Ana Aldama

Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients

Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients Dear Editors, Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, promotes the growth and maintenance of intercellular connections, serves as a neurotransmitter modulator, and participates in plasticity mechanisms, such as long-term potentiation and learning (Shoval and Weizman, 2005). Consequently, abnormal BDNF signaling can influence neuronal differentiation and synaptic function leading to altered brain development and functioning. The ability of BDNF to cross the blood–brain barrier (Pan et al., 1998) suggests that blood serum BDNF levels may reflect BDNF levels in the brain. However, reports about BDNF levels in the serum of schizophrenic patients have been somewhat inconsistent. Thus, an increase, no change, or a reduction in the concentration of BDNF in the blood of schizophrenics has been reported (Jockers-Scherübl et al., 2004; Pirildar et al., 2004; Toyooka et al., 2002). Post-treatment serum BDNF levels were not significantly different when compared with the baseline levels in schizophrenia patients (Pirildar et al., 2004). In turn, BDNF plasma levels in first-episode bipolar disorder patients have not yet been characterized. Here, we have analyzed the plasma level of BDNF in both first-episode schizophrenia and bipolar disorder patients upon admission to hospital and at various stages during a 1-year follow-up. This study consisted of 48 patients (mean age ± S.E. M., 23.7 ± 1 years) from the health catchment area of Vitoria (Alava, Spain), who experienced a first psychotic episode during the period 2002–2004. This sample of patients represents all first-episode patients that needed hospitalization and gave informed consent (75% of total) to participate in the study. There were no differences in age, gender, or clinical symptoms between patients included and excluded. Diagnoses were made at 12 months using the Structured Clinical Interview for DSM IV, SCID-I. 21 patients were diagnosed with schizophrenia, 14 with bipolar disorder, and the remaining 13 with non-specified psychotic disorders. Patients were treated after the first episode with atypical antipsychotics (62–68%), with lithium or other mood stabilizers together with atypical antipsy-chotics (23–26%), with typical antipsychotics (7–11%), or received no treatment (2–4%). Ranges in each treatment group indicate changes in the drugs administered initially at the onset of symptoms and during the first year of illness. Blood samples were collected upon arrival at the hospital emergency room and at 1, 6, and 12 months later, using glass whole-blood tubes containing K3-EDTA. Plasma was isolated by centrifugation …

Principal components of mania

OBJECTIVE An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS Patients of the sample were all medicated inpatients. CONCLUSIONS Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.

Epidemiology, Diagnosis and Management of Mixed Mania

The presence of depressive symptomatology during acute mania has been termed mixed mania, dysphoric mania, depressive mania or mixed bipolar disorder. Highly prevalent, mixed mania occurs in at least 30% of bipolar patients. Correct diagnosis is a major challenge. The DSM diagnostic criteria, the most widely adopted clinical convention, require a complete manic and complete depressive syndrome co-occurring for at least 1 week. However, recent alternative categorical and dimensional studies of manic phenomenology have shown that there are certain depressive symptoms or constellations that have special clinical importance when describing mixed states, such as depressed mood and anxiety symptomatology that do not overlap with manic symptoms.Patients with mixed mania are over-represented in the subgroup with severe and treatment-resistant symptoms. The course and prognosis of mixed mania are worse than that of pure manic forms in the medium and long term, with higher recurrence rates, higher frequency of co-morbid substance abuse and greater risk of suicidal ideation and attempts. Moreover, mixed manic episodes are usually associated with increased depression during follow-up, greater risk of rapid cycling course and higher prevalence of physical co-morbidities, principally related to thyroid function. All these factors are very relevant to selection of treatment.There are three crucial steps in the treatment of mixed mania — making the correct diagnosis, starting treatment early, and considering not only the acute state but also maintenance treatment and the patient’s long-term outcome. Although challenging, acute mixed episodes are treatable. To date there have been no controlled studies devoted exclusively to treatment of mixed mania, and the only controlled data available therefore derive from sub-analyses of randomised clinical trials. Both short-term and maintenance treatments of patients with mixed mania requires experience and usually involves the combination of different treatments. As a general rule, there is some consensus about discontinuing antidepressants during mixed mania. Olanzapine, aripiprazole or valproate semisodium (divalproex sodium) are first-line drugs for mild episodes; severe episodes of mixed mania usually require treatment with a combination of valproate semisodium or lithium plus an antipsychotic, preferably an atypical agent. Carbamazepine is also useful for the treatment of mixed mania. High-dose medications are sometimes needed to control the episode, and time to remission is usually longer than in pure mania. Importantly, patients with mixed manic episodes have more adverse events of psychopharmacological treatment. In some cases, electroconvulsive therapy is required.

Decreased levels of plasma glutamate in patients with first-episode schizophrenia and bipolar disorder

A variety of studies have suggested that glutamatergic neurotransmission is altered in schizophrenia and bipolar disorder. Here, we tested if plasma glutamate levels are altered in 56 patients diagnosed with schizophrenia, bipolar disorder or non-specified psychosis at the first psychotic episode and at various stages during one-year follow-up. A decrease in the levels of plasma glutamate was observed in all groups of patients at the first psychotic episode. Furthermore, plasma glutamate levels were restored after treatment in all instances. Decreased plasma glutamate levels at first psychotic episodes may reflect impaired glutamate signaling during the initial stages of schizophrenia and bipolar disorder.

Age-dependence of Schneiderian psychotic symptoms in bipolar patients.

Psychotic symptoms frequently occur in bipolar disorder, especially in younger patients. However, whether the association with younger age also extends to psychotic symptoms that have traditionally been associated with schizophrenia, such as Schneiderian first-rank symptoms (FRSs), is unclear. This study examined FRSs in bipolar I patients and their relationship to age and gender. The sample comprised 103 consecutive inpatients who met DSM IV criteria for bipolar disorder, manic or mixed. FRSs were rated with the Scale for the Assessment of Positive Symptoms (SAPS). Interaction between FRSs and gender and FRSs and age was assessed using logistic regression. A high rate of FRSs in manic and mixed patients was found with a higher frequency in men (31%) than in women (14%; P=0.038). A monotonic increase in the association between FRSs and younger age was apparent (odds ratios (OR) over five levels: 1.42; 1.00-2.01). These results confirm previous findings that FRSs are not specific to schizophrenia and suggest in addition that a dimension of nuclear psychotic experiences of developmental origin extends across categorically defined psychotic disorders.

The role of age in the development of Schneiderian symptoms in patients with a first psychotic episode

Objective:  The likelihood of developing psychotic symptoms greatly increases after puberty. In acute psychotic disorders, first rank symptoms (FRS) are prevalent and considered useful for the diagnostic process. The aim of this study was to test for a linear association between age and the probability of occurrence of FRS in patients with a first psychotic episode (FPE).