RGS4 genotype is not associated with antipsychotic medication response in schizophrenia.

The aims of the present study were to compare the allele frequencies of a common single nucleotide polymorphism located upstream of the regulator of G-protein signaling 4 (RGS4) gene (T > G, Rs 951436) in 219 Finnish patients with schizophrenia and in 389 control subjects, to analyze corresponding frequencies between two different subtypes of 93 schizophrenia patients according to their medication response, and to study the effect of this SNP on age at onset in schizophrenia. The RGS4 (T > G, Rs 951436) genotype was not associated with incidence or age at onset in schizophrenia. Neither was the RGS4 genotype associated with medication response with two different subpopulations with schizophrenia.

Relation between frontal 3-7 Hz MEG activity and the efficacy of ECT in major depression.

The efficacy of electroconvulsive therapy (ECT) in major depression has been linked to the accentuation of postconvulsive prefrontal electroencephalography slow-wave activity. We investigated the change in slow-wave activity (0.5-7 Hz) using whole-scalp magnetoencephalographic (MEG) recordings. The 3-7 Hz (theta) activity increased in the right frontal and occipital regions during the course of treatment. After four treatments, the increase of the theta activity in the left frontal cortex correlated with the efficacy of the ECT treatment. Moreover, the change of the ratio of left and right frontal theta activity to occipital theta activity had a positive correlation with the therapeutic effect. These findings suggest that an efficient ECT treatment increases MEG theta activity in the frontal cortex.

Disability pension for major depression in Finland.

OBJECTIVE: The authors' goal was to investigate the treatment received before receipt of a disability pension for major depression in a representative sample of depressed patients. METHOD: The medical statements for a random sample of 277 subjects drawn from the Disability Pension Register of the Social Insurance Institution were examined. The subjects selected represented individuals in Finland who were granted a disability pension because of DSM-III-R major depression during a 12-month period in 1993-1994. RESULTS: For 254 (92%) of the subjects, the statements regarding pension eligibility were written either by a psychiatrist or a psychiatric resident for patients who were currently being treated in psychiatric settings. There was an additional diagnosis of a comorbid mental disorder or a somatic disease contributing to disability in two-thirds of the statements. Overall, the statements indicated that 242 (87%) of the subjects were prescribed antidepressant medication, but only 24 (9%) received weekly psychotherapy, and only 11 (4%) received ECT. CONCLUSIONS: Most subjects granted a disability pension for major depression in Finland have comorbid mental or physical disorders contributing to their disability. Before receiving their pension, most received antidepressant treatment, but few received the established nonpharmacological treatments.

Inverse correlation between hallucinations and serum prolactin in patients with non-affective psychoses.

Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation was observed between clinical measures (total CPRS score, schizophrenia subscale score or depression and anxiety subscale score) and serum PRL.

Altered parallel auditory processing in schizophrenia patients.

Patients with schizophrenia have impaired auditory processing that has been demonstrated by diminished P50 response to paired auditory stimuli in event-related potential (ERP) studies. Cerebral processing can also be studied with magnetoencephalography (MEG). With a whole-head MEG, which enables one to simultaneously measure brain activity in both hemispheres, we investigated whether early parallel auditory processing is impaired in schizophrenia. Sequences of tones were monaurally presented to schizophrenia patients and healthy controls in a passive condition, and the event-related magnetic fields were recorded simultaneously over both auditory cortices. The interhemispheric latency difference of the P50m, but not that of the N100m, was significantly shorter in the patient group in the right-ear but not in the left-ear stimulus condition. Further, the ipsilateral P50m was significantly earlier in schizophrenia patients in the right-ear condition. This result suggests that schizophrenia affects the consecutive preconscious auditory processing in a different manner.

Polymorphisms of the interleukin-1 gene complex in schizophrenia.

