Bipolar Disorder Uncovered

Understanding And Treating Bipolar Disorders

Understanding And Treating Bipolar Disorders

Are You Extremely Happy One Moment and Extremely Sad The Next? Are You On Top Of The World Today And Suddenly Down In The Doldrums Tomorrow? Is Bipolar Disorder Really Making Your Life Miserable? Do You Want To Live Normally Once Again? Finally! Discover Some Highly Effective Tips To Get Rid Of Bipolar Disorder And Stay Happy And Excited Always! Dont Let Bipolar Disorder Ruin Your Life Anymore!

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Married To Mania

This eBook is the key to knowing if you are married to a bipolar spouse, and gives you the keys to what to do about it. Often, being married to a bipolar spouse can be one of the hardest things you go through in your life because emotions in your house can change drastically, and completely without warning. This book gives you the tools to deal with unexpected anger outbursts and guilt that many spouses feel. This book will teach YOU how to deal with feelings of guilt that you may feel towards yourself, even though you have done everything you possibly can to make your marriage work. When you get this eBook, you can order a physical copy of the book and get FREE shipping. Also, you get two bonus eBooks when you order: The Spouse's Guide to Bipolar Disorder Vocabulary, which give you the tools you need to talk to doctors and psychiatrists, and The Bipolar Disorder Rolodex which gives you the latest in bipolar disorder research. It is hard to go through a bipolar marriage without help; now you don't have to.

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Chronology Of Bipolar Disorder And Sud Comorbidity

The association between SUD and bipolar disorder remains unclear. Some have suggested that SUD is a consequence of the mood instability inherent in bipolar disorder, others that SUD is a risk factor for precipitating or perpetuating affective episodes, or an attempt at self-medication of symptoms. Studying the temporal relationship between the onset of SUD and bipolar disorder may be one way of addressing this relationship. Goodwin and Jamison (28) have suggested that SUD may initiate bipolar disorder by way of kindling and sensitization (40). In this model, repeated intermittent exogenous stressors (such as abuse of alcohol or cocaine) may initiate progressively more severe and frequent affective responses, eventually culminating in spontaneous mood episodes (40). With this theory in mind, Ananth et al. (41) have speculated that use of cocaine might contribute to a rapid-cycling pattern in bipolar disorder. For this model to hold true, the age of onset of bipolar disorder with...

Course Of Bipolar Disorder With

Although several studies have examined comorbidity of substance abuse and affective disorders (39,43-45), relatively little has been determined about the effect of substance abuse on the course of bipolar disorder. There is some evidence that the coexistence of bipolar disorder and SUD will worsen prognosis by way of producing mixed states, an increased risk of suicide and rehospitalization, and noncompliance. Mayfield and Coleman (26) suggested that rapid cycling might be precipitated by an increased abuse of alcohol. Himmelhoch et al. (36) reported that in a sample of 84 bipolar disorder who had bipolar disorder with associated alcoholism had an increased likelihood of rapid cycling and a slower time to recovery from affective episodes. They found that 13 of 67 patients with mixed mania or rapid-cycling disorder (both forms of bipolar illness are less likely to respond to treatment) had concurrent alcohol use disorder, and that these patients recovered more slowly than those with...

Diagnostic Difficulties In Patients With Bipolar Disorder And Comorbid Suds

There is a marked difficulty in diagnosing bipolar affective disorder in the presence of comorbid SUD because substantial overlap may exist between the symptoms of bipolar disorder and the intoxication and withdrawal states resulting from psychoactive substances. For example, stimulant intoxication can produce a syndrome indistinguishable from mania or hypo-mania, and substantial depressive symptoms upon withdrawal from the stimulants. In addition, the phenomenological overlap between bipolar disorder and attention deficit disorder is significant. In both disorders patients may experience hyperactivity, impulsivity, agitation, racing thoughts, and distractibility, which often makes it difficult to distinguish between the two syndromes (51).

Mania and manic depression bipolar disorder

Sleep deprivation tends to elevate the mood, as in depression, and this may worsen the mania and lead to further sleep restriction. Treatment with benzodi-azepines or sedating antipsychotics improves the insomnia in bipolar disorder. This also improves with lithium, but more slowly.

Bipolar disorder following stroke

As indicated in the previous chapter, a significant number of patients with secondary mania were also found to have episodes of depression. In contrast, however, other patients with secondary mania did not have episodes of depression within the period of study or prior to the stroke. We examined patients with bipolar disorder and compared them to patients with secondary mania but no evidence of depressive episodes (Starkstein et al. 1991). The most obvious concern in patients with mania but without episodes of depression is whether sufficient follow-up had been obtained to identify the existence of a bipolar disorder. The diagnostic categories of Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) (see Chapter 5) do not include unipolar mania and once a patient has had an episode of mania they are presumed to have a bipolar disorder. Although one cannot be sure that a patient with a single or recurrent episodes of mania will not have depression (similarly one cannot be sure...

