Psychophysiological differences in schizophrenics with and without delusional misidentification syndromes: a P300 study.

There is a debate on whether delusional misidentification syndromes (DMSs) and schizophrenia are distinct disorders. Information-processing deficits have been found in both. Since the P300 component of event-related potentials (ERPs) reflects attention and working memory (WM) mechanisms, the P300 elicited during a WM test was studied in schizophrenic patients with DMS in comparison to schizophrenic patients without DMS and controls. Nine schizophrenic patients with DMS, 11 without DMS and 11 healthy controls were tested with a computerized version of the digit span test of the Wechsler batteries. Auditory ERPs were measured during the anticipatory period of the test. P300 amplitude in prefrontal areas was found to be significantly reduced in schizophrenics without DMS and markedly less in DMS patients compared to controls. P300 latency in the central midline brain region was significantly prolonged in DMS patients compared to the other groups. Memory performance was significantly reduced in both patient groups as compared to healthy controls. The results may indicate abnormalities in both allocation of attentional resources and automatic orienting in schizophrenic patients with DSM. In contrast, even though schizophrenic patients without DMS exhibit partial similarities with patients suffering from DMS, they show excessive reduction of P300 amplitude located at the left frontal area. Future studies might clarify these issues.

Analysis of polymorphisms in the alpha-subunit of the olfactory G-protein Golf in lithium-treated bipolar patients.

OBJECTIVE: This study examines the alpha-subunit of the olfactory G-protein (G(olf)) as a possible candidate gene for bipolar disorder. The alpha-subunit of the G(olf) gene maps to a region on chromosome 18p that has been implicated in several linkage studies as a potential site of a bipolar disorder susceptibility loci. METHODS: We investigated whether two polymorphisms in the alpha-subunit of the G(olf) gene (A-->G in intron 3 and T-->G in intron 10) are associated with bipolar disorder in a sample of 149 bipolar patients under lithium treatment compared with 139 healthy controls using haplotype analysis. RESULTS: There was no evidence for an association between the investigated polymorphisms in the G(olf) gene and bipolar disorders, as well as to response to lithium treatment or common side effects, like hand tremor, weight gain and cognitive dysfunction. CONCLUSION: The results of the present study do not support the hypothesis that the G(olf) gene is a major susceptibility factor for bipolar disorders.

Obsessive-compulsive symptoms induced by atypical antipsychotics. A review of the reported cases.

Atypical antipsychotics (APs) are now widely in use in clinical practice. They exert a beneficial effect in patients with schizophrenic disorders, including cases resistant to traditional APs and negative symptoms. They have also enhanced the ratio of therapeutic efficacy to adverse effects. Atypical APs, mainly risperidone and olanzapine, have been used as adjunctive treatment in (selective) serotonin reuptake inhibitor [(S)SRI]-refractory cases with obsessive symptoms. However, de novo emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with clozapine, risperidone, olanzapine and quetiapine has been described in the literature. The reported cases and the possible pathogenetic mechanisms involved in their occurrence are discussed and reviewed.

Psychophysiological correlates of patients with delusional misidentification syndromes and psychotic major depression.

BACKGROUND: Psychotic major depression (PMD) and delusional misidentification syndromes (DMS) exhibit cognitive deficits. Since the P300 component of event-related potentials (ERPs) provides valuable information concerning cognition, we studied this component of ERPs in DMS and PMD patients. METHODS: Nine patients with DMS, 15 patients with PMD, and 11 healthy controls, matched for age, sex and educational level, were tested using the auditory P300 component of ERPs. RESULTS: Both patient groups showed significant reductions in P300 amplitude at the right frontal region, while DMS group showed significant attenuation of the P300 amplitude at the right parietal area. P300 latency was significantly prolonged in the central midline brain region in the DMS group. LIMITATIONS: The smallness of the sample size and the hypothetical post-hoc assignation of psychological function to regional activation. CONCLUSION: PMD and DMS patients may share similar psychophysiological alterations connected to the right frontal region, mediating automatic processes, while DMS are associated with dysfunction of effortful mechanisms and allocation of attentional resources involving the interhemispheric and right parietal circuitry.

Cytokine production in bipolar affective disorder patients under lithium treatment.

