Schizophrenia and the origins of shamanism among the Kwakiutl maritime cultures of Northwest North America: a hypothesis.
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Culture↗
Biomedical subjects
Rif S El-Mallakh
Publications and source records attributed to Rif S El-Mallakh.
Efficacy of olanzapine and haloperidol in an animal model of mania.
PURPOSE: Intracerebroventricular (ICV) administration of ouabain, a potent sodium pump inhibitor, has been used to model mania. Antipsychotic agents have demonstrated efficacy in the management of acute mania. This study was undertaken to determine the prophylactic efficacy of olanzapine and haloperidol in the ouabain mania model. METHODS: Male Sprague-Dawley rats (4-8/group) were treated with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open field locomotion was quantified at baseline and after ouabain administration. RESULTS: Ouabain caused a significant increase in open field locomotion (253.7+/-SEM 55.12 vs control 53.1+/-12.13 squares traversed in 30 min in the olanzapine experiments, P<0.05; and 236.5+/-41.42 vs 129.3+/-38.23, P<0.05 in the haloperidol experiments). Olanzapine alone at low dose (102.2+/-37.7) or high dose (151.2+/-49.2) did not alter open field activity. Low dose olanzapine (176.6+/-73.27) but not high dose (307.5+/-167.32) caused a modest reduction of the ouabain effect. Haloperidol alone significantly reduced motoric activity compared to control (55.6+/-18.0, P<0.05), and prevented ouabain-induced hyperactivity (60.3+/-33.1, P<0.05). CONCLUSION: Haloperidol, but not olanzapine, demonstrated efficacy in this mania model, but methodological details may have reduced the effect of olanzapine.
Analysis of Variance↗
Glial cell number and neuron/glial cell ratios in postmortem brains of bipolar individuals.
BACKGROUND: There are several lines of evidence implicating a glial abnormality in the pathophysiology of bipolar disorder. Previous studies have reported a wide range of abnormalities but with little consistency between their findings. METHODS: Sixty frozen postmortem temporal cortical brain samples from normal, schizophrenic, bipolar, and depressed subjects were obtained from the Stanley Neuropathology Consortium. Nissl stain was utilized to visualize cellular structures. The sections were analyzed for neuron and glial content using the computer programs SPOT Advanced and Metamorph. Three representative fields from each subject were counted and the average numbers obtained. RESULTS: There was no critical difference in glia number across the four diagnostic groups. Compared with normal controls, area occupied by glia was reduced in bipolar subjects (P = 0.018), and the ratio of glial area to neuronal area was reduced (P = 0.028). DISCUSSION: The percent glial space was substantially lower in bipolar disorder subjects compared to normal controls, suggesting that the glia may be smaller in bipolar subjects. The size reduction may be reflective of glial dysfunction. LIMITATIONS: Postmortem interval of 29.4 +/- S.D. 13.4 h may have affected cellular structure and reduced the quality of the staining.
Bipolar Disorder↗
Naturalistic long-term use of methylphenidate in bipolar disorder.
Antidepressant use seems to be problematic in bipolar disorder. The dopaminergic agent, bupropion, seems to be equally effective to serotoninergic agents but with greater safety. Methylphenidate is a stimulant medication that is sometimes used as an antidepressant in bipolar adults and is frequently used in children with comorbid bipolar and attention-deficit disorder. There are no data available for the safety of long-term methylphenidate in adults. A retrospective chart review of bipolar patients who received methylphenidate while attending a bipolar clinic was conducted. Data regarding side effects and symptoms were collected. Sixteen charts were reviewed. The mean duration of methylphenidate treatment was 14 months (+/-SD, +/-17.5 months; range, 1-60 months). Five had comorbid attention-deficit disorder, the remainder received the methylphenidate for depression. The mean dose was 16.3 mg/d (+/-SD, +/-8.7 mg/d; range, 5-40 mg/d). Several mild to moderate side effects were reported. Two patients (12.5%) discontinued methylphenidate because of adverse side effects. When available (44% of the sample), general assessment of function increased from (+/-SD) 48.3 +/- 9.9 to 69.3 +/- 10.6 (P = 0.006). Methylphenidate seems to be safe in the naturalistic setting. Controlled studies are needed to confirm its efficacy and safety in bipolar depression.
