Psychiatry and Clinical Neurosciences

Abstract  Several studies have discussed the relationships between T‐helper 1 (Th1) or Th2 cytokines and major depression. The aim of the present study was to investigate the relationships between Th1/Th2 cytokine balance and clinical phenotypes of acute‐phase major depression. A total of 82 subjects including 42 patients with major depressive disorder and 40 healthy controls were recruited. Serum cytokine levels of interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α) and IL‐10 were examined. Using ancova with age and body mass index (BMI) adjustments, there were no significant differences in serum IL‐1β, TNF‐α, and IL‐10 levels between patients with major depressive disorder and healthy controls. However, using ancova with BMI adjustment only, the results showed that patients with major depressive disorder had significantly higher TNF‐α levels than control subjects. In addition, using ancova with age and BMI adjustments, significantly higher serum IL‐1β level and IL‐1β/IL‐10 ratio were noted in patients with melancholic features than patients with non‐melancholic features. However, there were no significant differences in serum IL‐1β, TNF‐α and IL‐10 levels between patients with and without suicide attempt. In conclusion, serum TNF‐α, IL‐1β level and IL‐1β/IL‐10 ratio might play an important role in the psychopathology of acute‐phase major depressive disorder.

Abstract  The objectives of this retrospective, naturalistic study were to provide preliminary data on the effects of 6 months treatment with risperidone, olanzapine and quetiapine on behavioral disturbances, within a sample of outpatients with mild to moderate Alzheimer's disease, and on predictors of response. Between July 2005 and December 2005, data were collected from 58 consecutive outpatients with a DSM‐IV‐TR diagnosis of Alzheimer's disease with behavioral disturbances, who received a 6‐month treatment with risperidone, olanzapine or quetiapine. Primary outcome measures were Neuropsychiatric Inventory (NPI) total score and its items forming the basic core of behavioral disturbances in Alzheimer's disease: delusions, hallucinations and agitation/aggressiveness. Secondary outcome measures were Mini‐Mental State Examination (MMSE), Activities of Daily Living, Instrumental Activities of Daily Living and Clinical Insight Rating scale. Correlations between baseline MMSE score and improvements in behavioral disturbances were investigated. At 6 months mean NPI total score had fallen 43.5% in the risperidone group, 45.6% in the olanzapine group and 33.3% in the quetiapine group, with no significant between‐group differences. Global cognitive function showed no significant change from baseline to end‐point. Incidence of adverse events was low. A significant correlation was found between MMSE score and NPI total score and NPI item agitation decreases. Risperidone, olanzapine and quetiapine produced significant improvements in behavioral disturbances and were well tolerated. No significant differences emerged among treatments. The preliminary results also suggest that baseline cognitive function might influence treatment response.

Abstract Sixty percent of 536 new referrals to a psychiatric clinic at a general hospital complained of insomnia. Prevalence was high in all psychiatric categories, especially in physiologic disorders, somatoform disorders and mood disorders, followed by epilepsy. Complaints of difficulty in falling asleep were high in the physiologic and somatoform disorder groups. Complaints of nocturnal awakening were high in the anxiety and physiologic disorder groups, while complaints of early morning awakening were high in the organic and mood disorder groups. Prescription rates of hypnotics was most prevalent in the mood and adjustment disorder groups, whereas a non‐pharmacological approach, including psychological education and behavioral therapy, was applied mainly to the physiologic disorder group.

Abstract Hypocretin deficiency is involved in most cases of human narcolepsy. Although cataplexy is pathognomonic of narcolepsy, mechanisms of induction of cataplexy are largely unknown. Patterns of occurrence of cataplectic attacks (i.e. onset location, laterality, and propagation of attacks) in hypocretin receptor 2‐mutated narcoleptic Dobermans were characterized in order to understand the basic mechanism of this abnormal sleep‐related atonia. Most cataplexy attacks were bilateral (98%) and were initiated in the hind legs (80%). Progression of attacks was also seen (49%) and atonia during propagation was most often bilateral (94%). Involvement of abnormal inactivation of bilateral pathways to the spinal motoneurones due to a deficiency in hypocretin neurotransmission is suggested in the occurrence of cataplexy.

Aims:  Repeated exposure to heroin, a typical opiate, causes neuronal adaptation and may result in anatomical changes in specific brain regions, particularly the frontal and limbic cortices. The volume changes of gray matter (GM) of these brain regions, however, have not been identified in heroin addiction.

Methods:  Using structural magnetic resonance imaging and an optimized voxel‐based morphometry approach, the GM volume difference between 15 Chinese heroin‐dependent and 15 healthy subjects was tested.

Results:  Compared to healthy subjects, the heroin‐dependent subjects had reduced GM volume in the right prefrontal cortex, left supplementary motor cortex and bilateral cingulate cortices.

Conclusion:  Frontal and cingulate atrophy may be involved in the neuropathology of heroin dependence.

To visualize dreaming brain functions we studied hemodynamic changes in the visual cortex during the transition from non‐rapid eye movement (NREM) to rapid eye movement (REM) sleep, using a 24‐channel Near‐Infrared Spectroscopy (NIRS) imaging method. Results were compared to the activation in visual cortex by visual stimulation during wakefulness. Subjects were four healthy males between 25 and 49 years of age. Five all‐night polysomnographic and NIRS recordings were made. Increases in the oxygenated hemoglobin concentration in visual cortex were observed from nine of 14 REM periods. The activated areas were broader during REM sleep than during visual stimulation. These findings suggest that activation of visual cortex in REM sleep might represent dream‐related brain activity.

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), are the most prevalent psychiatric conditions, and are also among the most severe and debilitating. However, the precise neurobiology underlying these disorders is currently unknown. One way to combat these disorders is to discover novel biomarkers for them. The development of such biomarkers will aid both in the diagnosis of mood disorders and in the development of effective psychiatric medications to treat them. A number of preclinical studies have suggested that the brain‐derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of MDD. In 2003, we reported that serum levels of BDNF in antidepressant‐naive patients with MDD were significantly lower than those of patients medicated with antidepressants and normal controls, and that serum BDNF levels were negatively correlated with the severity of depression. Additionally, we found that decreased serum levels of BDNF in antidepressant‐naive patients recovered to normal levels associated with the recovery of depression after treatment with antidepressant medication. This review article will provide an historical overview of the role played by BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Particular focus will be given to the potential use of BDNF as a biomarker for mood disorders. BDNF is initially synthesized as a precursor protein proBDNF, and then proBDNF is proteolytically cleaved to the mature BDNF. Finally, future perspectives on the use of proBDNF as a novel biomarker for mood disorders will be discussed.

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.