BACKGROUND: Our knowledge concerning immune functioning in bipolar affective disorder (BAD) is limited, while lithium's immunomodulatory effects seem multiple and conflicting. Our aim was to evaluate cytokine production and lithium's effect on it in BAD patients, using ELISPOT technique as a sensitive tool. METHODS: Cytokine (IL-2, IL-6, IL-10 and IFN-gamma) production from isolated peripheral blood lymphocytes (PBLs) was evaluated (ELISPOT technique) in 40 euthymic BAD patients under chronic lithium treatment, in 20 healthy volunteers, and in 10 never medicated BAD patients before and after the introduction of lithium therapy. In all cases, cytokine plasma levels were also measured using ELISA. RESULTS: BAD patients under chronic lithium treatment had significantly lower numbers of IL-2, IL-6, IL-10 and IFN-gamma secreting cells compared to healthy volunteers. The number of cytokine secreting cells decreased in never medicated patients after 3 months of lithium treatment. In vitro stimulation of PBLs with lithium did not affect the number of cytokine secreting cells either in the patients or in the healthy volunteers. CONCLUSIONS: The significantly lower number of PBLs producing cytokines (IL-2, IL-6, IL-10 and IFN-gamma) in euthymic BAD patients under chronic lithium treatment result from the long-term (over 3 months) lithium administration. In vitro stimulation of PBLs with lithium did not change the number of cytokine producing cells. Our findings may be useful in elucidating possible downregulatory effects of lithium in humans.

Lymphocytes from bipolar and schizophrenic patients share common biochemical markers related to histone synthesis and histone cell membrane localization characteristic of an activated state.

In a previous communication, based on the total histone and histone variants' synthesis rates, biochemical parameters used for the characterization of the activation state of lymphocytes, we showed that a portion of the lymphocyte population obtained from peripheral blood of patients with bipolar disorder in the manic and/or depressed phases of the illness were in an activated state as opposed to normothymic patients and control subjects whose lymphocytes are in a resting, Go, state. In light of these previous findings, in the present investigation, we have analyzed total histone synthesis rates and the H2A and H3 histone variants' synthesis pattern of acid-extracted histones from the lymphocytes' nuclear fraction obtained from control subjects, patients with bipolar disorder in all phases of the illness, and patients with schizophrenia. Additional biochemical parameters, such as total cellular protein and DNA synthesis rates, were also studied. Moreover, recent findings from other investigators showed the association of histones on the plasma membrane fraction of PHA-activated, but not Go resting lymphocytes. Based on these results, acid-extracted proteins from the plasma membrane fraction obtained from control, bipolar patients in all phases of the illness, and schizophrenic patients were analyzed by immunoblotting using a polyclonal histone antibody, anti-H2B. All biochemical parameters tested show that a portion of the lymphocyte population from bipolar, i.e. manic and depressive, as well as schizophrenic patients are in an activated state and clearly indicate that the unusual for lymphocytes cell cycle-related histone biochemical properties are common to both disorders.

Obsessive-compulsive symptoms with olanzapine.

The emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with atypical antipsychotics, mostly clozapine, has been documented by numerous case reports (reviewed by Lykouras et al., 2003). In six recent reports involving nine cases, (Jonkers and de Haan, 2002; Lykouras et al., 2003) olanzapine was found either to cause de novo emergence or to exacerbate OC symptoms. In six of these cases olanzapine caused exacerbation and in three cases caused de novo emergence of OC symptoms.

Risperidone-induced obsessive-compulsive symptoms: a series of six cases.

Risperidone is a novel and atypical agent with a dual antagonistic effect on 5-HT and D receptors. Open-label reports and one controlled study suggest that risperidone addition is effective in patients with obsessive-compulsive disorder refractory to treatment with serotonin reuptake inhibitors. However, risperidone has also been implicated in the production or exacerbation of obsessive-compulsive symptoms. We report six cases (schizophrenia, five cases; psychotic depression, one case) in which risperidone was effective in the treatment of the psychotic symptoms but produced obsessive-compulsive symptoms (four cases) or caused exacerbation of previous obsessive-compulsive symptoms (two cases). In all but one case, obsessive-compulsive symptoms emerged shortly after initiation of risperidone treatment with a dose above 3 mg/day. The mechanisms and risk factors for risperidone and other atypical antipsychotics to induce or exacerbate obsessive-compulsive symptoms are as yet not clear. Risperidone-induced obsessive-compulsive symptoms appear to be dose-dependent and are probably produced by serotoninergic-dopaminergic imbalance. Close monitoring of the patients receiving risperidone, especially those vulnerable to the development of obsessive-compulsive symptoms, may be of value. Gradual escalation and low final dose may be helpful.(2) (2)