Suicidal behavior and growth hormone response to apomorphine test.

Several cerebrospinal fluid (CSF) studies have provided support for a possible role for the dopaminergic system as a biological correlate of suicidal behavior. Indeed, low CSF levels of the dopamine metabolite homovanillic acid (HVA) have been described in depressed patients with a history of suicide attempts. In this study, we assessed the dopamine receptor sensitivity in relationship to suicidal behavior by measuring growth hormone (GH) response to apomorphine 0.5 mg subcutaneously (sc) in 15 DSM-III-R (APA 1987) major depressive inpatients with a history of suicide attempts, compared to age-matched and gender-matched major depressive inpatients without a history of suicide. Patients with a history of suicidal behavior exhibited a significantly lower GH response to apomorphine than patients who never attempted suicide (t = 3.60, df = 1.28, p = 0.0012). Therefore, these results suggest that a blunted GH response to apomorphine could represent a biological marker of suicidal behavior.     

Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine

The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity.     

Change of diagnosis in schizophrenia and first-rank symptoms: An eight-year follow-up

Fifty-seven patients diagnosed as schizophrenic at the inception hospital admission, because they had Schneider's first-rank symptoms, were investigated 8 years for change of diagnosis. The average duration of their psychiatric contact after the admission was 5 years. During this period 88% still had a diagnosis of schizophrenia, but seven patients had been given other diagnoses. Change of diagnosis was significantly associated with “voices discussing” when it was the only first-rank symptom. The question of whether “voices discussing” should be included in the canon of Schneiderian first-rank symptoms is discussed.     

Cerebral blood flow changes associated with Schneiderian first-rank symptoms in schizophrenia

The authors examined the severity of Schneiderian first-rank symptoms in relation to regional cerebral blood flow (rCBF) with the use of PET. Eighty-seven schizophrenic patients were imaged during an eyes-closed condition during which they were instructed to relax and not perform any specific task (random episodic silent thought, or REST). Schneiderian symptoms were rated by using structured assessment instruments. The Schneiderian score of the patients was positively correlated with rCBF in right superior parietal cortex and negatively correlated with rCBF in left posterior cingulate gyrus and in left lingual gyrus. The results of this study demonstrate a cerebral pattern of activation related to Schneiderian symptoms and reinforce the hypothesis of an involvement of cortical areas that mediate space and body representation in such phenomena.     

Schneider's first rank symptoms of schizophrenia in Kenyan patients

ABSTRACT - Eighty‘psychotic’patients admitted to Mathare Psychiatric Hospital, Nairobi, were screened using the New Haven Schizophrenic Index (NHSI). Fifty-one (64 %) of these were positive and the rest negative. Of those positive 73 % had First Rank Symptoms (FRS) of schizophrenia as opposed to only 24 % in the group negative for schizophrenia. This difference is highly significant (P < 0.001). The commonest individual FRS were thought echo, thought insertion, delusional mood and auditory hallucinations in third per-son. The frequency distribution of FRS had no relation to sex or age. These results are compared and contrasted with the findings of similar studies in various cultures.     

Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Relation to duration of illness and depressive symptoms

The responses of serum prolactin (PRL) and growth hormone (GH) to the dopamine agonist apomorphine hydrochloride (0.75 mg subcutaneously) were studied in a large group of unmedicated hospitalized patients with functional psychoses. There were no differences in the GH response in various diagnostic groups. The PRL response was greater in patients with affective disorders. The GH response was inversely related to total duration of illness in the entire sample of patients, but this correlation was independent of age effect only in the group of patients with major depression. In schizophrenics, the effect of the two factors, age and duration of the illness, could not be separated. The apomorphine-induced GH response was significantly correlated with psychosis ratings and negative symptom scale scores. The apomorphine-induced PRL suppression correlated significantly with various measures of depression across diagnostic groups.     

Specificity of Schneider's first rank symptoms for schizophrenia in Malay patients.

