Cytokine profiles in drug-naive schizophrenic patients.

A large body of evidence concerning immunological abnormalities in schizophrenic patients seems to suggest a role of the immune system in the multifactorial pathogenesis of schizophrenia. We investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n=26) and drug-naive (n=7) schizophrenic patients and in healthy controls (n=33). Production of IL-2 and INF-gamma was significantly higher (respectively P=0.021 and P=0.001) in patients than in controls. These findings provide further evidence that immunological abnormalities are present in some schizophrenic patients.

Augmented type 1 cytokines and human endogenous retroviruses specific immune responses in patients with acute multiple sclerosis.

In vitro antigen- and mitogen-stimulated cytokine production were analysed in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). We also investigated whether immune responses to human endogenous retroviruses (HERV) could be detected in MS and whether these immune responses would be correlated with disease status by analysing cytokine production after stimulation of PBMC with HERV peptides. Results showed that mitogen-stimulated IL-2 and IFN-gamma was augmented and IL-10 was decreased in AMS compared to both SMS and healthy controls. Whereas the production of the metabolically active IL-12 (p70 heterodimer), was comparable in SMS, AMS and HC, production of the total IL-12 (p70 heterodimer and the p40 chain) were augmented in SMS compared to both AMS and HC. HERV-peptides IL-2 and IFN-gamma production was more frequent and more potent in AMS compared to both SMS patients and HC. HERV-specific type 2 cytokine production was more frequent and potent in SMS compared to AMS and HC. Thus a prevalent type 1 cytokine profile was seen in AMS patients, while IL-10 production predominated in SMS individuals.

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis.

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.

Treatment of depression in HIV-infected patients.

BACKGROUND: Pharmacological treatment of depression in HIV-infected patients has been found to be effective. This study assessed the efficacy and feasibility of treatment with fluoxetine and the best method of administering the drug to patients with HIV infection. METHODS: Sixteen seropositive and 16 seronegative patients, equally matched for age and sex, who had Hamilton Rating Scale for Depression scores of at least 16 and who received at least 20 mg/d of fluoxetine for 8 weeks were studied. RESULTS: Depression was alleviated in both groups. However, improvement in the seropositive patients occurred later. INTERPRETATION: The results confirm the effectiveness of fluoxetine in treating depression in people with HIV infection. The lack of adverse effects makes this treatment particularly suitable, especially because seronegative people take longer to respond to treatment.

Cytokines production in chronic schizophrenia patients with or without paranoid behaviour.

1. Several immunological abnormalities have been found in schizophrenia but their significance still remains largely unknown. In this study the authors analyzed mitogen-stimulated interleukin (IL)-2, Interferon gamma (IFN)-gamma and IL-10 (type 2 cytokine) production in a sample of 37 chronic schizophrenic patients as compared with a sample of 40 age and sex-matched controls with the aim to evaluate whether patients belonging to different diagnostic subtypes (i.e. paranoid patients vs non paranoid patients) could be immunologically different from each other. 2. The findings indicate that paranoid patients produce less IL-10 than the others and thus, from an immunological viewpoint, they are more similar to healthy controls. 3. Furthermore, neuroleptic medications were observed to differently affect IL-2 production; this preliminary finding might stimulate further studies aiming to get a link between different drug profile of action both in terms of clinical and receptorial profile and different immunological effects.

Family adaptation to institutionalised mentally retarded patients. A preliminary report on an Italian population.

Family interactive patterns were investigated in the relatives of 20 mentally retarded patients institutionalised in two centres in Northern Italy. Expressed emotion (EE) was used as evaluation instrument. The results show a surprisingly high rate (45%) of high EE, even in relatives of patients who did not live inside the family. High EE was positively correlated to the presence of behavioral disorders in the patients, as already shown for children with conduct disorders. Treatment implications are discussed; there is an opportunity for the implementation of a family psychoeducational approach, aimed both at managing the behavioural consequences of the disorder and at enhancing rehabilitation programmes.

Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients.

Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum immunoglobulins and C3 and C4 complement fractions were evaluated in 29 schizophrenic patients, 31 of their relatives and 20 healthy subjects. The patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3 months prior to the PB sample collection. When compared to healthy controls and their own relatives, the schizophrenic patients showed a lower level of CD4+ cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely, the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in schizophrenic patients in comparison to their relatives and controls, while the CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4 complement fraction levels among the three groups. The present data confirm the presence of immunological abnormalities in schizophrenic patients and suggest a possible role of environmental factors in the triggering of an autoimmune pathogenic mechanism.

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

[Mental retardation and family environment: role of emotional factors]. / Ritardo mentale e ambiente familiare: ruolo dei fattori emotivi.

The authors present data from an experimental study conducted on 20 institutionalized mentally handicapped adult patients. Relevant family variables were investigated by means of the Expressed Emotion (EE) scales, then compared with similar variables obtained in a matched sample of 20 schizophrenic patients and their families. Results show, in relatives of mentally handicapped patients, a higher rate of Warmth than in relatives of schizophrenics (p = 0.009), while other EE scales appear to reach similar values in both groups. Within the mentally handicapped family group, a higher rate of Emotional Over-involvement (p = 0.046) is shown by relatives of patients treated with neuroleptic drugs. The presence of high Warmth and Emotional Over-involvement, together with low Criticism and Hostility, may be interpreted as adaptation by the families to an organic disease with very early onset, clearer ad less rejecting than schizophrenia.

MRI and cognitive patterns in relapsing-remitting multiple sclerosis.

We studied the relationships between magnetic resonance imaging (MRI) and the Luria-Nebraska Neuropsychological Battery (LNNB) in 64 patients with relapsing-remitting multiple sclerosis (MS). MRI films were scored according to arbitrary descriptive criteria designed to emphasize patterns of alterations. Five groups were created: group 1 and 2 had typical discrete white matter lesions, group 3 had confluent lesions, group 4 had large discrete lesions and group 5 had only few small lesions. In addition, groups 2 and 3 had evidence of parenchymal atrophy. Groups 2 and 3 were the most impaired on the LNNB, but none of these patients was actually demented. Groups 1 and 5 were globally intact in spite of very different mean age and MRI pattern. Group 4 was composed of younger subjects with a shorter disease duration; they showed mild loss of attentive and abstracting abilities. We suggest that since their MRI was showing greater signs of local biological activity their mental deficits may be a transitory condition capable of two distinct outcomes: a favorable one as in groups 1 and 5, and a slowly progressive one associated with loss of brain tissue as in groups 2 and 3.

Enzymes of lysosomal origin in the cerebrospinal fluid and plasma of patients with multiple sclerosis.

Several lysosomal enzymes were determined in 47 and 62 samples of CSF and plasma, respectively, obtained from MS patients. CSF levels of most enzymes considered were significantly lower in patients when compared to those of the controls, whereas the plasma levels vary little and appeared to be influenced by the course of the disease. The most interesting result is the one concerning the beta-D-glucuronidase in the plasma: in relapsing-remitting patients in the still untreated acute phase, the levels remain noticeably diminished in comparison to controls. The data suggest the potential of using this enzyme to monitor the progression of the disease.

Expressed emotion and schizophrenia in Italy. A study of an urban population.

Forty-two schizophrenic patients and their close relatives took part in an Italian replication study of expressed emotion (EE). The patients were selected from the psychiatric ward of a general hospital in Milan and were subsequently followed up for nine months. All patients attended a community service clinic as out-patients, and all but one were prescribed neuroleptics for the duration of the study. Relatives were assigned to the high-EE group if they scored 4 or 5 on the emotional overinvolvement (EOI) scale, or showed hostility, or made six or more critical comments. On this basis, 18 (42%) families were rated as low EE and 24 (57%) as high EE. At follow-up, the admission rate for the 9-month period was significantly higher for the high-EE group (P less than 0.05). Furthermore, significantly fewer patients were readmitted from families showing high warmth (P less than 0.05). The presence of high warmth appeared to be associated with a lower admission rate, even in high-EE families.

The brain damage hypothesis of the seasonality of births in schizophrenia and major affective disorders: evidence from computerised tomography.