Adolescent↗
Chronic depression in bipolar disorder.
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Adolescent↗
Antipsychotic medications in the treatment of bipolar disorder.
Antipsychotic medications have been used to treat acute phases, and prevent relapses in, bipolar illness since their introduction into psychiatric practice. With the introduction of second generation antipsychotic medications, there has been renewed interest in the utility of this class of medications in managing manic-depression. It appears that all antipsychotic agents investigated have a potent acute antimanic property. This has been shown both in monotherapy and in combination with traditional mood stabilizing medications. The first generation antipsychotics appeared to worsen depression or induce a depressive-like state, but the second generation agents do not have this property and may have some antidepressant properties in bipolar patients. There is a dearth of controlled long term studies, but in open studies, both first and second generation agents appear to have a beneficial effect. Second generation antipsychotic agents appear to be a useful tool that may benefit bipolar patients. Adverse consequences of this group of medications appear to be the major limiting factors to their use. Antipsychotic medications play a very important role in the treatment of bipolar illness. This has become especially true since the introduction of second generation agents. There is a wealth of data documenting the use of these agents in bipolar mania. There are fewer studies examining relapse prevention. Finally, there are a small number of interesting studies suggesting utility in bipolar depression. This paper will critically review available randomized clinical trials utilizing antipsychotic agents in bipolar disorder.
Animals↗
Post lumbar-puncture headaches in schizophrenic and psychiatrically normal control subjects.
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Adult↗
Psychiatric disposition of patients brought in by crisis intervention team police officers.
BACKGROUND: As part of an effort to improve police interactions with mentally ill citizens, and improve mental health care delivery to subjects in acute distress, the University of Louisville, in conjunction with the Louisville Metro Police, established the crisis intervention team (CIT). CIT is composed of uniformed officers who receive extensive training in crisis intervention and psychiatric issues and who are preferentially called to investigate police calls that may involve a mentally ill individual. METHODS: In an effort to determine the characteristics of the individuals brought to the emergency psychiatric service (EPS) by CIT officers, a comparative (CIT vs. mental inquest warrant [MIW, a citizen-initiated court order to bring someone for psychiatric evaluation because of concerns regarding dangerousness] vs non-CIT/non-MIW), descriptive evaluation was performed. RESULTS: With the exception of a higher rate of schizophrenic subjects brought in by CIT (43.0% vs. 22.1%, non-CIT, P = .002), the demographics, diagnosis, and disposition of CIT-referred subjects were not different in any way from non-CIT patients. Subjects referred on MIWs were more likely to be admitted to a psychiatric hospital than non-MIW patients (71.6% vs. 34.8%, P < .0001), but CIT-referred hospitalization rates were not different from hospitalization rates of self-referred subjects (20.7% vs. 33.3%, ns). CONCLUSIONS: CIT officers appear to do a good job at identifying patients in need of psychiatric care.
Commitment of Persons with Psychiatric Disorders↗
Serotonin gene polymorphisms and bipolar I disorder: focus on the serotonin transporter.
The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.
Bipolar Disorder↗
Substance abuse: medical and slang terminology.
Substance abuse is among one of the major problems plaguing our society. It has come to the attention of several healthcare professionals that a communication gap exists between themselves and substance abusers. Most of the time the substance abusers are only familiar with the slang terms of abused substances, a terminology that medical professionals are usually unaware of. This paper is an attempt to close that communication gap, allowing health care professionals to understand the slang terminology that their patients use, thus enabling them to make appropriate treatment decisions. In addition, the article presents some key features (including active ingredient, pharmacological classification, medical use, abuse form, usage method, combinations used, effects sought, long-term possible effects, and detectability in urine) of the most commonly abused substances.
