Introduction: Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early-and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course.

Methods: Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed.

Results: Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder.

Conclusion: Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.

Bipolar disorder is a prevalent psychiatric disorder with a high rate of misdiagnosis and evidence of degenerative progression. Research indicates that the interval between bipolar episodes decreases steadily until the patient settles into a relatively frequent course of mania and depression. Various imaging techniques have been used in the understanding of the brain pathology underlying bipolar disorder through identification of patterns consistent with disruption of the normal brain activity in bipolar patients. These techniques have demonstrated evidence of abnormalities in the structure and function of the prefrontal cortex. In addition, the cerebellar vermis, which serves as an error-detection function to modulate the iterative network, appears to shrink with recurrent episodes. Functional imaging demonstrates that the anterior limbic network is overactivated and overresponsive in patients with bipolar disorder. In many patients, those deficits are often compensated for by activation of other brain areas. Ultimately, when the compensation fails, expression of bipolar symptoms arise. Using magnetic resonance spectroscopy, simple models can be constructed based on the hypothesis that mitochondrial function may be impaired in bipolar disorder. There is also increasing evidence that psychotropic medications can affect specific brain regions that are thought to be involved in the pathogenesis of psychiatric disorders. Glutamate levels appear to be elevated in untreated patients with bipolar disorder, which may cause glutamatergic neurotoxicity and negative therapeutic implications. Further advances in brain imaging may contribute to the improvement of available therapies and the understanding which treatments will be most suitable for specific patients.

Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.

Opioid use disorder (OUD) is a major public health problem in the United States. It has resulted in devastating consequences for people with this condition, including psychosocial and legal problems, in addition to contraction of infectious diseases such as HIV and hepatitis B and C. Furthermore, this disease can cause fatalities from drug overdoses and drug–drug interactions. OUD shatters families and destroys relationships. Effective treatment is crucial in order to curtail the consequences of this condition. The objective of this article is to provide a review of the pharmacotherapies currently being used to treat OUD.

In this article, we examined evidence for the acute treatment of depression in bipolar I disorder, focusing on double-blind, placebo-controlled studies with a definite primary outcome measure and published in peer review journals. Quetiapine and olanzapine/fluoxetine are currently approved by the FDA for the treatment of bipolar depression, and a number of additional agents (including other atypical antipsychotics, mood stabilizers, antidepressants, and novel compounds) have been studied with varying degrees of efficacy. The medication with the most evidence for efficacy in bipolar depression is quetiapine, with five studies showing positive efficacy compared to placebo. In contrast, five studies of lamotrigine were negative, although meta-analyses of the pooled have found some treatment effects. Two studies of olanzapine and olanzapine/fluoxetine and three small studies of divalproex showed significant efficacy in treating bipolar depression. Two studies of aripiprazole found no differences compared to placebo. Early research on lithium in bipolar depression had significant methodological flaws, and only one study of lithium met our primary search criteria. To better understand the role of antidepressants, we also examined studies of antidepressants as adjunctive treatment of bipolar depression in participants taking mood stabilizers or atypical antipsychotics. These studies reported mixed results for a variety of antidepressants, but the majority found no differences compared to placebo. Other studies of adjunctive treatment were also discussed. There has been one positive adjunctive study each of lamotrigine, omega-3 fatty acids, modafinil, and armodafinil, while there was one negative trial each of omega-3 fatty acids, ziprasidone, and levetiracetam.

We hypothesized that patients with bipolar disorder would demonstrate verbal recognition performance deficits consistent with processing efficiency theory, a theory about how emotional states modulate performance by interfering with working memory resources or increasing cognitive arousal/effort. We predicted that (1) a manic group (n = 26) would demonstrate slow reaction time (RT) and low accuracy, (2) a euthymic group (n = 23) would demonstrate slow RT to maintain high accuracy; and (3) a healthy comparison group (n = 25) would demonstrate fast RT and high accuracy. The groups were administered symptom-rating scales and compared on a computerized, trial-by-trial, directed forgetting in recognition task. This task requires participants to comply with an overt instruction to forget irrelevant studied words, and it places a relatively high demand on working memory. The manic group was impaired on directed-forgetting sensitivity; however, when RT was statistically controlled, the groups demonstrated similar directed-forgetting effects. These findings are consistent with processing efficiency theory. They suggest that bipolar patients perform directed forgetting in recognition by increasing effortful control at encoding at the expense of processing efficiency, although acute mania reduces the capacity for control, thereby impairing recognition performance. Problems with processing efficiency are viewed as trait characteristics of bipolar disorder that may be overlooked by traditional error-based assessments. (JINS, 2005, 11, 871–880.)

