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Six kindreds containing multiple cases of Manic-depressive illness (MDI) were genotyped with seven highly polymorphic microsatellite loci used in the construction of an index map for chromosome 21. The kindreds were also genotyped with a microsatellite polymorphism for PFKL, a chromosome 21 locus that has shown suggestive linkage to MDI in one pedigree [Straub et al., 1993: The American Society of Human Genetics]. Evidence of linkage was not found assuming either autosomal dominant or recessive inheritance. The nonparametric affected sib pair test did not yield significant evidence of linkage.

In the expanding vocabulary of manic depression, bipolar 1 disorder denotes episodes of depression alternating with mania (which may be psychotic); bipolar 2 describes depression alternating with hypomania (essentially a milder form of mania); bipolar 3 describes a first episode of mania precipitated by antidepressant medication; and bipolar 4 describes depression in someone who has been previously hyperthymic (expansive or “larger than life”). Readers of Andy Behrman's memoir may ask themselves which of these syndromes are being described. The press reviews cited on the book's cover suggest that psychiatrists will question Behrman's account. “Don't listen to them,” warns the Times …

Lithium has been demonstrated to be therapy of choice in the treatement and prevention of mania and manic depression. The narrow therapeutic range (0.5-1.2 mmol/L) and significant side effects are associated with lithium require continous control of the drug serum level. Fasting serum concentrations of lithium was determined in 160 patients (95 women and 65 men) treated at the University Department of Psychiatry, Sestre milosrdnice University Hospital, who received 300, 600 or 900 mg lithium per day. Serum lithium concentration was determined by the colorimetric method based on the sample lithium binding to azo dye 6-dodecyl-6-(2 ; ; -hydroxy-5 ; ; -(2 ; ;  ; ; -4 ; ;  ; ; -dinitrophenylazo)benzyl-13, 13-dimethyl-1, 4, 6, 11-tetraoxacyclotetradecane (Vitros Li slidesi, Ortho-Clinical Diagnostics, a Johnson-Johnson company, Kodak Ektachem analyzer). In the women receiving 300 (n=7), 600 (n=40) and 900 (n=48) mg lithium/day, the mean (range) serum lithium concentration was 0.39 (0.24-0.59), 0.60 (0.25-1.17) and 0.68 (0.24-1.17) mmol/L, respectively. Among men, none of the patients received a dose of 300 mg lithium/day. In the men administered 600 (n=23) and 900 (n=40) mg lithium/day, the mean (range) serum lithium concentration was 0.51 (0.26-0.99) and 0.65 (0.2-1.48) mmol/L rspectively. These results clearly point to the need of therapeutic monitoring, for both serious lithium side effects within therapeutic range and to the patient's thepapeutic compliance.

The tragic case of a 22-year-old woman, Sarah Lawson, suffering from manic depression, whose father has pleaded guilty to the charge of manslaughter and is awaiting his sentence after helping her to commit suicide, has called into serious question the level of support that people with severe mental health problems and their families are receiving in the community. The trust at the centre of the case is to set up an official inquiry.

Manic depression is part of my life, and as I have suffered both the agony of manic episodes and the despair of depressive ones, the thought of obtaining lasting happiness has a recurring appeal. Yet deep down I know this appeal to be false. Richard Bentall once proposed that happiness be classified as a mental disorder,1 but only as a device to parody psychiatric orthodoxy, and so did not intend it to be taken literally. He may have stumbled unwittingly, …

In an attempt to identify susceptibility loci for bipolar affective disorder, we are currently conducting a systematic genome screen with highly polymorphic microsatellite markers at an average marker spacing of 10 cM in a series of 75 families, comprising 66 families from Germany, eight families from Israel, and one family from Italy. The families were ascertained through index cases with bipolar affective disorder. The distribution of diagnoses is as follows: 126 individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with schizoaffective disorder of the bipolar type, 40 individuals with recurrent unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals with a diagnosis of schizophrenia. One hundred and seventy-one individuals are unaffected. Here, we present results from chromosome 10. Linkage analyses using a total of 33 microsatellite markers with parametric and non-parametric methods provided evidence for linkage at chromosomal region 10q25--q26. The highest two-point LOD score (2.86, theta = 0.05) was obtained for D10S217 using a dominant genetic model and a broad definition of affection status. The GENEHUNTER program localized the putative susceptibility locus within a ca 15-cM interval between markers D10S1483 and D10S217 with a maximum NPL(all) score of 3.12 (P = 0.0013). Positive linkage findings that have been reported by two independent studies further support the hypothesis of a susceptibility gene for bipolar affective disorder on 10q25-q26.

