Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is an interesting procedure in which a pacemaker-like device is attached to an electrode that wraps around the left vagus in the lower neck (Rush et al. 2000). Periodic stimulation of the vagus alters functional activity in multiple regions of the brain (Chae et al. 2003). Rush et al. (2005a) reported a randomized, sham-controlled study of VNS in treatment-resistant depression in 210 subjects with major depressive disorder and 25 bipolar depressed subjects. VNS and...

References

Altamura AC, Salvadori D, Madaro D, et al Efficacy and tolerability of quetiapine in the treatment of bipolar disorder preliminary evidence from a 12-month open-label study. J Affect Disord 76 267-271, 2003 Ames A 3rd CNS energy metabolism as related to function. Brain Res Brain Res Rev 34 42-68, 2000 Antelman SM, Caggiula AR, Kucinski BJ, et al The effects of lithium on a potential cycling model of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 22 495-510, 1998 Antelman SM, Levine...

Specificity Of Bipolar Depression

The biology of bipolar depression encompasses depressive episodes of bipolar disorder and the biology of the underlying illness that gives rise to the depressive episodes. Understanding the biology of bipolar depression should increase the effectiveness of its diagnosis and treatment. In our current nosology, mania or hypomania is required for diagnosis of bipolar disorder (First et al. 1996). Yet, for most patients, depression is the most salient feature of the illness the average patient with...

Dopamine Agonists

From a phenomenological point of view, bipolar depression presents as an opposite to mania. Whereas bipolar depression shows retarded activity, slow thinking, and low mood, mania shows enhanced activity, rapid thinking, and heightened or irritable mood. Such dichotomous presentation of a disorder is rare in nature. Himmelhoch (2000) suggested that bipolar depression is centered around volitional inhibition and that there is a relationship between bipolar depression and involuntary motor...

Antidepressantassociated Chronic Irritable Dysphoria

In 1987, Akiskal and Mallya introduced the notion of antidepressant-induced, chronic symptoms that include irritability and sleep disturbance in relatives of bipolar patients who have only manifested unipolar depressions. These patients developed a syndrome that consists of 1) unrelenting dysphoria, 2) severe agitation, 3) refractory anxiety, 4) unendurable sexual excitement, 5) intractable insomnia, 6) suicidal obsessions and impulses, and 7) histrionic demeanor (Akiskal and Mallya 1987). More...

Antipsychotics As Antidepressants

The introduction of the second generation of antipsychotics, with relatively less D2 blockade and significant serotonin 5-HT2A receptor blockade, suggested that these agents may be effective in bipolar illness without a significant depressogenic effect. This was insinuated in several short-term, placebo-controlled studies of second-generation anti-psychotics in acute mania (Keck et al. 2003a, 2003b Sachs et al. 2002 Tohen et al. 1999, 2000). In all of these studies, depressive scales were...

Misdiagnosis

Numerous clinical studies now confirm that about 40 of persons with bipolar disorder are initially misdiagnosed with unipolar depression (Ghaemi et al. 2001). In some cases, the problem is not so much misdi-agnosis as it is the natural history of the illness if depressive episodes precede manic episodes, then the current nosology, correctly applied, would lead to misdiagnosis. This is sometimes called pseudounipolar depression. However, about 90 of patients with bipolar disorder will have a...

Antidepressant Induced Mood Destabilization andor Rapid Cycling

Whether antidepressants can destabilize mood in the long run has been controversial. The best evidence for such an effect comes from three RCTs. In the first study, manic episodes were reported almost 2.5 times more frequently in bipolar type I patients with double-blind treatment of lithium plus imipramine (24 ) compared with lithium alone (10 ) over a mean 1.6-year follow-up (Quitkin et al. 1986). These results were statistically significant in the female subgroup. Depressive relapse rates...

Ketogenic Diet

The ketogenic diet (KD) has been used to treat epilepsy since the 1920s. The KD creates and maintains a state of ketosis as a result of changing the body's fuel from carbohydrates to fat. It is a treatment usually used in children with severe intractable epilepsy and has been found to be most effective for people with myoclonic seizures and minor motor seizures. It has also been helpful for people with tonic-clonic seizures and complex partial seizures. Although the diet seems to work best in...

Brain Energy Metabolism In Bipolar Depression

Bipolar disorder as manifested by its opposite poles of depression and mania is characterized by decreased or increased motoric and mental energy expenditure. Does such a unique presentation suggest altered states of brain energy metabolism in this disorder Although the brain makes up about 2 of our total body weight, it consumes about 20 and 25 of total body dioxide and glucose, respectively. Neural activity is dependent upon energy metabolism mainly for the active transport of ions and other...

Clinical Course

Severity of illness appears to be associated with suicide. First episodes requiring hospitalization may be particularly high risk. The time immediately after hospital admission and immediately after discharge ap pears to be a particularly vulnerable period for suicide. Hoyer et al. (2004) examined the characteristics of all first hospitalizations for affective disorder in Denmark between 1973 and 1993, finding that 3,141 of 53,466 patients committed suicide (6 ), and that the suicide risk was...