Bipolar disorder (BPD) is a severe psychiatric illness that is characterized by episodes of extreme mood states. The affective components of bipolar disorder have been studied extensively, but only recently have investigators begun to systematically examine its cognitive concomitants. Although executive dysfunction has been reported in this population, especially while patients are manic, the tasks administered in many previous studies have made it difficult to determine the specific executive abilities that were compromised. The present study examined 15 patients with bipolar disorder who were manic, 18 who were euthymic, and 18 healthy participants. Tests were selected to evaluate two specific aspects of executive functioning in these participants. The Object Alternation Task was given as a measure of inhibitory control, and the Delayed Response Task was included as a measure of spatial delayed working memory. All groups performed similarly on the Delayed Response Task. On the Object Alternation Task, however, the manic and euthymic patients committed significantly more perseverative errors than healthy participants. These results indicated that patients in the present sample had relatively normal working memory abilities, but had a deficit in behavioral self-regulation, which was evident across mood states. (JINS, 2005, 11, 163–172.)Location of work: Center for Bipolar Disorders Research, Department of Psychiatry, University of Cincinnati School of Medicine, Cincinnati, Ohio.

We hypothesized that patterns of sustained attention performance in bipolar disorder were consistent with processing efficiency theory—a theory of the relationship between central processing capacity and performance. We predicted (1) sustained attention deficits during mania because symptoms interfere with limited-capacity executive control processes resulting in decreased performance effectiveness; and (2) decreased processing efficiency during euthymia, as indicated by speed/accuracy tradeoffs, consistent with a stable phenotypic abnormality. Twenty-five manic bipolar, 23 euthymic bipolar, and 28 healthy comparison participants were compared on a continuous performance task and administered symptom-rating scales. The manic group was significantly impaired on overall perceptual sensitivity and demonstrated a significant linear decrease in performance over time, consistent with impaired sustained attention. The euthymic group evidenced significantly slower overall hit reaction time (RT), but when RT was controlled they performed similarly to the healthy group over time. Two discriminant functions combined to separate the groups on manic symptom severity and on-task effort/strategy use. These findings are consistent with processing efficiency theory. They suggest that euthymic patients sustain attention through effortful control at the expense of processing efficiency, while acute mania reduces the capacity for control and impairs sustained attention. Problems with processing efficiency are viewed as trait characteristics of bipolar disorder that may be overlooked by traditional error-based assessments. (JINS, 2005, 11, 49–57.)

Patients diagnosed with bipolar disorder (BPD), by definition, have problems with emotional regulation. However, it remains uncertain whether these patients are also deficient at processing other people's emotions, particularly while manic. The present study examined the ability of 25 manic bipolar patients and 25 healthy participants on tasks of facial recognition and facial affect recognition at three different presentation durations: 500 ms, 750 ms, and 1000 ms. The groups did not differ in terms of age, education, sex, ethnicity, or estimated IQ. The groups did not differ significantly on either a novel computerized facial recognition task or the Benton Facial Recognition Test. In contrast, the bipolar group performed significantly more poorly than did the comparison group on a novel facial affect labeling task. Although the patient group had slower reaction times on all 3 computerized tasks, the presentation duration did not have an effect on performance in the patients. This study suggests that patients with bipolar disorder are able to recognize faces, but have difficulty processing facial affective cues. (JINS, 2003, 9, 623–632.)

Although mesial temporal lobe brain damage is frequently associated with memory loss, it is unclear whether the deficit results entirely from a disruption in the processing of relevant information or whether it also reflects interference from irrelevant information. Directed forgetting is one procedure that can be used, along with standard tests of memory, to investigate this distinction. Seventeen patients with a diagnosis of complex–partial seizures of temporal lobe origin and 17 healthy volunteers were compared on lexical decision, free recall, and recognition tests in a directed-forgetting paradigm. These tests created a memory profile to measure the influence of task relevant and irrelevant information in implicit and explicit memory. Compared with healthy volunteers, the patients were significantly impaired on the memory tasks overall [F(5,25) = 5.01, p < .01]. Specifically, directed forgetting in lexical decision and recognition both discriminated between the groups [stepdown F(1,26) = 6.84, η2 = .26, p < .05 and stepdown F(1,25) = 5.36, η2 = .13, p < .05, respectively]. The results suggest that interictal memory performance in temporal lobe epilepsy may be disrupted in part because of a deficit in the differential processing of task relevant and task irrelevant information, particularly at retrieval. (JINS, 1999, 5, 549–555.)

Of 38 adult patients admitted for first-episode psychosis, 20 reported childhood abuse, with equal prevalence in men and women. Patients with histories of childhood abuse had significantly more dissociative symptoms, but not more severe psychiatric symptoms. Childhood abuse was not related to rate of recovery and was only marginally related to longer stays in hospital. Although childhood abuse did not affect recovery during first-episode psychosis, it may contribute to a chronic course in some patients.