Timing and the rhythm of the mind.
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Journal Article↗
Biomedical subjects
J Zohar
Publications and source records attributed to J Zohar.
Posttraumatic stress disorder: diagnosis and epidemiology, comorbidity and social consequences, biology and treatment.
Epidemiological studies clearly indicate that posttraumatic stress disorder (PTSD) is becoming a major health concern worldwide even if still poorly recognized and not well treated. PTSD commonly co-occurs with other psychiatric disorders, and several symptoms overlap with major depressive disorders, anxiety disorders and substance abuse; this may contribute to diagnostic confusion and underdiagnosis. This anxiety disorder provokes significant occupational, psychiatric, medical and psychosocial disability, and its consequences are enormously costly, not only to the survivors and their families, but also to the health care system and society. Work impairment associated with PTSD is very similar to the amount of work impairment associated with major depression. The pathophysiology of PTSD is multifactorial and involves dysregulation of the serotonergic as well as the noradrenergic system. A rational therapeutic approach should normalize the specific psychobiological alterations associated with PTSD. This can be achieved through the use of antidepressant drugs, mainly of those that potentiate serotonergic mechanisms. Recent double-blind placebo-controlled studies report the efficacy of selective serotonin reuptake inhibitors. Several cognitive-behavioral and psychosocial treatments have also been reported to be efficacious and could be considered when treating PTSD patients.
Antidepressive Agents↗
Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.
OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.
Adolescent↗
Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways.
Obsessive-compulsive disorder (OCD) is a severe and disabling anxiety disorder with a marked genetic contribution. Pharmacological data indicated involvement of the serotonergic and dopaminergic systems. We studied the association between OCD and six candidate genes encoding important components of the serotonergic and dopaminergic pathways in 75 biologically unrelated patients and 172 ethnically matched controls (Ashkenazi and non-Ashkenazi Jews). Polymorphisms in the following genes were studied: tryptophan hydroxylase (TPH), serotonin 2A receptor (HTR2A), serotonin 2C receptor (HTR2C), serotonin transporter (5-HTT), dopamine receptor D4 (DRD4), and dopamine transporter (DAT1). The genotypic and allelic distribution of all polymorphisms tested did not show statistically significant differences between patients and controls. Our results suggest that these polymorphisms do not play a major role in the genetic predisposition to OCD, although a minor contribution cannot be ruled out.
Carrier Proteins↗
Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial.
The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.
Adrenergic beta-Antagonists↗
Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors.
OBJECTIVE: Anxiety disorders are the most common mental health disorders. While the older tricylic antidepressants (TCAs) are efficacious in the treatment of many anxiety disorders, recent studies with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have emphasized the role of serotonin in the aetiology of these conditions. METHOD: We reviewed the efficacy, safety and tolerability of TCAs and SSRIs in the treatment of the most common anxiety disorders, specifically, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder. RESULTS: Both the TCA and SSRI antidepressants are effective in treating a wide variety of anxiety disorders. SSRIs, due to their greater safety and tolerability, should be the preferred choices in treating anxiety disorders in those instances where TCAs and SSRIs are considered equally effective. In the cases of OCD and social phobia, SSRIs are almost always preferable given that the TCAs do not appear effective in these disorders. CONCLUSION: Further research is needed on the naturalistic long-term use of the TCAs and SSRIs in the treatment of anxiety disorders.
Antidepressive Agents, Tricyclic↗
Obsessive compulsive disorder: serotonin and beyond.
OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder--about 2% of the population suffer from OCD--and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.
Dopamine↗
Increased olfactory sensitivity in first episode psychosis and the effect of neuroleptic treatment on olfactory sensitivity in schizophrenia.
Olfactory sensitivity to two odorants, isoamyl acetate and androstenone, was assessed in 19 male schizophrenic patients and 10 control subjects. Tests were performed during a drug-free period and 2-3 weeks after initiation of neuroleptic drug therapy. Olfactory sensitivity in schizophrenic patients was significantly impaired during the drug-free period and neuroleptic treatment further reduced olfactory sensitivity in these patients. The same olfactory tests were administered to 22 first-episode-psychosis patients, 12 first-episode-schizophrenia and 10 brief-psychotic-disorder patients, as well as to 20 age-matched control subjects. The first-episode-psychosis patients had significantly higher sensitivity to isoamyl acetate and to androstenone, but the incidence of anosmia to androstenone was not higher in the first episode patient group as compared to the control group. We conclude that olfactory dysfunction in schizophrenic patients, and possibly other forms of psychosis, is mainly due to long-term effects of commonly used neuroleptic drugs.