Why The Common Association Between Comorbid Substance Use Disorders And Bipolar Disorder

Several possible explanations for the frequent co-occurrence of bipolar disorder and SUD are described below. One possibility that has been suggested is that this high association is due to a common causal pathway (e.g., common disturbance in neurotransmitter systems and or postreceptor signaling pathways, or genetic predisposition) (17,18). Another possibility might be related to the nature of the symptoms of mania. Manic patients may exhibit behavioral disinhibition and engage in high-risk behaviors such as speeding, spending sprees, or excessive use of psychoactive substances. Bipolar disorder patients may engage in excessive use of alcohol even when they usually do not drink during their euthymic periods (19,20). This latter theory rests on the premise that alcoholism is secondary to the affective illness. A third suggested explanation for the frequent co-occurrence is referral bias (21). This explanation, referred to as Berkson's bias (22), states that patients with two or more...

Affective Disorder Syndromes

Major depression has a lifetime prevalence of about 15 percent and is about 15 times as common as bipolar disorder (manic-depressive disorder). Major depression is about twice as common in women as in men in all countries and cultures and does not vary in occurrence among different races. It may occur at any age, but the majority of cases occur in adulthood. Studies suggest a genetic predisposition because there is an increased incidence of major depression and alcoholism in relatives of patients with this mood disorder. The diagnosis of depression is often overlooked, especially in patients with chronic neurological disease. The Diagnostic and Statistical Manual, 4th edition (DSM-IV) criteria for this diagnosis requires either that the patient have a depressed mood or that the patient have a sustained loss of interest and pleasure. Some depressed patients have a depressed affect or become withdrawn or irritable but do not admit to or complain of feelings of sadness. Almost all,...

Depression and Psychiatric Misdiagnosis

Hypothyroidism is linked to psychiatric depression more frequently than hyperthy-roidism. The physical symptoms associated with unipolar depression (discussed more in Chapter 24) overlap with hypothyroidism and can cause the psychiatric misdiag-nosis. Sometimes, psychiatrists find that hypothyroid patients can even exhibit certain behaviors linked to psychosis, such as paranoia or aural and visual hallucinations (hearing voices, seeing things that are not there). This used to be called myxedema madness. Interestingly, roughly 15 percent of all patients suffering from depression are found to be hypothyroid. Chapter 24 discusses depression and unmasked hypothyroidism, as well as simultaneous depression and hypothyroidism. Bipolar disorder and lithium are also discussed in detail.

Psychosocial Approaches

Some, albeit limited, empirical support. One is family or marital therapy, particularly psychoeducational approaches that focus on teaching patients and their family members about bipolar disorder and how to manage it and effective ways to communicate and solve family problems (Miklowitz & Goldstein, 1997 Miklowitz et al., 2000). Asecond is interpersonal and social rhythm therapy, an individual therapy that focuses on helping the patient understand and renegotiate the interpersonal context associated with mood disorder symptoms (Frank, Swartz, & Kupfer, 2000). Patients learn to stabilize sleep wake rhythms and other daily routines, particularly in the face of environmental triggers for disruption. A third treatment is individual cognitive-behavioral therapy, in which patients learn to identify, evaluate, and restructure cognitive distortions, and develop illness management strategies such as behavioral activation, drug compliance monitoring, and the appropriate use of support systems...

Diagnosis Prevalence and Prognosis

Children's depressive disorders tend to be longer and more severe than those of adults. Although most children will recover, depression can leave them socially, cognitively, and educationally impaired. Several variables including severity, family dysfunction, and gender predict the duration of a depressive episode. The average duration of a major depressive episode is reported to be 32 to 36 weeks, with longer durations in females. The rate of recovery is slow, with the greatest improvement starting between the 24th and 36th week. Within 6 months of onset, the depressive episode has remitted for 40 of the children. At one year, 80 of the children are no longer experiencing a depressive episode. The average duration of dysthymia is 3 years. A chronic course is reported for a significant percentage of depressed children. Depressive disorders are recurrent, with about 75 experiencing another episode within 5 years. Most depressed youths simultaneously experience additional psychological...

Efficacy Research on Psychotherapy

Bipolar disorder Psychotherapies are not efficacious for all conditions (for example, interpersonal psychotherapy (IPT) has been shown to be ineffective in two studies with opiate abusers). However, for several disorders, psychotherapies have been shown to be as effective as psychotropic interventions (e.g., cognitive-behavioral therapy CBT for Panic Disorder, CBT and IPT for Bulimia Nervosa). For other disorders, psychotherapy is an invaluable adjunct to medication (e.g., bipolar disorder, Schizophrenia).

Structural Abnormalities

Bipolar disorder correlates in postmortem brain (reviewed in Harrison, 2002 Rajkowska, 2000). To this end, morphometric and immunocytochemical changes in neurons and glia as well as synaptic and dendritic markers have been reported, with studies targeting some but not all subdivisions of the frontal cortex, anterior cingulate, hippocampus, and brainstem. A loss of glia is the best replicated and most robust finding, affecting orbital frontal (ventral prefrontal) and prefrontal cortex (BA9), as well as the cingulate (subgenual, pregenual). Glial abnormalities are seen in both bipolar and unipolar disorder, and are most consistent in patients with a positive family history of mood disorder. Neuronal abnormalities are less consistently identified and generally involve a decrease in size, not number. Synaptic terminal and dendritic abnormalities, in support of aberrant cellular plasticity or impaired neurodevelopment, are also reported but appear to be a more selective marker of bipolar...

