Anxiety and salivary cortisol were measured in subjects performing simulated public speaking (SPS), a procedure that has been neurobiologically related to panic disorder. The subjects were divided into three groups: 18 symptomatic panic... more
Anxiety and salivary cortisol were measured in subjects performing simulated public speaking (SPS), a procedure that has been neurobiologically related to panic disorder. The subjects were divided into three groups: 18 symptomatic panic patients, 16 nonsymptomatic, drug-treated panic patients, and 17 healthy controls. In the experimental session, subjective anxiety (Visual Analogue Mood Scale) and the total score of the Bodily Symptom Scale (BSS) were higher in symptomatic patients than in controls, with nonsymptomatic patients in between. Measures of cortisol taken at home showed that the level was higher at 9:00 h than at 23:00 h in every group, indicating a normal circadian regulation of the hypothalamic-pituitary-adrenal (HPA) axis in panic patients. Also in every group, the level of cortisol was high at the beginning of the experimental session and decreased after 70 min. This fall parallels the decrease in anxiety and BSS ratings, and appears to reflect habituation of initial,...
1. Although a diagnosis of obsessive-compulsive disorder (OCD) can be made with the specification" poor insight"(PI), this subtype remains understudied. To investigate the subtype, 78 OCD patients were characterized by degree of... more
1. Although a diagnosis of obsessive-compulsive disorder (OCD) can be made with the specification" poor insight"(PI), this subtype remains understudied. To investigate the subtype, 78 OCD patients were characterized by degree of insight, reevaluated after treatment, and compared with 20 schizophrenics with OCD (OCD+ S). At the pretreatment assessments in OCD patients, 28 subjects with poor or delusional insight (PI) were distinguished from 50 subjects with fair or good insight using the insight question of the ...
Twenty-eight nondepressed patients with DSM-III obsessive-compulsive disorder completed both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Leyton Obsessional Inventory (LOI) once a week for a total of three times change. In... more
Twenty-eight nondepressed patients with DSM-III obsessive-compulsive disorder completed both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Leyton Obsessional Inventory (LOI) once a week for a total of three times change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global scores, the Y-BOCS was found to be more reliable than the LOI. Correlations were also obtained for the baseline period between the Y-BOCS and Leyton scores. At the end of a 14-week trial of clomipramine, the Y-BOCS and the LOI were again administered along with a Physician and Patient Global Rating of change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global Ratings. This last finding suggests that the Y-BOCS is a better measure of clinical change than is the LOI.
Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM)... more
Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon ...
Personal genomic analysis was used for molecular diagnosis and pharmacogenomics in a 53-year-old female suffering from alternating depressive and dysphoric episodes. A total of 52 genes and 108 SNPs were analyzed in the whole genome.... more
Personal genomic analysis was used for molecular diagnosis and pharmacogenomics in a 53-year-old female suffering from alternating depressive and dysphoric episodes. A total of 52 genes and 108 SNPs were analyzed in the whole genome. Results from the pharmacogenomic analysis were consistent with the pharmacological history and indicate mutations associated with low monoaminergic tone, but also a hyperactive 5HT2A receptor, a feature that associates to a high probability of developing a bipolar condition, especially under 5-hydroxytryptamine potentiating pharmacology. This aligns with the patient developing dysphoria with high clomipramine. The pharmacokinetic genomics pointed out to some absorption, distribution, metabolism, and excretion (ADME) alterations that can lower or nullify drug's activity. A personalized regimen was proposed, with a positive outcome after 1 year.
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to... more
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response reve...
INTRODUCTION: Tricyclic antidepressants are used in the treatment of various pain syndromes. The antidepressant clomipramine inhibits predominantly the reuptake of serotonin in the central nervous system. The mechanism of its analgesic... more
INTRODUCTION: Tricyclic antidepressants are used in the treatment of various pain syndromes. The antidepressant clomipramine inhibits predominantly the reuptake of serotonin in the central nervous system. The mechanism of its analgesic effect is not fully understood. The AIM of the present study was to find experimentally any dose-effect dependence in the analgesic effect of clomipramine and the involvement of the 5-НТ2 and 5-НТ3 receptors in the mechanism of this effect. Material and methods: Fifty male Wistar rats were used in the study allocated to five groups (10 animals each): a saline treated control group, one positive control group treated with metamizole and three experimental groups treated with intraperitoneally administered clomipramine in doses of 5, 10 and 20 mg/kg bw, respectively. To study the role of 5-НТ2 and 5-НТ3 receptors in this effect we used another five groups (10 animals each): control, positive control and three experimental groups treated with clomipramin...
A single dosage of several antidepressants produces an increased rate of firing in lateral septal nuclei of the rat. The objective of the present study was to clarify the long-term treatment action of clomipramine on the septal nuclei of... more
A single dosage of several antidepressants produces an increased rate of firing in lateral septal nuclei of the rat. The objective of the present study was to clarify the long-term treatment action of clomipramine on the septal nuclei of the rat. A progressive increase of firing rate appeared after long-term treatment with clomipramine (1.25 mg/kg, IP; twice a day, for 25 days). The most noticeable firing increase occurred in the lateral septal nuclei, which primarily receive serotonergic innervation. Irregular changes occurred in the corpus callosum and cingulum. Finally, in other poorly innervated serotonergic septal regions, the treatment lacked effects. This suggested that the action of clomipramine was primarily due to interaction with the serotonergic system.
To assess the clinical and polysomnographic features of narcolepsy in Saudis. All patients diagnosed to have narcolepsy in the Sleep Disorders Center at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between March 1998... more
To assess the clinical and polysomnographic features of narcolepsy in Saudis. All patients diagnosed to have narcolepsy in the Sleep Disorders Center at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between March 1998 and December 2005 based on the International Classifications of Sleep Disorders Diagnostic and Coding Manual criteria were included. A data entry form collecting the demographic, clinical features, medications, referring specialty, prior diagnoses and daytime sleepiness was used. All patients underwent polysomnography followed by multiple sleep latency. Forty-seven patients with a mean age of 28.9 +/- 1.9 years were included. The mean age at onset of symptoms was 20.5 +/- 1.4 years. The interval between symptoms onset and diagnosis was 8.4 +/- 1.2 years. While 22 (46.8%) of the patients were referred to the sleep disorders clinic by different specialties, 25 (53.2%) patients sought an appointment in the sleep disorders clinic directly. Only 3 patient...