Acute Disease↗
Is there sexual dimorphism in obsessive-compulsive disorder?
The present review addresses the question of sexual dimorphism in obsessive-compulsive disorder. It enumerates examples that could be interpreted to suggest the existence of such dimorphism from the fields of epidemiology, phenomenology, pharmacology, neuropsychology, neuroimaging and genetics. We conclude that data, at this point, are too scarce to warrant a firm conclusion. On the contrary it seems that there are enough indications in the literature that hint at the possibility of sexual dimorphism to stimulate further research in the field.
Female↗
Treatment resistant depression: methodological overview and operational criteria.
A wide variety of definitions are used for Treatment Resistant Depression (TRD), considering various criteria and different concepts. Some of the key issues are: the diagnosis, the treatment adequacy in terms of dose and duration, the treatment response assessment and the number of failed therapeutic trials required. Systematic research has been characterizing the concept and criteria to define the different variables involved. Lack of consensus on these issues limits comparison across clinical trials and interpretation of treatment efficacy in the management of treatment resistant patients. Through reanalyzes of available data, we point out the limits of TRD definitions and propose conceptual and operational criteria for a collaborative research project on TRD. It appears that a number of variables commonly associated to treatment resistance are independent of patients characteristics and mainly refer to misdiagnosis and inadequate treatment. The proposed criteria are intended for therapeutic trials in TRD, combining the evaluation of treatment efficiency and the validation of the concept of TRD itself. Major depression with poor response to two adequate trials of different classes of antidepressants is proposed for an operational definition of TRD. Rationale for this definition is discussed in contrast to alternative definitions.
Antidepressive Agents↗
A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder.
OBJECTIVE: To compare the efficacy of clomipramine hydrochloride (CMI), a serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD). METHOD: Following a 2-week, single-blind placebo washout phase, 17 PD outpatients completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key outcome measures included panic attacks frequency, the NIMH Global Scales for Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger State Anxiety Scale. RESULTS: Both CMI and DMI led to significant improvement from baseline placebo state in panic attacks frequency and behavioral ratings (p<0.001). CMI led to a greater reduction in the frequency of panic attacks (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety, Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No difference was found between the drugs on the NIMH Global Impairment Scale and the Hamilton Somatic and Psychic Scales. CONCLUSION: Both drugs appeared to have significant therapeutic effects in patients with PD, but CMI appeared to be more effective. The effectiveness of the serotonergic drug suggests that the role of the serotonergic system in the pathogenesis of PD should be further explored.
Adult↗
Evidence for striatal modulation in the presence of fixed cortical injury in obsessive-compulsive disorder (OCD).
A patient with obsessive-compulsive disorder (OCD) onset resulting from a traumatic head injury underwent longitudinal brain imaging evaluation. Structural and functional brain imaging studies were repeatedly performed before and after treatment. Computerized tomography (CT) demonstrated bilateral prefrontal contusions immediately following the trauma and prior to the onset of OCD. Magnetic resonance imaging (MRI) demonstrated bilateral cortical abnormalities in the prefrontal and anterior-temporal regions a few months following the onset of OCD. Almost concurrently, single photon emission computerised tomography (SPECT) demonstrated bilateral perfusion deficits in fronto-temporal regions, and asymmetric increased perfusion in the anterior striatum. Six months later, after clinical improvement, a second SPECT study demonstrated improvement of brain perfusion, mostly in the striatum. The reflection of these results on a possible model of brain pathogenesis in OCD, and the role of brain imaging in neuropsychiatric evaluation, are demonstrated.
Adult↗
Orbitofrontal cortex dysfunction in obsessive-compulsive disorder? II. Olfactory quality discrimination in obsessive-compulsive disorder.
BACKGROUND: Olfactory quality discrimination is a putative marker of orbitofrontal cortex function in mammals. As this portion of the cerebral cortex was repeatedly implicated in the pathophysiology of obsessive-compulsive disorder (OCD) this study was designed in an attempt to quantify this behavioural function in OCD patients. METHODS AND RESULTS: Olfactory quality discrimination was compared in OCD patients and healthy controls. Thirty two subjects participated in the study: 16 (13 women and 3 men) medication free OCD outpatients and 16 sex and age matched healthy controls. Olfactory tests consisted of determination of detection thresholds to isoamyl acetate, and a three way forced choice quality discrimination task, using isoamyl acetate, citral and eugenol as stimuli. No significant differences in sensitivity and performance of the quality discrimination task between the two groups were found. Within the OCD group the more severely affected patients (Y-BOCS>29) performed significantly better than the less severely affected (Y-BOCS<30) patients on the more difficult part of the quality discrimination task. Within this subgroup of patients the correlation between performance on the olfactory task and a previously reported alternation task tended to be negative as compared to a significantly positive correlation in the control group. CONCLUSIONS: It seems that olfactory quality discrimination may prove to be a useful noninvasive marker of prefrontal cortex function in OCD. Furthermore, the organization of functional modules within the orbitofrontal cortex, rather than a simple dysfunction, may prove to characterize OCD.