Humans↗
Serious rash with lamotrigine after carbamazepine discontinuation: a case report.
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Anticonvulsants↗
Differential response of bipolar and normal control lymphoblastoid cell sodium pump to ethacrynic acid.
BACKGROUND: While the pathogenesis of manic-depressive, or bipolar, illness is unknown, an excess of intracellular sodium and calcium concentrations is thought to contribute to the development of the illness. Previous work has demonstrated a reduced adaptive response of the sodium pump to ethacrynic acid in lymphocytes obtained from bipolar subjects compared to psychiatrically normal controls. METHODS: To further examine this phenomenon, we investigated several aspects of sodium pump response (transcription, translation, activity, and intracellular ion concentration) in lymphoblastoid cell lines derived from bipolar subjects and matched normal controls. Cells were treated with ethacrynic acid 100 microM for 3 days. RESULTS: Normal control-derived cells exhibited an upregulation of sodium pump mRNA synthesis, protein expression, pump-specific binding and activity, and were able to maintain a normal intracellular sodium concentration. Cells derived from bipolar individuals did not alter sodium pump parameters in any way, and consequently, had a higher intracellular sodium concentration. LIMITATIONS: While bipolar lymphoblasts were from an inbred Old Order Amish population, the normal controls were from an outbred population. CONCLUSIONS: The results suggest that bipolar illness is associated with an abnormality in cellular sodium homeostatic regulation.
Adult↗
Dialysis of saliva improves accuracy of saliva lithium determinations.
BACKGROUND: Saliva lithium (Li) determinations have been explored as a potential alternative to plasma levels. Unfortunately, this method has been shown to be unreliable. Saliva has two major components: the aqueous and the mucopolysaccharide portions. METHODS: Since Li is likely to distribute only in the aqueous fraction, we dialyzed the saliva through a 3000 Da filter to isolate the aqueous component and determine the Li level in it. RESULTS: Lithium levels in the dialyzed saliva agreed more closely with plasma levels (Spearman's rho = 0.901, p < 0.001) than did whole saliva (Spearman's rho = 0.775, p = 0.012). CONCLUSION: Dialysis of saliva may contribute to more accurate saliva Li levels.
Adult↗
Follow-up after inpatient psychiatric hospitalization with partial control of the system responsiveness variable.
One of the most significant predictors of prompt rehospitalization following psychiatric hospital discharge is missing follow-up out-patient appointments. Previous studies have suggested that system responsiveness accounted for much of the variance in predicting compliance with aftercare. Collaborations established at our institution allowed us to partially control this variable, opening the way to explore other obstacles to aftercare. All severely mentally ill subjects discharged from our hospital are provided follow-up appointments within two weeks. We retrospectively evaluated compliance with aftercare appointment and investigated factors that were associated with compliance. Eighty-one subjects were evaluated. Twenty-seven (33.8 %) did not attend their first follow-up appointment. Subjects with a primary substance-related syndrome were the most likely to miss their appointment (83.3%, chi 2 = 17.02, p = .0045), as were uninsured patients (51.6%, chi 2 = 8.79, p = .003). There was a trend for individuals not previously involved with their aftercare providers to miss their appointment (48.9%, chi 2 = 3.35, p = .067). Despite partial control of the system responsiveness variable, compliance with aftercare was suboptimal. This was due to a combination of client vulnerability variables and uncontrollable system responsiveness factors.
Adolescent↗
Effect of ethacrynic acid on sodium pump alpha isoforms in SH-SY5Y cells.
