Dopamine release in the prefrontal cortex increases flattening of the glucocorticoid rhythm, which may underpin prefrontal dysfunction in bipolar disorder patients, conclude researchers.

Previous studies have shown that bipolar disorder patients have abnormal glucocorticoid secretion, dopaminergic neurotransmission, and prefrontal cortex function, explain Sarah Gartside, from Newcastle University in the UK, and colleagues.

Believing that flattening of the diurnal glucocorticoid rhythm, which is common in bipolar disorder, modulates dopaminergic transmission in the prefrontal cortex, leading to functional abnormalities, the team administered corticosterone 50 µg/ml or 0.5% ethanol vehicle to the drinking water of male rats for 13??”15 days.

Compared with animals given vehicle, those treated with corticosterone had a flattened diurnal rhythm in blood corticosterone concentrations, with levels significantly lower before the diurnal peak and significantly higher at the nadir of the rhythm, and significant adrenal gland atrophy.

Corticosterone-treated animals had significantly increased basal dopamine levels compared with those given vehicle, the team reports in the journal Neuropsychopharmacology. Analysis revealed that depolarization-evoked release was also enhanced, while local blockade of terminal D2 autoreceptors failed to normalize release to control values.

In the ventral tegmental area, levels of mRNAs coding tyrosine hydroxylase and the vesicular monoamine transporter 2, as measured using in situ hybridization, were significantly increased in rats treated with corticosterone compared with vehicle-treated rats.

“The finding of increased dopamine release in the prefrontal cortex suggests a causal link between the neuroendocrine abnormalities observed in mood disorders, and some of the cognitive symptoms of these conditions: the prefrontal cortex plays a key role in cognitive functions including working memory, selective attention, goal directed behavior, and behavioral inhibition with prefrontal dopaminergic neurotransmission strongly influencing these functions,” the researchers write.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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For bipolar disorder patients, longer admission to hospital is associated with more severe executive functioning deficits at discharge, the results of a US study indicate.

A more severe disease course in bipolar disorder is associated with greater cognitive impairments, with cognitive deficits in euthymic patients predicted by a greater number and longer duration of mood episodes.

To determine whether length of hospitalization to stabilize from an acute episode of mood disturbance is linked to cognitive functioning, Boaz Levy, from Harvard Medical School in Boston, Massachusetts, and colleagues studied 41 patients with bipolar disorder.

In all, 20 patients had a hospital stay that lasted longer than the median stay of 12 days, while the remaining 21 patients had a shorter stay. The participants were administered a neuropsychological battery at discharge and group differences in clinical data and test performance were analyzed.

There were no significant differences between long- and short-stay patients in terms of age at onset of bipolar disorder, previous number of psychiatric admissions, number of psychiatric medications taken on the day of testing or diagnostic subtype on admission. There were also no differences in depressive or manic symptoms, gender, marital status, age, or years of education.

Patients with longer hospital stays had significantly worse performance than those with a short hospital stay on immediate recall and recognition of the figure’s parts on the Rey Complex Figure Test, as well as marginally significant impairment of delayed recall and significant impairments in overall verbal memory.

In addition, performance on tests of executive functioning was significantly worse for patients with longer hospital stay compared with those with a short stay, specifically on the Stroop, Wisconsin Card Sorting Test, and Controlled Oral Word Association Test. There were no significant differences in attention, working memory, and IQ.

The team concludes in the journal Comprehensive Psychiatry: “The current data indicate that longer duration of hospital stay is correlated with more severe deficits in executive functioning during the phase of early remission.

“These results illuminate the challenges patients with bipolar disorder may face after discharge from a long inpatient admission and underscore the need to develop better care for their outpatient recovery.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Elevated mood and decreased sleep can discriminate juvenile-onset bipolar disorder (JO-BP) from attention-deficit hyperactivity disorder (ADHD) in children as young as 3 years of age, study results suggest.

“Considerable controversy surrounds the nature of the earliest symptom expression of childhood-onset bipolar illness and its prodromes,” explain Robert Post (Pennsylvania State University Medical School, Hershey, USA) and team.

They add that childhood-onset BP shows a high degree of comorbidity with ADHD and, although differential characteristics emerge later in the course of illness evolution, it is difficult to distinguish one disorder from the other in early childhood.

To gain a better insight into the symptom evolution of these disorders, the researchers examined the course of individual symptoms over the first 10 years of life in 27 children with bipolar disorder with or without ADHD, who were diagnosed before 9 years of age, and 22 children with ADHD alone.

The children were rated by a parent for the severity of 37 symptoms. These were drawn from literature describing common presentations of childhood psychopathology and were rated on a scale from 0 to 3, with 3 representing the most severe degree of impairment in the child’s usual family, social, or educational roles.

The team found the symptoms of hyperactivity, impulsivity, and decreased attention span were highly prevalent and showed a similar course in both groups.

“This might be expected because not only are these classic symptoms of ADHD, but are common in bipolar illness itself,” note the researchers.

However, extended periods of mood elevation and decreased sleep were significantly more common in the bipolar children than in those with ADHD, and were strong differentiators between the two disorders from as young as 3 years of age. Furthermore, the differences between bipolar children and those with ADHD regarding these symptoms increased in magnitude over the first 10 years of life.

Depressive and somatic symptoms were later differentiators that became significant from around 7 years of age.

Irritability and poor frustration tolerance differentiated the two groups only in their greater incidence and severity in bipolar children, compared with a more moderate incidence and course in those with ADHD.

Writing in the journal Bipolar Disorders, Post and team conclude: “These findings suggest the importance of examining juvenile- and adolescent-onset bipolar cohorts separately, especially when considering the earliest or prodromal manifestations of the full-blown illness.

“Those who receive a formal Schedule for Affective Disorders and Schizophrenia for School Age Children-confirmed bipolar diagnosis by an average age of 5 show the beginning of symptom separation from those with ADHD in the first few years of life, which then progressively increases in magnitude.”

Commenting on the implications of the findings, they add: “One can be hopeful that earlier recognition, diagnosis, and concerted treatment with one or more mood stabilizers or atypical antipsychotics in the context of appropriate psychosocial therapies, in lieu of treatment as usual, might yield a better outcome and, ultimately, a more benign course of illness.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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