Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The KSV model of the schizophrenias proposes that up to 70% of schizophrenics have a pathogenic allele, or abnormal expression, of the KALIG-1 gene which is located at Xp22.3. This gene encodes a nerve-cell adhesion molecule (N-CAM) like protein, and is deleted in 66% of patients with Kallmann's syndrome, anosmia with secondary hypogonadism. Although superficially distinct, the schizophrenias and Kallmann's syndrome show numerous parallel trait defects which occur with a similar sex distribution. These defects are usually more profound in Kallmann's syndrome. Occasionally, Kallmann's patients exhibit additional defects, such as ichthyosis, which are due to the further deletion or translocation of adjacent genes. Since schizophrenics exhibit virtually all known trait defects in Kallmann's except these, it suggests that the aberrant genes are defective, but not deleted in schizophrenia. It also appears that compensatory mechanisms, involving serine proteases, are active in schizophrenia, which largely preserve fertility, but at the expense of an increased vulnerability to develop a psychosis by an episodic disruption of the blood-CSF barrier. Consequently, schizophrenia is rare in Kallmann's patients, while most schizophrenics are capable of reproduction.
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PMID:The Kallmann's syndrome variant (KSV) model of the schizophrenias. 846 Dec 65

Osteoporosis is a common problem in postmenopausal women. It has been linked to estrogen deficiency, other neuroendocrine processes such as hypercortisolemia and male hypogonadism, nutritional deficiencies, and other mechanisms. Some of these changes have been also reported in male and female patients with mental disorders, especially those receiving psychotropic medications. Therefore, bone mineral density was measured by dual-photon absorptiometry in the lumbar spine and in the femoral neck of 33 female and 35 male consenting psychiatric inpatients admitted consecutively. Patients were diagnosed as having major depressive disorder (N = 21), schizophrenia (N = 33), schizoaffective disorder (N = 7), mania (N = 2), and adjustment disorder (N = 5). Plasma levels of prolactin, estrogen, cortisol, and testosterone were also measured in a subgroup of these patients. It is reported that female patients, but especially male patients, had a highly significant decrease in bone mineral density when compared with age- and sex-matched normal data. It is suggested that psychiatric patients treated with antidepressants or neuroleptics might have decreased bone mineral density than is normal for their age and sex, and may be at an increased risk for fractures. These results may be related to low levels of gonadal hormones, especially in male subjects. Data should be confirmed with a larger number of patients with and without medications to distinguish between diagnosis-related and treatment-related effects.
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PMID:Decreased bone mineral density in medicated psychiatric patients. 855 40

Kallmann syndrome and schizophrenia share several clinical features, including dysfunctional olfactory ability, hypogonadotrophic hypogonadism, an excess of affected males, and psychiatric presentation. Because of this congruence, it has been proposed that up to 70% of male schizophrenics might have mutations affecting the function or expression of the gene mutated in Kallmann syndrome, KAL-X. We identified and studied 9 unrelated males with schizophrenia (as defined by DSM-IIIR criteria) who also have severe anosmia (first percentile of normal range) and low sex drive (seventh percentile of the normal range), and we sequenced the exons and the intron-exon junctions of the KAL-X gene for each. We found no mutations, and conclude that schizophrenia is rarely, if ever, due to a mutation in the coding sequence or splice junctions of KAL-X.
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PMID:Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia. 1005 Sep 64

The prevalence of schizophrenia is about 1% worldwide. Individuals with schizophrenia are at increased risk for osteoporosis and fractures for several reasons, including poor diet, lack of exercise, cigarette smoking, and polydipsia. Some antipsychotic medications may further increase the risk of fractures by causing dizziness, orthostatic hypotension, and falls. Studies in women with hyperprolactinemia resulting from pituitary tumors have demonstrated high rates of osteoporosis believed to result from hypoestrogenism. Similarly, hyperprolactinemia in men results in hypogonadism and bone loss. Preliminary surveys have indicated that schizophrenia patients also may have elevated rates of osteoporosis and pathological fractures, possibly resulting in part from the long-term administration of antipsychotic agents that produce hyperprolactinemia and secondarily lower estrogen and testosterone levels. This potential complication of treatment with certain antipsychotic agents requires careful study and could represent a serious public health problem.
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PMID:Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents. 1265 Jun 84

Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medical condition, worsening prognosis and contributing to the high rate of morbidity and mortality. Depression is associated with suicide, the leading cause of premature death in patients with schizophrenia; obsessive-compulsive symptoms may worsen prognosis; alcohol and substance use disorders are associated with a poor outcome; and comorbid medical conditions, including cardiac and pulmonary disease, infectious diseases, diabetes, hyperlipidemia, hypogonadism, and osteoporosis, are often underrecognized and undertreated. The new generation of antipsychotic medications has improved the potential outcome of patients with schizophrenia. Providing optimal treatment for patients and fully realizing the potential of these new agents require focused attention on detection, recognition, and treatment of comorbid psychiatric and medical conditions in patients with schizophrenia.
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PMID:Detection and management of comorbidity in patients with schizophrenia. 1268 63

Patients with schizophrenia frequently develop drug-induced hyperprolactinaemia and consequent hypogonadism. Reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism has been well documented in medical, but not psychiatric, disorders. Little attention has been given to the potential risk of developing osteoporosis secondary to anti-psychotic-induced hyperprolactinaemia. Three cases are presented that illustrate how this debilitating but silent disease may affect even those young individuals with schizophrenia.
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PMID:Reduced bone mineral density in patients with schizophrenia receiving prolactin raising anti-psychotic medication. 1487 Sep 61

Hyperprolactinaemia is an important but neglected adverse effect of antipsychotic medication. It occurs frequently with conventional antipsychotics and some atypical antipsychotics (risperidone and amisulpride) but is rare with other atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, ziprasidone). For this reason the terms 'prolactin-sparing' and 'prolactin-raising' are more useful than 'atypical' and 'conventional' when considering the effect of antipsychotic drugs on serum prolactin. During antipsychotic treatment prolactin levels can rise 10-fold or more above pretreatment values. In a recent study approximately 60% of women and 40% of men treated with a prolactin-raising antipsychotic had a prolactin level above the upper limit of the normal range. The distinction between asymptomatic and symptomatic hyperprolactinaemia is important but is often not made in the literature. Some symptoms of hyperprolactinaemia result from a direct effect of prolactin on target tissues but others result from hypogonadism caused by prolactin disrupting the normal functioning of the hypothalamic-pituitary-gonadal axis. Symptoms of hyperprolactinaemia include gynaecomastia, galactorrhoea, sexual dysfunction, infertility, oligomenorrhoea and amenorrhoea. These symptoms are little researched in psychiatric patients. Existing data suggest that they are common but that clinicians underestimate their prevalence. For example, well conducted studies of women treated with conventional antipsychotics have reported prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for galactorrhoea. An illness-related under-function of the hypothalamic-pituitary-gonadal axis in female patients with schizophrenia may also contribute to menstrual irregularities. Long-term consequences of antipsychotic-related hypogonadism require further research but are likely and include premature bone loss in men and women. There are conflicting data on whether hyperprolactinaemia is associated with an increased risk of breast cancer in women. In patients prescribed antipsychotics who have biochemically confirmed hyperprolactinaemia it is important to exclude other causes of prolactin elevation, in particular tumours in the hypothalamic-pituitary area. If a patient has been amenorrhoeic for 1 year or more, investigations should include bone mineral density measurements. Management should be tailored to the individual patient. Options include reducing the dose of the antipsychotic, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist and prescribing estrogen replacement in hypoestrogenic female patients. The efficacy and risks of the last two treatment options have not been systematically examined. Antipsychotic-induced hyperprolactinaemia should become a focus of interest in the drug treatment of psychiatric patients, particularly given the recent introduction of prolactin-sparing antipsychotics. Appropriate investigations and effective management should reduce the burden of adverse effects and prevent long-term consequences.
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PMID:Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. 1545 28