Although the excess of schizophrenic births in the winter and early spring has been replicated and some non-conclusive work supports the same seasonal birth trend in patients with major affective disorders, the aetiopathogenetic foundations of this phenomenon remain uncertain. The primary role of perinatal seasonal factors that predispose to the development of schizophrenia via induction of brain damage has been invoked, as has a tendency for patients to conceive during the spring and early summer. In order to test these two hypotheses, cerebral ventricular size and cortical atrophy in 206 schizophrenics and 107 patients with major affective disorders were assessed by CT and analysed in relation to month of birth. Compared with schizophrenics born during the remainder of the year, those born between December and April, particularly in cases lacking a family history of schizophrenia, showed increased chances for ventricular enlargement, but not for cortical atrophy. No association between season of birth and central or cortical atrophy was found for patients with major affective disorders. This suggests that the brain-damaging effect played by perinatal seasonal factors has both a disease and an anatomical specificity.

CT scan abnormalities and outcome of chronic schizophrenia.

The authors evaluated the relationship between brain morphological characteristics assessed by means of computerized tomography and the 2-year clinical and social outcomes of 18 patients with chronic schizophrenia. Cerebral structural abnormalities, especially cortical atrophy, were associated with a poorer outcome in several areas of clinical and social functioning.

CD4+ lymphocyte subsets in the cerebrospinal fluid of multiple sclerosis and non-inflammatory neurological diseases.

We studied paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from 18 inactive multiple sclerosis (MS) patients and 10 with non-inflammatory neurological diseases. By means of a dual-colour cytofluorimetric micromethod we were able to count 1500 cells on average in each CSF sample. We found a significant reduction of CD45RA+ and CD4+CD45RA+ cells in the CSF of MS patients. Similarly, CD45RA+ and CD4+CD45RA+ CSF/PB ratios were lower compared with controls. The reduction of suppressor-inducer T-cells did not correlate with CD8+ cell levels in the CSF. The CD4+ subset ratio (CD4+CD45RA-/CD4+CD45RA+) was significantly increased in the CSF of MS patients. Our data suggest that the reduction of CD4+CD45RA+ cells in the PB is not due to a segregation of such cells in the CSF. Conversely, CSF changes reflect changes in the PB similar to these found for other T-cell subsets.

Emotional profiles of families with a heart-operated patient: a pilot study.

Family interaction is a basic factor in determining the quality of life of patients undergoing heart surgery. The present study investigates the emotional attitudes in the relatives of 10 heart-operated patients. The results indicate that a high amount of relatives' emotional overinvolvement and warmth tends toward a correlation with lower anxiety and depression scores, and with a better 12-month outcome of the illness.

Multimodality evoked potentials in HIV infected subjects: a longitudinal study.

18 subjects with symptomless HIV infection were investigated with multimodal evoked potentials for possible CNS involvement and again after an 8-12 month interval. 13 subjects showed neuropsychological changes, which were confirmed at the second examination. The 5 subjects found normal remained so at the second examination. On WAIS assessment the only patient to earn pathological scores was the one with the greatest evoked potentials changes. Thus the evoked potentials procedure proved capable of identifying early CNS involvement by HIV infection.

Lymphocyte subsets in schizophrenic disorders. Relationship with clinical, neuromorphological and treatment variables.

Peripheral blood lymphocyte subsets and serum immunoglobulin levels were assessed in 42 patients and 37 healthy controls. 24 patients were free from neuroleptic medication and 15 had never been treated with neuroleptics. 31 patients had a diagnosis of schizophrenia (DSM-III criteria) and 11 a diagnosis of a disorder of the schizophrenic spectrum. As compared to healthy subjects, the drug naive schizophrenic patient group showed an increase of T suppressor lymphocytes, while the drug-treated schizophrenic group showed an increase of T helper lymphocytes. The drug-treated schizophrenic group differed from the drug naive one relative to a decrease of T suppressor lymphocytes. As compared to healthy subjects, the drug naive spectrum disorder patients showed an increase of absolute number of lymphocytes, while the drug treated spectrum group showed an increase of B lymphocytes. These findings did not correlate with any clinical or neuromorphological variables taken into account.