OBSESSIVE COMPULSIVE DISORDER
(Page 2)

Rippere V
Med Hypotheses (England) Sep 1984, 15 (1) p3-13

Two cases of obsessional ruminations apparently secondary to functional hypoglycaemia are described. Both patients are young Caucasian males with obsessional histories at the start of dietary treatment of 18 and 6 years, respectively. In both cases, reactive hypoglycaemia was confirmed by glucose tolerance test. The first case made a complete recovery on dietary treatment which has lasted over two years; previous treatment with drugs, behaviour therapy, and counselling were unsuccessful The response of the second case has been less outstanding due to poor compliance, but improvement and worsening have been systematically related to the extent of his adherence to the suggested dietary regimen. These cases raise questions for further research on this neglected subgroup of obsessional patients.

Rippere V
Br J Clin Psychol (England) Nov 1983, 22 (Pt 4) p314-6

Chronic obsessional ruminations may prove resistant to psychological treatment because they are not psychological in nature but epiphenomena of brain dysfunction secondary to nutritional factors. The case is described of a chronic, treatment-resistant ruminator who made a dramatic and lasting recovery when a high protein breakfast was added to his elimination diet regimen, undertaken when years of psychological and pharmacological treatment had failed. Biochemical and clinical evidence supports the hypothesis that hypoglycaemia secondary to inappropriate diet was the cause of his disorder. Dietary contributions to obsessional ruminations should probably be sought early on in the assessment of such patients.

Blier P; Bergeron R
Neurobiological Psychiatry Unit, McGill University, Montreal, Quebec, Canada.
Int Clin Psychopharmacol (England) Mar 1996, 11 (1) p37-44

Given that an important proportion of patients with obsessive-compulsive disorder (OCD) fail to respond adequately to serotonin (5-HT) reuptake inhibitors (SRI), augmentation strategies aimed at enhancing further 5-HT transmission by different mechanisms were attempted sequentially in 13 SRI-resistant patients. Addition of the 5-HT1A l beta-adrenergic antagonist pindolol did not alter OCD symptomatology but produced a rapid improvement of depressive symptoms. The 5-HT1A agonist buspirone as well as 5-hydroxytryptophan, the immediate precursor of 5-HT, added to the SRI-pindolol regimen, were not effective in attenuating the intensity of OCD. Tryptophan, added to the SRI-pindolol regimen, produced a significant improvement after 4 weeks, with further amelioration after 6 weeks (36% decrease of the Yale-Brown Obsessive Compulsive Score), which was maintained with treatment prolongation.

Monteleone P; Catapano F; Tortorella A; Di Martino S; Maj M
Institute of Psychiatry, Second University of Naples, Italy.
Psychoneuroendocrinology (England) 1995, 20 (7) p763-70

The circadian rhythms of melatonin and cortisol were evaluated in seven outpatients with obsessive-compulsive disorder (OCD) before and after 8 weeks of fluoxetine treatment (20 mg/day in the first 2 weeks, and 40 mg/day afterwards), and in seven healthy subjects matched to patients on age, sex and season of testing. The results confirm our previous findings of a decreased 24-h production of melatonin (p < .05; two-way ANOVA with repeated measures) and of an increased circadian secretion of cortisol (p < .01) in OCD patients with respect to matched controls, and show, for the first time, that these hormonal alterations do not significantly change after 2 months of fluoxetine administration, in spite of a good clinical improvement. These data suggest that the normalization of the biochemical changes underlying the altered endocrine parameters in obsessive-compulsive patients is not necessary for effective therapy or clinical remission.

Fineberg NA; Cowen PJ; Kirk JW; Montgomery SA
Academic Department of Psychiatry, St Mary's Hospital, London, UK.
J Affect Disord (Netherlands) Oct 1994, 32 (2) p97-104

We studied the neuroendocrine responses produced by intravenous L-tryptophan (TRP) in 16 untreated patients with obsessive compulsive disorder (OCD) and 16 matched healthy controls. The increase in plasma growth hormone seen following TRP was significantly greater in the OCD patients, while TRP-induced prolactin release did not differ from controls. Taken in conjunction with findings from other neuroendocrine studies the data suggest that some aspects of 5-HT1A neurotransmission may be increased in OCD. This increase may represent a compensatory change which promotes adaptation to stress in non-depressed OCD patients.

Barr LC; Goodman WK; McDougle CJ; Delgado PL; Heninger GR; Charney DS; Price LH
Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven.
Arch Gen Psychiatry (United States) Apr 1994, 51 (4) p309-17

METHODS: The effects of short-term tryptophan depletion were examined in 15 patients with DSM-III-R obsessive-compulsive disorder who had demonstrated symptom reduction following treatment with serotonin reuptake inhibitors. Patients received a 24-hour, low-tryptophan (160-mg/d) diet followed the next morning by a drink of 15 amino acids. A double-blind, placebo-controlled cross-over design was used.