Evidence on the efficacy and safety of atypical antipsychotics in children and adolescents with schizophrenia is limited. The purpose of this review is to assess the published data on the use of atypical antipsychotics in children and adolescents with schizophrenia alone and with comorbid disorders, and to establish benefit-risk guidelines for clinicians.Risperidone, olanzapine and clozapine were found to be effective in the treatment of aggression and mania. Risperidone, and possibly also olanzapine, may be the drugs of choice in children with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition properties and may be administered as an augmenting agent in children and adolescents with schizophrenia and comorbid anxiety and mood disorders. Compared with the typical antipsychotics, the atypical drugs seem to be more effective, better tolerated and lead to better patient adherence. Importantly, the atypical antipsychotics have a lower propensity to induce extrapyramidal symptoms and a potential (shown so far only in adults) to improve cognitive function and inhibit suicidal behaviour (especially clozapine). Yet, the adverse effects associated with these agents, especially weight gain, which may also have long-term effects, can lead to non-compliance in the young population. In children and adolescents receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does not have a pro-appetite effect), particularly those with obesity or a family history of diabetes mellitus, fasting blood glucose and lipid levels must be monitored frequently. Weight gain might be better controlled when the children and their parents are properly informed about this adverse effect and diet is regulated. Another major disadvantage of the atypical antipsychotics, especially risperidone, is their association with hyperprolactinaemia, which can lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, all seen also with typical antipsychotics. Other atypical antipsychotics, namely olanzapine and ziprasidone, have been reported to be prolactin sparing in adults, but may not be completely devoid of hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels should be assessed routinely in young patients treated with atypical antipsychotics. Further, children and adolescents with hyperprolactinaemia-related effects should be switched to a prolactin-sparing agent, such as quetiapine. All atypical antipsychotics may induce sedation and they are not devoid of extrapyramidal symptoms (especially risperidone). The use of typical antipsychotics has been limited to patients who are resistant to atypical antipsychotics, intolerant to their adverse effects, or require injections or depot preparations. Further double-blind, placebo-controlled trials and long-term safety assessments are needed before definitive conclusions can be reached about the place of atypical antipsychotics in the therapeutic armamentarium of childhood-onset schizophrenia.
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PMID:Benefit-risk assessment of atypical antipsychotics in the treatment of schizophrenia and comorbid disorders in children and adolescents. 1555 47

Schizophrenic illness is associated with high rates of osteoporosis, the etiology of which remains obscure, but which may be at least partly explained by the prolactin-raising properties of antipsychotic medication. Conventional antipsychotics all cause hyperprolactinemia, whereas a limited number of atypical antipsychotic drugs do not. To investigate this further, we designed a cross-sectional comparison study between groups taking either prolactin-raising or prolactin-sparing antipsychotic medication. Participants were required to be premenopausal women with a diagnosis of schizophrenia, and to have received exclusively either prolactin-raising (n = 26), or olanzapine (n = 12) antipsychotic medication. Half of the subjects in the prolactin-raising group were being treated with conventional (n = 13), and half with newer "atypical," antipsychotic drugs (n = 13). Subjects had lumbar spine and hip bone mineral density (BMD) evaluated by a dual-energy x-ray absorptiometer (DEXA) scan. A blood sample was taken to measure prolactin and sex hormone axis measures. The results demonstrated that the group taking prolactin-raising medication had higher rates of bone pathology, compared with the olanzapine group. High prolactin levels were related to measures of hypogonadism and low BMD values. Within the prolactin-raising group, those taking newer atypical compounds had higher levels of prolactin, lower levels of sex hormones, and lower BMD values than the group taking conventional antipsychotic medication. These findings suggest that the high rates of osteoporosis associated with schizophrenia may result from hypogonadism secondary to antipsychotic-induced hyperprolactinemia, and that the prolactin-raising profile of antipsychotic drugs should be considered when choosing an antipsychotic drug.
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PMID:Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? 1564 97

Psychoneuroendocrinology deals with the overlap disorders pertaining to three different specialties. Awareness about the somatic manifestations of psychiatric diseases and vice versa is a must for all the clinicians. The knowledge of this interlinked specialty is essential because of the obscure presentation of certain disorders. Our first case was treated as depressive disorder, whereas the diagnosis was hypogonadism with empty sella. Our second patient was managed as schizophrenia and the evaluation revealed bilateral basal ganglia calcification and a diagnosis of Fahr's disease. We report these cases for their unusual presentation and to highlight the importance of this emerging specialty.
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PMID:Two interesting cases highlighting an oblivious specialty of psychoneuroendocrinology. 2380 89


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