Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting

N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.<br /

Cognitive and psychosocial impairment in remitted bipolar patients

There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000– March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1) all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2) there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities) and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3) cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long–term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder.There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000- March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1) all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2) there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities) and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3) cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long-term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder

Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat’s life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat’s prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia

Hippocampus size does not correlate with body mass index in bipolar disorder

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Transthyretin: No association between serum levels or gene variants and schizophrenia

It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.http://www.sciencedirect.com/science/article/B6T8T-4K12CM6-2/1/78223a224d1392e250f7562405e6796

Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493)

Effects of N-acetylcysteine on amphetamine-induced sensitization in mice

Objective: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. Methods: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. Results: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Conclusion: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification