Bipolar Affective Illness Research Articles

Evolutionary aspects of bipolar affective illness.

Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation (mania and depression) sometimes of extreme intensity. The development and maintenance of such states in evolution can betoken a possibility of their adaptive character, enabling adaptation to an unfavorable external situation (depression) and a mobilization to using resources when available (mania). In the article, the main focus is put on the evolutionary aspect of "bipolarity" and manic/hypomanic states. Molecular-genetic studies show that in evolution, the genes connected with a predisposition to BD have been conserved. In the paper, the evolutionary adaptive concepts connected with the functioning of Homo sapiens during the middle and late Pleistocene periods were discussed as well as the "mismatch" theories associated with not befitting brain functioning to contemporary conditions. The benefits of mania and hypomania, also in the context of their link to depression were delineated, indicating their relationship to the increase in reproductive success. They result from such features of mania/hypomania as increased exploratory, psychomotor and sexual activity, and prompt risk-taking. The reproductive success can be connected with hyperthymic and cyclothymic temperaments, most frequently occurring in subjects with BD. The hyperthymic temperament often leads to increased social status and a tendency to leadership, and the cyclothymic temperament can increase creativity. Examples of the relationship between manic/hypomanic states and the phenomenon of emigration as well as the advancement of American society are provided.

Study on Prescribing Pattern of Drugs among Outpatients with Bipolar Affective Disorder in a Tertiary Care Teaching Hospital

Published on:June 2022 Journal of Young Pharmacists, 2022; 14(2):203-206 Original Article | doi:10.5530/jyp.2022.14.38 Authors: Safal NK1, Bharath Raj K C1,*, Shrinivasa Bhat U2, Shreyas K1, Pratheeksha NM1, Manali RL1 1Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed to be University), Mangaluru, Karnataka, INDIA.2Department of Psychiatry, Justice K. S. Hegde Charitable Hospital, NITTE (Deemed to be University), Mangaluru, Karnataka, INDIA. Abstract: Background: Recurrent periods of depression and mania characterize a multiplex condition called bipolar disorder. Bipolar affective illness is currently treated with a broad number of medications. Mood stabilizer therapy can be used to treat depression or mania without raising the likelihood of a relapse. Antiepileptic, antipsychotic, and antidepressant medications are also indicated and commonly used to treat bipolar illness in clinical practice. Materials and Methods: A prospective observational study was conducted at Justice K. S. Hegde Charitable Hospital for six months among 80 outpatients who were diagnosed with bipolar disorder to study the prescribing pattern of bipolar affective disorder drugs of drugs prescribed. A suitable data collecting form was designed to collect and record the information. The details of drug usage, including frequency, dose, and route of administration, were collected to study prescribing patterns for bipolar affective disorder drugs. Results: 80 prescriptions were analyzed. Males (n=57, 71.25%) were more than females (n=23, 28.75%). The majority of the patients (n=46, 57.5%) belonged to the age group 21 to 40 years. The most commonly prescribed class of drug was mood stabilizers (n=90, 44.34%). Lithium (n=38, 47.5%) was the most frequently prescribed drug. Conclusion: Mood stabilizers were the most commonly prescribed medication class, and the most commonly prescribed medicine was lithium for the management of the bipolar affective disorder. By assisting with prescription analysis and prescribing trends, a clinical pharmacist can help improve a patient’s quality of life. Studies can help psychiatrists get feedback on their current prescribing practices.Key words: Prospective, Prescribing pattern, Bipolar affective disorder drugs, Mood stabilizers, Lithium.

Beneficial effect of lithium in female patient with bipolar affective illness and psoriasis

Objectives. Psoriasis makes a relative contraindication for lithium treatment which can exacerbate its symptoms or induce it itself. On the other hand, lithium exerts immuno-modulatory activity. Case study. In this paper, a case of a female patient is presented. The patient has been treated since 2012 for bipolar affective illness (bipolar disorder – BD) and psori­asis, which occurred for the first time during a depress­ive episode. Despite intensive pharmacological treatment, both as inpatient and outpatient, a satisfactory improvement of affective illness has not been obtained. After the introduction of lithium, a remission of BD was achieved as well as a reduction of psoriatic changes, which have been maintained until now (2021). Conclusion. The remission of Bipolar Disorder (BD) on lithium can suggest that the patient belongs to the group of the so-called excellent lithium responders. In the presen­ted case remission of psoriasis was observed during lithium treatment. This case report must be treated with caution because remission could be spontaneous and the patient needs further observation.