The frequency of Schneider's first rank symptoms (FRS) was studied in 221 Malay patients with functional psychosis. The prevalence of FRS in schizophrenia was 26.7%. The most common symptoms were voice arguing, passivity phenomena and somatic passivity. In the absence of organic brain dysfunction, the specificity of FRS for schizophrenia was 87.8%, and their positive predictive value was 90.6%. These findings indicate that although FRS is not pathognomonic of schizophrenia, their presence should be regarded as strongly suggestive of schizophrenia in the absence of organic etiology. FRS do not however occur with sufficient frequency to have potential diagnostic in schizophrenia.     

Frequency of occurrence of Schneider's first rank symptoms in schizophrenia

Summary We investigated the frequency of first rank symptoms (FRS) among patients hospitalised for schizophrenia for the first time in their life. The diagnosis was made in a Schneider oriented psychiatric hospital; 47% of the patients showed FRS. The frequency of FRS depends on the age and sex of the patient and on the existence of somatic findings but is independent of the level of their intellectual capacity or of the duration of the observation time.     

Growth hormone response to apomorphine in obsessive-compulsive disorder.

Several lines of evidence suggest that dopamine plays a role in the pathophysiology of obsessive-compulsive disorder (OCD). Indeed, some trials have shown the efficacy of neuroleptic addition in the treatment of OCD patients. In this study, we assessed the growth hormone (GH) response to 0.5 mg apomorphine(sc) in 8 drug-free inpatients (6 male, 2 female; mean age +/- SD = 34.7 +/- 12.6) meeting DSM-III-R criteria for OCD without major depression and compared their responses with those of 8 healthy male volunteers (mean age = 27.1 +/- 8.5). The groups did not differ in their mean GH peak response: 12.4 +/- 9.7 ng/mL in OCD patients versus 21.1 +/- 14.2 ng/mL in normal controls (F = 0.9, df1, 14, P = 0.37). These results do not support the hypothesis of dopaminergic overactivity in OCD. In fact, the completely blunted GH response to apomorphine in 2 OCD patients suggests the biological heterogeneity of OCD. Some dopaminergic disturbances could be observed in patients with comorbid diagnoses or patients unresponsive to serotonin reuptake inhibitors, but the results of this study require confirmation from a larger sample with a precise assessment of comorbidity.     

Increased growth hormone response to apomorphine in Parkinson disease compared with multiple system atrophy

BACKGROUND: Parkinson disease (PD) is often difficult to distinguish from parkinsonian syndromes of other causes in early stages of the disease. In search of a suitable endocrinologic challenge test, we investigated dopaminergic sensitivity in patients with de novo parkinsonian syndromes. OBJECTIVE: We measured the growth hormone (GH) response to a subthreshold dose of the dopamine 1-dopamine 2 receptor agonist apomorphine hydrochloride to differentiate parkinsonian syndromes from PD. PATIENTS AND METHODS: Seventeen patients with a clinical diagnosis of PD, 16 patients with a clinical diagnosis of multiple system atrophy, and 11 healthy controls. The GH response to a subthreshold dosage of apomorphine and to somatorelin (GH-releasing factor) was tested in a randomized order; on the third day the protocol was repeated with a clinically effective dose of apomorphine. RESULTS: The GH response to the low dose of apomorphine was significantly increased in patients with PD when compared with patients with multiple system atrophy or the control subjects (multivariate analyses of covariance; univariate F test, all P<.05). In contrast, there were no significant group differences with use of the higher dose of apomorphine or in the somatorelin-induced GH release. CONCLUSIONS: The GH response to a subthreshold dose of apomorphine appears to be a useful tool to identify patients with PD vs multiple system atrophy. The enhanced GH response to a subthreshold dopaminergic stimulus may reflect a hypersensitivity of the extrastriatal dopamine receptors in PD.     

