Among research projects and theoretical considerations concerning the origin of hallucinations psychological studies play a major role. The latter most frequently deal with auditory hallucinations, being a pathognomonic sign of schizophrenia.
Aim – The paper presents research .findings and clinical observations indicating that hallucinations occur not only in the mentally ill, but also in various mental states associated with disturbance of auditory stimuli perception in healthy individuals.
Review – The article presents results of studies on the features of hallucinations, their contents, and the effect of medication on their alleviation. Psychological theories are based on a wide spectrum of disorders in the mechanism of information processing. A review of these theories suggests that hallucinations result from disturbances at various stages of this process. While some authors believe that it is disturbance of the stimulus input (due to attention disorders, affective attitudes, or receptor deficits) that is responsible for hallucinations, others consider semantic memory impairment (i.e. information retrieval from long-term memory) to be their source. Moreover, the role of a number of other factors is emphasized, including disorders in the process of planning or in perception of context; cultural influences or the pressure of the social environment.
Conclusions – An analysis of these concepts suggests that disturbances at any stage of information processing may contribute to the development of hallucinations. It should be assumed with some caution that prevalence of disturbances at some stage may depend on many factors stage as personality, anatomical, biochemical and psychophysiological efficiency of the CNS functioning, social influences, and adaptation.
Aims – Firstly, to establish whether the amounts of superoxide radicals and other reactive oxygen species (ROS) generated by blood platelets are the same in individuals with schizophrenic disorders and in healthy volunteers, and secondly, to assess the amount of superoxide radicals and other reactive oxygen species (ROS) produced in platelets stimulated with a strong agonist, such as thrombin.
Subjects – Participants in the study were 42 patients (24 men and 18 women) aged 18-36, hospitalized for schizophrenic disorders of paranoid type (according to DSM-IV criteria), and 31 healthy volunteers (students and staff members of the Medical University in Łódź) matched for age and gen der.
Method – Superoxide radical generation was measured using the method described by Jahn and Hansch, while production of other reactive oxygen species (i.e. H2O2, singlet oxygen, hydroxyl free radicals, organic free radicals) – by means of chemiluminenscence.
Results – A significant increase in ROS generation was found in patients with schizophrenic disorders. Moreover, they differed from the healthy controls both in their superoxide radical generation and in the blood platelet response to thrombin stimulation.
Discussion – The results suggest oxidative stress in blood platelets of individuals with schizophrenic disorders. The findings correspond to these reported by other authors indicating the presence of various oxyreductive disorders in persons with schizophrenia. Blood platelet reactivity to thrombin stimulation noted in in vitro studies in persons treated for schizophrenic disorders differs from that in healthy people. The meaning of this finding requires further research.
Conclusions – Oxidative stress and altered reactivity of blood platelets may have a pathophysiological role in schizophrenia.
Vascular dementia is due to brain lesions resulting from vascular dysfunction of various origin. The treatment of vascular dementia usually consists in amelioration of cerebral blood supply.
Aim – to assess clinical efficacy of vinpocetine in relation to its dosage in the treatment of vascular dementia.
Subjects – 58 vascular dementia patients aged 65.8 lat ± 8.7 years.
Method – Vascular dementia was diagnosed according to NINDS-AIREN criteria. Dementia severity was assessed pre – and post-treatment using the Mini Mental State Examination (MMSE) and Clinical Global Impression – CGI scales. Prior to treatment the mean MMSE score was 19.6, while CGI mean score was 3. 72. None of the patients received any long-term nootropic medication during that time. The mean duration of treatment was 189.1weeks.
Results – In patients receiving 30 mg of vinpocetine daily a statistically significant increase was found post-treatment: by 1.3 point on the MMSE and by 37 point on CGI. No significant change in the patients' state was noted in the group treated with 15 mg/daily – their dementia had not aggravated in the course of the follow-up period (i.e. over 3 years on the average). Conclusions – The findings confirm a neuroprotective effect of vinpocetine in vascular dementia. The dose of 15 mg/daily prevents deterioration of vascular dementia, while the dose of 30 mg/daily may result in an improvement of cognitive functions.
Aim – to present some more recent information concerning vascular dementia.