Auditory mismatch negativity in bipolar disorder: a focused review.

The auditory mismatch negativity, a component of the event-related potential elicited by an unexpected stimulus in a sequence of acoustic stimuli, provides an objective measure of the accuracy of the echoic information processing of the human brain in vivo. Auditory mismatch negativity is also a useful probe of cortical glutamatergic N-methyl-d-aspartate receptor activity and disturbance. Notably, auditory mismatch negativity is consistently impaired in schizophrenia. Because of the wide spectrum extending from bipolar affective illness and schizoaffective psychosis to typical schizophrenia, we examined the literature on auditory mismatch negativity in bipolar disorder with the aim to find any neurophysiological dysfunction concerning pre-attentive information processing shared by these clinical conditions. This focused review includes 26 original articles published in peer-reviewed journals and indexed in the National Institutes of Health National Library of Medicine (PubMed) search system. Overall, evidence is consistent with the finding that auditory mismatch negativity is impaired in bipolar disorder with psychotic features, even though to a lesser extent than in schizophrenia. It must be acknowledged that, in a few twin and family studies, mismatch negativity abnormalities were not specifically associated with bipolar disorder. In conclusion, auditory mismatch negativity research supports the involvement of the N-methyl-d-aspartate system in the pathophysiology of bipolar disorder, as previously assessed for schizophrenia, thus creating an intriguing trait d'union between these two mental illnesses and stimulating the development of novel therapeutic agents. With additional replication and validation, auditory mismatch negativity may be further considered as a correlate of a common psychopathology of schizophrenia and bipolar spectrum illnesses.

A renoprotective role of chitosan against lithium-induced renal toxicity in rats

BackgroundLithium (Li) is considered as the first therapeutic line for treatment of bipolar affective disorders and manic-depressive illness. Renal toxicity can be categorized as the most common undesirable side effect of Li therapy. Therefore, the present study aimed to reveal efficiency of chitosan (CS) as a natural chelator against renal toxicity induced as a result of Li injection. During current experiment, the renal functions (urea, creatinine, blood urea nitrogen (BUN), uric acid and total protein) were determined in serum samples. The urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) was assayed through measuring its level in urine samples. Moreover, markers of the oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and lipid peroxidation product (LPO)) were assessed in renal tissues. In addition, histopathological and ultrastructural examinations were carried out in that tissue.ResultsIt was found that Li injection caused significant (P < 0.05) elevation in serum urea, creatinin and BUN levels associated with decline in uric acid and T. protein. Moreover, Li increased the urinary excretion of NAG significantly (P < 0.05). Administration of CS orally restored levels of these measurements to normalcy in CS pre-treated group through lowering urea, creatinin, BNU levels and urinary excretion of NAG with enhancing uric acid and T. protein levels.On the other hand, it was found that Li caused significant (P < 0.05) elevation in the LPO level associated with decline in activity of the antioxidant system in the renal tissues. Likewise, it caused severe alterations in the renal levels at histopathological and ultrastructural levels. The treatment with CS reduced the renal LPO associated with stimulating the antioxidant system through increasing levels of SOD, CAT, GPx and GSH in addition to its beneficial role against the histopathological abnormalities.ConclusionsThe CS exhibited promising role in the protection against the oxidative stress and renal toxicity induced as a result of Li injection.

Staging of unipolar affective illness

In this article, a concept of staging of unipolar affective illness (recurrent depression) is presented. In respective subchapters, three most important aspects of this issue have been discussed: 1) staging of unipolar affective illness; 2) staging of treatment-resistant depression; and 3) conversion of unipolar into bipolar affective illness. The evidence for so called neuroprogression of the illness, accumulated in recent years, has allowed for a classification of staging based on a concept of allostasis and allostatic load. In the course of illness, changes in neuroendocrine system (mainly hypothalamic pituitary-adrenal (HPA) axis), immunological system, mechanisms of oxidative stress, neurotransmitters, neurotrophic factors as well as structural and functional changes of the brain occur. In their paper of 2007, Fava and Tossani elaborated a concept of staging of unipolar affective illness presenting a continuum model of five consecutive stages with specific clinical features. In the present paper, a concept of treatment-resistant depression and staging of treatment resistance is presented in the context of several models. An important determinant of treatment-resistant depression is so called subthreshold bipolarity which is connected with worse efficacy of antidepressant drugs. In the course of illness, there is a possibility of changing diagnosis from recurrent depression into bipolar affective illness. The studies on this issue show that frequency of such diagnostic conversion is 1,5% of depressed patients per year.

