Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study

ObjectiveWe performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT).MethodA comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: “major depressive disorder”, “unipolar depression”, “brain-derived neurotrophic factor”, and “electroconvulsive therapy”.ResultsA total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17–0.96). Additionally, we found significant heterogeneity between studies (I² = 73%).ConclusionOur findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD.     

Ultra-brief pulse ECT in bipolar and unipolar depressive disorder: differences in speed of response

Objectives:  There is little evidence for differences in response and speed of response to electroconvulsive therapy (ECT) between patients with bipolar and patients with unipolar depressive disorder. In the only prospective study to date, Daly et al. (Bipolar Disord 2001; 3: 95–104) found patients with bipolar depression to show more rapid clinical improvement and require fewer treatments than unipolar patients. In this study, response and speed of response of patients with unipolar and bipolar depression treated with ultra-brief pulse ECT were compared.
Methods:  All patients (n = 64) participated in a randomized trial comparing ultra-brief pulse bifrontal ECT at 1.5 times seizure threshold and unilateral ECT at 6 times seizure threshold. Thirteen patients (20.3%) had DSM-IV-defined bipolar depression. The Hamilton Rating Scale for Depression and Clinical Global Impression scale were administered at baseline and repeated weekly during and after the course of treatment by a blinded rater. At the same time point, the Beck Depression Inventory and the Patient Global Impression scale were administered. Speed of response was analyzed using survival analyses.
Results:  Patients with bipolar and unipolar depression did not differ in rates of response or remission following the ECT course, nor in response to unilateral or bifrontal ECT. Patients with bipolar depression, however, showed a more rapid response than patients with unipolar depression.
Conclusions:  Patients with bipolar depression tend to show more rapid clinical improvement with ECT than patients with unipolar depression.     

Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life

Objectives: Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders. We addressed these issues by examining data from a prospective longitudinal community study to (i) determine the cumulative incidence of mood episodes and disorders in the first three decades of life; (ii) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa; and (iii) determine the clinical and treatment characteristics of these subjects. Methods: Using the Munich‐Composite International Diagnostic Interview, clinically trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects (aged 14–24 at baseline and 21–34 at third follow‐up). Results: The estimated cumulative incidence at age 33 was 2.9% for manic, 4.0% for hypomanic, 29.4% for major depressive, and 19.0% for minor depressive episodes; overall, 26.0% had unipolar major depression, 4.0% bipolar depression, 1.5% unipolar mania, and 3.6% unipolar hypomania (no major depression). Overall, 0.6% and 1.8% had unipolar mania or hypomania, respectively, without indication for even minor depression. A total of 3.6% of the initial unipolar major depression cases subsequently developed (hypo)mania, with particularly high rates in adolescent onset depression (< 17 years: 9%). A total of 49.6% of the initial unipolar mania cases subsequently developed major depression and 75.6% major or minor depression. While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases, bipolar cases did not significantly differ in mania characteristics from unipolar mania cases. Conclusions: Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood, a time period when both the recognition and the intervention rates by the healthcare system are rather low. ‘Conversion’ to bipolar disorder is limited in initial unipolar depression, but common in initial unipolar mania. The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings.     

A 15-year prospective follow-up of bipolar affective disorders: comparisons with unipolar nonpsychotic depression

Goldberg JF, Harrow M. A 15‐year prospective follow‐up of bipolar affective disorders: comparisons with unipolar nonpsychotic depression.
Bipolar Disord 2011: 13: 155–163. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Outcome studies have previously documented substantial functional disability among individuals with bipolar disorder, although few follow‐up studies have examined the prospective course of illness beyond 10 years’ duration. Methods: A total of 95 patients with mood disorders (46 with bipolar I disorder and 49 with unipolar nonpsychotic depression) were assessed 15 years after index hospitalization. Logistic and linear regression models were used to identify predictors of global functioning, work disability, and social adjustment. Results: At 15‐year follow‐up, good overall functioning was significantly less common among subjects with bipolar disorder (35%) than unipolar depression (73%) (p < 0.001). Work disability was significantly more extensive in bipolar than unipolar disorder subjects (p < 0.001). Logistic regression indicated that good outcome 15 years after index hospitalization was significantly predicted by a unipolar rather than bipolar disorder diagnosis and the absence of a depressive episode in the preceding year. Past‐year depressive, but not past‐year manic, syndromes were associated with poorer global outcome and greater work disability. In addition, subsyndromal depression was significantly associated with poorer global, work, and social outcome among bipolar, but not unipolar disorder subjects. Conclusions: A majority of individuals with bipolar I disorder manifest problems with work and global functioning 15 years after an index hospitalized manic episode Recurrent syndromal and subsyndromal depression disrupts multiple domains of functional outcome more profoundly in bipolar than unipolar mood disorders. The prevalence, and correlates, of impaired long‐term outcome parallel those reported in shorter‐term functional outcome studies of bipolar disorder.     