Adolescent↗
Orbitofrontal cortex dysfunction in obsessive-compulsive disorder? I. Alternation learning in obsessive-compulsive disorder: male-female comparisons.
BACKGROUND: We have previously reported a significant negative correlation between severity of symptoms and performance of an alternation learning task in female obsessive-compulsive disorder (OCD) patients. The present study was aimed at exploring this relationship between alternation learning and OCD symptom severity in male OCD patients. METHODS AND RESULTS: Eighteen female obsessive-compulsive disorder patients and 14 male non-depressed, drug free, OCD patients participated in the study. Measures of dorsolateral prefrontal function (Wisconsin Card Sorting Test) and orbitofrontal cortex function (object alternation learning) showed no significant differences between the sexes. The relationship between orbitofrontal cortex function and severity of OC symptoms was significantly different between the sexes (z=2.44. P=0.007). While this correlation was negative in the females it was positive in the males. CONCLUSIONS: These results may indicate sexual dimorphism in OCD.
Adult↗
Response to missile attacks on civilian targets in patients with panic disorder.
BACKGROUND: The complex interaction that exists between biological and cognitive factors determines the reaction of panic-disorder patients to stressors. The current study was conducted to systematically assess the behavioral effects of a real, life-threatening event on panic-disorder patients. METHOD: Sixty-five panic-disorder patients completed structured telephone interviews during the first 4 weeks of the Persian Gulf War. Evaluation included frequency of panic attacks, anxiety levels, and function levels both during and between air raid alarms. RESULTS: The findings indicate that panic-disorder patients, despite high levels of anxiety, did not demonstrate an increased frequency of panic attacks during the Persian Gulf War. In addition, the majority of patients reported good-to-high levels of functioning during the crisis in both everyday and alarm-related functioning. Grouping of subjects according to proximity to risk or current antipanic treatment did not produce significant differences in the frequency of panic attacks or levels of anxiety. CONCLUSION: The findings suggest that vulnerability of patients with panic disorder to a "panic-stricken" response does not increase during real-life stressors. The lack of increased frequency of panic attacks observed under these circumstances provides additional support for the opinion that panic and fear are two distinct entities.
Adult↗
Healing environment in psychiatric hospital design.
Mental health professionals have long speculated that the physical environment in which treatment occurs has an impact on both the treatment process and its outcome. The few empirical studies that evaluated the effects of psychoenvironmental design have shown encouraging results and demonstrated clinically desirable behavioral changes and even reduced psychopathology. In view of the concept that architecture is a tool in the therapeutic process, the design and execution of the psychiatric hospital in the Chaim Sheba Medical Center at Tel-Hashomer, Israel, were conducted by a multidisciplinary team of architects, mental health professionals, and administrators. The hospital contains three acute inpatient wards and a day care and large outpatient clinic. Its operation began in 1991. This paper deals with the merging of "user-friendly" architectural and environmental design components that create an integral healing environment. The paper discusses the positive effects of specific components on patients and staff, and suggests that our model of psychoenvironmental approach to psychiatric hospital design can provide an important and effective tool in the pursuit of a humane, efficient containment and reduction of severe psychopathology.
Architecture↗
Generalized seizures caused by fluoxetine overdose.
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Adult↗
Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan.
The serotonergic system has been implicated in both the aetiology and pharmacological treatment of obsessive compulsive disorder. In pharmacological challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT2C as well as 5HT1A and 5HT1D receptors, was associated with a transient exacerbation of obsessive compulsive symptoms. Chronic administration of mCPP was found to bring about some relief of these symptoms. Sumatriptan is an antimigraine agent, which interacts most potently with 5HT1D receptors. In the cases to be presented, we report the effects of chronic administration of Sumatriptan to three severe, treatment resistant, OCD patients. Following chronic administration of sumatriptan, these patients, who have been resistant to any former pharmacological treatment, responded with an improvement in their depression and a modest reduction in their obsessive compulsive symptoms.
Adult↗