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Joseph Zohar

Publications and source records attributed to Joseph Zohar.

At least 37 records · Page 2Linked to original sources
PubMed2004

Beyond refractory obsessions and anxiety states: toward remission.

At the Sixth International Obsessive-Compulsive Disorder Conference (IOCDC), held November 13-15, 2003, in Lanzarote, Spain, 2 issues were discussed that are of great importance to future research on obsessive-compulsive disorder (OCD). The first of these is the possible inclusion of obsessive-compulsive spectrum disorders (OCSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. OCSD resemble OCD in their clinical symptoms, associated features, comorbidity, family/genetics, etiology, and neurocircuitry, as well as their selective response to treatment with serotonin reuptake inhibitors. The second issue is considering remission as the ultimate goal of treatment for OCD instead of just symptom reduction, as has been suggested in other disorders. These and other issues should be discussed at future meetings of the IOCDC and influence how we conceptualize the disorder and design future treatment trials.

Anxiety Disorders↗
PubMed2004

The role of dopamine in obsessive-compulsive disorder: preclinical and clinical evidence.

Obsessive-compulsive disorder (OCD) is a frequent and chronic psychiatric disorder that has been linked closely to the serotonin system mainly because of the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). A limitation of the serotonin hypothesis of OCD is that a substantial number of the patients with OCD show no significant improvement after an adequate trial with SSRIs. There is substantial evidence that these patients may benefit from addition of antipsychotics to their ongoing SSRI treatment, suggesting that dopamine also might play a role in the pathophysiology of OCD. In this review, the preclinical and clinical evidence on the role of dopamine in OCD is summarized.

Animals↗
PubMed2004

Serotonin-1D hypothesis of obsessive-compulsive disorder: an update.

Support for the serotonin-1D (5-HT(1D)) hypothesis of obsessive-compulsive disorder (OCD) and related conditions comes from a variety of sources. Some pharmacologic challenges with the 5-HT(1D) agonist sumatriptan, and case reports in which prolonged administration of 5-HT(1D) agonists was associated with a therapeutic effect, suggest that 5-HT(1D) may play a role in obsessive-compulsive symptoms. Genetic studies have also found that polymorphism of the 5-HT(1D) gene may be preferentially transmitted to those patients with OCD. However, taking into account that OCD is a heterogeneous syndrome, the 5-HT(1D) hypothesis requires further investigation in order to disentangle the role of the 5-HT(1D) receptor in this common and often severe disorder.

Humans↗
PubMed2003

Brain reactivity to specific symptom provocation indicates prospective therapeutic outcome in OCD.

A pertinent question in biological psychiatry is what differentiates responders and non-responders to pharmacological treatment. One possibility is that individual differences in the symptomatic spectrum as well as in the underlying biology of the disorder lead to the known 40% failure in pharmacological treatment. Our study aimed to maximize individual brain markers of obsessive-compulsive disorder (OCD) by applying single photon emission computed tomography (SPECT) during a provoked symptomatic state prior to and following treatment. Four brain SPECT scans were obtained from 26 OCD patients prior to and at 6 months of sertraline treatment. At each time point, two SPECT scans were performed in a counterbalanced order of two specific states; one a symptom-provoking condition and the other a relaxed condition. At 6 months of treatment, patients were divided into responders and non-responders according to a predetermined clinical criterion. Prospective responders showed significantly lower brain perfusion in the dorsal-caudal anterior cingulum and higher brain perfusion in the right caudate, when compared to non-responders, only during symptom provocation. When pre- and post-treatment scans during symptom provocation were compared, only responders showed significant change in brain response: increased perfusion in the left anterior temporal cortex and prefrontal cortex at 6 months' treatment. These findings suggest that obtaining functional brain imaging during specific symptom provocation emphasizes individual differences in brain reactivity. Thus can indicate prospective responders to symptom-related treatment in OCD and mark the relevant brain regions for effective response to treatment.