Answers on p 379. A 72 year old man with manic depression, who had recently started lithium treatment, presented to casualty with a two day history of severe nausea and vomiting. His serum urea and electrolytes were normal (sodium 139 mmol/l, potassium 4.1 mmol/l, creatinine 94 mmol/l, and urea 5 …

Publisher Summary This chapter focuses on the biological aspects of depression. Depression is a state of low spirits or vitality. Psychiatrists divide depression into two types: endogenous, which is no apparent external cause, and reactive, which is an identifiable external cause, and while such a division may be of some value regarding ancillary treatment, there is currently no evidence to suggest that the biochemical changes that may be causally linked to the illness differ or any evidence that the ways in which the patient should be assisted by drugs differ substantially. Other international classifications of depression are based on the mono- and bipolar dichotomies that separate those patients with depressive symptoms only from those that fluctuate between depression and mania (i.e., manic depression) or have only manic symptoms. There are four major approaches to understanding the biochemical etiology of depression—namely, the analysis of postmortem brain of depressed suicide victims for neurotransmitters and their metabolites, the analysis of cerebrospinal fluid from depressed patients, the investigation of peripheral markers of neurotransmitter receptors by studying blood cells, for example, platelets and lymphocytes, and endocrine disturbances, which appear to be linked to the onset and duration of depression.

In manic–depressive disorder, the monotonic, humor/receptor, excess/deficit, i.e. gain, theories have prevailed for many years, even though there is increasing evidence of a timing abnormality that may or may not be related to gain. In addition, the manic–depressive course is clearly multimodal and unpredictable except in revealing but rare cases, yet the system is real, and thus presumably deterministic, clearly suggesting a dynamic instability. A wide range of disciplines was reviewed by the author. Those data that were significantly different by standard tests were considered. However, averaged values were always questioned. During this review, higher water compartmentalization differentials were found in manic–depressive patients. Also indicated, event-related potential components differed in latency correlations, suggesting action potential firing event dyscorrelation (Equation 2). In conclusion, the manic–depressive action potential firing events may be dyscorrelated in a space–time reference frame.

The application of molecular genetics to the study of mental disorders has begun in earnest. Most of the initial interest has focused on the functional psychoses as these common and debilitating disorders have long been known to have a significant genetic component. A number of groups have now reported data from RFLP linkage studies of both schizophrenia and bipolar affective disorder (manic-depression). Unfortunately the results are already conflicting with early findings of linkage unconfirmed by subsequent studies.

The long anticipated ‘genetic revolution’ in neuropsychiatry has yet to have an impact on the practice of clinical medicine. Excitement in the 1980s over major genetic breakthroughs in schizophrenia and manic depression, for example, has been replaced in the late 1990s by the sobering realization that most common neuropsychiatric disorders are multifactorial. Despite considerable effort and resources, no ‘causative’ genetic variation has been identified that plays a definitive major role in any common neuropsychiatric disorder.

Recent reports on susceptibility loci for manic depression have sparked lively debate. The pros and cons of these findings are discussed from a methodological vantage point, with implications for linkage studies generally.

How the health service deals with severe mental illness which might pose a danger to others is always a matter of concern to the public. But it is often overlooked that it is the sufferer who is at the greatest risk. My daughter, who suffered from manic depression, received no treatment and committed suicide, aged 26, in September 1995. I have been trying to ascertain what went wrong, how she could have been helped, and who is interested in preventing such tragedies in the future. So far I have had little success. It seems as if general practitioners are not as well informed about mental illness as they might be. My daughter had registered with a general practitioner in the south of England on starting a job there towards the end of 1994. She presented with severe weight loss and gastric disturbance; in January 1995 I …

▪ Abstract How lithium works in manic-depressive illness is unknown. Recently, however, a powerful hypothesis has been gaining momentum. Distinguished by its testability and clinical implications, the inositol depletion hypothesis of lithium action is relevant to treatment of lithium side effects, to the development of new compounds with the clinical profile of lithium, and to new experimental treatment of depression.

A cytopathic 'stealth' virus was cultured from the cerebrospinal fluid of a patient with a bipolar psychotic disorder who developed a severe encephalopathy leading to a vegetative state. DNA sequencing of a polymerase chain reaction-amplified product from infected cultures has identified the virus as an African green monkey simian cytomegalovirus (SCMV)-related stealth virus. The virus is similar to the SCMV-related stealth virus isolated from a patient with chronic fatigue syndrome. The findings support the concepts that stealth viruses can account for a spectrum of dysfunctional brain diseases and that some of these viruses may have arisen from live polio viral vaccines.

