

Adult↗
PubMed2001

Clinical features of panic attacks in schizophrenia.

Since reports have underscored that panic attacks (PA) may be an identifiable state occurring in schizophrenia, we studied the symptomatology of PA in a group of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous panic attacks, not related to phobic fears or delusional fears, and for the 12 remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid subtype of schizophrenia tends to be more often associated with a history of panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; chi2 = 3.5, P =.06). It seems that there are at least two types of PA in schizophrenic patients. The first one could be independent from the psychotic feature, with no psychopathological link. The second kind of PA could be directly related to a schizophrenic disorder, and found in patients with the paranoid subtype.

Adult↗
PubMed2001

Hemodynamic, renal, and endocrine responses to acute ET(A) blockade at different ANG II plasma levels.

Angiotensin (ANG) II effects may be partly mediated by endothelin (ET)-1. This study analyses the hemodynamic, renal, and hormonal responses of acute ET(A) receptor antagonism (LU-135252) at two ANG II plasma levels in eight conscious dogs. Protocol 1 involved a 60-min baseline, followed by two doses of ANG II for 60 min each (4 and 20 ng. kg(-1). min(-1)), termed ANG II 4 (slightly increased) and ANG II 20 (pathophysiologically increased ANG II plasma concentration). Protocol 2 was the same as protocol 1 but included 15 mg/kg iv LU-135252 after the baseline period. Protocol 3 was a 3-h time control. ANG II without LU-135252 did not increase plasma big ET-1 and ET-1, whereas LU-135252 increased ET-1 transiently after injection. This transient ET-1 increase was not reflected in urinary ET-1 excretion. The ANG II induced decreases in sodium, water, and potassium excretion, glomerular filtration rate, and fractional sodium excretion were not different with and without LU-135252. Mean arterial pressure increased during ANG II and was not lower with LU-135252 (-6 mmHg, not significant). Most importantly, during ANG II 20 LU-135252 prevented the decrease in cardiac output. Simultaneously, systemic vascular resistance increased 40% less, pulmonary vascular resistance was maintained at baseline levels, and central venous and wedge pressure were lower. Because ANG II stimulated endothelin de novo synthesis should just have started after 2 h of ANG II infusion, there must be mechanisms other than blocking the coupling of de novo synthesized endothelins to the ET(A) receptors to explain the effects of acute ET(A) receptor inhibition in our setting.

Aldosterone↗
PubMed2001

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.

Acute Disease↗
PubMed2001

Is substance abuse in schizophrenia related to impulsivity, sensation seeking, or anhedonia?

OBJECTIVE: The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence. METHOD: Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview's section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. RESULTS: The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia. CONCLUSIONS: As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.

Adult↗
PubMed2000

Validation and factorial structure of a standardized neurological examination assessing neurological soft signs in schizophrenia.

Although neurological soft signs (NSS) have been consistently reported in patients with schizophrenia, their clinical relevance, the actual impact of treatment or their evolution during the disease are not well clarified, possibly because of methodological limitations of the available tools. We have developed a new standardized examination integrating the assessment of 23 NSS selected from the literature and the rating of well-validated scales for assessment of extra-pyramidal symptoms. We examined 161 subjects (controls, n=48; patients with schizophrenia, n=95; or recurrent mood disorder, n=18). Half of the patients were neuroleptic-free. Schizophrenic patients had significantly higher total score (14. 6+/-8) than mood disorder patients (12.0+/-7) and controls (5.0+/-2). Internal consistency (Cronbach's alpha=0.85) and inter-rater reliability were good. Principal component analysis found five consistent factors ('motor coordination', 'motor integrative function', 'sensory integration', 'involuntary movements or posture', 'quality of lateralization'). This scale thus confirmed a factorial structure in agreement with the conceptual areas of interest explored by NSS and should be a useful tool for assessment of the different dimensions of neurological dysfunction in schizophrenia.

Adult↗
PubMed2000

Genetic vulnerability to drug abuse.

Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

Female↗
PubMed2000

Histamine H2 receptor gene variants: lack of association with schizophrenia.

A role of histaminergic neuronal systems in schizophrenia was suggested by an association with several polymorphisms located in the coding region of the histamine H2-receptor (H2R) gene (Orange et al, Mol Psychiatry 1996; 1: 466-469). Using either the reference method of direct sequencing or restriction endonuclease digestion of PCR products amplified from DNA, we could not confirm the existence of these polymorphisms in 53 Swedish controls, 52 French controls and 88 French schizophrenics. In contrast, we detected a G543A transition in the coding region of the gene that was not found in the British population. This allelic variation, which was observed in 15% of the controls with no homozygotes, did not change the amino acid sequence of the receptor. We also analyzed a 1.8-kb nucleotide sequence of the promoter region in which we detected two additional polymorphisms that may modulate the expression of the H2R gene. The first one was a A-592G transition located in the minimal promoter of the gene and found in;10% of controls with no homozygotes. The second one was a G-1018A transition located in an enhancer element of the promoter and was found in;20-30% of controls (with;2-4% homozygotes). DNA analysis of the 88 French schizophrenic subjects revealed that the incidence of the three polymorphisms was not significantly different in this population. In conclusion, the present findings may suggest a surprisingly high variability of the H2R gene polymorphisms in different geographical areas but do not support an association of these allelic variations with schizophrenia.

Female↗
PubMed2000

Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia.

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

Adult↗
PubMed1999

Renal and hemodynamic effects of losartan in conscious dogs during controlled mechanical ventilation.