RESULTS: The diet and the amino acid drink reduced free plasma tryptophan levels by a mean of 84% 5 hours later. Short-term tryptophan depletion did not significantly change mean ratings of obsessions and compulsions. In contrast, mean depression ratings were significantly increased with tryptophan depletion compared with the control (tryptophan-supplemented) testing.

CONCLUSION: Maintenance of serotonin reuptake inhibitor-induced improvement of obsessive and compulsive symptoms, unlike remission of depressive symptoms, may not depend on ongoing short-term availability of serotonin.

Monteleone P; Catapano F; Del Buono G; Maj M
Institute of Psychiatry, First Medical School, University of Naples, Italy.
Acta Psychiatr Scand (Denmark) Jun 1994, 89 (6) p411-5

Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.

Goodman WK; McDougle CJ; Barr LC; Aronson SC; Price LH
Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06519.
J Clin Psychiatry (United States) Jun 1993, 54 Suppl p16-26

Biological approaches to the patient with treatment-resistant obsessive compulsive disorder are briefly reviewed. The most commonly employed strategy involves combining a potent serotonin reuptake inhibitor (SRI) (e.g., clomipramine or fluvoxamine) with another medication that may exert effects on the brain serotonin system. Open-label reports regarding the addition of tryptophan, fenfluramine, lithium, or buspirone to ongoing SRI therapy of obsessive compulsive disorder are encouraging. However, the anti-obsessive compulsive efficacy of SRI-lithium and SRI-buspirone combination therapy has not been confirmed in recent controlled trials. Preliminary evidence suggests that addition of neuroleptic may benefit SRI-refractory obsessive compulsive disorder patients who have a comorbid chronic tic disorder. Other biological approaches (e.g., electroconvulsive therapy and psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant obsessive compulsive disorder. Finally, an algorithm is proposed for those patients with obsessive compulsive disorder who fail to respond to an adequate trial with a potent SRI. (115 Refs.)

Goodman WK; McDougle CJ; Price LH
Clinical Neuroscience Research Unit, Yale University School of Medicine, New Haven, CT 06519.
J Clin Psychiatry (United States) Apr 1992, 53 Suppl p29-37

The authors briefly review studies of the efficacy of potent serotonin reuptake inhibitors (SRIs) (e.g., clomipramine, fluvoxamine) in obsessive compulsive disorder (OCD) and compare the use of antidepressants in the treatment of depression and OCD. They propose an algorithm for those patients with OCD who fail to respond to an adequate trial with a potent SRI and discuss the promise and limitations of adding tryptophan, fenfluramine, lithium, buspirone, or a neuroleptic to ongoing SRI therapy. Other biological approaches (e.g., ECT, psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant OCD. (68 Refs.)

Lucca A; Lucini V; Piatti E; Ronchi P; Smeraldi E
Istituto di Ricovero e Cura a carattere scientifico H. San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy.
Psychiatry Res (Ireland) Nov 1992, 44 (2) p85-91

Fasting plasma tryptophan (TRP) levels and ratios of total plasma tryptophan to the sum of five large neutral amino acids (LNAAs)--tyrosine, phenylalanine, leucine, isoleucine, and valine--that compete with tryptophan for passage across the blood-brain barrier were found to be significantly lower in a group of 28 patients with major depression compared with 29 normal subjects and 21 patients with obsessive-compulsive disorder (OCD). The OCD group was divided in two subgroups: patients with OCD alone and patients with a co-diagnosis of major depression. Since it has been considered that these biological parameters reflect brain tryptophan and serotonin levels, our results suggest their importance in relation to the presence or absence of depressive symptoms. The values of the other LNAAs and their sum did not differ significantly among the groups.

Catapano F; Monteleone P; Fuschino A; Maj M; Kemali D
Institute of Psychiatry, First Medical School, University of Naples, Italy.
Psychiatry Res (Ireland) Dec 1992, 44 (3) p217-25

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.

Baumgarten HG; Grozdanovic Z
Institute of Anatomy, University Clinic Benjamin Franklin, Free University of Berlin, Germany.
Br J Psychiatry Suppl (England) 1998, (35) p13-20

BACKGROUND: Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRIs).

METHOD: The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour.

RESULTS: In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.

CONCLUSIONS: We hypothesise that continuous treatment with SSRIs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Abbott MH; Folstein SE; Abbey H; Pyeritz RE
Am J Med Genet (United States) Apr 1987, 26 (4) p959-69

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine beta-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B6. The overall rate of clinically significant psychiatric disorders was 51%, predominated by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive - compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 +/- 27 (1 SD); and an IQ of less than or equal to 79 was two-thirds more common among vitamin B6-nonresponsive patients compared to vitamin B6-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B6-nonresponsive patients.