Managing the risk of lithium-induced nephropathy in the long-term treatment of patients with recurrent affective disorders

Lithium has been the most effective psychopharmacological drug in the long-term treatment of patients with recurrent unipolar and bipolar affective illness. As a result of its widespread and longtime use in patients with recurrent affective disorders, psychiatrists have become increasingly aware of the whole spectrum of lithium's potential side effects. One of the side effects associated with its chronic use is lithium-induced nephropathy. In a recent cross-sectional study published in BMC Medicine, Alberto Bocchetta et al. add further information to this topic, demonstrating that duration of lithium treatment is associated with impaired glomerular function in patients with recurrent or chronic affective disorders. The present paper will discuss the implications of this and other related recent research on our management of patients with recurrent affective disorders. In this context the importance of shared decision making and close monitoring of kidney function is highlighted, including the regular assessment of the glomerular filtration rate, to provide best possible care to our patients maintained on lithium treatment.See related research article here http://www.biomedcentral.com/1741-7015/11/33

Mania associated with complicated hereditary spastic paraparesis

Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient's father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

Mechanisms of Illness Progression in the Recurrent Affective Disorders

Along with genetic vulnerability, multiple environmental factors convey liability to illness progression, including: (1) distal and proximal stressors; (2) recurrence of episodes; and (3) comorbid cocaine abuse. Recurrence of each of these can increase responsivity (sensitize) to themselves and cross-sensitize to the two other factors and drive illness progression as seen clinically in increases in cycle acceleration, severity or duration of episodes, treatment refractoriness, disability, cognitive dysfunction, and premature death. Some mechanisms appear common to all three types of sensitization, such as decreases of brain-derived neuroprotective factor (BDNF) in hippocampus and blood, as well as increases in BDNF in the nucleus accumbens, suggesting the possibility that single treatments could ameliorate several of these factors at once. A potential example is N-acetylcysteine (NAC), which decreases bipolar affective illness severity (Berk et al. Biol Psychiatry 64:468–475, 2008) and cocaine reinstatement and craving (Baker et al. Ann N Y Acad Sci 1003:349–351, 2003; LaRowe et al. Am J Addict 15:105–110, 2006). Mechanisms of illness progression also involve epigenetic changes and add further rationale to the existing empirical clinical evidence of the importance of early recognition, treatment, and prevention of affective episodes. Adequate treatment could prevent or ameliorate both the increases in pathological factors and erosion of adaptive factors that propel illness exacerbation and treatment resistance. This view of the sensitization and cross-sensitization among stressors, episodes, and abused substances should lead to a fundamental re-conceptualization of the recurrent affective disorders not as benign, isolated episodes of “mental” illness, but as severe, potentially progressive and lethal medical disorders of brain and body that deserve careful life-long monitoring and treatment.

P02-47 Catatonia in autism and other neurodevelopmental disorders

Objective:This paper reviews the presence of catatonia in neurodevelopmental disorders, with emphasis on autism spectrum disorders. Clinical presentations are reviewed, followed by catatonia treatment algorithms including lorazepam and ECT.Method:A literature review of catatonia in autistic, developmentally disabled and neurologically impaired populations was conducted. This was combined with the author's experience with patients with autism as well as traumatic, infectious and congenital brain injuries, all of whom developed frank catatonia.Results:Catatonia is a unique neurobiological syndrome with multiple psychiatric, neurological, medical and drug-related etiologies. Most commonly associated with bipolar affective illness, catatonia has also been found in 12-17% of patients with autism. Other neurodevelopmental disorders may similarly present with catatonia. Blueprints for treatment of catatonia include lorazepam and electroconvulsive therapy. While current literature supports the appropriateness, safety and efficacy of ECT for catatonia in autistic and developmentally disabled populations, treatment barriers may persist. The following cases are presented:Pt 1: A 14 year-old female with encephalitis of unknown origin and profound catatonia. Cultural barriers prevented treatment.Pt 2: A 20 year-old male with high-functioning autism and catatonia characterized by alternating stupor and extreme psychomotor agitation with self-injury.Pt 3: A 15 year-old male with congenital agenesis of the cerebellum and vermis in frank catatonic stupor mistakenly attributed to his disability.Conclusion:Catatonia is readily diagnosed in a variety of neurodevelopmental conditions including autism, and is eminently treatable with lorazepam and/or ECT in this population. Treatment barriers should be recognized and remedied.