Interpersonal Psychotherapy

Randomized controlled trials of IPT showed that it relieved depression better than control conditions and with roughly equivalent efficacy to antidepressant medications. Moreover, IPT helped patients to build social skills, which medication alone did not. The success of IPT in studies of outpatients with Major Depressive Disorder led to its testing for patients with other mood and nonmood diagnoses, including major depression in medically ill patients, depressed geriatric and adolescent patients, mothers with postpartum depression, Dysthymic Disorder, and as an ad-junctive treatment for bipolar disorder it has also been

Gender Similarities and Differences

Two studies that examined gender-related aspects of BDD found that the clinical features of the disorder appear to be similar in men and women. One of these studies (N 188) found, however, that women were more likely than men to focus on their hips and weight, camouflage with makeup and pick their skin, and have comorbid bulimia nervosa (Phillips and Diaz 1997). In addition, the study found that men were more likely to be unmarried be preoccupied with body build, genitals, and hair thinning use a hat for camouflage and have alcohol abuse or dependence. In the other study (N 58), women were more likely to focus on their breasts and legs, check mirrors and camouflage, and have bulimia, panic disorder, and generalized anxiety disorder men were more likely to focus on their genitals, height, and excessive body hair, and have bipolar disorder (Perugi et al. 1997a).

Suggested Reading

Madhusoodanan, S., Brenner, R., Araujo, L., & Abaza, A. (1995). Efficacy of risperidone treatment for psychosis associated with Schizophrenia, Schizoaffective Disorder, bipolar disorder or senile Dementia in 11 geriatric patients A case series. Journal of Clinical Psychiatry, 56, 514-518.

Antimanic And Mood Stabilizers

In comparison to the data available for the use of antidepressant drugs, research with antimanic drugs is more limited. In part this is because alternatives to lithium and antipsychotics have only recently become widely available and in part because clinical research involving people afflicted with bipolar disorder is inherently difficult, especially long-term studies. While there is general agreement that the monoamine systems are involved in antidepressant responses, the neural systems involved in the mechanism of antimanic drugs are poorly defined. TABLE 8.7. Treatment Recommendations for Patients with Bipolar Disorder by the American Psychiatric Association (2002) A comprehensive review of the diagnosis and treatment of bipolar disorder has recently been published by the American Psychiatric Association (2002). Treatment recommendations are listed in Table 8.7.

Antipsychotic and Atypical Antipsychotic Drugs

While only approved by the FDA for the treatment of drug-resistant schizophrenia, the atypical antipsychotic drug clozapine has been shown to be effective in the treatment of mania and dysphoric mania (McElroy et al., 1991 Alphs and Campbell, 2002). Eighty-six percent of 14 bipolar patients with psychotic features showed significant improvement, and 7 of these patients were followed for an additional 3- to 5-year period with no further hospitalizations (Suppes et al., 1992). Other studies suggest clozapine is also effective in maintenance treatment of patients with bipolar disorder (Alphs and Campbell, 2002). Because of the risk of potentially fatal agranulocytosis, clozapine should not be used unless other first-line agents or traditional antipsychotic drugs have failed. antipsychotics. Olanzepine, risperidone, and quetiapine are all being studied as both monotherapy and as an adjunctive therapy for treatment of acute mania. Of the three, olanzapine is the best studied, with...

Neuropsychiatric Syndromes

The relationship between psychotic bipolar disorder and schizophrenia is unclear, but certainly within schizophrenia, full-fledged manic syndromes occur and serious depressive episodes are common. These can occur either during psychotic episodes or when psychotic symptoms are either absent or stable. The lifetime risk for major depression is very high, with perhaps a third to a half of patients experiencing at least one such episode. This problem contributes to the very high risk of suicide in schizophrenia approximately 10 percent of patients may kill themselves.

Right hemisphere lesion location

The lesion location in the Berthier et al. study (1996) was restricted to the right hemisphere in 7 of the 9 cases (78 ) while the remaining two patients had bilateral hemispheric damage. Thus, the Berthier study demonstrated that patients may develop bipolar disorder without having a family history of mood disorder. Secondly, there were a significant number of patients who had rapid cycling disorder and movement disorders associated with their stroke. This may suggest the importance of subcortical lesions in rapid cycling mood disorder. The most

Personality Disorders

Personality-disordered patients can be very difficult to treat. Sometimes the complexities encountered in attempting to treat these patients' symptoms can actually signal the presence of a personality disorder. Splitting is a characteristic defense used by borderline patients, who have a tendency to see others, including caregivers, as either all good or all bad. These distortions may cause disruption among members of the treatment team if distrust or negative attitudes about one another arise from the patient's distorted reports. The use of dialectic behavioral treatment (DBT), as described by Linehan, has been quite effective in the treatment of these patients (94). Important aspects of the treatment include consistent limit setting and frequent, direct communication among members of the treatment team to prevent disruptions. Medication management of these patients often leads to polypsychopharmacotherapy in an attempt to ameliorate anxious, depressive, impulsive, and...

Treatment of mania following stroke

A controlled double-blind treatment trial of secondary mania has not been conducted. Based on small series and anecdotal case reports, however, lithium has been the most commonly used treatment for secondary mania. There are reports, however, indicating that some cases have not responded to treatment with lithium. Some of these patients had a better response to carbamazepine or valproate and some did not respond to treatment. The treatment responses for the 19 patients in our study of bipolar disorder and mania only are shown in Fig. 28.1. Although there are clearly some patients who did not respond following treatment, most of the episodes of mania improved with treatment using lithium. Figure 28.1 (a) Bipolar group schematic templates of computed tomography scan slices showing largest cross-sectional area of lesion for manic-depressive patients. Lesions mainly involved the right head of the caudate and right thalamus. Longitudinal evolution of mood disorder for individual patients...