Adult↗
PubMed2003

The relevance of differential response to trauma in an animal model of posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder affects 20%-30% of those exposed. Clinical studies employ stringent inclusion-exclusion criteria, yet animal studies include the entire exposed population as the study population. We examined the effect of grouping prestressed rats according to magnitude of response on the statistical analysis of results. METHOD: Response magnitude to predator exposure was assessed and used to group the animals into "diagnostic" groups. Two extremes were studied (clearly "maladapted" and clearly "well adapted" rats) using arbitrarily selected cutoff behavioral criteria (CBC). The data for the middle group were discarded for reasons of clarity. Hypothalamic-pituitary-adrenal axis and heart-rate variability were analyzed for the entire exposed population and then according to the CBC. RESULTS: A single 10-min exposure to a predator caused fear-related behaviors in only 25.3% of exposed rats. Compared with control subjects and well-adapted exposed rats, maladapted rats exhibited significantly higher plasma corticosterone and corticotropin concentrations, increased sympathetic activity, diminished vagal tone, and increased sympathovagal balance. These differences surfaced only when data were analyzed according to CBC. Animals respond to stress heterogeneously, resembling humans. Overlooking this heterogeneity may obscure the results of data analysis. CONCLUSIONS: Animals can be divided into distinct groups according to magnitude of response and be studied accordingly.

Adrenocorticotropic Hormone↗
PubMed2003

Fluvoxamine as effective as clomipramine against symptoms of severe depression: results from a multicentre, double-blind study.

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated. METHOD: A double-blind, multicentre study was conducted in 86 severely depressed inpatients (>or= 25 on the 17-item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run-in, 86 patients were randomised to receive fluvoxamine or clomipramine (100-250 mg/day) for 8 weeks. RESULTS: Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17-item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (>or= 50% decrease in 17-item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment-related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%). CONCLUSION: Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile.

Adult↗
PubMed2003

Alternation learning in OCD/schizophrenia patients.

In continuation of our previous studies on orbitofrontal cortex function in obsessive compulsive disorder (OCD) we studied a group of OCD patients with schizophrenia in comparison with a group of schizophrenia patients. In order to test orbitofrontal cortex function we again used an alternation learning task. We found no difference between the two groups in the performance of this task. The relationship between severity of OC symptoms and alternation learning was curvilinear. Thus, in the low range of symptom severity the correlation between alternation learning and symptom severity was negative, while in the high range it was positive. The positive correlation in the severely affected patients is essentially the same as that found in severe "pure" OCD patients, which we have previously reported. We conclude that the data indicate independent orbitofrontal cortex function in OCD, irrespective of comorbidity.

Adult↗
PubMed2003

WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults.

What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Adult↗
PubMed2003

WCA Recommendations for the long-term treatment of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a common and disabling condition. In addition to combat-related PTSD, the disorder occurs in civilians exposed to severe traumatic events, with the community prevalence rate for the combined populations reaching as high as 12%. If left untreated, PTSD may continue for years after the stressor event, resulting in severe functional and emotional impairment and a dramatic reduction in quality of life, with negative economic consequences for both the sufferer and society as a whole. Although PTSD is often overlooked, diagnosis is relatively straightforward once a triggering stressor event and the triad of persistent symptoms-reexperiencing the traumatic event, avoiding stimuli associated with the trauma, and hyperarousal have been identified. However, comorbid conditions of anxiety and depression frequently hamper accurate diagnosis. Treatment for PTSD includes psychotherapy and pharmacotherapy. The latter includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Only SSRIs have been proven effective and safe in long-term randomized controlled trials. Current guidelines from the Expert Consensus Panel for PTSD recommend treatment of chronic PTSD for a minimum of 12-24 months.

Antidepressive Agents, Tricyclic↗
PubMed2003

Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge.