BDNF blood levels after non-invasive brain stimulation interventions in major depressive disorder: A systematic review and meta-analysis

Objectives. To evaluate whether the antidepressant effects of novel non-invasive brain stimulation (NIBS) therapies are associated with neurotrophic effects, indexed by peripheral brain-derived neurotrophic factor (BDNF) levels. Methods. Systematic review and meta-analysis. We included trials published in PubMed/Medline from the first date available to June 2014 measuring BDNF blood levels before and after repetitive transcranial magnetic stimulation or transcranial direct current stimulation in depression. Results. Eight datasets (n = 259) were included. These studies enrolled mostly treatment-resistant depression patients, who received daily stimulation sessions on the left dorsolateral prefrontal cortex. BDNF did not increase after NIBS (Hedges’ g = 0.03, 95% CI = –0.21 to 0.27), even when examining each intervention separately. Meta-regressions did not identify the influence of any clinical and demographic predictors on the outcome. Finally, Begg's funnel plot did not suggest publication bias and results were robust according to sensitivity analysis. Conclusions. Peripheral BDNF levels do not increase after NIBS in depression. Such biomarker might, therefore, not be suitable to index NIBS antidepressant response. Further trials are needed, particularly exploring non-medicated populations, performing subsequent BDNF assessments in a larger timeframe and employing more intensive NIBS treatment protocols.     

Agitated Depression: Unipolar? Bipolar? or Both?

The classification of agitated depression (major depressive episode (MDE) plus psychomotor agitation) in mood disorders is unclear. DSM-IV is neutral on this point. As antidepressants may increase agitation, a better understanding of agitated depression is important for clinical practice. Study aim was to find if agitated depression was closer to bipolar or to unipolar disorders, by studying its association with variables typically related to bipolar disorders (early onset, many recurrences, more atypical features, more bipolar family history), and by studying its association with bipolar II disorder. Consecutive 151 unipolar and 226 bipolar II psychoactive drug-free MDE outpatients were interviewed with the Structured Clinical Interview for DSM-IV, when presenting for MDE treatment. Agitated MDE patients were compared with nonagitated MDE patients. Statistics were t test for means, two-sample test of proportion, and logistic regression (STATA 7). Agitated MDE was present in 85 patients (22.5%). It had significantly more bipolar II disorder patients (80.0% vs. 54.1%, p = 0.0000), more females, lower age at onset, longer duration of illness, more MDE recurrences, more atypical features, more MDE symptoms, and more family history of bipolar disorders, than nonagitated MDE. To control for the possible confounding effect of bipolar II disorder, logistic regression was used. All the significant differences became nonsignificant. Results might suggest that agitated MDE might be closer to the bipolar spectrum than to unipolar disorder, because it was associated with variables typically distinguishing bipolar from unipolar disorders, and with bipolar II disorder. Further studies on this topic are needed.     

Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications

A number of lines of converging evidence suggest that brain-derived neurotrophic factor (BDNF) may play a role in the onset and treatment of bipolar disorder. We review pertinent data on BDNF from several different areas of preclinical and clinical investigation that suggest novel theoretical and treatment implications for the recurrent affective disorders.

Data from several recent studies have also converged showing that the val66met allele of BDNF, a common single nucleotide polymorphism (SNP), is associated with selective minor deficits in cognitive functioning in subjects with schizophrenia, bipolar illness, and normal controls. Yet, paradoxically, the better functioning val66val allele of BDNF appears to be associated with an increased risk for bipolar disorder and perhaps early onset or rapid cycling. All the primary antidepressant modalities, as well as the mood stabilizers lithium and valproate, increase BDNF. Stressors decrease BDNF and this effect can be blocked by antidepressants. Serum BDNF is low in proportion to the severity of mania and depression and increases with clinical improvement.