Hormones Mood and Cognition

Similar observations are reported with thyroid hormones (T3 and T4), which are crucial for normal brain development and function. Hypothyroidism during fetal life (a condition known as cretinism) produces short stature, sexual immaturity, and severe mental defects in afflicted individuals. In adulthood, hypothyroidism is often associated with depression, bipolar disorder, low energy, appetite and sleep changes, poor concentration, memory impairments, and apathy. The similarity of these symptoms with clinical depression routinely prompts clinicians to test thyroid functions to distinguish between the two conditions. The reverse interaction between affective illnesses, particularly major depression, and thyroid hypofunction has also been documented recently. As with cortisol, hyperthyroidism (as in Grave's disease) presents with several psychiatric symptoms including insomnia, irritability, agitation, major depression, Attention-Deficit Hyperactivity Disorder, paranoia, and most often,...

Content Of The Program

The content of the program was based on our review of the literature, our survey results, and staff experiences in working with families. Most families wanted in-depth information about serious mental illness and how the medications could help. In addition, many families wanted to know what to do when prescribed medicine didn't work. They were interested in finding help in the community and knowing what resources were available for their ill relatives. Because caring for an ill relative can be very stressful, stress-reduction techniques and problemsolving methods were included in the program. Sometimes four videos relating to families and their experiences with mentally ill relatives would be shown in lieu of stress-reduction techniques or problem solving. The videos chosen were the three Bonnie Tapes, which discuss mental illness from the points of view of a family, a patient, and the patient's sister. The fourth video, Families Coping with Mental Illness, shows 10 persons discussing...

Psychiatric Misdiagnosis

When people experience the exhaustion of too much thyroid hormone and the natural anxiety that accompanies it, but do not notice or report other physical manifestations such as a fast pulse or hyperdefecation (which can also be attributed to anxiety), they are often misdiagnosed with anxiety disorders. Unfortunately, it is women especially who may suffer from continuous and classic psychiatric misdiagnoses. One reason for this is that thyroid disorders occur much more frequently in women. Another reason is that thyrotoxic symptoms can mimic either unipolar depression or bipolar disorder, both diagnosed in women more frequently than men (see Chapter 24). Unipolar depression can manifest with irritability and sadness, poor appetite, weight loss, sleeplessness, no energy, a lack of sex drive, anxiety, and panic. Thyrotoxic symptoms unfortunately mimic these same manifestations. Finally, thyrotoxicosis can sometimes cause euphoric mood swings, a characteristic of a mania, which is present...

Gilles de la Tourette Syndrome and Other Tic Disorders

Clinical Manifestations and Associated Disorders.Tics are defined as simple or complex repetitive movements that occur out of background of normal motor activity. They are usually fast (myoclonic) but can be slow (dystonic). They increase with fatigue and after stress and decrease with concentration. y GTS is characterized by chronic waxing and waning motor and vocal tics, usually beginning between the ages of 2 and 21 years. It affects boys more frequently than girls. About half the patients start with simple motor tics, such as frequent eye blinking, facial grimacing, head jerking, or shoulder shrugging, or with simple vocal tics such as throat clearing, sniffing, grunting, snorting, hissing, barking, or other noises. Complex motor tics include squatting, hopping, skipping, hand shaking, and ritualized movements such as compulsive touching of objects, people, or self. Complex vocal tics include semantically meaningful utterances, including shouting of obscenities and profanities...

Activation in a Subgroup of Patients with Tourette Syndrome

The one downregulated gene, IMPA2, is also of interest. IMPA2 plays a crucial role in the phosphatidylinositol signaling pathway. In the brain, its expression is substantially higher in subcortical regions, most prominently in the caudate, a region shown in many neuroimaging studies to be involved in TS and OCD.3536 It is also considered to be a strong candidate gene for bipolar disorder.3738

Biological Approaches

The primary treatments for bipolar disorder are pharmacological. Lithium carbonate was the first mood stabilizer to come into wide use. It appears to be effective for about 50-60 of patients in controlling the acute symptoms of the disorder and preventing future episodes. Anticonvulsant medications such as divalproex sodium (Depakote), carba-mazepine (Tegretol), oxcarbazepine (Trileptal), and lamot-rigine (Lamictal) are now used as substitutes for or in conjunction with lithium, usually for lithium-refractory patients, patients who complain of lithium's side effects, or patients with atypical presentations (e.g., mixed episodes or rapid cycling). Atypical antipsychotic agents such as olanzapine (Zyprexa) are also in use as primary, first-line agents. Medications for bipolar disorder have negative side effects. For example, lithium and divalproex sodium are associated with weight gain, nausea, and trembling. One study found that almost 60 of patients were inconsistent with their...

