Imaging studies among schizophrenic patients reveal brain structural alterations. These alterations are present at the beginning of the disease and they can also undergo further progression. The most characteristic changes are: lateral ventricular enlargement and decreased grey matter volume of speciﬁ c areas, mostly in the superior temporal gyrus and in the middle temporal area (nucleus amygdaloideum, hippocampus, parahippocampal gyrus). Less repeatable are results of studies of decreased volumes of frontal and parietal brain lobes. Psychotropic drugs are believed to modulate these changes. The most common alteration after typical antipsychotic drugs is enlargement of basal nuclei. Atypical antipsychotic drugs may cause lesser decrease of grey matter volume, what is visible along with disease progression. Some studies even show increased volume of grey matter in some brain structures, rather after short-term atypical antipsychotic drugs therapy. On the other hand other data conﬁ rm correlation of antipsychotic treatment (particularly long-term treatment) with decrease of grey matter volume and lateral ventricular enlargement. It is also difﬁ cult to differentiate between antipsychotic drugs inﬂ uence and consequences of the disease process. Second generation antipsychotics have some properties indicating their neuroprotective effects, and classical antipsychotics may exhibit neurotoxic effects. Time of treatment is also an important factor – long term observation of treatment may lead to completely different effects than short term observation. Prospective studies among patients in the ﬁ rst episode of treatment so far did not provide evidence of speciﬁ c antipsychotic drugs effects.
The purpose of this paper is to review the results of the neuroendocrine aspects of the ﬁ rst episode of the schizophrenic psychosis. Contemporary neurodevelopmental concept of schizophrenia, factors associated with impaired brain development and structural markers of the disturbance sensitizing the brain to stress factors, which may contribute to the development of psychosis have been discussed. The review of neurohormonal dysfunction in ﬁ rst episode psychosis focuses on three areas: the stress axis, the secretion of prolactin and sex hormones.
Stress can be a factor that initiates the occurrence of psychotic disorders, including the ﬁ rst episode of schizophrenic psychosis. This paper describes the mechanisms regulating the production of stress hormones and the relationship between the levels of stress axis through the feedback system. The data showing the relationship between the onset of psychotic disorders (including ﬁ rst episode of schizophrenia), more severe stress response and larger changes in the hippocampus are presented.
Elevated levels of prolactin (hyperprolactinemia) is common in patients with schizophrenia and is regarded as a side effect of antipsychotic drugs whose pharmacological mechanism is to block DRD2 receptors. Hyperprolactinemia has been found in some patients with ﬁ rst-episode schizophrenia, which had never received antipsychotics. Clinical and molecular genetic analysis seem to indicate that prolactin may be important as a factor in the pathogenesis of schizophrenia, especially in the development of the ﬁ rst episode, in the presence of stress factors.
Changes in sex hormones (estrogen and testosterone) can also be important in the pathogenesis of schizophrenia, including the ﬁ rst episode. Effects of estrogens may be correlated, among others, with the ealier onset of schizophrenia in men compared to women.
Emerging evidence suggests that the immune system may signiﬁ cantly contribute to seizures and epilepsy. The kindling and status epilepticus models of epilepsy provide valuable tools with which to study mechanisms underlying epileptogenesis. Epileptogenesis refers to a dynamic process that progressively alters neuronal excitability and causes reorganization of neuronal networks before the ﬁ rst spontaneous seizure occurs. The inﬂ ammatory changes during epileptogenesis include gliosis and activation of microglia, blood–brain barrier damage and an increase in the expression of proinﬂ ammatory cytokines. Several studies have demonstrated that the activation of proinﬂ ammatory pathways inﬂ uences neurotransmitter systems and neuronal excitability, thereby contributing to epileptogenesis. The inﬂ ammatory pathways represent a promising new target for the development of new drugs, that can prevent epileptogenesis. Various pharmacologic studies report inhibition of seizures and blocking the epileptogenesis by using nonsteroidal anti-inﬂ ammatory drugs and immunosuppressants.
Background. Long-term use of lithium is the best-documented pharmacological prophylaxis of recurrences in bipolar disorder (BD). The beneﬁ cial effect of lithium prophylaxis is associated with a number of clinical and neurobiological factors. This paper attempts to evaluate the effectiveness of lithium prophylaxis in relation to schizotypal personality traits.
Methods. The study included 70 patients with bipolar disorder (49 women and 21 men), aged 31–82 years (59 ± 12 years) who have received lithium carbonate for a minimum of 5 years (5–37, average 15 years). The level of schizotypy and its various dimensions such as unusual experiences, cognitive disorganization, introversion and anhedonia, and impulsive nonconformity were assessed by the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) questionnaire. The results were correlated with the prophylactic efﬁ cacy of lithium assessed, using the so-called Alda scale, in the range of 0–10.
Results. In the whole group, the effectiveness of lithium on the Alda scale was 5,9 ± 2,7 and was similar in women (5,82 ± 2,8) and men (6,1 ± 2,6). The average value of each dimension was also similar in men and women and showed no correlation with age and with the length of lithium administration. Signiﬁ cant negative correlation between the effectiveness of lithium prophylaxis, and severity of cognitive disorganization dimension (r = -0,236 p = 0,025) was demonstrated, whereas no such correlation with other dimensions of schizotypy such as unusual experiences (r = -0,121), introversion and anhedonia (r = -0,166), impulsive nonconformity (r = -0,032) was found. Correlation between the effectiveness of lithium and impulsive nonconformity was positive in men (r = 0,214) and negative in women (r = -0,148) but not statistically signiﬁ cant.
Conclusions. Cognitive disorganization dimension measured by the scale of the O-LIFE is a negative factor associated with long-term efﬁ ciency of lithium in bipolar disorder.
Burning mouth syndrome (BMS) is characterized by chronic burning sensations, pain, paresthesia and dryness within an oral mucosa. BMS can be a variant of neuropathic pain and may be connected with dopaminergic dysfunction of nigrostriatal system. We describe a case of patient with diagnosis of burning mouth syndrome in which a treatment with olanzapine resulted in a rapid, signiﬁ cant improvement of symptoms. The probable mechanism of therapeutic action of olanzapine may be due to the effect of the drug on dopaminergic and histaminergic receptors and, additionally, on noradrenergic and serotonergic receptors.
Trazodone is an antidepressant compound with antagonist 5-HT2 and serotonine transporter properties. It is metabolized by cytochrome CYP3A4. Fluconazole is an antifungal medication and it is characterized by biotransformation by the same cytochrome CYP3A4. The drug-drug interaction between both compounds may increase trazodone efﬁ cacy/toxicity by decreasing trazodone metabolism and clearance.
Case description. An 42-years old men treated systematically with trazodone 150 mg took 1 dose of 100 mg of ﬂ uconazole. The somnolence, fatigue, attention problems and changes in subjective perceiving of speed while driving a car occurred that led to some dangerous trafﬁ c situations.
Connclusion. This description suggest drug-drug interaction between trazodone and ﬂuconazole based on the biotransformation by the same cytochrome CYP3A4. Moreover the interaction was potentially dangerous in the context of daily activities that is driving a car in this case.