Onset of Depressive Episodes Is Faster in Patients With Bipolar Versus Unipolar Depressive Disorder

Depressive episodes can have a very fast onset (< 1 hour) or start very slowly (> 1 month). This interesting aspect, pointing to different neurophysiological pathomechanisms, has not been systematically evaluated so far. The aim of this study was to describe speed of onset of depressive episodes in a consecutive sample of patients with at least 1 depressive episode and to investigate potential differences between patients with major depression versus bipolar affective disorders concerning this variable. We examined 158 consecutive adult patients with major depression (N = 108) and bipolar disorder (N = 50) diagnosed according to criteria of the International Statistical Classification of Diseases, 10th revision, by applying the structured Onset-of-Depression Inventory. Patients with acute critical life events preceding the onset were excluded from final analyses. Data were collected between December 2001 and January 2007. There was a significant positive association between speed of onset of the present depressive episode and that of the preceding depressive episode (rho = 0.66, p < .001). Patients with bipolar disorder developed full-blown depressive episodes significantly faster than patients with major depression (p < .001): Whereas depressive episodes began within 1 week in 58% of patients with bipolar disorder, this was the case in only 7.4% of patients with major depression. Intraindividually, the speed of onset of depression is similar across different episodes. In the absence of acute critical life events, fast onset of depressive episodes (within 1 week) is common in bipolar disorder but rare in major depression. This aspect might be useful to identify depressive episodes occurring within a bipolar affective illness and might characterize a subgroup of patients with a distinct neurobiology.

P.2.e.002 Val/Met polymorphism of COMT gene in patients with bipolar affective illness treated with lithium

P.2.e.002 Val/Met polymorphism of COMT gene in patients with bipolar affective illness treated with lithium

The Neurocognitive Signature of Psychotic Bipolar Disorder

Psychotic bipolar disorder may represent a neurobiologically distinct subgroup of bipolar affective illness. We sought to ascertain the profile of cognitive impairment in patients with bipolar disorder and to determine whether a distinct profile of cognitive deficits characterizes bipolar patients with a history of psychosis. Sixty-nine outpatients with bipolar I disorder (34 with a history of psychotic symptoms and 35 with no history of psychosis) and 35 healthy comparison subjects underwent a comprehensive neurocognitive battery. All three groups were demographically matched. Despite preserved general intellectual function, bipolar I patients overall showed moderate impairments on tests of episodic memory and specific executive measures (average effect size = .58), and moderate to severe deficits on attentional and processing speed tasks (average effect size = .82). Bipolar I patients with a history of psychosis were impaired on measures of executive functioning and spatial working memory compared with bipolar patients without history of psychosis. Psychotic bipolar disorder was associated with differential impairment on tasks requiring frontal/executive processing, suggesting that psychotic symptoms may have neural correlates that are at least partially independent of those associated with bipolar I disorder more generally. However, deficits in attention, psychomotor speed, and memory appear to be part of the broader disease phenotype in patients with bipolar disorder.

Differentiation of executive and attention impairments in affective illness

Executive impairments have been reported in affective illness, but the influence of attention on executive performance has not been fully considered. The purpose of this study was to investigate whether executive impairments in affective illness were independent of attention impairments, and whether independent executive impairments were specific to bipolar (BP) affective illness. Forty-two individuals with major affective disorders [20 unipolar (UP) depression and 22 BP disorder] were compared with 40 healthy controls on measures of attention and executive function. None of the patients were currently experiencing an episode of affective illness. As expected, both UP and BP patient groups showed significant neuropsychological impairments relative to controls. Significant differences in performance on executive function measures were also observed between UP and BP patients, even after the influence of attention had been taken into account. These impairments were not attributable to current levels of affective symptomatology or to medication. A single neuropsychological dissociation appears to be present between UP and BP affective illness, with BP individuals showing a specific executive deficit that is independent of attention impairment on the Hayling Sentence Completion Test (HSCT).