Assessment of the val66val BDNF allele and a range of other SNPs as potential vulnerability factors for bipolar illness and its early onset could facilitate studies of early intervention, help reduce long delays between the onset of first symptoms and the first treatment, and help in the prediction of individual patient’s likelihood of responding to a given treatment.     

Reduced subgenual cingulate volumes in mood disorders: a meta-analysis

OBJECTIVE: Converging evidence suggests that the subgenual cingulate (SGC) is implicated in regulation of mood and in the pathophysiology of mood disorders. Our objective was to carry out the first meta-analysis of SGC volumes in patients with mood disorders. METHODS: We reviewed 10 volumetric magnetic resonance imaging studies of SGC volumes in patients with unipolar depression and bipolar disorders. For meta-analysis, we used standardized differences between means (SDMs) and random effects models. In the search for sources of heterogeneity, we subdivided the studies on the basis of diagnosis and presence of family history. RESULTS: The volumes of left and right SGC in patients with mood disorders were significantly reduced relative to healthy control subjects (SDM -0.38, 95% confidence interval [CI] -0.67 to -0.1 and SDM -0.2, 95% CI -0.4 to -0.007, respectively). There were significant SGC volume reductions in patients with unipolar (left SGC SDM -0.5, 95% CI -0.92 to -0.07; right SGC SDM -0.33, 95% CI -0.64 to -0.02,), but not bipolar, disorder. Patients with a positive family history of mood disorders showed significant left SGC volume decrease (SDM -0.52, 95% CI -0.96 to -0.07), which was not present among subjects without family history of mood disorders. There was no association between age and SGC volumes. CONCLUSION: The available evidence suggests the existence of left and less robust right SGC volumetric reductions in patients with mood disorders, predominantly in those with unipolar depression. The effect size of this difference was moderate and increased in more homogeneous subgroups of patients with a positive family history. The clustering of SGC abnormalities in patients with a family history, their presence early in the illness course and their lack of progression with age make SGC a candidate for a primary vulnerability marker, although studies in unaffected high-risk subjects are missing.     

Role of BDNF in bipolar and unipolar disorder: Clinical and theoretical implications

A number of lines of converging evidence suggest that brain-derived neurotrophic factor (BDNF) may play a role in the onset and treatment of bipolar disorder. We review pertinent data on BDNF from several different areas of preclinical and clinical investigation that suggest novel theoretical and treatment implications for the recurrent affective disorders.Data from several recent studies have also converged showing that the val66met allele of BDNF, a common single nucleotide polymorphism (SNP), is associated with selective minor deficits in cognitive functioning in subjects with schizophrenia, bipolar illness, and normal controls. Yet, paradoxically, the better functioning val66val allele of BDNF appears to be associated with an increased risk for bipolar disorder and perhaps early onset or rapid cycling. All the primary antidepressant modalities, as well as the mood stabilizers lithium and valproate, increase BDNF. Stressors decrease BDNF and this effect can be blocked by antidepressants. Serum BDNF is low in proportion to the severity of mania and depression and increases with clinical improvement.Assessment of the val66val BDNF allele and a range of other SNPs as potential vulnerability factors for bipolar illness and its early onset could facilitate studies of early intervention, help reduce long delays between the onset of first symptoms and the first treatment, and help in the prediction of individual patient’s likelihood of responding to a given treatment.     

Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, has been implicated in both mood disorders and suicidal behavior. This study has examined the association between the BDNF gene Val66Met polymorphism and mood disorders, age of onset and suicidal behavior in a Chinese sample population. The genotype and allele frequencies for the BDNF gene Val66Met polymorphism did not differ comparing depression groups (total, bipolar disorder or major depression) and control subjects. Furthermore, it was not demonstrated that this BDNF polymorphism was associated with age of onset or suicidal history in our mood disorder patients. Based on these results, it seems reasonable to suggest that this polymorphism is unlikely to play a major role in the genetic susceptibility to mood disorders. Given the fact that the positive association between BDNF gene Val66Met polymorphism and bipolar disorder has only been demonstrated for a Caucasian population but not for a Japanese analog or our Chinese sample, it appears likely that this association is ethnicity dependent.     

