P. Pancheri

Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes

Cannabis consuming schizophrenic patients are younger at onset, are likely to have started abuse before onset of schizophrenia and show more prominent positive symptoms than nonabusers. It has been suggested that cannabis is a risk-factor for schizophrenia. Our aim was to assess prevalence and pattern of cannabis use in 125 chronic male schizophrenic subjects and its impact on socioepidemiological and clinical variables as well as which disorder precedes the other in onset. Assessment of consumption was made with a semi-structured clinical interview. Clinical status was assessed by means of the SANS, SAPS, PANSS and BPRS scales. Cannabis consumption was found in 54 subjects (43 %), 66.7 % of whom started it at least three years before onset of schizophrenia. Consumers were younger and with lower negative symptoms, specially abusers and polysubstance abusers. Family history positive for psychosis was more frequent in consumers, especially when consumption started before onset of schizophrenia. Subjects whose onset of schizophrenia preceded the beginning of cannabis abuse had more positive symptoms than those who started abuse before the onset of schizophrenia. On these grounds, our sample could be subdivided into two main groups, one that uses substances to counter distressing symptoms of schizophrenia and another in which cannabis might be one of the factors predisposing to the disease; the former had less negative symptoms than nonabusers. Our data support both heterogeneity of schizophrenia and genetic susceptibility to environmental agents.

Psychopathological dimensions of depression: a factor study of the 17-item Hamilton depression rating scale in unipolar depressed outpatients.

BACKGROUND Agreement on the factor structure of the Hamilton Depression Rating Scale (HDRS) has not been consistent among studies, and some investigators argued that the scales factor structure is not reliable. This study aimed at shedding more light on this debated issue. METHODS We studied 186 adults with unipolar depression (Major Depressive Disorder, n=80; Dysthymic Disorder, n=71; Depressive Disorder Not Otherwise Specified, n=25; Adjustment Disorder, n=10). They had no comorbid DSM-IV axis I or axis II disorders, and had received no treatment with antidepressant drugs in the previous 2 months. The factor structure of the scale was studied using the principal factor method, followed by oblique rotation. Factor scores were computed for each subject using the regression method. RESULTS Using the scree-test criterion for factor extraction, we obtained a four-factor solution, explaining 43.8% of total variance. The four factors extracted were identified as (1) somatic anxiety/somatization factor; (2) a psychic anxiety dimension; (3) a pure depressive dimension; and (4) anorexia factor. Patients with Major Depressive Disorder scored significantly higher than patients with other diagnoses on the pure depressive dimension. LIMITATIONS These results need to be replicated in different cultures, using analogous factoring techniques. CONCLUSIONS Though not exhibiting factorial invariance in the stricter sense of the term, the 17-item HDRS did exhibit a relatively reliable factor structure. Our analysis provides further evidence that the scale is multidimensional. However, as long as the multidimensional character of the scale is taken into account the scale should be able to play a useful role in clinical research.

A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-l-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder

S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression.

Cannabis and neurological soft signs in schizophrenia: absence of relationship and influence on psychopathology.

Background: Cannabis is a possible risk factor for the onset of schizophrenia and can induce neurocognitive, behavioural and motor co-ordination alterations. The aim of this study was to evaluate the role of cannabis in the occurrence of neurological soft signs (NSS) and, considering that this drug has been related to positive symptoms, whereas NSS have been linked to negative symptoms, we also examined the role of clinical features. Methods: The study investigated NSS in 25 male cannabis-consuming and 25 male non-consuming schizophrenic patients, using the Neurological Evaluation Scale. Clinical features were studied using SANS and SAPS. Results: Significant differences emerged after comparison analysis, with more NSS in non-consuming patients. The SANS subscales Alogia and Anhedonia-asociality were also statistically significant in this group of patients. Discussion: If non-consuming patients show a higher incidence of both NSS and negative symptoms, which, according to the literature, seem to be associated, then these findings suggest that NSS are relatively independent from cannabis, but not from clinical features.

Deficit of Executive Functions in Schizophrenia: Relationship to Neurological Soft Signs and Psychopathology

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups (‘good performers’ and ‘poor performers’) that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The ‘poor performers’ group showed greater severity of NSS: significant differences emerged for the NES total score and for the ‘sequencing of complex motor acts’ score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.

Neurological soft signs and cerebral measurements investigated by means of MRI in schizophrenic patients

Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic prevalence in schizophrenic patients, and correlations between NSS and the most frequently cerebral alterations. The aim of this study was to investigate, by means of MRI, the quantitative alterations of cortical and subcortical structures and their correlation with NSS in a sample of schizophrenic patients. Linear measures of lateral ventricular (Evans ratio), third ventricular (Third Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan and Heinrichss Neurological Evaluation Scale (NES). Lateral ventricular enlargement showed to be correlated with right stereoagnosia item (p=0.001). Hippocampal atrophy, with right stereoagnosia item (p=0.023), with forefinger-right thumb opposition (p=0.004), forefinger-left thumb opposition (p=0.029 and face-hand extinction (0.26). Third ventricle enlargement showed to be correlated with forefinger-right thumb opposition (p=0.001), forefinger-left thumb opposition(p=0.021) and total sensorial integration (p=0.012). Cerebellar atrophy showed to be correlated with rhythmic drumming item (p=0.042), forefinger-right thumb opposition (p=0.007), forefinger-left thumb opposition (p=0.026), left specular movements (p=0.049), face-hand extinction (p=0.001), right-left confusion (p=0.005) and with left forefinger-nose index (p=0.032). Results obtained confirm the correlation between NSS and neuroanatomical alterations in schizophrenia.