Types of Depression More Frequent in Bipolar than in Unipolar Affective Illness: Results of the Polish DEP-BI Study

Background: The aim of the study was to assess the relative frequency of various kinds of depression in patients with bipolar and unipolar affective illness. The study was performed in the framework of the DEP-BI project aimed at assessing the prevalence of bipolar disorders among depressive outpatients treated by psychiatrists in Poland. Methods: Eight-hundred and eighty patients (237 male, 643 female) participated in the study. The patients were classified into the following diagnostic categories: bipolar affective illness type I, type II, bipolar spectrum disorder and unipolar affective illness. The various kinds of depression in each group were assessed by means of a semistructured questionnaire added to the diagnostic interview. Results: In the group of bipolar patients, a significantly higher frequency of psychotic depression in male compared to female patients was observed. Male bipolar patients compared with unipolar depressed ones had significantly more episodes of psychotic depression (odds ratio, OR, 4.29) and atypical depression (hypersomnia and hyperphagia; OR 2.82), and those with bipolar spectrum had more episodes of treatment-resistant depression (OR 2.56). Female bipolar patients compared with unipolar depressed ones had significantly more frequently an early onset of depression (before 25 years; OR 2.95) and postpartum depression (OR 2.48). On the other hand, the percentage of agitation, irritability, distractibility, thought racing and panic attacks during depression was not different in patients with bipolar and unipolar affective illness either in males or females. Conclusions: Some kinds of depression occur with a higher frequency in patients with bipolar compared to unipolar affective illness. The occurrence of a given type of depression may constitute an aid for the diagnosis of bipolar illness. The results of this study did not confirm the concept of bipolar mixed depression based on the presence of anxiety symptoms occurring during the depressive episode. The limitation of our study may be the lack of formal criteria or a structured interview to assess the symptoms occurring during depressive episodes.

A novel technique to evaluate fluctuations of mood: implications for evaluating course and treatment effects in bipolar/affective disorders

Several psychiatric conditions are associated with frequent fluctuations of affect. In this study, we propose a new technique to uniformly score depression and mania objectively and use a new mathematical technique to model the frequent fluctuations in mood using simulated data. Our main aim is to examine the usefulness of this measure for evaluating treatment effects or course of illness, especially in bipolar or unipolar affective illness to quantify mood fluctuations. We use a prototypical model, which takes into account the mean, the standard deviation (SD) and the coefficient of variation (CV = SD*100/mean) of the mood scores of the subjects over a user-defined period. We utilize simulated data of subjects for euthymia, minor depression, minor mania, severe depression, severe mania and cyclic bipolar illness (manic depression, MDP). We propose an objective method to quantify the mood of the subjects at weekly intervals (the interval can be user-defined) using a scale of 1-9 (1-4 = degrees of depression, 5 = euthymia, 6-9 = degrees of mania). These scores can be sampled according to the convenience and feasibility of the measurements, which can be derived from various clinical scales or by observation of the subjects in hospitals or other environments. We derive a new mathematical technique to arrive at a normalized measure for each of these conditions of simulated data in addition to the mean, SD and approximate entropy (ApEn). We utilize three sets of data, one to train the model to classify the condition of the subjects and the other two to test the reliability of the technique. We are able to successfully classify the condition of the subjects over a 52-timepoint period (length can be days or weeks depending upon the sampling rate). The New Index (NI) correlates significantly only with the mean (r(2) = 0.78), but not with the SD or ApEn score. These results indicate that it may be beneficial to reduce data according to the techniques we propose so that there is greater uniformity within which to compare future studies to evaluate treatment effects, not only in rapid-cycling MDP but also in other affective disorders. This method may be suitable for the meta-analysis of several studies, although different scales have been used in each of those studies. Our measure derived from simulated data has shown sufficient deviation of all the abnormal states from the euthymic state. The advantages and pitfalls of these techniques are further discussed to evaluate affect in various disorders. However, future prospective studies must address the importance of this measure in comparison with mean, SD and ApEn scores or other nonlinear measures of these time series. We are evaluating other nonlinear dynamic models, which may provide a continuous measure with which to identify different degrees of fluctuation of mood.