Bipolar disorders and suicidal behaviour

Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour. Bipolar Disord 2002: 4(Suppl. 1): 21–25. © Blackwell Munksgaard, 2002
Major depressive disorder is the leading cause of suicide, particularly in the absence of adequate treatment. The aim of this paper is to analyse the relationship between different forms of major mood disorders and suicidal behaviour. Population-based epidemiological surveys as well as clinical studies on the clinically explorable suicide risk factors in bipolar and unipolar depressive disorders are reviewed. The present literature shows that patients with bipolar disorders are at higher risk of attempted and completed suicide than that of patients with unipolar major depression. Contrasting only bipolar I and bipolar II patients, current findings indicate that the rate of prior suicide attempt is higher in bipolar II patients, and bipolar II disorder is overrepresented in depressed suicide victims. Among patients with different clinical manifestations of major mood disorders (unipolar major depression, bipolar I and bipolar II disorder), bipolar patients in general, and bipolar II subjects in particular carry the highest risk of suicide.     

Hyperintense MRI lesions in bipolar disorder: A meta-analysis and review

Background: Cortical and subcortical hyperintensities in magnetic resonance imaging (MRI) scans are thought to represent areas of ischemic damage to brain tissue. Researchers have focused on the possible role these lesions may have in psychiatric disorders, including bipolar disorder. In 1997, the proposed ‘vascular mania’ diagnosis suggested utilizing not only the presence of strokes, but also confluent hyperintensities in its diagnostic criteria. This study was conducted to use meta-analytic techniques to investigate the association of hyperintensities and bipolar illness and to evaluate the current state of the literature.

Methods: Using the PubMed and MEDLINE databases, we conducted a systematic literature search of studies investigating hyperintensities in subjects with bipolar disorder and controls or other psychiatric illnesses. We identified 44 publications from which 35 studies were included for review and 27 were selected for meta-analysis. Summary statistics of the prevalence were estimated through odds-ratios and confidence interval. Heterogeneity of the results across studies was tested using Q-statistics.

Results: Meta-analysis identified an odds ratio of 2.5 (95% CI 1.9, 3.3) for hyperintensities in bipolar subjects compared to controls; however, there was significant heterogeneity among the studies (Q-statistics = 32; p = 0.04). This finding was most prominent for adolescents and children where the odds ratio was 5.7 (95% CI 2.3, 13.7). Deep white matter hyperintensities (odd ratio 3.2; 95% CI 2.2, 4.5) and subcortical grey matter hyperintensities (odds ratio 2.7; 95% CI 1.3, 2.9) were more strongly associated with bipolar subjects. There were no differences between bipolar subjects and controls for perivascular hyperintensities (odds ratio 1.3; 95% CI 0.8, 1.9). Though hyperintensities were numerically greater in bipolar subjects, meta-analysis did not demonstrate any significant differences between bipolar subjects and unipolar depression subjects (OR 1.6; 95% CI 0.9, 2.7) nor subjects with schizophrenia (OR 1.5; 95% CI 0.9, 2.7).

Conclusions: This meta-analysis continues to support the association of bipolar disorder and hyperintensities, especially in the deep white matter and subcortical grey matter. It also highlights the increased incidence in children and adolescence with bipolar disorder. However, hyperintensities are not specific to bipolar disorder, but appear at similar rates in unipolar depression and schizophrenia. Thus, the role of hyperintensities in the pathogenesis, pathophysiology, and treatment of bipolar disorder remains unclear. Further studies are required that are large enough to decrease the heterogeneity of the samples and MRI techniques, assess size and location of hyperintensities, and the impact on treatment response. Coordination with newer imaging techniques, such as diffusion tensor imaging (DTI) may be especially helpful in understanding the pathology of these lesions.     