Activation of the inflammatory response system has been related to the pathophysiology of schizophrenia by several recent studies. Schizophrenic patients have varied levels of proinflammatory cytokines, such as interleukin (IL)-1, -6, and tumor necrosis factor (TNF)alpha in their peripheral blood or cerebrospinal fluid. These cytokines can modify the metabolism of neurotransmitters, influence neural development, and IL-1 has been implicated in acute, and, on the other hand, chronic neurodegeneration. They could therefore be of primary pathogenic importance, either in the acute disease or during those stages of brain development which possibly influence the sensitivity of a person to schizophrenia in later life. The cytokine regulation of brain development and its possible neuroimmune involvement in the pathogenesis of schizophrenia has been raised. One indication of the pathogenic role of IL-1 in schizophrenia would be a demonstration of the difference between schizophrenic patients and healthy controls at the gene level. Therefore we analyzed the polymorphism of the IL-1 gene complex in 50 schizophrenic patients and in 400 healthy blood donors. The following allelisms were analyzed: IL-1beta gene: base exchange polymorphisms at the positions -511 (relative to the transcriptional start site); IL-1alpha gene: base exchange polymorphism at the position -889; IL-1 receptor antagonist (IL-1RA) gene: variable numbers of 86-base pair tandem repeats in intron 2. The frequencies of the IL-1beta (-511) allele 1, IL-1alpha (-889) allele 2, and IL-1RA allele 1 were somewhat, but not significantly, higher in the schizophrenic patients as compared to the controls. These alleles are known to be located on the same haplotype. The number of carriers of this haplotype was significantly higher in the schizophrenia patients (17/50 vs 81/400) than in the controls (P=0.026, chi2). The frequencies of this haplotype were 0.38 and 0.27, respectively (P=0.0266, chi2). The number of homozygotes of this haplotype was significantly higher in the schizophrenia patients (P=0.0006, chi2). These data suggest that the cytokine aberrations in schizophrenia are, at least partly, genetically determined.

Reversal of cerebral asymmetry in schizophrenia measured with magnetoencephalography.

It has been suggested that schizophrenic patients fail to develop left-hemisphere dominance because of an early disturbance in neuronal development. This hypothesis has been supported by some post-mortem. CT and magnetic resonance imaging (MRI) studies, while other in-vivo studies have given contradicting results. We used 122-channel whole-head magnetoencephalography and MRI to locate the sources of auditory evoked responses in 19 schizophrenic patients and in 20 healthy controls. Auditory evoked responses were detected in all subjects. The left-right hemisphere asymmetry of cerebral sources for auditory evoked responses was markedly dispersed among patients when compared with controls. The source locations for left auditory cortex were clearly anterior with respect to the right hemisphere in 32% of the patients, while the corresponding prevalence of this abnormal asymmetry was 0% in controls (p = 0.008. Fisher's exact test). The reversed asymmetry appeared to be associated with a shorter anterior-posterior distance between the auditory cortex and the anterior tip of the temporal lobe in the left side when compared with the right side. The reversed asymmetry was associated with higher PANSS general psychopathological score, and especially with higher guilt feelings and motor retardation scores. The large 2.5-fold standard deviation in the inter-hemispheric anterior posterior difference in the location of the auditory cortex among patients (p 0.001 for the difference in the magnitude of variance between controls and patients) clearly reflects the dispersion of the left right asymmetry into both direction, and three of the patients with 'normal asymmetry' had a greater left-right asymmetry than any of the controls. Markedly greater reversal of hemispheric asymmetry among patients implies that regulation of the development of brain asymmetry is disturbed among schizophrenic patients. Abnormality in the cerebral asymmetry may be a crucial factor in the development of schizophrenic disorder in a substantial proportion of patients. The results suggest that the reversed asymmetry is associated with the higher severity of general psychopathological symptoms.

Plasma interleukin-1 beta and sleep architecture in schizophrenia and other nonaffective psychoses.

OBJECTIVE: It has been reported that sleep deprivation may enhance interleukin (IL)-1 beta production of healthy subjects. Furthermore, patients with acute psychoses have been reported to exhibit higher levels of IL-1 beta than healthy controls. The present study examined polysomnographic sleep and morning IL-1 beta plasma values in 20 drug-free patients with acute nonaffective psychoses. METHODS: Ten patients with DSM-III diagnosis of schizophrenia, five with delusional disorder, and five with atypical psychosis underwent polysomnographic sleep registrations and their morning blood levels of IL-1 beta were measured. RESULTS: IL-1 beta values correlated negatively with the length of the sleep period (p = 0.010) and the relative time of rapid eye movement (REM) sleep (p = 0.038), and positively with REM latency (p = 0.043). CONCLUSIONS: It is concluded that reduced sleep, possibly especially reduced REM sleep, may be a reason for increased morning IL-1 beta values in these patients. Additional studies on IL-1 beta in psychiatric patients should consider the possibility of sleep disturbances as a possible explanation for deviations in IL-1 beta levels.

No differences in phospholipase-A2 activity between acute psychiatric patients and controls.

The phospholipase-A2 activity in plasma from 62 psychiatric patients admitted in an acute state to psychiatric hospital was determined by a fluorometric assay and compared to that of age- and sex-matched controls. Contrary to earlier findings, no significant differences were found between patients and controls.