Review – Vascular dementia, an important cause or decline in the functioning of the elderly, is defined as an impairment of cognitive functions resulting from ischemic, ischemic-hypoxic, or hemorrhagic brain lesions. The diagnosis of vascular dementia requires cognitive impairment (often predominantly subcortical), vascular brain lesions demonstrated by imaging, and exclusion of other causes of dementia. Vascular dementia develops usually as a complication of multiple cortical and subcortical strokes, but sometimes is due to a single strategic stroke, multiple lacunes, or hypoperfusive lesions. Some forms of vascular dementia, such as e.g. the CADASIL, are determined by genetic factors. Interventions aimed at risk factors for atherosclerosis and cardiovascular diseases play an important role in both primary and secondary prevention vascular dementia. Management of vascular dementia involves the treatment of atherosclerosis and its complications, as well as administration of anticholinergic medications in order to ameliorate the patients' cognitive functioning.
Aim – the paper presents one or well documented theories of the origin of dementia in Alzheimer's disease, concerning amyloid-beta precursor protein cleavage.
Review – There at least two pathways of this protein proteolytic degradation, i.e. either amyloidogenic, generating amyloid beta, or non-amyloidogenic, generating soluble proteins. Amyloid beta, which is a major component of senile plaques in the brain of patients with Alzheimer's disease, is generated via the amyloidogenic pathway from amyloid-beta precursor protein through its sequential proteolityc cleavage catalyzed by beta- and gamma-secretases. Beta-secretase and gamma-secretase were identified as membrane-tethered aspartyl proteases. The presenilins are required for the proteolytic cleavage catalyzed by gamma-secretase. Mutations in the genes encoding for presenilins and amyloid-beta precursor protein are the cause of early-onset familial Alzheimer's disease. For these reasons secretases are considered an important therapeutic target in Alzheimer's disease.
Conclusion – The proteolytic cascade hypothesis is well documented, but it may relate only to a small part or pathways leading to the pathology of brain injury with subsequent dementia in Alzheimer's disease.
Aims – to discuss the role of glutamatergic transmission abnormality in schizophrenia, with an emphasis on the pathology of the glutamatergic system receptors and on interrelationships between the glutamatergic, dopaminergic and GABA-ergic systems. Moreover, the paper describes the structure and function of glutamic acid receptors, and especially of NMDA receptor, also in the context of experiments with phencyclidine and ketamine.
Review – Numerous research findings suggest an important role of glutamatergic transmission impairment in the pathogenesis of schizophrenia. The action of phencyclidine and ketamine (chemical compounds with a marked affinity to NMDA receptor of the glutamatergic system) results in the onset of symptoms resembling schizophrenia in their clinical pattern. This is regarded as due to an imbalance between the excitiatory action of the glutamatergic system and inhibitory action of the GABA-ergic system, altering function of other neurotransmission systems.
Conclusions – The glutamatergic system dysfunction seems to play and important part in the pathogenesis of schizophrenia. Abnormal function of this system adversely affects the dopaminergic system functioning, which relates to the now commonly accepted dopaminergic hypothesis of schizophrenia. New therapeutic strategies may be developed, since in the field of schizophrenia research various groups became interested in the role of the glutamatergic system.
Aims – to present the use of glycine and its analogues (D-serine and D-cycloserine) in the treatment of schizophrenia, in order to normalize neurotransmission within the glutamatergic system. Moreover, available research results are presented concerning administration of these substances in addition to various neuroleptics, as well as efficacy and safety of such therapy.
Review – Glycine as a co-modulator of glutamatergic NMDA receptor is necessary for its normal functioning. It is assumed that adjunctive glycine in neuroleptic treatment should result in all amelioration of transmission within the glutamatergic system and in consequence– in symptom relief in schizophrenia.
Conclusions – A majority of presented studies indicate beneficial effects of glycine, D-serine and D-cycloserine in schizophrenic patients, especially as regards negative symptoms. Such outcomes was reported particularly when these substances had been added to classical and atypical neuroleptics (except for clozapine). No favourable effects were obtained in clozapine adjuvant therapy, which may be due to a supposed direct action of this medication on NMDA receptor, and to its rivalry with glycine for receptor sites. Safety of the treatment with glycine and its analogues is emphasized.
Objective – In this paper we describe changes occurring in GABA-ergic and serotoninergic systems in anxiety disorders and preclinical models of anxiety.
Review – The presented results underlie the importance of GABA-ergic and serotonergic interactions in anxiety disorders. Existing experimental data report the decreased number of GABA-A receptors in patients suffering from anxiety disorders. Moreover, the preclinical and clinical studies confirm the importance of serotonergic system in anxiety reactions. The role of serotonergic transmission in anxiety reactions is variable and depends on the activated structure and receptor type. The changes in GABA-ergic and serotonergic systems in anxiety disorders are more than empirical facts since the main drugs used in the treatment of anxiety are those acting on GABA-A receptors (benzodiazepines), 5-HT1A receptors (buspiron) and serotonin transporter (selective serotonin reuptake inhibitors).