Genetic and Biological Predispositions

Bipolar disorder unquestionably runs in families. Concordance rates between identical twins average 57 and between fraternal twins, 14 (Alda, 1997). The family pedigrees of bipolar probands are characterized by increased rates of bipolar disorder, unipolar disorder, and alcoholism. At least 20 of the first-degree relatives of bipolar patients have major affective disorders (Gershon, 1990). Although several gene loci have been identified, there is a particularly promising set of findings linking bipolar disorder to loci on the long arm of chromosome 18. This linkage is strongest among families of bipolar patients who are co-morbid for Panic Disorder (MacKinnon et al., 1998). There is also growing evidence that a variant in the serotonin transporter gene, which might lead to instabilities in the regulation of serotonin within the CNS, may be related to the onset of bipolar disorder (Collier et al., 1996). Bipolar disorder is presumed to involve imbalances in the activity of...

Antidepressant Medications

There are different forms of major depression, including one seen in bipolar disorder in which individuals have episodes of not only depression but also forms of mania melancholia, characterized by symptoms like a distinct quality of sadness, inability to experience pleasure, and early morning awakening and atypical depression, which is more responsive to environmental events and associated with an increase in appetite and need for sleep. The presence of depressive symptoms that fall below the threshold of criteria for major depression is called by various names dysthymia (which is a chronic lower-grade depression and still impairing), depressive symptoms in response to negative life events, and minor depression.

Depression and Anxiety

It's important to understand that depression is a vast topic, and there are many different types of depression. For the purposes of this chapter, we'll be limiting the discussion to the most common type of depression frequently associated with hypothyroidism. Known in clinical circles as either major depression or unipolar depression, this form is characterized by one low or flat mood. This is distinct from bipolar depression, characterized by two moods a high(er) mood and a low(er) mood, which typically cycle. A few symptoms of bipolar depression can sometimes be confused with thyrotoxicosis, but as discussed in Chapters 4 and 6, the exhaustion that accompanies thyrotoxicosis is not present in people with mania associated with bipolar disorder. In fact, people with bipolar disorder who are in a manic phase have boundless energy, which is the opposite of what occurs in thyrotoxicosis. (Such energy is usually a major clue for doctors.) What can be confused with, or aggravate,...

Vascular disease and age of onset

Fujikawa et al. (1995) examined 20 patients who developed bipolar disorder after age 50 (late-onset mania) who were prospectively identified. These patients were compared with 20 age- and sex-matched patients who developed affective disorder before age 50 and 20 patients who developed major depression after age 50. Patients with focal neurological symptoms were excluded as the authors were interested in looking for evidence of silent cerebral infarction on magnetic resonance (MR) scan. The incidence of silent cerebral infarction in patients with late-onset

Presenting for Treatment

Tohen and colleagues (9) reported fairly low rates of lifetime SUD in first-episode manic patients. The authors reported that the lifetime prevalence of drug abuse or dependence in patients admitted for a first episode of mania was 17.1 (24 among women and 6 among men). In contrast, Keck et al. (10) reported much higher lifetime prevalence of SUD in their patients hospitalized for the first time for treatment of a manic or mixed episode. They reported a 38 prevalence of alcohol use disorders and a 32 prevalence of drug use disorder in their 34 first-episode manic patients. When these patients were compared with the 37 who had had multiple episodes of mania, no differences were found in the prevalence rate of SUDs. In another study (involving predominantly multiple-episode manic patients), Keck and colleagues (11) found that of the 106 bipolar disorder patients admitted for a manic or mixed episode who completed the 12-month follow-up, 55 (52 ) met...

Prevalence of SUD in Community Surveys

The prevalence of comorbid bipolar disorder and SUD will vary depending on the type of sample the estimates are calculated on. The prevalences discussed in this chapter are of 1) SUD in non-treatment-seeking bipolar disorder patients, 2) SUD in bipolar disorder patients seeking treatment, and 3) bipolar spectrum disorder in substance abusing patients presenting for treatment.

Mood Disorders Definitions

The DSM-IV definition of major depression is familiar to most clinicians, and includes either depressed mood or loss of interest or pleasure and five or more symptoms from a list of nine present during the same 2-week period. For children and adolescents, depressed mood or loss of interest are not required if irritable mood is present, and failure to make expected weight gains is an alternative symptom to weight loss. Dysthymia, indicated by at least 2 years of depressed mood in adults, may be diagnosed in children and adolescents if present for at least 1 year and, as with major depression, irritable mood may be considered equivalent to depressed mood. Note that dysthymia should not be diagnosed when criteria for major depression are met. Bipolar disorder is an important comorbid mental disorder in adults with SUD and has been the subject of some clinical observations regarding relationships with adolescent SUD (e.g., Refs. 103, 104). Little systematic information is available on...

Decision to Initiate Medication Treatment

Treatment should follow a careful assessment of symptoms and course, a review of general health status, a formal diagnosis, and in some cases physical examination and laboratory testing (Depression Guideline Panel, 1993). This can usually be accomplished in one visit, especially if medically relevant history and past psychiatric and substance abuse history are available. Once a diagnosis of major depression or bipolar disorder has been made, medication treatment is usually indicated. Medication treatment should be initiated with the understanding that the choice of agent may be significantly affected by presenting symptoms and concurrent psychiatric, medical, or substance abuse diagnoses. Concomitant supportive, educational, and or cognitive psychotherapy is usually indicated, although in severe depression or mania significant modifications in the methodology and goals of psychotherapy are usually required, and these will change over time depending on the extent and rate of clinical...