Depression after surgery for acoustic neuroma.

The purpose of this study was to establish the frequency and pattern of depressive disorders after surgery for acoustic neuroma, and to look for associations. Twenty seven patients with acoustic neuroma underwent thorough psychiatric assessment before surgery and at three and 12 months after surgery. Three patients had a depressive disorder in the preoperative assessment. Of the remaining 24 patients, nine (38%) had a depressive disorder at the three month check up. Deterioration of hearing was the only postoperative detriment associated with a depressive disorder (P = 0·024). All nine patients with a depressive disorder were women (P = 0·001), giving them a 69% incidence. None of the patients without preoperative depression required inpatient treatment for depressive disorder, but three patients out of nine still had a depressive disorder 12 months after surgery.

Atypical lymphocytes in schizophrenia.

Blood was drawn from 18 inpatients fullfilling the DSMIII criteria for schizophrenia and their 15 age- and sex-matched clinically infection-free controls before and after neuroleptic treatment. Blood films were stained with MGG solution, mixed, and subsequently read in random order by one observer. The lymphocytes were examined by light microscopy and classified into six types: normal lymphocytes, Downey type I atypical lymphocytes, Downey type III atypical lymphocytes, stress lymphocytes, plasmocytoid lymphocytes, and large granular lymphocytes. Downey type I and III atypical lymphocytes were classified into small, medium, and large lymphocytes. Schizophrenic patients had significantly more Downey type III medium size cells before treatment (p = 0.019 before treatment and p = 0.056 after treatment) and less Downey type I small size cells (p = 0.113 before treatment and p = 0.026 after treatment). Our study supports the idea of a possible subgroup of schizophrenia exhibiting immunological aberrations. In the present study, we found morphologically more specified cells which could be involved in this alteration.

Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders.

Plasma levels of interleukin (IL)-1 beta and IL-6 were measured in 60 acutely hospitalized psychiatric patients and in 60 healthy controls by enzyme-linked immunosorbent assay (ELISA). Almost no IL-6 was detected in the plasma of the patients or controls. The mean level of IL-1 beta was found to be significantly higher in schizophrenic patients than in their corresponding controls (P = 0.03). The acute schizophrenics, but not the group of chronic schizophrenics, contributed to this increase. No correlation with age, duration of illness or overt psychopathology was found. The neuroleptic medication did not prove to have a significant effect on the plasma IL-1 beta levels. There was no difference between non-psychotic affective disorder patients (N = 17) and the controls.

Globus pharyngis, commonly associated with esophageal motility disorders.

OBJECTIVES: To evaluate the role of gastrointestinal and psychiatric etiology in globus sensation. METHODS: The study population consisted of 32 consecutive patients with globus sensation without dysphagia referred to the Department of Otorhinolaryngology in Helsinki University Hospital. Eleven patients were excluded from the study: two because of advanced age, one prisoner, and six patients refused further studies. Only two patients (6%) were found to have abnormal otorhinolaryngological status. These patients were also excluded from the study. Esophagogastroduodenoscopy, 24-h pH recording, esophageal manometry, and Bernstein acid perfusion test were carried out in 21 patients (13 females, eight males, mean age 49 yr). Psychiatric evaluation was done in 20 patients; one patient refused the psychiatric consultation. RESULTS: Abnormal endoscopy was found in 12/21 (57%) of the patients, with antral gastritis and hiatal hernia being the most common findings. Two patients had esophagitis. Sixty-seven percent demonstrated abnormalities in esophageal manometry, the most frequent finding being a nonspecific esophageal motility disorder (29%). pH monitoring was normal in 16/21 of patients (76%), whereas the Bernstein test showed positive results in 13/21 (62%). With DSM IIIR as the diagnostic tool, five of 20 patients (25%) received a psychiatric diagnosis. CONCLUSIONS: Globus sensation has a multiple etiology, and local reasons are rare but should first be ruled out. Abnormalities in esophageal motility are commonly found, and these patients seem to be sensitive to esophageal acidity. Esophageal manometry and ambulatory 24-h pH recording should be included in the evaluation of a globus patient. The number of psychiatric disorders does not differ from that in the general population. Treatment of globus sensation should be directed toward the abnormality found behind the symptom.

Plasma and cerebrospinal fluid interleukin-1 beta and interleukin-6 in hospitalized schizophrenic patients.

