Innovative solutions to novel drug development in mental health.

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders.

MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals.

The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years), 17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.

A method for the assessment of the functional neuroanatomy of human sleep using FDG PET.

Although sleep is characterized by relative behavioral inactivity, cortical activity is known to cycle in well-defined periods across this state. Cognitive function during sleep has been difficult to define, although disturbances in sleep are known to result from, and to cause, various human pathologies, including neuropsychiatric disorders. Assessment of brain function in humans (related to cognitive operations) during sleep has been limited, until recently, to surface electrophysiologic recordings that limit analysis of regional function, particularly in deep structures. The current report describes one method of assessing human forebrain activation during sleep using the [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) method and positron emission tomography (PET) measures of regional cerebral glucose utilization. In comparison with other functional brain imaging techniques (e.g., assessment of blood flow or functional magnetic resonance imaging), this method offers the advantage of a more naturalistic study of sleep since subjects do not have to sleep in a scanning device. This leads to a higher rate of successful completion of studies. The primary disadvantage of this method is the decreased temporal resolution necessitating assessments of global sleep states (e.g., REM or NREM) as opposed to assessing events within a sleep state (e.g., sleep spindles or rapid eye movements).

Sleep as a mediator of the stress-immune relationship.

OBJECTIVE: To evaluate the role of sleep in the relationship of intrusive thoughts/avoidance behaviors to natural killer cell (NKC) number and function. METHOD: Twenty-nine individuals seeking treatment for bereavement-related depression were studied in the sleep laboratory. Background and clinical variables, including the Impact of Event Scale (IES) and the Hamilton Rating Scale for Depression (HRSD), were administered during the week preceding a 3-night sleep study. Blood samples were collected upon awakening after the second or third night of sleep. RESULTS: Greater frequency of intrusive thoughts and avoidance behaviors was associated with more time spent awake during the first non-rapid eye movement period (NREM-1) and lower NKC number (p values < .01). Greater time spent awake during NREM-1 was associated with lower NKC numbers (p < .05). Regression analyses revealed that the significant relationship between symptoms of intrusion/avoidance and NKC number was no longer significant when time spent awake during NREM-1 was entered into the regression equation. Time spent awake during NREM-1 accounted for 12% of the variance in NKC number (p < .05), whereas intrusion/avoidance accounted for 7% of the variance in NKC number (NS). CONCLUSIONS: These results suggest that EEG-assessed sleep may be a significant correlate of the stress-immune relationship.