There are several psychiatric illnesses that are difficult to treat with drugs. Among these are schizophrenia, manic depression, and profound depression; many of these may involve a tendency to suicide. In 1938 U. Cerletti conducted convulsive experiments on pigs using power-line current applied to electrodes at various sites. The effect of current duration was also investigated. As yet it is not known which areas in the brain are the optimum targets for the therapeutic use of cranially applied current to treat psychiatric illnesses, although the frontal lobes appear to be the best targets.

Many of the recent studies reporting genetic linkages for mental illnesses such as schizophrenia and manic depression have been retracted. The authors of this article argue that the fundamental reason for the difficulties in this research field lies in the strongly held preconceived belief that the primary cause of these illnesses is in fact genetic. All scientists hold preconceived ideas. However, such ideas are more likely to result in erroneous conclusions in the study of human behavior than in other more ‘objective' research areas. Moreover, it is especially important that researchers studying human behavior be aware of their biases and learn to compensate for them because of the social consequences of their work.

Linkage between stuttering and manic-depression has been postulated to account for the reported association between these conditions, in three large pedigrees. This finding permits a novel and potentially more productive sampling strategy to be used in future linkage studies.

Suppose it is 2011. The Humane Genome Project (HGP) finished 5 years ago, making new forms of genetic screening of very young embryos and foetuses possible. Older types of screening can now be carried out earlier and more reliably (e.g., to screen for the sex of the foetus and for ethnically-related conditions such as sickle cell anaemia). Young foetuses can now also be screened for predisposition to other conditions. Imagine these include so-called “deviances” such as homosexuality, alcoholism, criminality and manic depression (Tyler 1991); inherited dispositions to disease such as Parkinsonism or certain cancers and to mental illness; physical defects ranging from short-sightedness to quadriplegia; mild mental handicap; and personality traits ranging from general “intelligence” to athleticism.

In Chapter 1 the major studies of offspring of parents with affective disorders were discussed and their general findings were noted. Across the various projects a generally dismal picture emerged: children of mothers and fathers with depression or manic depression were significantly more likely to have diagnoses and impairment than were children of normal parents. In this chapter the findings are reviewed in greater detail, with primary interest in the studies that employed direct interview methods and DSM III criteria. Such studies permit us to compare rates of disorder across studies, by different parental diagnoses.

Neil Cole has been the State Member for Melbourne since 1988 and was a Melbourne City Councillor for 3 years. He was the first Member of Parliament in Australia to confront the stigma of mental illness by publicly acknowledging his manic depression. Prior to entering parliament he was a Community Lawyer at Flemington Community Legal Service for 7 years. Neil was National Convenor of the Nuclear Free Zone Secretariat (1986-88), Chairperson Joint Parliamentary Economic and Budget Review Committee (1991-92) and Shadow Attorney General from 1992 to 1995. He is Deputy Chair of the Joint Parliamentary Law Reform Committee of the Victorian Parliament. Neil has written three plays with 'Alive at Williamstown Pier' being his first. He is currently employed as a consultant to the Mental Health Research Institute at Royal Park Melbourne.

This book is written by a man with bipolar affective disorder and his doctor, who is also a personal friend of his. It is divided into several sections and has a foreword by a famous person with manic depression: Stephen Fry. Dr Tony Hughes and Stephen Fry also collaborated on the recent television

New national guidance for England and Wales encourages doctors to spot and treat bipolar disorder sooner and more accurately. Bipolar disorder, formerly known as manic depression, affects around 1% of the population and takes an average of eight years to be correctly diagnosed. It is associated with the highest suicide rate of any mental illness—one in seven people who are untreated commit suicide—but it …

Lithium, despite its simple structure, has numerous biological effects. It also has a remarkable therapeutic effect in the prophylactic treatment of manic depression, and is finding a role in controlling aggressive and self-mutilating behavior. The special feature of lithium is that it only acts on overactive systems to bring them back to normal, without affecting the stable system. The mechanisms of action of this simple cation are still largely unknown although the inositol depletion theory is the most widely accepted model. A recent paper described a different molecular mechanism for its effect on development, which may also explain its action in manic depression.

A sample of 202 Kuwaiti college students (63 men and 139 women; Mage = 21.6 yr., SD = 2.4) responded to the Thalbourne, et al.'s Manic-Depressiveness Scale. In a factor analysis with a varimax rotation, 14 of 18 items had significant loadings (>.3) on the first factor, including 8 items of the original depression scale. 6 items significantly loaded on the second factor, including 3 items of the original mania scale. This did not match the hypothetical structure of the scale.