Interleukin (IL)-1 beta and IL-6 levels in plasma and cerebrospinal fluid (CSF) of 14 medicated schizophrenic patients and 9 controls were measured by enzyme-linked immunosorbent assay. Almost no detectable levels of IL-6 in plasma or CSF from patients or controls were found. With regard to mean plasma or CSF levels of IL-1 beta there were no statistically significant differences between the two groups investigated. The dose of neuroleptic medication the patients used did not correlate with the IL-1 beta plasma levels. For the whole series of subjects (n = 23) or for the schizophrenic patients (n = 14) no correlation between the plasma and CSF levels of IL-1 beta was found.

Is there a seasonal variation in the interferon-producing capacity of healthy subjects?

Induced production of interferon-alpha (IFN-alpha) and IFN-gamma was studied in 101 blood samples from 49 healthy subjects during 1 year. The results indicate a seasonal variation of the IFN-producing capacity, with a decrease in summertime, in Finland.

Do reversed depressive symptoms occur together as a syndrome?

Although the DSM-IIIR diagnostic criteria for major depression include hypersomnia, increase in appetite, and in children and in adolescents irritability, there is no general agreement on the existence of a depressive syndrome with reversed vegetative symptoms. Our findings suggest that these reversed depressive symptoms may not occur together as a syndrome. However, they may share an enhanced responsiveness to moclobemide treatment.

Interferon-alpha as adjuvant treatment in chronic schizophrenia.

The therapeutic use of interferon (IFN)-alpha administered as adjuvant medication in chronic schizophrenia was investigated. Natural leukocyte IFN-alpha was given to 9 long-term hospitalized chronic schizophrenic patients daily as subcutaneous injection of 3 million units 5 times a week. The trial followed a placebo-controlled double-blind crossover design. Each treatment period lasted for 8 weeks with a 2-week washout period in between. IFN-alpha did not prove to be beneficial for the total group of patients. Yet, 3 patients improved during the IFN-alpha drug period. The clinical improvement was seen as better social competence and less affective tension in the ward surroundings.

Plasma concentrations of remoxipride and haloperidol in relation to prolactin and short-term therapeutic outcome in schizophrenic patients.

Plasma concentrations of remoxipride and haloperidol as well as prolactin (PRL) were determined in 20 patients with acute symptoms of schizophrenia. Ten patients received remoxipride and ten patients haloperidol for a period of 6 weeks. A significant linear correlation was found between the plasma level of remoxipride and the dosage applied (P less than 0.02) as well as between the corresponding haloperidol dosage and plasma concentration (P less than 0.05). In both patient groups a significant reduction in psychopathology was observed during the trial period (P less than 0.001). In the haloperidol group this was associated with a clearcut elevation of plasma PRL, whereas in the remoxipride group after an initial rise for 4 weeks, the mean PRL level returned to baseline at the end of the study.

Prolactin response to submaximal stimulation by TRH in nonaffective psychoses.

Nonaffective psychotic symptoms are heterogeneous and probably caused by mixed biopathology. A preliminary investigative tool to study pituitary dopamine activity, the prolactin response to submaximal stimulation by thyrotropin-releasing hormone (TRH) (mini-TRH test) was correlated in 20 subjects with nonaffective psychoses to positive psychotic symptoms as assessed by the Comprehensive Psychiatric Rating Scale psychosis subscale. A significant positive correlation was observed between the response and ratings of nonparanoid symptoms, especially nonparanoid delusions and disrupted thoughts. Because, in addition to pituitary dopamine activity, there is evidence to suggest that the response reflects extrapituitary dopamine activity as well, the results extend the evidence that nonparanoid acute productive psychotic symptoms may be associated with hypoactivity rather than with hyperactivity of brain dopaminergic systems.

Remoxipride and haloperidol in schizophrenia: a double-blind multicentre study.

Ninety-two patients with schizophrenia were included in a double-blind multicentre parallel-group trial comparing remoxipride and haloperidol. The mean daily dose during the last week of treatment was 316 mg (range, 150-600 mg) in the remoxipride group and 8.7 mg (range, 5-20 mg) in the haloperidol group. The study period was six weeks with at least one day of washout. Both Clinical Global Impression (CGI) rating, and Brief Psychiatric Rating Scale (BPRS) total scores declined at the end of the trial compared with pretreatment values in both groups. No significant differences were found between the remoxipride and haloperidol groups with regard to the treatment outcome. Treatment-emergent extrapyramidal symptoms were statistically more frequent and more severe during haloperidol than during remoxipride treatment. Haloperidol-treated patients reported also significantly more concentration difficulties. Severe extrapyramidal side effects in the haloperidol group and clinical ineffectiveness in the remoxipride group were the most frequent reasons for premature discontinuation of treatment.