Lee M.A.; Cameron O.G.; Gurguis G.N.M.; Glitz D.; Smith C.B.; Hariharan M.; Abelson J.L.; Curtis G.C.
Cleveland VA Med Ctr, Psychiatry Service, 10000 Brecksville Road,Brecksville, OH 44141 US
Biological Psychiatry (United States) 1990, 27/10 (1083-1093)

Ten patients with obsessive -compulsive disorder (OCD) and 13 normal control subjects received intravenous infusions of 2 x 10sup -sup 6 g/kg of clonidine and normal saline on separate days. Responses to the drug relating to plasma growth hormone (GH), 3-methoxy-4-hydroxyphenylglycol (MHPG), heart rate, blood pressure, and several symptoms were determined. Additionally, platelet alphainf 2-adrenoreceptor binding was measured in most of the subjects. GH, MHPG, blood pressure, and heart rate responses to clonidine did not differ between groups. As expected, patients reported more symptoms than normal subjects, and clonidine was sedating for both groups. Patients did not differ from normal subjects in the symptom response to clonidine. The maximum number of binding sites (B(max)) for tritiated clonidine was significantly greater in OCD patients than in normals. This pattern of alphainf 2-adrenoreceptor status is different than the patterns in major depression and panic anxiety.

Hermesh H.; Weizman A.; Shahar A.; Munitz H.
Geha Psychiatric Hospital, Beilinson Medical Center, 49 100 Petah Tiqva Israel
Acta Psychiatrica Scandinavica (Denmark) 1988, 78/1 (8-10)

Vitamin Binf 1inf 2 and folate serum levels were studied in 30 patients with obsessive compulsive disorder (OCD), and in two control groups comprised of 30 chronic schizophrenics and 30 normal healthy subjects. Six patients (20%) of the OCD group had abnormal low levels of vitamin Binf 1inf 2. This prevalence was significantly higher than that of the control groups. No clinical neurological or haematological abnormalities accompanied the reduced vitamin Binf 1inf 2 levels. Possible implication of this finding for the pathophysiology of OCD in a subgroup of patients and the possibility that the Binf 1inf 2 deficiency could be the consequence rather than the cause of OCD are suggested.

Levine J
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Eur Neuropsychopharmacol (Netherlands) May 1997, 7 (2) p147-55

Inositol is a simple polyol precursor in a second messenger system important in the brain. Cerebrospinal fluid inositol has been reported as decreased in depression. A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed. Significant overall benefit for inositol compared to placebo was found at week 4 on the Hamilton Depression Scale. No changes were noted in hematology, kidney or liver function. Since many antidepressants are effective in panic disorder, twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, four week, random-assignment crossover treatment trial of inositol 12 g per day. Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol compared to placebo. Side-effects were minimal. Since serotonin re-uptake inhibitors benefit obsessive compulsive disorder (OCD) and inositol is reported to reverse desensitization of serotonin receptors, thirteen patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each. Inositol significantly reduced scores of OCD symptoms compared with placebo. A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients, did not show any beneficial effects. A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients, with on clearly significant therapeutic effects. Antidepressant drugs have been reported to improve attention deficit disorder (ADDH) with hyperactivity symptomatology. We studied oral inositol in children with ADDH in a double-blind, crossover, placebo-controlled manner. Eleven children, mean age 8.9 +/- 3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight. Results show a trend for aggravation of the syndrome with myo- inositol as compared to placebo. Recent studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism. However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism. Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment. Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors. Inositol 6 g daily was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients, without effect. These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors, including depression, panic and OCD, and is not beneficial in schizophrenia, Alzheimer's ADDH, autism or ECT-induced cognitive impairment.

Fux M; Levine J; Aviv A; Belmaker RH
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Am J Psychiatry (United States) Sep 1996, 153 (9) p1219-21

OBJECTIVE: Earlier studies reported that inositol, a simple polyol second messenger precursor, was effective in controlled trials for patients with depression and panic. In this study its effectiveness in obsessive - compulsive disorder was investigated.

METHOD: Thirteen patients with obsessive - compulsive disorder completed a double-blind, controlled crossover trial of 18 g/day of inositol or placebo for 6 weeks each.

RESULTS: The subjects had significantly lower scores on the Yale-Brown Obsessive Compulsive Scale when taking inositol than when taking placebo.

ONCLUSIONS: The authors conclude that inositol is effective in depression, panic, and obsessive -compulsive disorder, a spectrum of disorders responsive to selective serotonin reuptake inhibitors.

