Management commentary

It is perhaps prudent to preface any discussion about this diagnostic category by standing back and looking at diagnoses more broadly. In no other branch of medicine does pathophysiology linearly track phenomenology, yet we are limited to phenomenological-based diagnostic boundaries. Biomarkers have shown scant respect for the most commonly used diagnostic categories, and treatments too have minimal diagnostic specificity. The only clear caveat perhaps is lithium, whose profile of efficacy is in the domain of classical bipolar disorder and the cyclical recurrent mood disorders. For the rest, we need to acknowledge that we are parsing the clouds on an overcast day. The counterpoint is that we need to make major clinical and treatment decisions on the basis of a very incomplete evidence base, drawing on the basis of experience, interpretation and bias simultaneously from the bipolar and unipolar literature, without a clear pathophysiological foundation

Molecular hydrogen: an overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia

Hydrogen gas is a bioactive molecule that has a diversity of effects, including anti-apoptotic, anti-inflammatory and anti-oxidative properties; these overlap with the process of neuroprogression in major psychiatric disorders. Specifically, both bipolar disorder and schizophrenia are associated with increased oxidative and inflammatory stress. Moreover, lithium which is commonly administered for treating bipolar disorder has effects on oxidative stress and apoptotic pathways, as do valproate and some atypical antipsychotics for treating schizophrenia. Molecular hydrogen has been studied pre-clinically in animal models for the treatment of some medical conditions including hypoxia and neurodegenerative disorders, and there are intriguing clinical findings in neurological disorders including Parkinson’s disease. Therefore, it is hypothesized that administration of hydrogen molecule may have potential as a novel therapy for bipolar disorder, schizophrenia, and other concurrent disorders characterized by oxidative, inflammatory and apoptotic dysregulation

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

BACKGROUND: Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson\u27s disease, schizophrenia, depression, autism, and chronic fatigue syndrome. DISCUSSION: While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson\u27s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines. SUMMARY: This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders

Medical error

South African Psychiatry Review - May 200

Reproductive hormones as psychotropic agents?

The female preponderance in unipolar mood and anxiety disorders is well documented, with a double to triple lifetime prevalence compared to males. Much of this increased vulnerability is in the childbearing years. Hormones are a tempting explanation, although other biochemical factors such as cytokines may also be important. Psychosocial factors are clearly involved, including role issues.South African Psychiatry Review - May 200

Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature

How to Cite This Article: Ghanizadeh A, Berk M. Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature. Iran J Child Neurol. 2015 Winter;9(1):99-102.AbstractAutism is a disorder of unknown etiology. There are few FDA approved medications for treating autism. Co-occurring autism and epilepsy is common, and glutamate antagonists improve some symptoms of autism. Ceftriaxone, a beta-lactam antibiotic, increases the expression of the glutamate transporter 1 which decreases extracellular glutamate levels. It is hypothesized that modulating astrocyte glutamate transporter expression by ceftriaxone or cefixime might improve some symptoms of autism. This case report of a child with autism and epilepsy suggests a decrease in seizures after taking cefixime.References Selassie AW, Wilson DA, Martz GU, Smith GG, Wagner JL, Wannamaker BB. Epilepsy beyond seizure: a population-based study of comorbidities. Epilepsy Res 2014;108(2): 305-315.Sansa G, Carlson C, Doyle W, Weiner HL, Bluvstein, Barr W, et al. Medically refractory epilepsy in autism. Epilepsia 2011; 52(6): 1071-1075.Ghanizadeh A. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism. Dis Markers; 2013;35(5): 281-286.Yamada T, Kawahara K, Kosugi T, Tanaka M.Nitric oxide produced during sublethal ischemia is crucial for the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures. Neurochem Res 2006:31(1): 49-56.Zeng, LH, Ouyang Y, Gazit V, Cirrito JR, Jansen LA, Ess KC, et al. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2007; 28(2): 184-196.Zeng LH, Bero AW, Zhang B, Holtzman D. M. , Wong M. Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex. Neurobiol Dis 2010; 37(3): 764-771.Nizzardo M, Nardini M, Ronchi D, Salani S, Donadoni C, Fortunato F, et al. Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms. Experimental Neurology 2011; 229: 214–225.Harada M, Taki MM, Nose A, Kubo H, Mori K, Nishitani H and T. Matsuda. Non-Invasive Evaluation of the GABAergic/Glutamatergic System in Autistic Patients Observed by MEGA-Editing Proton MR Spectroscopy Using a Clinical 3 Tesla Instrument. J Autism Dev Disord 2010 Apr;41(4):447-54. doi: 10.1007/s10803-010-1065- 0.Polleux, F. and J. M. Lauder. Toward a developmental neurobiology of autism. Ment Retard Dev Disabil Res Rev 2004;10(4): 303-317.Maezawa I, Jin LW. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 2010;30(15): 5346-5356.Ghanizadeh A. Targeting neurotensin as a potential novel approach for the treatment of autism. J Neuroinflammation 2010;7(1): 58.Ghanizadeh A. Transplantation of GABAergic cell line as a novel hypothesized treatment for autism. Epilepsy & Behavior 2010;19(4): 664.Kim SY, Jones TA. The effects of ceftriaxone on skill learning and motor functional outcome after ischemic cortical damage in rats. Restor Neurol Neurosci 2013;31(1):87-97. doi: 10.3233/RNN-2012-120245.Ghanizadeh A.Could fever and neuroinflammation play a role in the neurobiology of autism? A subject worthy of more research. Int J Hyperthermia 2011;27(7): 737-738.Ghanizadeh A. May lovastatin target both autism and epilepsy? A novel hypothesized treatment. Epilepsy Behav 2011;20(2): 422.Ghanizadeh A. Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism. Eur Rev Med Pharmacol Sci 2012;16(9): 1313-1314.Ghanizadeh A. Physical exercise and intermittent administration of lactulose may improve autism symptoms through hydrogen production. Med Gas Res 2012;2(1): 19.Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi MR, Hassanzadeh E, et al. Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 2013 Jan;225(1):51-9. doi: 10.1007/s00213-012- 2796-8. Epub 2012 Jul 11.Wang DD, Englot DJ, Garcia PA, Lawton MT, Young WL. Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo. Epilepsy Behav 2012;24(3): 314-318.Librizzi L, Noe F, Vezzani A, Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann Neurol 2012;72(1): 82-90.Gasior MK, Nieoczym SD, Wlaz P. Clavulanic acid does not affect convulsions in acute seizure tests in mice. J Neural Transm 2012;119(1): 1-6.Beheshti Nasr SM, Moghimi A, M. Mohammad-Zadeh M, Shamsizadeh A and Noorbakhsh SM. The effect of minocycline on seizures induced by amygdala kindling in rats. Seizure 2013;22(8): 670-674.Erickson CA, Posey DJ, Stigler KA, Mullett J, Katschke AR,McDougle CJ. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 2007;191(1): 141-147.Thabet F, Al Maghrabi M, Al Barraq A, Tabarki B. Cefepime-induced nonconvulsive status epilepticus: case report and review. Neurocrit Care 2009;10(3): 347-351