Jesús Ramírez-Bermúdez

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy (1H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a 1H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study.

IMPORTANCE Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. OBJECTIVES To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. INTERVENTIONS Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. MAIN OUTCOMES AND MEASURES Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. RESULTS Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. CONCLUSIONS AND RELEVANCE Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.

Possible Mechanisms of Neurodegeneration in Schizophrenia

Brain morphological alterations in schizophrenic patients have led to the neurodevelopmental hypothesis of schizophrenia. On the other hand, a progressive neurodegenerative process has also been suggested and some follow-up studies have shown progressive morphological changes in schizophrenic patients. Several neurotransmitter systems have been suggested to be involved in this disorder and some of them could lead to neuronal death under certain conditions. This review discusses some of the biochemical pathways that could lead to neurodegeneration in schizophrenia showing that neuronal death may have a role in the etiology or natural course of this disorder.

Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders

Dehydroepiandrosterone (DHEA) is synthesized in the brain and several studies have shown that this steroid is a modulator of synaptic transmission. The effect of DHEA, and its sulfate ester DHEAS, on glutamate and GABA neurotransmission has been extensively studied but some effects on other neurotransmitter systems, such as dopamine, serotonin and nitric oxide, have also been reported. This review summarizes studies showing the effect of DHEA and DHEAS on neurotransmitter systems at different levels (metabolism, release, reuptake, receptor activation), as well as the activation of voltage-gated ion channels and calcium homeostasis, showing the variety of effects that these steroids exert on those systems, allowing the discussion of its mechanisms of action and its relevance to psychiatric disorders.

Alzheimer's disease: critical notes on the history of a medical concept.

It is generally accepted that Alois Alzheimer, the German neuropathologist and clinician, discovered the disease that carries his name, after the clinicopathological study of a 51-year-old woman named Auguste D. who presented a dementia syndrome. The pathological study of the brain revealed the presence of neurofibrillary tangles and senile plaques. Emil Kraepelin coined the eponym Alzheimers disease in the 8th edition of his textbook Clinical Psychiatry. However, several critical aspects of this history have been pointed out by historians of psychiatry. This article provides a narrative of the best-known facts leading to the formation of the original concept but also presents an informed discussion of the main critical points: 1. The descriptions of senile plaques and neurofibrillary tangles in the context of dementia before Alzheimers report. 2. The presence or absence of arteriosclerotic changes in the brain of Auguste D. 3. The presence of noncognitive symptoms in August D. 4. The influence of social, political and economic issues in the formation and selection of medical concepts.

Epilepsy and multiple sclerosis: Increased risk among progressive forms

Multiple sclerosis (MS) patients are at higher risk for epilepsy. Epilepsy was frequent among our MS patients (6.55%). Progressive MS forms were associated with higher incidence of epilepsy (p=0.021). Partial motor seizures were observed in five patients (62.5%) and generalized tonic-clonic in three (37.5%). Electroencephalogram (EEG) revealed epileptic activity in 62.5%. A high percentage of MS patients with epilepsy (37.5%) reported intoxication as the most severe form of adverse effect of antiepileptic therapy.

Cerebrospinal fluid homovanillic acid is correlated to psychotic features in neurological patients with delirium

OBJECTIVE The aim of this study was to determine if cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) are related to the clinical features of delirium in a group of patients with acute onset neurological illness. METHODS Fifty-one patients with probable acute brain infection were classified as delirious and nondelirious according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) and Delirium Rating Scale (DRS). CSF HVA concentration was analyzed by high-performance liquid chromatography. RESULTS Delirium was present in 60.8% of the total sample. HVA levels were not significantly different between delirious and nondelirious patients. Remarkably, patients with psychotic symptoms shown higher levels of CSF HVA as compared to nonpsychotic patient values. In addition, HVA levels were positively correlated to specific items of DRS such as delusions (r=0.463, P=.001), hallucinations (r=0.438, P=.001), cognitive dysfunction (r=0.286, P=.042) and fluctuation of symptoms (r=0.280, P=.046) in the total sample. Subanalyses excluding patients taking antipsychotic drugs revealed that HVA CSF levels were higher in those patients with delusions, and furthermore, the dopamine metabolite remained positively correlated to delusion subscale of DRS. CONCLUSIONS Our results suggest that psychotic symptoms in delirious patients may be related to increased dopamine neurotransmission, as reflected by increased CSF HVA concentration, providing direct evidence to support the dopaminergic theory of psychosis.

Severe impulsiveness as the primary manifestation of multiple sclerosis in a young female

Abstract  Severe impulsiveness in the absence of apparent neurological signs has rarely been reported as a clinical presentation of multiple sclerosis (MS). An 11‐year‐old female developed progressive and sustained personality disturbances including disinhibition, hypersexuality, drug abuse, aggressiveness and suicide attempts, without neurological signs. She was given several unsuccessful psychopharmacological and psychotherapeutic interventions. At age 21, a diagnosis of MS was made, confirmed by imaging, laboratory and neurophysiological studies. Although unusual, MS may produce pure neurobehavioral disturbances. In the present case, widespread demyelinization produced a complex behavioral disorder, with features compatible with orbitofrontal and Klüver–Bucy syndromes.

Schizophrenia-like psychosis associated with right lacunar thalamic infarct

Thalamic dysfunction has been associated with schizophrenia and other psychotic disorders. We describe an adult patient with a lacunar infarct in the posterior region of the right thalamus exhibiting a paranoid schizophrenia-like psychosis as the only clinical manifestation. Neuropsychological assessment showed alterations in visuospatial memory and executive functions at follow up. This case highlights the role of information processing by the thalamus in the development of delusions. We suggest that dysfunction of the right mediodorsal and pulvinar thalamic nuclei disrupts both thalamic sensory processing and thalamo-prefrontal circuits mediating belief evaluation, leading to delusional beliefs.

Delusional parasitosis in neurological patients

OBJECTIVE Delusional parasitosis has been described in a wide range of patients with general medical conditions, but there are few reports about its frequency and possible pathogenic mechanisms in neurological patients. This paper describes this delusional syndrome in a sample of neurological patients. METHODS We reviewed all clinical charts of hospitalized patients at the neuropsychiatry ward of a neurological center, from January 2005 to June 2009. Cases with delusional parasitosis were described in terms of demographic, clinical and brain imaging features. RESULTS From a total sample of 1598 patients, we identified 636 patients with neurological disease (39.80%); of these, four patients showed delusional parasitosis (0.62% of the neurological sample). Their diagnoses were brain cysticercosis (n=1), cerebrovascular disease (n=2), and dementia due to vitamin B12 deficit (n=1). They were women in late life, with depressive features. Three of them had significant cognitive decline. Two of them had paraesthesia and pruritus related to peripheral neuropathy. One of them had pruritus of unknown origin (possibly hallucinatory). CONCLUSIONS Delusional parasitosis was infrequent in this sample of hospitalized neurological patients. Female sex, advanced age, depressive features, cognitive decline, pruritus and paraesthesia of peripheral or central origin may contribute to delusional parasitosis in this population.