***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder ; however , their precise role remains unclear . In this study , we aim ed to evaluate  neuro‐immune changes  in a prospect i ve study on children of patients with bipolar disorder Background —The Framingham Coronary Heart Disease ( CHD ) prediction score is recommended for global risk assessment in subjects prone to CHD . Recently , C-reactive protein ( CRP ) has emerged as an independent predictor of CHD . We sought to assess the potential of CRP measurements to enhance risk prediction based on the Framingham Risk Score ( FRS ) in a large cohort of middle-aged men from the general population . Methods and Results —We measured  CRP  and traditional cardiovascular risk factors at baseline in 3435 white men of German nationality , 45 to 74 years of age . All men were drawn from 3 r and om sample s of the general population in the Augsburg area located in Southern Germany in 1984 to 1985 , 1989 to 1990 , and 1994 to 1995 ( response rate , 80 % ) , and the FRS was calculated in all of them . Outcome was defined as nonfatal and fatal coronary events , including sudden cardiac death . During an average follow-up of 6.6 years , a total of 191 coronary events occurred . Cox regression showed a significant contribution of  CRP  to coronary event risk prediction independent of the FRS ( P = 0.0002 ) . In stratified analysis for 5 categories of FRS , CRP significantly added prognostic information to the FRS in subjects in 2 intermediate risk categories ( P = 0.03 and P = 0.02 ) . Conclusions —Our results suggest that CRP enhances global coronary risk as assessed by the FRS , especially in intermediate risk groups . This might have implication s for future risk assessment There is evidence that major psychiatric discords such as schizophrenia ( SZ ) and bipolar disorder ( BD ) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins . Brain-derived neurotrophic factor ( BDNF ) is the most widely distributed neurotrophin in the central nervous system ( CNS ) , and performs many biological functions such as promoting the survival , differentiation , and plasticity of neurons . Variants in the BDNF gene increase the risk of SZ and bipolar disorder . Chronic administration of drugs used to treat SZ and BD , such as lithium , valproate , quetiapine , clozapine , and olanzapine , increases BDNF expression in rat brain . To examine serum BDNF , three groups of chronically medicated DSM-IV SZ patients , on treatment with clozapine ( n=27 ) , typical ( n=14 ) , and other atypical antipsychotics ( n=19 ) , 30 euthymic BD patients , and 26 healthy control had 5 ml blood sample s collected by venipuncture . Serum BDNF levels were significantly higher in SZ patients ( p<0.001 ) when compared to either controls or euthymic BD patients . Increased BDNF in SZ patients might be related to the course of illness or to treatment variables . Prospect i ve studies are warranted BACKGROUND The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants . Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder . The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression . METHODS In a double-blind , placebo-controlled study , 21 patients with DSM-IV bipolar II disorder , depressive phase on therapeutic levels of lithium or valproate  were r and omly assigned to treatment with pramipexole ( n = 10 ) or placebo ( n = 11 ) for 6 weeks . Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale . RESULTS All subjects except for one in each group completed the study . The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect . A therapeutic response ( > 50 % decrease in Montgomery-Asberg Depression Rating Scale from baseline ) occurred in 60 % of patients taking pramipexole and 9 % taking placebo ( p = .02 ) . One subject on pramipexole and two on placebo developed hypomanic symptoms . CONCLUSIONS The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression Brain-derived neurotrophic factor ( BDNF ) is a key mediator of neuronal plasticity in the adult . BDNF is known to be stored in human platelets and to circulate in plasma , but the regulation and function of BDNF in peripheral blood is still poorly understood . In this prospect i ve study , we have examined 140 healthy , non-allergic adults ( 20 - 60 years old ) to eluci date the impact of age and physical parameters on BDNF levels in human platelets and plasma . There was a wide concentration range of BDNF in serum ( median : 22.6 ng/ml ) , platelets ( median : 92.7 pg/10(6 ) platelets ) and plasma ( median : 92.5 pg/ml ) . BDNF levels in plasma decreased significantly with increasing age or weight , whereas platelet levels did not . When matched for weight , there were no significant gender differences regarding BDNF plasma levels . However , women displayed significantly lower platelet BDNF levels than men . In addition , platelet BDNF levels changed during the menstrual cycle . In conclusion , we demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF levels in peripheral blood UNLABELLED Changes in inflammatory cytokines and dysfunction of the neurotrophic system are thought to be involved in the pathology of bipolar disorder ( BP ) . We investigated whether inflammatory and neurotrophic factors were changed in BP . We also investigated whether treating BP with valproic acid ( VPA ) plus low-dose ( 30 or 60 mg/day ) dextromethorphan ( DM ) is more effective than treating it with VPA only , and whether DM affects plasma cytokines and brain derived neurotrophic factor ( BDNF ) levels . In a 12-week , r and omized , double-blind study , patients were r and omly assigned to the VPA+DM30 , VPA+DM60 , or VPA+Placebo groups . The Young Mania Rating Scale ( YMRS ) and Hamilton Depression Rating Scale ( HDRS ) were used to evaluate symptom severity , and ELISA to analyze