Vadnal R.; Parthasarathy L.; Parthasarathy R.
Dr. R. Vadnal, Mental Hlth./Behavioural Scis. Serv., VA Medical Center, 800 Zorn Avenue, Louisville, KY 40206 United States
CNS Drugs (New Zealand) 1997, 7/1 (6-16)

Myo-inositol is a ubiquitous carbohydrate that is present in large amounts in brain tissue and is involved in neuronal signalling and osmoregulation. This sugar is an essential component of the inositol signalling system, which is a postreceptor second messenger signalling system found in many cells. Myo-inositol is the precursor of membrane inositol phospholipids, which are critically linked to a number of CNS receptor signalling systems, including muscarinic, serotonergic, adrenergic, metabotropic and histaminergic systems, and those linked to cholecystokinin, tachykinins, neurotensin, platelet activating factor and other transmitters. Upon stimulation of these receptors, a signal is transmitted through a guanosine triphosphate (GTP)-binding protein (G(q)), which then activates the enzyme phospholipase C. This results in the release of a second messenger, inositol 1,4,5-trisphosphate (InsPinf 3), from membrane inositol phospholipids. InsPinf 3 then causes the release of free intracellular calcium into the cytosol, activating a number of enzymes or receptors. Myo-inositol in the brain is derived from 3 sources: (i) receptor stimulation (a salvage pathway); (ii) de novo synthesis from glucose; and (iii) uptake of dietary myo-inositol through plasma membrane myo-inositol transporters. Most myoinositol is probably derived from the first 2 sources, which are controlled through the lithium-sensitive enzyme myo-inositol monophosphatase (IMPase). This enzyme acts upon myo-inositol monophosphates, hydrolysing them to release free myo-inositol . Recent biochemical, molecular and crystallographic studies have demonstrated that the overall metabolism of brain inositol is closely modulated by this enzyme. Lithium salts, which are commonly used in various psychiatric conditions, inhibit this enzyme, and this action has been implicated as a therapeutic mechanism of action of lithium. A change in the availability of CNS inositol may lead to altered brain cell signalling pathways and, eventually, to the development of a neuropsychiatric disorder. Recent evidence indicates that myo-inositol has psychoactive effects, with initial studies demonstrating effectiveness in the treatment of depression, panic disorder and obsessive - compulsive disorder. At present, the exact mechanism of these clinical effects is uncertain. The development of various inositol system-based drugs may lead to future psychoactive drugs designed to modulate a second messenger cascade of events rather than a receptor system, and will lead to further understanding of CNS disease from a post-receptor second messenger perspective.

Rasmussen SA
Am J Psychiatry (United States) Oct 1984, 141 (10) p1283-5

Obsessive -compulsive patients with symptoms resistant to clomipramine were treated by lithium or L -tryptophan augmentation. The improvement noted supports the hypothesis that increasing serotonergic neurotransmission ameliorates obsessive symptoms.

Hermesh H; Weizman A; Shahar A; Munitz H
Geha Psychiatric Hosp, Beilinson Medical Ctr, Sackler School of Medicine, Tel Aviv Univ, Israel.
Acta Psychiatr Scand (Denmark) Jul 1988, 78 (1) p8-10

Vitamin B12 and folate serum levels were studied in 30 patients with obsessive compulsive disorder (OCD), and in two control groups comprised of 30 chronic schizophrenics and 30 normal healthy subjects. Six patients (20%) of the OCD group had abnormal low levels of vitamin B12. This prevalence was significantly higher than that of the control groups. No clinical neurological or haematological abnormalities accompanied the reduced vitamin B12 levels. Possible implication of this finding for the pathophysiology of OCD in a subgroup of patients and the possibility that the B12 deficiency could be the consequence rather than the cause of OCD are suggested.

Bajulaiye R.; Addonizio G.
New York Hospital-Cornell Medical Center, Westchester Division, 21Bloomingdale Road, White Plains, NY 10605 United States
International Journal of Geriatric Psychiatry (United Kingdom) 1992, 7/2 (139-142)

Presented is the case of a 75-year-old woman with obsessive compulsive disorder with an unusual age of onset at age 72 years. The patient was resistant to various treatments, but responded to lithium augmentation of fluoxetine.

Ruegg R.G.; Evans D.L.; Comer W.S.; Golden R.N.
Psychiatry Dept, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160 US
Lithium (United Kingdom) 1992, 3/1 (69-71)

Fluoxetine is a potent serotonin uptake inhibitor effective in the treatment of obsessive compulsive disorder (OCD). However, clinical response is often partial. Lithium carbonate (Li) has been used to potentiate clomipramine and doxepine treatment of OCD. We report our experience using Li to augment fluoxetine in four OCD patients

Hahn G.
Engelstrasse 18,W-8520 Erlangen Germany
Fortschritte der Medizin (Germany) 1992, 110/9 (86)

No abstract.

Uebelhack R, Franke L, Schewe HJ
Department of Psychiatry, Humboldt-Universitat zu Berlin (Charite), Germany.
Pharmacopsychiatry 1998 Sep;31(5):187-92

Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.