Embryonic Stem Cell Opportunities in Developmental Toxicity and Cognitive Disorders

Exposure of pregnant rats to valproic acid, a drug with bipolar disorder indications, resulted in changes in the allocation and function of serotoner-gic neurons that were similar to disease phenotype in patients.2 We are currently undertaking pioneer studies using chemical biology associated with hESC technology to investigate abnormal neuronal development and functional impairments that result from chemical insult and potentially underlie autism.

Chronic Fatigue Syndrome Research Clinical Presentation

Search Case Definition requires the presence of at least 6 months of persistent, unexplained fatigue that interferes with multiple domains of daily life, is not relieved by rest, and is accompanied by at least four of the following symptoms cognitive impairment, sore throat, tender neck or lymph nodes, muscle pain, joint pain, headaches, unre-freshing sleep, and more than 24 hours of post-exertional malaise. Importantly, the research case definition precludes classification as CFS if a patient has an identifiable medical cause to be fatigued. Similarly, subjects with certain psychiatric conditions cannot be classified as CFS in research studies. Exclusionary psychiatric conditions include Schizophrenia, bipolar disorder, or melancholic major depression. It is important to realize that the CFS case definition was devised for research purposes, and the concept of exclusionary conditions is critical to avoid confounding CFS with other medical disorders. In clinical settings the list of...

Altered Expression of Developmental and Other Proteins

The migration of neurons from the ventricular zone to their proper positioning in the cortex is well orchestrated and requires a multitude of neural events including start signals, cell-cell recognition, cell adhesion, motility, and stop signals. Since schizophrenia appears to involve disturbances in cortical migration, researchers have focused their attention on some of the molecules thought to play a role in this process. One such candidate is a protein called reelin. Reelin is thought to help guide newly arriving migrating neurons to their proper destination, though the precise mechanism is presently unknown. A recent study (Impagnatiello et al., 1998) revealed that patients with schizophrenia only have about half of the normal levels of reelin and its transcript in all of the brain areas examined (prefrontal and temporal cortex, hippocampus, caudate nucleus, and cerebellum). Interestingly, while reelin levels are normal in patients with other psychiatric disorders such as unipolar...

Schizophrenia Adolescent And Childhood

Besides developmentally expectable phenomena that are not pathological, numerous psychiatric syndromes can present with symptoms of psychosis. The most common of these include depression, bipolar disorder, Anxiety Disorders, substance-related conditions, Personality Disorders, behavioral disorders, and pervasive Developmental disorders. In addition, developmental speech and language disorders as well as the corrective self-talk that may be seen in some youths with developmental disabilities can lead an examiner to believe that a young person is experiencing hallucinations. Of note, there appears to be a group of young people who have perceptual disturbances and substantial difficulties with affect regulation, interpersonal

Impulse Dyscontrol and Aggression Syndromes

Aggression may occur in patients with other medical or neurological conditions, producing global brain dysfunction. With a reduced level of consciousness and altered sleep-wake cycles, patients with delirium (due to electrolyte derangements, infection, drugs, or postsurgical or postictal conditions) may experience transitory ill-formed delusions and misperceptions leading to aggression. Encephalitis secondary to herpes simplex virus can become manifest with aggressiveness and may be associated with memory difficulties, irritability, distractibility, apathy, and restlessness. Childhood attention-deficit disorder, although it becomes manifest generally with attentional impairment, may be associated with destructive behavior when it is severe. Self-mutilation in association with aggression is a prominent feature of both the Lesch-Nyhan and the Prader-Willi syndromes, and may be seen in any condition that causes mental retardation. Finally, aggression in the context of a general...

Clinical Description and Course

Bipolar I Disorder affects men and women with equal frequency, but bipolar II patients are more frequently women. Women appear to have a preponderance of depressive episodes over manic or hypomanic episodes, whereas the reverse appears true of men. Similarly, the first onset of bipolar disorder is usually a depressive episode in a woman and a manic episode in a man. Bipolar disorder is associated with high personal, social, and economic costs. About 33 of bipolar I patients cannot maintain employment in the 6 months after a manic episode over 50 show declines in occupational functioning over the 5 years after an episode. The suicide rate is believed to be about 30 times greater than the normal population. Bipolar disorder is also associated with marital dysfunction and high rates of divorce, general health complications, legal problems, and problems in the adjustment of children (Coryell, Andreasen, Endicott, & Keller, 1987 Coryell et al., 1993 Goldberg, Harrow, & Grossman, 1995 Dion,...


The diagnosis of ADHD remains difficult, with no single test to assess it and a heavy reliance on subjective measures. A comprehensive evaluation of ADHD in adults or children should assess the presence or absence of symptomatology, differential diagnosis from other disorders that mimic ADHD, and the possibility of comorbid psychiatric disorders. At a minimum, the evaluation should include a clinical interview, a medical evaluation conducted within the past year, standardized behavior rating scales from parents and teachers, and direct observation of the patient. The evaluation for both children and adults includes a family history as well as documentation regarding developmental, social, and academic functioning. An evaluation for adults should also include information regarding their childhood via academic records and transcripts and retrospective-childhood ratings by the adult patient and a parent or another individual who knew the patient as a child. Common conditions that may...

Clinical History

Patients with impulse dyscontrol or aggression may not offer any complaints, yet family members may relate a detailed account. The spouse or relatives may note the patient's impulsiveness in everyday activities and an inability to resist performing inappropriate activities both at home and in public. The clinician should inquire about the use of both inappropriate words and physical actions. Additionally, family members should be asked about the presence of sudden outbursts or episodes of rage involving destructive behavior to property, abusive actions involving others, or self-mutilation.