Brain-derived neurotrophic factor as a potential risk locus for bipolar disorder: Evidence,limitations, and implications

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, proliferation, and plasticity. Over recent years both neurotrophic and synaptic plasticity models of pathogenesis for mood disorders have been advanced. Thus,BDNF has been considered a plausible candidate gene for bipolar disorder, as well as for other mood disorder phenotypes. Two recent family-based association studies have provided evidence that one or more sequence variants within or near theBDNF gene show an association with disease susceptibility. These findings are of substantial interest and may open up a new chapter in our understanding of the causation and treatment of bipolar disorder. However, as is to be expected in the investigation of complex genetic disorders, there have also been negative reports. It is important that the positive findings are replicated in large independent samples and that functional studies can confirm and characterize the pathogenic relevance of this genetic variation.     

Critical role of brain-derived neurotrophic factor in mood disorders

The purpose of this review is to integrate what is currently known about the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BD). We reviewed the pre-clinical and clinical papers demonstrating that BDNF plays a role in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Pre-clinical studies suggest that the expression of BDNF might be a downstream target of antidepressant treatments and mood stabilizers such as lithium and valproate, and that BDNF exerts antidepressant activity in animal models of depression. Furthermore, BDNF protects against stress-induced neuronal damage, and it might affect neurogenesis in the hippocampus, which is thought to be involved in the pathogenesis of mood disorders. Clinical studies have demonstrated that serum levels of BDNF in drug-naive patients with MDD are significantly decreased as compared with normal controls, and that BDNF might be an important agent for therapeutic recovery from MDD. Moreover, recent findings from family-based association studies have suggested that the BDNF gene is a potential risk locus for the development of BD. These findings suggest that BDNF plays a critical role in the pathophysiology of mood disorders and in the activity of therapeutic agents in patients with mood disorders. New agents capable of enhancing BDNF levels may lead aid the development of novel therapeutic drugs for patients with mood disorders.     

Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder?

The authors reviewed magnetic resonance imaging volumetric imaging results in major mood disorders, particularly comparing similarities and differences from studies of bipolar disorder and unipolar major depression. Abnormalities of cerebral brain regions appear inconsistently in mood disorders and, when present, typically consist of decreased frontal or prefrontal cortical volumes in both unipolar depression and bipolar disorder. In contrast, subcortical and medial temporal abnormalities are more commonly observed and are different between these two major classes of affective illness. Specifically, whereas structural enlargement of the basal ganglia and amygdala have been observed in bipolar disorder, in unipolar depression, these structures appear to be smaller in patients than healthy subjects. These findings suggest that affective illnesses may share in common an underdeveloped or atrophied prefrontal region, leading to loss of cortical modulation of limbic emotional networks. The effect of this loss results in unipolar depression or cycling (mania with depression) depending on the abnormalities of the subcortical structures involved. The cerebellum may also play a role in the presentation of mood disorders. This hypothesis remains speculative as much more research is needed to specifically examine how morphometric brain abnormalities translate into the neurophysiologic deficits that produce mood disorders.     

International randomized-controlled trial of transcranial Direct Current Stimulation in depression

Background

Evidence suggests that transcranial Direct Current Stimulation (tDCS) has antidepressant effects in unipolar depression, but there is limited information for patients with bipolar depression. Additionally, prior research suggests that brain derived neurotrophic factor (BDNF) Val66Met genotype may moderate response to tDCS.

Elevated sorbitol concentration in the cerebrospinal fluid of patients with mood disorders

This study was undertaken to test the hypothesis that a specific pathophysiological mechanism of diabetic neuropathy, namely increased polyol pathway flux, could be operative in patients with bipolar and unipolar mood disorders. Numerous studies have shown abnormalities of carbohydrate metabolism, including high rates of diabetes mellitus, in patients with mood disorders. Several studies have found that peripheral neuropathy is a risk factor for depression in diabetics. Furthermore, increased polyol pathway flux results in elevated sorbitol concentrations in peripheral tissues and cerebrospinal fluid (CSF) of diabetics with neuropathy. The purpose of this study was to determine whether sorbitol concentration is elevated in the CSF of non-medically ill patients with mood disorders. Lumbar punctures were performed on 30 subjects - 10 with bipolar mood disorder, 10 with unipolar mood disorder, and 10 age-matched normal controls, and CSF sorbitol concentrations were measured, using a gas chromatographic-mass spectroscopic technique. The mean+/-standard deviation of CSF sorbitol concentrations differed among the three groups as follows: bipolar (22.9+/-4.6 micromoles/l) > unipolar (19.0+/-2.8 micromoles/l)>normal control (15. 6+/-1.9 micromoles/l). One-way ANOVA showed significant (P=0.0002) differences among the three groups. Post-hoc tests indicated a significant (P<0.05) difference between bipolars and normal controls, bipolars and unipolars, and unipolars and normal controls. Further investigation is needed to determine the pathophysiological significance of this novel finding of elevated sorbitol concentration in the CSF of patients with mood disorders.     