Comorbidity in bipolar disorder is the rule rather than the exception more than 60% of bipolar patients have a comorbid diagnosis and is associated with a mixed affective or dysphoric state; high rates of suicidality; less favourable response to lithium and poorer overall outcome. There is convincing evidence that rates of substance use and anxiety disorders are higher among patients with bipolar disorder compared to their rates in the general population. The interaction between anxiety disorders and substance use goes both ways: patients with bipolar disorder have a higher rate of substance use and anxiety disorder, and vice versa. Bipolar disorder is also associated with borderline personality disorder and ADHD, and to a lesser extent with weight gain. As more than 40% of bipolar patients have anxiety disorder, it is indicated that while diagnosing bipolar patients, systematic enquiry about different anxiety disorders is called for. This also presents a therapeutic challenge, since agents that effectively treat anxiety disorders are associated with the risk of induced mania. Therefore, the treating psychiatrist needs to carefully evaluate the potential benefit of treating the anxiety against the potential cost of inducing a manic episode. A possible solution would be to use, when possible, a non-pharmacological intervention, such as a cognitivebehavioural approach. Alternately, it is suggested that the clinician attempts to ensure that the patient receives adequate treatment with mood stabilizers before slowly and carefully attempting the addition of anti-anxiety compounds with a relatively lower risk of mania induction (e.g. SSRIs compared to TCAs).

Anxiety↗
PubMed2003

Neuroimaging communality between schizophrenia and obsessive compulsive disorder: a putative basis for schizo-obsessive disorder?

Four major brain regions have been repeatedly implicated in the pathophysiology of obsessive compulsive disorder (OCD) in in vivo neuroimaging studies: the caudate nucleus, the orbitofrontal cortex, the anterior cingulate gyrus and the mediodorsal thalamic nucleus. The present review describes the neuroimaging studies on schizophrenia, pertaining to these brain regions. Our working hypothesis is that such common brain regions, if dysfunctional in schizophrenic patients, would be candidates for a neural network subserving the newly emerging syndrome of schizo-obsessive disorder. Findings, though, are controversial. We conclude that further studies, aimed at specific monitoring of these brain regions, in patients suffering from the schizo-obsessive syndrome are warranted.

Brain↗
PubMed2003

Noradrenaline in mood and anxiety disorders: basic and clinical studies.

The neurotransmitter noradrenaline is known to be involved in a range of physiological and psychological processes, and dysfunctions of this neurotransmitter system have been implicated in a range of psychiatric disorders. However, the clinical utility of targeting the noradrenergic system in the treatment of such disorders has been somewhat overshadowed by the availability of agents selective for the serotonin system. A number of antidepressants with increased, but varying, selectivity for the noradrenergic system have become available in recent years, including mirtazapine, bupropion and, most recently, the first truly selective noradrenaline reuptake inhibitor, reboxetine. This review brings together current thinking on the role of noradrenaline in the aetiology and therapy of mood disorders to encourage a rational, evidence-based approach to the treatment of such disorders, and to provide suggestions and guidelines for future research in the area.

Animals↗
PubMed2002

Motivation to serve in the military influences vulnerability to future posttraumatic stress disorder.

High motivation and belief in a cause have been reported to be protective against posttraumatic stress disorder (PTSD), while below-average intellectual functioning and poor educational achievements have been reported to increase vulnerability to PTSD. The main goal of this study was to assess the effect of education, and intellectual and behavioral functioning on the risk for future PTSD. Data collected before exposure to trauma, on intellectual and behavioral functioning, and educational achievements of 901 male Israeli adolescents who had performed pre-induction screening tests by the Israeli Draft Board, and were later diagnosed with PTSD, were compared with a control group of adolescents who were not later diagnosed with PTSD. Future PTSD patients had significantly lower intelligence, fewer years of formal education and lower scores on a scale assessing motivation to serve in the military, in comparison with the control group, with effect sizes (ES) ranging from 0.14-0.34. In contrast, future PTSD patients scored significantly higher on a scale assessing social functioning, ES=0.13. However, when controlling for the differences in motivation to serve, all of these differences disappeared. In this cohort, although slightly below average intellectual functioning and formal education, and better social functioning, independently increased vulnerability to suffer from PTSD, these associations disappeared when the future PTSD patients' lower motivation to serve in the military was included in the analysis. This suggests that low motivation to serve in the military might increase vulnerability for PTSD.

Adolescent↗