L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study.

BACKGROUND: Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. METHODS: Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10. RESULTS: General linear model repeated measure showed significant effects for Time × Treatment interaction on total Y-BOCS [F (2.10, 88.42) = 8.66, p < 0.001], obsession [F (1.88, 79.34) = 4.96, p = 0.01] and compulsion [F (1.88, 79.11) = 4.57, p = 0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86 ± 2.89 (mean ± SD) in the L-carnosine group compared to 5.86 ± 2.88 in the placebo group. CONCLUSION: L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons.

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.

Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial.

BACKGROUND: Major depressive disorder (MDD) exerts a high health and financial burden on society. The conventional pharmacotherapies for MDD are partially effective and the response to medication often starts with some delay. There are recent reports of antidepressant effects for oral ketamine. METHODS: We employed a double-blind controlled trial to examine the time course of the therapeutic effect of ketamine when combined with the conventional administration of sertraline. A total of 81 patients participated in the study and were scored with the Hamilton Depression Rating Scale (HDRS) at baseline and at 2, 4 and 6 weeks after the start of the trial RESULTS: General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HDRS scores, with significant difference at all time points post treatment. Early improvement was significantly greater in the ketamine group (85.4%) compared to the placebo group (42.5%). We did not observe any side effects for ketamine administration. LIMITATIONS: Our follow up was limited to 6 weeks post initiation of treatment and cannot reveal the potential long-term adverse effects of oral ketamine and the sustainability of its benefit. CONCLUSION: Altogether, our results suggest that oral ketamine may be considered as suitable adjuvant to sertraline in relieving depressive symptoms.

Acetaminophen as Adjuvant to Risperidone in Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: Although the pathogenesis of schizophrenia is still uncertain, a variety of predisposing mechanisms have been implicated including inflammatory cascades. The present study was conducted to investigate the effectiveness of acetaminophen as a cyclooxygenase inhibitor in treating patients with schizophrenia. Method: A double-blind clinical trial was performed on 52 patients with chronic schizophrenia. Patients received risperidone (up to 6 mg/day) plus either acetaminophen (975mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6, and 8 weeks post therapy. Results: Compared to the placebo group, the acetaminophen group showed no significant difference in any subtypes of PANSS. Moreover, the side effect profiles of the 2treatment regimens were not significantly different. Conclusion: Acetaminophen adjuvant to risperidone showed no significant effect in ameliorating symptoms of schizophrenia. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (registration number: IRCT201410251556N67).

Single whisker experience started on postnatal days 0, 5 or 8 changes temporal characteristics of response integration in layers IV and V of rat barrel cortex neurons.

Neonatal single whisker experience changes the response properties of spared barrel neurons to deflections of principal and adjacent whiskers. However little is known about the temporal characteristics of the paired whisker inputs. To address this issue we used computer controlled mechanical displacement of paired whiskers in control and plucked animals (plucking of all whiskers but D2 started at 0, 5 and 8 postnatal days). The principal whisker (PW) and its caudal adjacent whisker (AW) were deflected simultaneously or serially at different inter-stimulus intervals (10, 20, 30, 50 and 100 ms). Neuronal responses were recorded in D2 spared barrel both in layers IV and V. In the control group, combined deflection of AW prior to PW led to suppression of ON and OFF responses to PW deflection both in layers IV and V. The magnitude of this suppression was strongly dependent on the inter-stimulus intervals (ISIs). At almost all tested ISIs, whisker plucking from P0, P5 and P8 weakened suppressive interactions in layers IV and V barrel neurons for both ON and OFF responses. The most decrease in inhibitory interactions was observed in P5 plucked animals. Principal whisker-evoked ON responses were increased only in P0 plucked animals both in layers IV and V. AW-evoked ON responses are decreased in P5 plucked animals in layer IV. The available data suggest that sensory experience can modulate temporal aspects of response integration and receptive field properties of layers IV and V neurons in barrel cortex. These changes have different critical periods.

Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. METHOD: A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. RESULTS: Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). CONCLUSIONS: Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

The Effect of Clinical Exposure to Patients on Medical Students' Attitude Towards Mental Illness.

BACKGROUND: Stigma of mental disorders causes a reduction in seeking help from the health care professionals and is evident across the world. OBJECTIVES: The current study aimed to compare medical students' attitude towards mental illness after two different psychiatry clerkships in terms of the level of clinical exposure to patients with mental illness. PATIENTS AND METHODS: Through a quasi-experimental study, all of the 4th-year medical students were invited to enroll this study conducted in Tehran University of Medical Sciences (TUMS). They were non-randomly assigned into two different psychiatry clerkships from January 2009 to January 2010. One group was enrolled in the traditional lecture-based course (low-exposure) while the second group participated in a novel method with increased hours of patient exposure (high-exposure). Attitude towards mental illness (AMI) was measured by a 22-item questionnaire before and after the clerkship and data were compared between the two groups in terms of changing attitude towards mental illness in five different categories. RESULTS: A total of 211 participants were enrolled in the study (115 female) of which 115 students (54.5%) were in low-exposure group and 96 students (45.5%) in the high-exposure group. Generally, AMI scores did not differ between the two groups and did not show any significant changes before and after the psychiatry clerkship. The only exceptions to this were AMI4 category (the concept of etiology of the mental illness), which significantly improved after the clerkship in the low-exposure (P = 0.011) and the high-exposure groups (P = 0.024), respectively. CONCLUSIONS: Exposure of medical students to patients with mental illness did not improve attitude towards mental illness and psychiatric conditions.

Correlation of neurological soft signs and neurocognitive performance in first episode psychosis.

Neurological soft signs and neurocognitive impairments are commonly observed in first episode psychosis but the correlation of these factors remains controversial. Here, we evaluated 30 patients with remitted first episode psychosis and 30 healthy controls for the presence and severity of neurological soft signs (using the Neurological Evaluation Scale--NES) and for neurocognitive impairments (using seven subtests of the Cambridge Neuropsychological Test Automated Battery--CANTAB). NES score was higher in patients compared to controls. Neurocognitive impairment was evident in patients in the following domains: working memory, spatial recognition memory, attention set shifting, planning and inhibition. The NES revealed significant correlations with spatial working memory performance and Intra-Extra Dimensional Set Shifting (as a component of executive function). These correlations were observed both in patients and in controls. Planning and inhibition showed correlation with the total NES score and the sequencing of complex motor acts in both groups. In addition, spatial span and spatial recognition memory showed significant correlation with total NES score and the sequencing of complex motor acts in controls. The correlation between sequencing of complex motor acts and specific domains of neurocognitive tasks suggests that similar neuroanatomical substrates might be implicated in these processes.