Conclusions – The data confirm the importance of GABA-ergic, serotonergic systems and interactions between these systems in occurrence and treatment of anxiety disorders.
Aim – to outline the role of β-endorfin in alcohol addiction syndrome.
Review – β-endrfin, all endogenous opioid peptide, is functionally connected with the mesolimbic reward system playing the most important part in alcohol addiction. The system consists of positive (reward) and negative or aversive (punishment) reinforcement. Imbalance between the two components of the system is responsible for the individual's seeking drugs to restore the balance. One of the ways may involve the endogenous opioid system activation. Clinical observations and laboratory studies have shown that alcohol consumption increases concentration of endogenous opioid peptides. Persons at high risk for alcohol abuse (as determined by their family history), as compared to a low risk group, had by about 50% lower basal plasma β-endorfin concentration. Alcohol consumption results in an increase in this peptide level, compensating for its deficiency. Alcoholics were found to have decreased levels of β-endorfin both in the early and late phase of abstinence. Moreover, laboratory studies indicate differences between alcohol-preferring and alcohol-avoiding animals in β-endorfin levels. Clinical and laboratory observations suggest that certain genetic factors (single-nucleotide polymorphism) may increase the individual's vulnerability to alcohol abuse.
Conclusions – It is possible that decreased β-endorfin plasma concentrations and decreased activity of the opioid system may facilitate alcohol abuse rather than result from alcoholism. This problem may be important in the treatment of patients with alcohol addiction.
Aim – to present a review of the literature on posttraumatic epilepsy, one of the major complications after cranio-cerebral trauma.
Review – The overall risk of late posttraumatic epilepsy varies from 2% to 23% and clearly depends on head trauma severity. The time interval between trauma and posttraumatic seizures is of various length. Over 50% of late seizures occur within one year of injury, 70-80% within two years. According to many authors, significant risk factors are: loss of consciousness or posttraumatic amnesia of over 24 hours duration, focal signs in the neurological examination and shown in CT, especially in cases of frontal lesions and damage to paraventricular-subcortical structures, intracranial hematoma and diffuse contusion, depressed skull fracture, penetrating injury, or of early posttraumatic seizures. Despite a poor prognostic value of EEG, the presence of paroxysmal activity is a risk factor. In view of the high prevalence rates of posttraumatic epilepsy the issue of preventive treatment is widely disputed.
Conclusions – Current research findings suggest that anti-epileptic treatment should be provided if an early posttraumatic seizure is reported. Moreover, irrespectively of the seizure onset, anti-epileptic drugs should be administered to patients at high risk for posttraumatic epilepsy.
Aim – The authors present most recent results of in vitro and in vivo studies concerning neuroprotective activity of EGb 761.
Review – Numerous studies have been carried out for many years in search for effective methods of prevention and therapy of neurodegenerative processes. Various groups of medicines (i.e. antioxidants, antagonists of glutamatergic receptors, neurotrophic factors, substances adjusting cellular metabolism, inhibitors of apoptosis, and immunosuppressive drugs) may act as neuroprotective agents sweeping away free radicals. EGb 761 activity has a number of underlying mechanisms, with a pivotal role of oxidative stress prevention. Moreover the drug ameliorates cellular metabolism, and inhibits both the process of apoptosis and beta-amyloid toxicity.
Conclusions – Preclinical trials indicate that EGb 761, a standardized Ginkgo biloba leaf extract, can inhibit the development of neurodegenerative processes.
Aim – Psychotic disorders following topiramate administration in five patients diagnosed with epilepsy are reported.
Case reports – in 4 patients organic delusional disorder was diagnosed, and in one case – organic psychosis. The clinical picture in all the patients resembled that of acute epileptic psychosis. Psychotic symptoms developed within 5-7 months since topiramate introduction as add-on therapy in the dose 75-200 mg/d, in combination with carbamazepine or valproate. The onset of psychosis was preceded by such symptoms as loss of appetite, weight loss, concentration, attention and memory impairment, sleep disturbance, and mood disorders. Discontinuation of topiramate treatment and administration of neuroleptics usually led to normalization of the patients' mental state, although this could be attained after various time intervals. \
Comment – The reported findings suggest a relationship between topiramate treatment and development of psychotic disorders. The latter may be due to possibly topiramate-induced disorders in the GABA-ergic system.