In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml. kg-1. min-1 iv) or not and received losartan (100 micrograms. kg-1. min-1 iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted approximately 18% more sodium (69 +/- 7 vs. 38 +/- 5 micromol. min-1. kg-1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 +/- 0.3 vs. 4.5 +/- 0.2 ml. min-1. kg-1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 +/- 0.6 vs. 2.6 +/- 1.0 micromol. min-1. kg-1) and glomerular filtration rate (3.8 +/- 0.3 vs. 3.8 +/- 0.4 ml. min-1. kg-1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 +/- 0.7 to 7.8 +/- 1.3 ng ANG I. ml-1. h-1 during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.

Angiotensin Receptor Antagonists↗
PubMed1999

Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan.

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 +/- 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 microg. min-1. kg-1 losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn. s. cm-5 in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 +/- 0.7 to 2.5 +/- 0.5 ng ANG I. ml-1. h-1, and plasma ANG II decreased from 11.9 +/- 3.0 to 8.2 +/- 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Angiotensin II↗
PubMed1998

Dopamine D3 receptor gene variants and substance abuse in schizophrenia.

In an association study of the Bal I polymorphism in the dopamine D3 receptor (DRD3) gene in a French Caucasian population, global comparison of patients with schizophrenia (n = 89, DSM-III-R criteria) and controls (n = 52) led to non-significant differences. However, the homozygosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.047) and in neuroleptic responder patients as compared to treatment-refractory patients (n = 19; P = 0.037). The combined characteristics treatment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorphism DRD3 gene is associated with predisposition to substance abuse and/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positive association of this polymorphism with opiate dependence (see companion article by Duaux et al) and the involvement of DRD3 in both pharmacodependence mechanisms and antipsychotic effects of neuroleptics.

Comorbidity↗
PubMed1998

Renal nerves are not involved in sodium and water retention during mechanical ventilation in awake dogs.

BACKGROUND: The role of renal nerves during positive end-expiratory pressure ventilation (PEEP) has only been investigated in surgically stressed, anesthetized, unilaterally denervated dogs. Anesthesia, sedation, and surgical stress, however, decrease urine volume and sodium excretion and increase renal sympathetic nerve activity independent of PEEP. This study investigated in awake dogs the participation of renal nerves in mediating volume and water retention during PEEP. METHODS: Eight tracheotomized, trained, awake dogs were used. The protocol consisted of 60 min of spontaneous breathing at a continuous positive airway pressure of 4 cm H2O, followed by 120 min of controlled mechanical ventilation with a mean PEEP of 15-17 cm H2O (PEEP), and 60 min of continuous positive airway pressure. Two protocols were performed on intact dogs, in which volume expansion had (hypervolemic; electrolyte solution, 0.5 ml x kg(-1) x min(-1)) and had not (normovolemic) been instituted. This was repeated on the same dogs 2 or 3 weeks after bilateral renal denervation. RESULTS: Hypervolemic dogs excreted more sodium and water than did normovolemic dogs. There was no difference between intact and renal-denervated dogs. Arterial pressure did not decrease when continuous positive airway pressure was switched to PEEP. Plasma renin activity, aldosterone, and antidiuretic hormone concentrations were greater in normovolemic dogs. The PEEP increased aldosterone and antidiuretic hormone concentrations only in normovolemic dogs. CONCLUSIONS: In conscious dogs, renal nerves have no appreciable contribution to sodium and water retention during PEEP. Retention in normovolemic dogs seems to be primarily caused by an activation of the renin-angiotensin system and an increase in the antidiuretic hormone. Excretion rates depended on the volume status of the dogs.

Aldosterone↗
PubMed1996

[Münchhausen syndrome by proxy: a challenge for medicine].

In Münchhausen syndrome by proxy, a subject, usually a mother, pretends her child has a serious medical disorder. After simulating ficticious symptoms, or even producing clinical signs such as convulsions, fever, bleeding, vomiting, diarrhea or skin eruptions, the mother repeatedly takes her child to different hospitals for care. During hospitalization, the mother shows great concern for the child and is highly cooperative with the health care team. The consequences may be unwarrented, often invasive, investigations and therapy with a very high risk of morbidity and mortality. The underlying psychopathological structure is difficult to apprehend. Narcissic fragility and borderline personality are the must frequent, but passive-dependent hysteric personality or sadomasochist behavior can be found and depression is often associated. The main, if not the sole, benefit for the mother lies in the leading role she plays during the repeated hospitalizations in front of the admizing medical staff. Rare cases of adult-adult Münchhausen syndrome by proxy have also been reported. Physicians should be aware of this syndrome in order to avoid unintentional participating in this morbid scenario by performing useless invasive examinations or by prescribing dangerous medication. Psychiatric treatment and sometimes legal action are required to avoid this particular kind of child abuse.

Child↗
PubMed1996

[Münchhausen syndrome by proxy between two adults].

OBJECTIVES: Münchhausen syndrome by proxy has been well described in the case of a women producing or pretending symptoms in one of her children, leading that child to have numerous medical interventions. The case of two adults has been seldom described and the differences in the psychopathological features of the two situations are not well known. METHODS: We report our observation of a Münchhausen syndrome in a married couple where the wife injected tranquilizers to her husband, inducing repeated episodes of coma. Complex interactions between the pathological personalities of the husband and wife were present. Prominent features of the wife's personality included a narcissistic deficiency, poor defenses and signs of depression. DISCUSSION: Practioners should be aware of this peculiar pathology to avoid delayed diagnosis and its dramatic consequences. Appropriate medical, psychiatric, as well as legal measures must be taken.

Adolescent↗