Elias Angelopoulos

Indication of increased phase coupling between theta and gamma EEG rhythms associated with the experience of auditory verbal hallucinations

Electroencephalographic oscillations, with different spectral contents, recorded in various brain sites are assumed to play an important role in the information processes underlying cognition as well as the abnormal brain functioning observed in nosological entities that affect neuronal connectivity such as schizophrenia. In the present study we investigated the interaction of EEG rhythms during the experience of auditory verbal hallucinations (AVHs). For this purpose we analyzed data obtained from patients suffering from persistent AVHs, focusing on the mode that the phase of theta oscillations modulate the amplitude of the broad gamma EEG oscillations. Our results indicate increased phase coupling between theta and gamma rhythms observed in the left frontotemporal cortices during AVHs, under eyes closed condition. The average differences of theta-gamma coupling between hallucinatory and resting stages in the left temporal area were found to be statistically significant. These results suggest that a theta-gamma interaction may be involved in the production and experience of AVHs in patients suffering from schizophrenia.

Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia

There is evidence that the duration of untreated psychosis may affect both the course and outcome of treatment in schizophrenic patients. In the present study, we used neuroendocrine probes to test the hypothesis that untreated psychosis may induce time-dependent changes in central serotonergic and dopaminergic neurotransmission. Prolactin responses to the administration of clomipramine (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16 never-treated male patients with DSM-IV diagnoses of schizophreniform or schizophrenic disorders of paranoid subtype, both before and after 5 weeks of treatment with haloperidol. In the drug-free state, schizophrenic patients exhibited significantly increased prolactin responses to clomipramine administration compared with both the healthy control subjects and the schizophreniform patients. Maximum prolactin responses to clomipramine in the total group of patients were positively correlated with the duration of psychotic illness and negatively correlated with changes in Positive and Negative Syndrome Scale (PANSS) total, negative symptoms and general psychopathology scores after 5 weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge in the drug-free state were lower in the schizophreniform group than in the control and the schizophrenic groups, but the differences did not reach statistical significance. The results provide evidence that the persistence of psychotic psychopathology induces secondary neuroadaptive effects, which seem to involve changes in central serotonergic function.

Neuroendocrine responsivity to clomipramine challenge test in neuroleptic naive psychotic patients before and after treatment with haloperidol

Abstract The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5–40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5–10 mg/day, mean 9.7) and high (15–40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.

Effects of Piracetam on Single Central Neurons

Piracetam, when applied microiontophoretically and/or by hydropneumatic pump on the somatosensory cortex and hippocampus of the rat, affected neuronal activity by depressing or facilitating the spontaneous firing rate, depending on the area studied. Its effect were either additive or counteracting the actions of glutamate, gamma-aminobutyric acid and acetylcholine, when administered together on the same neuron, thus supporting the assumption that its action is directed towards specific membrane elements, presumably the synaptic sites.

Brain functional connectivity during the experience of thought blocks in schizophrenic patients with persistent auditory verbal hallucinations: An EEG study

Thought blocks (TBs) are characterized by regular interruptions in the stream of thought. Outward signs are abrupt and repeated interruptions in the flow of conversation or actions while subjective experience is that of a total and uncontrollable emptying of the mind. In the very limited bibliography regarding TB, the phenomenon is thought to be conceptualized as a disturbance of consciousness that can be attributed to stoppages of continuous information processing due to an increase in the volume of information to be processed. In an attempt to investigate potential expression of the phenomenon on the functional properties of electroencephalographic (EEG) activity, an EEG study was contacted in schizophrenic patients with persisting auditory verbal hallucinations (AVHs) who additionally exhibited TBs. In this case, we hypothesized that the persistent and dense AVHs could serve the role of an increased information flow that the brain is unable to process, a condition that is perceived by the person as TB. Phase synchronization analyses performed on EEG segments during the experience of TBs showed that synchrony values exhibited a long-range common mode of coupling (grouped behavior) among the left temporal area and the remaining central and frontal brain areas. These common synchrony-fluctuation schemes were observed for 0.5 to 2s and were detected in a 4-s window following the estimated initiation of the phenomenon. The observation was frequency specific and detected in the broad alpha band region (6-12Hz). The introduction of synchrony entropy (SE) analysis applied on the cumulative synchrony distribution showed that TB states were characterized by an explicit preference of the system to be functioned at low values of synchrony, while the synchrony values are broadly distributed during the recovery state. Our results indicate that during TB states, the phase locking of several brain areas were converged uniformly in a narrow band of low synchrony values and in a distinct time window, impeding thus the ability of the system to recruit and to process information during this time window.