Candidate Genes

The candidate gene approach is useful if previous research has identified specific biological substrates that are associated with the disorder. For example, if a disorder is known to be associated with elevated or depleted levels of a specific neurotransmitter, plausible candidate genes can be identified that influence some aspect of this neurotransmitter system. Candidate gene studies have identified several intriguing associations between genes in the dopamine and serotonin systems and psychological traits and disorders such as novelty seeking, neuroticism, Attention-Deficit Hyperactivity Disorder, Schizophrenia, and Bipolar Disorder. However, subsequent studies often fail to replicate the initial results, suggesting that these genes may have relatively small effects.

Psychosocial Factors

Bipolar disorder is affected by psychosocial stress. Two domains have been studied negative affective relationships within the patient's family, and stressful life events. Regarding the former, prospective studies indicate that bipolar patients who, following an acute illness episode, return to family or marital environments that are high in expressed emotion (containing relatives who are highly critical, hostile, or emotionally overinvolved) are more likely to relapse at 9-month or 1-year follow-up than patients who return to low-key family environments (for a review, see Miklowitz, Wendel, & Simoneau, 1998). It is not clear whether stress within the family is a primary eliciting factor for symptoms, whether bipolar symptoms in patients evoke family conflicts, or whether patients' symptoms and family conflicts are both traceable to third variables such as a shared genetic vulnerability to mood disorder. Episodes of bipolar disorder often follow major life events (Johnson & Roberts,...


Bipolar disorder is a genetically- and biologically-based illness of mood states. It takes a tremendous economic, social, and personal toll on sufferers and their family members. Recent advances in biological psychiatry and psychosocial research have clarified some of the predisposing factors for the disorder and have identified triggers for the disorder's cycling. Advances in its pharmacological and psychological management are being translated into treatment algorithms that have the potential to improve community-based care for this often debilitating disorder.


Figure 3.7 The expression profiles of six genes that are specifically regulated in patients with TS. The x-axis indicates the subject groups TS Tourette syndrome AGM age-and gender-matched controls CE children with epilepsy CH children with headache H healthy controls BS bipolar disorder and schizophrenia AE adult epilepsy NF neurofibromatosis type 1 PP Parkinson's disease and progressive supranuclear palsy. The y-axis indicates the relative expression value for each gene. All the values were normalized to the average of the patients with TS and expressed as mean SEM. (From Tang, Y. et al., Arch. Neurol., 62, 210-215, 2005. With permission.)

Early Age of Onset

Some studies have suggested that bipolar disorder patients with comorbid SUD have an earlier age of onset of bipolar disorder (32,33). Feinman and Dunner (32) reported that earlier age of onset was more common among bipolar patients with comorbid substance abuse than among bipolar patients without substance abuse dependence or among primary substance abuse dependence patients who subsequently developed bipolar disorder. Winokur et al. (30) found a significantly earlier onset of bipolar alcoholics with primary affective disorder. The risk factor of age of onset is reviewed in more detail below, under Chronology of Bipolar Disorder and SUD Comorbidity.


The NCS found that males were significantly more likely than females to have a lifetime history of dependence (9.2 vs 5.9 ). In contrast, the ECA Study found that lifetime drug use disorders are equally prevalent among male and female drug users (4). Among patients with bipolar disorder, the data currently available on this issue are conflicting. Some studies have found that substance abuse is higher in males than in females (12,30,32,34). Another study does not support this finding Tohen and colleagues (9), in a prospective study of patients hospitalized for their first manic or mixed episode, found that women were more than six times as likely as men to have a history of comorbid substance abuse or dependence (10 of 25 40 vs. 1 of 16 6.3 ). Discrep-

Mixed Mania

The majority of studies in bipolar disorder patients have reported higher rates of SUD in patients with mixed rather than classic episodes (12,33,35-38). Keller et al. (35) reported that bipolar patients with the mixed and rapid-cycling forms of the illness were more likely to abuse alcohol than patients with pure mania and pure depression. Sonne and colleagues (33) also found that bipolar disorder patients who abused substances were more likely to experience rapid cycling and to have dysphoric and irritable mood states than patients who did not abuse substances. Feinman and Dunner (32) noted that complicated and secondary, compared to primary, bipolar disorder patients had a greater percentage of rapid cycling. Primary bipolar disorder refers to patients with no past or present history of alcohol or substance abuse. Complicated bipolar refers to patients whose primary bipolar disorder was complicated by substance abuse that began after the onset of the bipolar disorder, and secondary...


The fact that severe depressive states are not simply normal reactions to distressing life events has been recognized since the time of the ancient Greeks. However, it was not until the latter half of the 20th century that the diagnoses of major depression and bipolar disorder came to be fully defined and accepted as the two most important forms of mood disorders. Most of what is known about these conditions and their treatment has been learned in the past 50 years. An increasing body of clinical research has advanced our understanding of the theoretical basis and underlying causes of these illnesses and refined our knowledge of brain function and the mechanism of action of antidepressant and antimanic medications. The treatments discovered in the past 50 years have had a tremendously beneficial impact on millions of people suffering from these devastating conditions. Further, as our knowledge continues to grow, new treatments are being explored every day. As the rapid pace of...