Infarct as a Stress Agent: Life History and Personality Characteristics in Improved versus Not-Improved Patients after Severe Heart Attack

Fifty-eight male subjects admitted to an intensive coronary care unit were interviewed and underwent psychometric testing on the second--third day after a severe heart attack (infarct). Seven-ten days following admission, the clinical condition of the patients was evaluated by the attending cardiological staff and rated on a three point scale. The patients were divided, on the basis of the clinical rating, into two groups: improved (N = 25) and non-improved (N = 33). Life history characteristics, MMPI personality profiles, and State-Trait anxiety scores were then compared for the two groups. The not-improved group showed the higher scores on almost all the MMPI scales, higher anxiety scores and more work-related problems than the improved group. Such data give some empirical support to the hypothesis that the physiological and hemodynamical conditon of the cardiac patient is in some way correlated with the patients style of coping with stress, and his history of previous life stress situations.

Development of Obsessive-Compulsive Symptoms during Clozapine Treatment in Schizophrenia and Its Positive Response to Clomipramine

The arising of obsessive-compulsive (OC) symptoms during clozapine treatment of schizophrenia has been described by several clinicians although recently criticised [1–9]. Checking rituals and contamination obsessions with clozapine treatment were reported by Patil [10] in 1992, while Baker et al. [1] reported cleaning, washing, sexual and, again, contamination obsessions; Cassady and Thaker [2] added religious obsessions to the list. None of the patients had any prior history of OC symptoms. Cases have also been described where clozapine seems to have acted upon a pre-existing OC symptomatology [5]. Only in a few cases symptoms were also assessed by means of rating scales [5, 11]. The dosage of the drug at which the first symptoms would arise ranges from 125 to 800 mg/day [2, 11]. The latency of appearance of OC symptoms as related to the beginning of clozapine treatment ranges from 2 months to 1 year of treatment [1–6]. Patients who favourably respond to clozapine develop obsessive thoughts and compulsions at the same time. These symptoms disappear after clozapine suspension and reappear with its reintroduction. Since clozapine withdrawal is usually followed by psychotic relapse, anti-obsessive drug trials were made as add-on. A marked reduction of compulsive rituals has been reported with a daily fluoxetine dosage of 20, 40, 60 mg [2, 5, 10] and 50 and 75 mg of sertraline [3, 6]. Fluvoxamine, added to clozapine, yielded also fair results [11]. To our knowledge clomipramine treatment of clozapine-induced OC symptoms has been reported in only 1 case at the dosage of 100 mg with improvement of symptomatology [3].

Personality, endocrine and immune changes after eight months in healthy individuals under normal daily stress.

The impact of stress and its neuroendocrine correlates on immune function are well established and individual variations could be attributed to modulation by personality characteristics. To assess the influence of everyday life stress and personality on neuroendocrine and immune function, we administered, to 18 healthy adults, the Minnesota Multiphasic Personality Inventory (MMPI) to assess their personality, the State-Trait Anxiety Inventory to measure anxiety, the Reaction Scheme Test to assess their coping reaction style, the Life Events Survey to assess the impact of stressful life events, and the Subjective Stress Questionnaire to assess perceived stress. The endocrine evaluation comprised prolactin, cortisol, and growth hormone plasma levels, while the immunological evaluation assessed T4, T8, and T11 lymphocyte percentages, as well as natural killer cell count and activity. All evaluations were made at baseline and after 8 months. We found a reduction of the T11 lymphocyte percentage to be accompanied by a reduction in the scores of the MMPI scale of Subtle Defensiveness and by an increase in the scores of the Social Introversion Scale. A positive correlation was found between prolactin and T4 lymphocyte percentage. These preliminary data show that some personality and endocrine measures correlate with immune function.

Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness

Several investigations have suggested pineal gland abnormalities in the pathogenesis of schizophrenia. The pineal volume on brain magnetic resonance imaging scans was calculated in 15 male schizophrenic inpatients and in 16 matched control subjects. The statistical comparison found a significant difference of pineal gland volume between schizophrenics and controls (P = 0.022), with a smaller pineal volume in the schizophrenics. These results do not confirm the previous data of Schizophrenia Res. 14 (1995) 253, showing no significant pineal volumetric differences between schizophrenics and normal controls. Since the present study is based on a smaller but more homogeneous sample of patients, this could reduce the heterogeneity features of the schizophrenic disease. No correlation was found between pineal volume and clinical and psychopathological features of the schizophrenic subjects. Volume reduction in schizophrenia could be at least partially included in the wider brain developmental abnormalities of the illness or in the late effects of previous neuroleptic treatments.