BACKGROUND: Ethacrynic acid (ECA), a diuretic that has several cellular actions, increases expression of the sodium and potassium-activated adenosine triphosphatase (Na, K-ATPase or Na pump) in normal lymphocytes, but not in lymphocytes of bipolar patients. While this has been proposed to be important in the pathophysiology of bipolar illness, the response of neural tissues to ECA is unknown. METHODS: Human neuroblastoma SH-SY5Y cells differentiated with 10-microM retinoic acid were treated with various ECA concentrations for 3 days, and changes in Na-pump alpha-isoform expression were quantified with densitometric analysis of Western bands. RESULTS: Expression of alpha1 and alpha3 Na pump isoforms significantly increased with 10-5 M ECA. Cells treated with 10-6 or 10-7 M ECA showed no change in Na-pump expression, while cells treated with 10-4 M ECA died. The alpha2 isoform could not be detected in differentiated SH-SY5Y cells. CONCLUSIONS: The effect of ECA on alpha1-isoform in neural tissue is similar to that observed in lymphocytes. As alpha3 isoform is not expressed in lymphocytes, however, we conclude that lymphocytes are an incomplete model of neural tissue.
Bipolar Disorder↗
Intracerebroventricular administration of ouabain as a model of mania in rats.
BACKGROUND: Human bipolar illness is characterized by mood state- and diagnosis-associated abnormalities of cellular cation distribution and transport. These include reduced sodium pump activity and expression and increased intracellular sodium. If these alterations are related to the pathophysiology of the disease, rather than secondary or ancillary abnormalities, then one would expect that modeling of these changes in vivo would produce lithium-preventable behavioral abnormalities. METHODS: Ouabain, a potent inhibitor of the sodium pump, was administered intracerebroventricularly to male rats previously fed lithium-containing food or plain rat chow. Locomotion was then quantified in an open field. RESULTS: Ouabain increased locomotion 300% over baseline. Lithium pretreatment prevented the ouabain-induced hyperlocomotion response. CONCLUSION: Inhibition of central nervous system sodium pump with ouabain produces a plausible animal model of mania. This model may be useful for preclinical screening of potential mood stabilizers.
Animals↗
Antidepressant exposure in bipolar children.
BIPOLAR disorder is increasingly diagnosed in children and adolescents. Given that antidepressants may precipitate mania, and with increased use of antidepressants in youths, it is reasonable to ask whether antidepressant administration might play a role in inducing earlier manic episodes. We reviewed all consecutive admissions with a diagnosis of bipolar disorder to a university-affiliated children's hospital, and collected information regarding previous exposure to antidepressants and stimulants. The mean age of diagnosis of bipolar disorder in our cohort was 12 +/- SD 3.47 years. Children who received prior antidepressant and/or stimulant treatments had an earlier bipolar diagnosis (10.7 +/- 3.05 years) than children never exposed to these medications (12.7 +/- 4.3 years; one-tailed t = -1.33, df = 22, p = .099, power = .93). Stimulants appeared to be tolerated for a longer duration than antidepressants (55.5 +/- 20.42 months vs. 6.7 +/- 8.22 months, t = 6.6, df =12, p = .0001). Despite methodological imperfections, results indicate that children exposed to antidepressants appear to be diagnosed with bipolar disorder earlier than those never exposed to these medications. Although far from conclusive, these data are consistent with the hypothesis that antidepressant treatment is associated with a manic episode earlier than might occur spontaneously.
Adolescent↗
Use of antidepressants to treat depression in bipolar disorder.
For decades, clinicians and researchers did not distinguish between bipolar and unipolar depression. The safety and efficacy of antidepressants for the treatment of unipolar depression were studied, and the data were applied to the treatment of bipolar depression without validation. As evidence has accumulated that antidepressants may adversely affect the course of bipolar illness, more research has been focused on that problem. Current evidence suggests that although antidepressants are clearly effective in the acute treatment of type I and type II bipolar depression, they are also associated with a variety of adverse outcomes. They may induce a switch to mania or hypomania at a rate two or three times the spontaneous rate. Long-term use may destabilize the illness, leading to an increase in the number of both manic and depressed episodes; induce rapid cycling (at least four episodes a year); and increase the likelihood of a mixed state. Antidepressants should be used with caution in the treatment of bipolar depression.
Acute Disease↗