The modern conception of mood disorders emerged in the 19th and 20th centuries. As the scientific method began to influence the methodological approaches used to understand mental disorders, anecdotal and impressionistic work began to be replaced by more observational and longitudinal approaches. The work of Emil Kraepelin is one of the most notable in this regard (Kraepelin, 1921). Through meticulous longitudinal observation, Kraepelin proposed that recurrent affective illnesses were distinct from other mental disorders and could be conceptualized as manic-depressive insanity, now referred to as bipolar disorder. In part due to the influence of psychoanalytic theories, in the 1950s and 1960s depressions were grouped based on whether they were thought to have been caused by a stressful life event as opposed to having emerged spontaneously, presumably due to a chemical imbalance. The shift from a brainless view of mental illness in the 1950s to a mindless view of mental illness in the...

Valproic Acid

Valproic acid (dipropylacetic acid) is currently approved by the FDA for acute treatment of manic episodes associated with bipolar disorder. While it does not have FDA approval for maintenance treatment, it has become the most widely used medication in both acute and maintenance treatment of bipolar disorder in the United States. In a large multisite study, valproic acid did not differ from placebo in the length of time to recurrence of mania or depression in patients with bipolar disorder undergoing maintenance treatment (lithium also failed in this study) (Bowden et al., 2002). It is widely believed that this was a result of the high drop-out and noncompliance rate for all treatments in this study rather than a true reflection of lack of maintenance efficacy. Several open-label studies have shown efficacy for valproic acid in the maintenance therapy of bipolar disorder (American Psychiatric Association, 2002), as discussed below.


Impaired attention span and memory, hypervigilance, systolic flow murmurs, skin changes (warm, moist, smooth), EKG changes (sinus tachycardia, atrial fibrillation), psychiatric problems (depression, mania, bipolar disorder, manic psychosis), chorea, thyrotoxic penodic paralysis, thyroid storm, ocular features

Cyclothymic Disorder

Kraepelin (1921) emphasized that cyclothymia is on a continuum with full-blown bipolar (manic-depressive) disorder and, indeed, may be a precursor to it. Four lines of evidence strongly support this continuum model and suggest that cyclothymia is an integral part of the bipolar disorder spectrum. First, the behavior of cyclothymics is qualitatively similar to that of patients with full-blown bipolar disorder cyclothymia merges imperceptibly with Bipolar II (individuals who exhibit major depressive and hypomanic episodes, but not manic episodes), and sometimes Bipolar I (individuals who exhibit both major depressive and manic episodes), Disorder at the behavioral level (Akiskal et al., 1977 Akiskal, Khani, & Scott-Strauss, 1979 Depue et al., 1981). Second, equivalent rates of bipolar disorder have been reported in the first- and second-degree relatives of cyclothymic and Bipolar I patients (Akiskal et al., 1977 Depue et al., 1981 Dunner, Russek, Russek, & Fieve, 1982), and increased...


A common, often primary, symptom, hyperactivity is observed in a variety of medical and behavioral disorders, including bipolar disorder, Schizophrenia, autism, developmental disabilities, metabolic disorders, endocrine disorders, toxic exposure (e.g., lead poisoning), and other neurological conditions (brain tumor, encephalitis, Parkinson's disease, etc.). Hyperactivity is not in itself a cause for concern. Instead, it is a nonspecific symptom whose significance depends on demographic and situational factors and


Until recently, psychotherapeutic approaches to patients with bipolar disorder received scant research attention. Jamison et al. (52) found that patients with bipolar disorder were far more likely to value psychotherapy than were physicians who treated bipolar patients, despite the fact that most of the physicians surveyed were practicing psychotherapists. Many different types of psychotherapy for both bipolar disorder and SUD have been utilized (53-59). However, few studies have examined which psychotherapies should be used in bipolar disorder patients with comorbid SUD (60). Treatment of comorbid disorders may occur sequentially (the patient is treated first for SUD and then for the psychiatric disorder) or in parallel (the patient is treated simultaneously for both disorders usually treatment is delivered for each at different sites in unrelated clinical programs). However, since these forms of treatment have not produced favorable outcomes for patients with coexisting bipolar...

Movement disorder

Berthier et al. (1996) examined 9 patients with bipolar affective disorder with cerebrovascular lesions. Of the 9 patients with bipolar disorder, 8 had no family history of bipolar disorder in first-degree relatives. One patient had a father who committed suicide during a stress-induced depression. Two patients had a personal history of depressive disorder prior to the onset of stroke and the mean age at onset of mood disorder was 51.2 9 years. In 8 of the 9 cases, the first affective episode was depressive (89 ) while, in the remaining case the onset of the disorder could not be determined. Furthermore, the mean time from the stroke to the onset of mania was 8.6 7 SD months (range 2-24). The mean duration of follow-up was 4.8 7 SD years. In addition, 7 of the 8 patients who had neurological findings had evidence of movement disorder with or without associated motor or sensory deficit. Three patients had hemidystonia, one patient oral-lingual dystonia, one patient hemichorea, two...

Body Chemistry

Mental illness in many cases results not from purely emotional causes but from homeostasis gone awry. If a neurotrans-mitter substance is produced in too great or too small an amount, the effect on the rest of the nervous system may bring about the symptoms of clinical depression, bipolar disorder, or other mental illness.