plasma cytokine and BDNF levels . We recruited 309 patients with BP and 123 healthy controls . Before treatment , patients with BP had significantly higher plasma cytokine and lower plasma BDNF levels than did healthy controls . After treatment , HDRS and YMRS scores in each group showed significant improvement . Plasma cytokine levels tended to decline in all groups . Changes in plasma BDNF levels were significantly greater in the VPA+DM60 group than in the VPA+Placebo group . CONCLUSION patients with BP have a certain degree of systemic inflammation and BDNF dysfunction . Treatment with VPA plus DM ( 60 mg/day ) provided patients with BP significantly more neurotrophic benefit than did VPA treatment alone BACKGROUND There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events . While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder , little is known about the neurobiological basis underlying this association . The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events ( TE )  have lower brain-derived neurotrophic factor ( BDNF ) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE . METHODS One-hundred and sixty-three consecutively recruited bipolar out patients were assessed by Structured Clinical Interview for DSM-IV ( SCID ) and st and ard protocol in order to evaluation psychopathology and clinical features . The reported TE was assessed using DSM-IV stem criteria for trauma ( as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder ) . Subjects were divided into 2 groups according to presence or absence of lifetime TE . The levels of BDNF , comorbidity and other clinical features were compared between groups . RESULTS After adjusting for confounders , results indicated that bipolar patients with a history of TE have alcohol abuse/dependence ( p < 0.001 ) , anxiety comorbidity , and lower levels of serum BDNF ( p < 0.01 ) compared to those without a history of TE . There was no difference between the 2 groups in age of onset , presence of psychosis , other substance abuse and dependence , rapid cycling or suicide attempts . CONCLUSIONS Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients . It is possible that a decrease in BDNF levels may account for increased comorbidity , but further prospect i ve studies are required to confirm this Molecules that are involved in neuronal intercommunication and adaptability of neural networks , such as brain-derived neurotrophic factor ( BDNF ) , are targets of pathophysiological investigation in bipolar disorder ( BD ) . Quetiapine is an attested treatment in this disorder , used in acute mood episodes . The aim of this study was to report prospect i ve changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine  along a 16 week follow-up . Assessment s were performed at baseline and weeks 2 , 4 , 8 and 16 with the Young Mania Rating Scale , the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale . In these visits , serum BDNF levels were measured . Mixed effect models were used to investigate longitudinal changes . Twenty-five patients were included for this analysis , seventeen in a current depressive episode and eight in a manic/mixed episode . A significant improvement from baseline to endpoint was displayed . In the mixed model , significant main effects for episode and time appeared , and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode , but a decrease in BDNF levels with time in those with a manic/mixed episode . BDNF may be a biomarker with differential response according to the polarity of mood episodes BACKGROUND Recent reports have suggested a role for brain-derived neurotrophic factor ( BDNF ) in psychiatric disorders . Decreased serum BDNF levels have been reported in major depression , but the cause of this decrease has not yet been investigated . The goal of this study was to assess blood BDNF and a platelet activation index , PF4 . METHODS Forty-three drug-free patients ( 27 female , 16 male ) diagnosed with major depression and 35 healthy control subjects ( 18 female , 17 male ) were assessed for plasma , serum , and blood BDNF content . Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods , and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale . RESULTS Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects . In whole blood , BDNF levels were unaltered in the depressed subjects compared with control subjects . The serum/blood BDNF ratio was lower in patients with major depression . Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects . CONCLUSIONS Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release . Secretion of BDNF seems to be independent of platelet reactivity ; other mechanisms are therefore probably involved and need to be eluci date Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor ( BDNF ) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder ( BD ) . In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania , ten bipolar patients were prospect ively examined at inpatient unit admission and discharge . Diagnoses were made using the Structured Clinical Interview for DSM-IV , SCID-I. Serum BDNF levels were measured by s and wich ELISA . The results showed that BDNF levels were decreased in BD patients during mania when compared to controls ( p=0.013 ) but this difference was no longer significant after treatment ( p=0.126 ) . A sharp increase in BDNF levels was found after treatment of the episode of acute mania ( p=0.010 ) . These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania . Further studies design ed to vali date the use of BDNF as a marker of treatment response in bipolar disorder are warranted 
    Output:
    
No differences in peripheral BDNF levels were observed between affective states overall .
Longer illness duration was associated with higher BDNF levels  in bipolar disorder patients .