Growth hormone response to growth hormone releasing hormone in depression and schizophrenia

Growth hormone releasing hormone, a 44-amino acid peptide (GHRH-44), was administered (1 micrograms/kg i.v.) to 6 normal controls, 10 schizophrenic subjects, and 7 depressed subjects. A significantly lower growth hormone (GH) response was found in the schizophrenic and depressed groups. Two molecular forms of GH, 22K GH and 20K GH, were also measured but did not further differentiate the three groups of subjects.     

Reduced growth hormone response to apomorphine in schizophrenic patients with poor premorbid social functioning

Summary The apomorphine-induced growth hormone (GH) response of 16 drug-free schizophrenic patients and nine control subjects were studied. The sub-group of nine patients with poor premorbid psychosocial functioning had a significantly lower GH response than the controls. Additional evidence for state dependent effects is provided.     

Cerebral ventricular enlargement in chronic schizophrenia. An association with poor response to treatment

Response to neuroleptic drug treatment in ten chronic schizophrenic patients with enlarged cerebral ventricles was compared with ten similar patients with normal ventricles. The groups were closely matched for age, age at onset of illness, years of illness and hospitalization, drug dosage, and plasma neuroleptic concentration as measured by radioreceptor assay. Response was significantly worse in the patients with enlarged ventricles. This finding supports the notion that ventricular enlargement is clinically relevant in patients with chronic schizophrenia and that patients with this abnormality may have a biologically different illness than similar patients without it.     

A cross-cultural study of the frequencies of Schneider's first rank symptoms of schizophrenia

The Syndrome Check List (SCL) as detailed by Wing et al. (1) was used on patients belonging to various cultural groups admitted to a London hospital. On the basis of combined Catego diagnosis of schizophrenia and paranoid schizophrenia the frequency of patients with first rank symptoms (FRS) for each group was calculated. It was found that the frequencies of FRS showed cultural differences and that these differences were less when groups were relatively culturally similar. These findings are compared with findings elsewhere. The clinical dilemma presented by these findings is discussed.     

Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man

Summary The stereospecificity of the D-2 receptor mediating the growth hormone (GH) response to apomorphine (Apo) and the D-2 receptor regulating prolactin (PRL) secretion were investigated in 10 normal men by examining the effects of cis-flupenthixol (cis-Fx) and trans-flupenthixol (trans-Fx). cis-Fx (1 mg six hourly times four doses) antagonized the GH response to Apo HCl (0.5 mg sc) and increased basal serum PRL concentrations whereas the transisomer showed no effect. These findings (a) provide further evidence that the GH response to Apo is mediated by stimulating dopamine (DA) receptors, and, (b) demonstrate stereospecificity of the DA receptor mediating the GH response to Apo and the DA receptor regulating PRL secretion.     

Growth hormone responses to graded doses of apomorphine HCl in schizophrenia

Growth hormone (GH) responses to graded doses of apomorphine HCl (APO) were established in 14 normal males, ages 18-50, and 10 drug-free schizophrenic (SCZ) subjects; 99% confidence intervals were calculated for normal subjects' GH responses to graded doses of APO. Patients' GH peak levels were found to be outside the interval only when they had positive symptoms of psychosis. When they are actively psychotic, the schizophrenics' GH response to small doses of APO is more sensitive than that of normals.     

Growth hormone response to apomorphine and family patterns of illness

Sixty-five psychotic probands were divided into three groups (low, intermediate, and high) on the basis of the GH response to the dopamine receptor agonist apomorphine. Two hundred and sixty-five first-degree relatives of the probands were diagnosed according to SADS-DSM-III methods, and the relatives of the three groups of probands were compared so as to detect familial differences in the incidence of DSM-III Axis I disorders, schizotypal personality disorder, and antisocial personality. Although the morbid risk of schizophrenic spectrum disorder was only 3.1% in the relatives of the high GH probands, the morbid risk for disorders of the schizophrenic spectrum was 17.0% and 10.7% in the relatives of the intermediate and low GH probands, respectively. These data provide preliminary evidence that there may be a psychotic subtype that is characterized by supersensitivity of the dopamine system that is familially, and perhaps genetically, distinct from the bulk of the schizophrenias.