Evidence that the urban environment specifically impacts on the psychotic but not the affective dimension of bipolar disorder

High rates of psychotic disorders and psychotic symptoms have been found in urban environments but reports for bipolar affective illness have been inconsistent, possibly due to failure to stratify for comorbid psychotic symptoms. It was hypothesised, therefore, that any effect of urbanicity on the bipolar phenotype would be moderated by comorbid psychotic symptoms. In a random, representative population cohort of 7049 adults with no history of non-affective psychotic disorder, the cumulative incidence of bipolar and psychotic symptoms and syndromes, assessed with the CIDI, was examined over five levels of population density of place of residence. Similarly, the degree of comorbidity between broadly and narrowly defined bipolar phenotypes on the one hand, and the dichotomous presence of broadly (17.2%) and narrowly defined (3.8%) psychotic symptoms on the other, was examined as a function of population density of place of residence. The rate of bipolar disorder, however defined, was progressively higher in more urbanised areas. However, in models of bipolar phenotypes, a strong interaction between comorbid psychosis and level of urbanicity was apparent, indicating that the greater the degree of psychotic comorbidity, the greater the effect size of the urban environmental factor. For bipolar disorder without psychosis, no effect of urbanicity was apparent. The results suggest differential environmental causal effects on affective and cognitive dimensions of bipolar psychopathology that are nevertheless strongly comorbid within the same categorically defined disorder, possibly due to the effect of shared genetic risk factors.

Preliminary findings of uncoupling of flow and metabolism in unipolar compared with bipolar affective illness and normal controls

Cerebral metabolism (CMR for glucose or oxygen) and blood flow (CBF) have been reported to be closely correlated in healthy controls. Altered relationships between CMR and CBF have been reported in some brain disease states, but not others. This study examined relationships between global and regional CMRglu vs. CBF in controls and medication-free primary affective disorder patients. Nine bipolars, eight unipolars, and nine healthy controls had [ 15O]-water positron emission tomography (PET) scans at rest, and [ 18F]-fluorodeoxyglucose PET scans during an auditory continuous performance task. Patients had [ 15O]-water and FDG PET scans in tandem the same day; controls had an average of 45 ± 27 days between scans. Maps of regional coupling were constructed for each subject group. In controls and bipolars, global and virtually all regional correlation coefficients for CMRglu and CBF were positive, albeit more robustly so in controls. However, correlative relationships in unipolars were qualitatively different, such that global and most regional measures of flow and metabolism were not positively related. Unipolars had significantly fewer positive regional correlation coefficients than healthy controls and bipolars. These were significantly different from controls in orbital cortex, anterior cingulate, posterior cingulate, and posterior temporal cortex, and different from bipolars in pregenual anterior cingulate. In unipolars, the degree of flow–metabolism uncoupling was inversely correlated with Hamilton depression scores, indicating the severity of uncoupling was directly related to the severity of depression. These preliminary data suggest abnormal relationships between cerebral metabolism and blood flow globally and regionally in patients with unipolar depression that warrant replication and extension to potential pathophysiological implications.

Neurobiological principles of bipolar affective disorders

The neurobiology of bipolar affective illness can be described in a model with structural and functional components, which also address the role of stressors, coping mechanisms, and psychophysical disposition. More data exist on depressive than on manic patients or on patients switching from one clinical pole to the other. Structural and functional chronobiological alterations appear to play a major role in the pathophysiology of bipolar illness. From an anatomical view, neurobiological abnormalities are primarily confined to limbic-striatal-pallidal-thalamocortical circuits. The whole cascade of neural signaling is changed starting from neurotransmitters and neuromodulators to receptor-mediated intracellular signal transduction targeting nuclear gene expression. Transnosological factors such as suicidal tendency appear to essentially modulate those changes. Replicated data on decisive neurobiological differences between bipolar and unipolar affective disorders are currently not yet available.

Impaired heart rate variability in euthymic bipolar patients.

Power spectral analysis of heart rate variability (HRV) has recently been shown to be a reliable non-invasive test for quantitative assessment of the central sympathovagal interaction that modulates cardiovascular autonomic function. We studied 39 euthymic bipolar patients and 39 controls, matched for age and sex. A high-resolution electrocardiogram was obtained during complete rest. Spectral analysis of R-R intervals was performed by the fast Fourier transform algorithm. Euthymic bipolar patients at rest are characterized by markedly low HRV, independent of specific drug treatments. While these results of autonomic stability in euthymic bipolar patients are counter-intuitive, the findings may be important in understanding pathophysiology of bipolar affective illness.