Chromosome

In an older study of an Amish pedigree, Ginns et al. 1996 reported suggestive linkage signals at marker D6S7. Another report of findings related to chromosome 6 comes from Dick et al. 2003 , who conducted genome-wide linkage analyses on 1,152 individuals mostly Caucasian from 250 families in the multisite NIMH Genetics Initiative bipolar survey. Bipolar I disorder and SABP diagnostic criteria were derived from DSM-III-R, and bipolar II and recurrent major depression UPR were diagnosed following...

Physiological Studies

Before direct brain imaging studies were available, bipolar depression was studied using electroencephalograms, evoked potentials, and neu-ropsychological tests. As summarized in Table 2-3, these experiments have produced interesting leads that are consistent with subtle abnormalities in arousal, lateralization, and susceptibility to impulsivity in TABLE 2-2. Specificity of transmitter-related data in bipolar disorder Response to orthostasis, bipolar gt unipolar Distribution of receptors in...

Course of Illness

Differences also exist between bipolar and unipolar depression in the course of those conditions Table 1-2 . Kraepelin 1921 viewed the course of illness as the key diagnostic validator that differentiated illnesses. In the case of bipolar disorder, its earlier age at onset differentiates it from unipolar depression, which has a later age at onset range, with a median in the late 20s to early 30s. Follow-up studies of depressed patients with an age at onset below 25 or 30 indicate that such...

Chromosome X

With a 1 1 equal gender distribution, it is counterintuitive to suggest that susceptibility for bipolar illness inheritance may be X-linked. However, there appears to an association whereby disease inherited from the father may be more severe, suggesting a possible contributing effect on the X chromosome. Analyses of the NIMH Genetics Initiative pedigrees waves 1 and 2 153 families support linkage to the X chromosome on Xp22.1, with a heterogeneity LOD of 2.3 Mclnnis et al. 1999 . More...

The Bipolar Spectrum

The above discussion of ways to differentiate bipolar from unipolar depression is also relevant to the general concept of a bipolar spectrum. The notion of a bipolar spectrum begins from the fact that many patients do not meet classical definitions of unipolar depression or bipolar disorder type I or II. As shown in Figure 1-1, many patients appear to demonstrate features of bipolarity such as the depressive phenomenology or the illness course mentioned above, and yet the inability to diagnose...

Overdiagnosis

Despite the evidence that bipolar misdiagnosis has not decreased in the past decade, some clinicians and researchers express concern about possible overdiagnosis of bipolar disorder. This concern is especially voiced in relation to discussion of broadening the definition of the bipolar spectrum. Differential diagnosis of depression Secondary Clear psychosocial stress, clear medical illness FIGURE 1-3. How the polarity-based approach to bipolar disorder in DSM-IV-TR can lead to misdiagnosis....

Studies of Neurotransmitter Function

Neurotransmitter function in bipolar and nonbipolar depressions has been investigated using transmitter metabolite levels in body fluids, receptors on peripheral cells, and receptor function using agonist or neuroendocrine challenge techniques. The studies were guided by a series of simple and heuristically useful hypotheses, summarized in Table 2-1. Despite supporting data for each hypothesis, each also had contradictory findings. At a fairly early stage, it was possible to reject hypotheses...

Phenomenology

At a superficial level, the phenomenology of bipolar depression can be described as twofold past mania or hypomania and current depression. The diagnosis of past manic or hypomanic episodes is where the standard DSM-IV-TR-based approach to bipolar depression begins and ends. This is a necessary but insufficient approach to diagnosing bipolar depression. While the presence of past manic or hypomanic episodes in the depressed patients meets the diagnostic criteria for bipolar depression, the...

The Validators Of Diagnosis

The classic validators of psychiatric diagnoses were first discussed by Eli Robins and Samuel Guze in 1970 in reference to schizophrenia. They identified five validators signs and symptoms, delimitation from other disorders, the follow-up study outcome , family history, and laboratory tests. The basic rationale for having multiple validators for a psychiatric diagnosis is the absence of a gold standard. Whereas in medicine clinicians often argue over a potential diagnosis only to have the...

Clinical Specificity

The basic depressive syndrome consists of the inhibition of goal-directed and reward-related activity, experienced as anhedonia and anxious pessimism. Biological models for depression have focused largely on the effects of uncontrollable stressors. These models have moderate pharmacological validity but lack evidence of specificity for bipolar disorder Machado-Vieira et al. 2004 Nestler et al. 2002 . The core depressive or melancholic syndrome appears essentially identical in unipolar and...

Depressive Phenomenology

The current symptoms of bipolar depression have been thought by many to be similar to those seen in unipolar depression. Yet it appears that there are differences between unipolar and bipolar in the phenom-enological presentation of depression. These likely differences are highlighted in Table 1-1. Atypical depressive symptoms seem to be more common in bipolar than in unipolar depression Agosti and Stewart, 2001 Benazzi 1999, 2001a Ghaemi et al. 2002 Mitchell et al. 2001 . In the National...

Digfast A Mnemonic for Mania

DIGFAST is a mnemonic aid for the following concepts Distractibility An inability to maintain one's concentration, as opposed to the decreased concentration of depression, where one is unable to initiate concentration. In mania, this leads to the initiation of multiple tasks, none of which are finished. Insomnia A decreased need for sleep, as opposed to the decreased sleep of depressive insomnia. The patient sleeps less, but has intact or increased energy the next day. Alternatively, there is...