BDNF and ARTEMIN are increased in drug-naïve non-depressed GAD patients: Preliminary data

Objective. While the role of neuronal and glial plasticity are well established in the pathophysiology of mood disorders, the pattern and measures of neuronal and glial cell line-derived neurotrophic factors are unknown in generalized anxiety disorder (GAD). The present study evaluates brain-derived neurotrophic factor (BDNF) and Artemin (ARTN) plasma levels in GAD patients. Methods. Fourteen drug-naïve GAD patients without major depression were enrolled and plasmatic levels of BDNF and ARTN mRNA were measured by RT-PCR, and compared to matched healthy controls. Results. The results showed an unexpected increase in mRNA levels of both BDNF and ARTN in patients with GAD, that appeared almost doubled when compared to healthy controls. In comparison, both BDNF and ARTN are reduced in patients with major depressive disorder. Further, the results are intriguing and might involve distinguishing pathophysiological pathways. Conclusions. This is the first report of increased levels of a neurotrophic factor and of a glial cell line-derived neurotrophic factor family member in GAD patients. While further studies to confirm these results and the functional meaning in terms of pathophysiology of GAD are needed, the potential conceptual and clinical meanings are discussed.     

Pituitary gland volume in adolescent and young adult bipolar and unipolar depression

OBJECTIVES: Few studies have examined pituitary gland size in mood disorders, particularly in adolescents. We hypothesized increase in the pituitary gland size in early-onset mood disorders. METHODS: Thirty subjects between the ages of 13 and 20 years participated in the study. Three groups (control, bipolar I depression and unipolar depression) of 10 subjects each (4 male, 6 female) underwent volumetric magnetic resonance imaging at 1.5 T. RESULTS: Analysis of covariance (covarying for age, sex and intracranial volume) revealed a significant difference in pituitary gland volume amongst the groups [F(2,24) = 7.092, p = 0.014]. Post hoc analysis revealed that controls had a significantly smaller pituitary gland volume than both bipolar patients (p = 0.019) and depressed patients (p = 0.049). Bipolar and depressed subjects did not differ significantly from each other with regard to pituitary gland volume (p = 0.653). Control females had larger pituitary glands than control males [F(1,8) = 10.523, p = 0.012], but no sex differences were noted in the mood disorder groups. CONCLUSIONS: Pituitary glands are enlarged in adolescents with mood disorders compared to controls. Healthy young females have larger pituitary glands than males, but such a difference is not evident in individuals with unipolar depression or bipolar disorder. These findings provide new evidence of abnormalities of the pituitary in early onset mood disorders, and are consistent with neuroendocrine dysfunction in early stages of such illnesses.     

Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

Hasselbalch BJ, Knorr U, Bennike B, Hasselbalch SG, Greisen Søndergaard MH, Vedel Kessing L. Decreased levels of brain‐derived neurotrophic factor in the remitted state of unipolar depressive disorder. Objective: Decreased levels of peripheral brain‐derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness. Method: Whole‐blood BDNF levels were measured in blood samples from patients with unipolar disorder in a sustained state of clinical remission and in a healthy control group. Participants were recruited via Danish registers, a method that benefits from the opportunity to obtain well‐matched community‐based samples as well as providing a high diagnostic validity of the patient sample. Results: A total of 85 patients and 50 controls were included in the study. In multiple linear regression analyses, including the covariates age, gender, 17‐item Hamilton Depression Rating Scale scores, body‐mass index, education, smoking and physical exercise, patients with unipolar depressive disorder had decreased levels of BDNF compared to healthy control individuals [B = ?7.4, 95% CI (?11.2, ?3.7), = 0.21 P < 0.001]. No association between course of clinical illness and BDNF levels was present. Conclusion: Whole‐blood BDNF levels seem to be decreased in patients remitted from unipolar depressive disorder, suggesting that neurotrophic changes may exist beyond the depressive state.