Manic symptoms induced by olanzapine

We present the case of a never medicated patient with a diagnosis of DSM-IV paranoid schizophrenia in which olanzapine therapy induced manic symptoms. The latter remitted after drug discontinuation.

The Influence of Levodopa and the COMT Inhibitor on Serum Vitamin B12 and Folate Levels in Parkinson’s Disease Patients

Serum folate and vitamin B12 levels were measured in 67 consecutive Parkinson’s disease patients treated either with levodopa + dopa decarboxylase inhibitor (DDC-i) plus catechol-O-methyltransferase inhibitors (COMT-i) or only with levodopa + DDC-i. The data were compared to 67 age-matched controls. Our findings show that levodopa-treated Parkinson’s disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.

Indication of Disrupted Temporal Structure in the Case of Thought Blocks in Schizophrenia: The Role of the Metastable Balance

This study is aimed at investigating probable disruption of the metastable balance relevant to a disruption of the mental processes observed in the neurophenomenal level. This disruption was found to occur under dense auditory verbal hallucinations (AVHs) which are accompanied by thought blocking (TB) phenomena. The entropy that quantifies the complexity of the spontaneous coupling has been used to describe the observed transitions. According to our findings, the high synchrony-derived entropy (SE) defines a metastable state, where formations of cortical areas are able to coordinate transiently under the demands of stimulus-oriented processes or other internal cognitive associations. It was also found that the disruption of the sensitive balance to the side of oversynergy (overconnectedness) rather than the side of independence (coincidental coupling) is relevant with functional fixations under the specific symptom of schizophrenia. An introduced measure relative to the persistence of coupling indicated that the overcoupled brain areas exhibit a kind of “stiffness” in processing incoherent phasic components. Our consideration enhances the understanding of the role the metastability plays in the interpretation of deeply subjective phenomena, such as AVHs and TBs that affect the normal information routing in the brain.

Mood regulation in bipolar disorders viewed through the pendulum dynamics concept

Bipolar disorders have been characterized by powerful fluctuations of energy, mood, and thinking patterns. Mood episodes (manic or depressive) could be considered as deviations of a psycho-physiological index above or below a conventionally defined value called ‘normothymia’. In the present study, we analyzed the feedback techniques used to suppress the oscillatory activity exhibited on an inverted pendulum device. Subsequently, we examine the degree that this multimodal feedback design could be considered on a hypothetical pendulum where the mood plays the role of the suspended mass, and the force balance compensation circuitry is substituted by drug-specific therapeutic interventions. The study does not concern a model of bipolar illness that could simulate numerically various phases of mood episodes but focuses on the functional similarities regarding the correction treatments applied on the two different oscillating systems giving a potential perspective of how techniques of feedback control may enhance the conceptualization of the treatment schemes followed in recent guidelines for biological treatment of bipolar disorders. Our theoretical consideration, along with observations on clinical level, gives support to the concept that the compensation of the mood oscillations should be adaptive with selective therapeutic interventions that compensate the excited system in different time scales.

P.2.075 Neuroendocrine responsivity to clomipramine challenge test in neuroleptic naive psychotic patients before and after treatment with haloperidol

The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5-40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5-10 mg/day, mean 9.7) and high (15-40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.