Fernando Mosquera

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.

First episode in bipolar disorder: misdiagnosis and psychotic symptoms

BACKGROUND This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis.

Psychoeducation and cognitive-behavioral therapy in bipolar disorder: an update

Objective:  To review the available literature on psychoeducation and cognitive‐behavioral therapy (CBT) in bipolar disorder (BD) and to give an integral view of these therapies.

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.

Long-term efficacy of a psychological intervention program for patients with refractory bipolar disorder: A pilot study

The aim of this research was to test the long-term efficacy of combined standard treatment (pharmacotherapy and adjunctive psychosocial treatment based on a cognitive-behavioral model) compared with standard drug treatment for patients with recurrent bipolar disorder. Twenty patients selected according to DSM-IV-TR criteria were randomized to 1) combined treatment or 2) control treatment. A multigroup experimental design with repeated assessment measures (pre-treatment, post-treatment, 6-month follow-up, and 12-month follow-up) was used. Results of the repeated measurement analysis showed a significant increment in scores of Global Activity Functioning within the combined treatment group during the follow-up, which was not observed in the control treatment group. Therefore, the effectiveness of psychotherapy tends to increase with time, and this improvement is not significant until 12 months of follow-up.

Use of olanzapine in dysphoric mania

BACKGROUND The simultaneous presentation of both manic and depressive symptoms has long been recognized. Nevertheless, a variable prevalence of dysphoric mania has been reported. The aim of this study was to estimate the prevalence of dysphoric mania among hospitalized patients and to assess the effectiveness of olanzapine in this type of patients. METHODS Eighty-six patients who met DSM-IV criteria for mania were evaluated at admission with a protocol that included McElroys criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633]. Treatment was administered according to clinical need, using mood stabilizers combined with antipsychotics. Sequential assessments were conducted throughout the study. RESULTS Forty-four patients (51.2%) fulfilled McElroys criteria for dysphoric mania. Fourteen of these dysphoric patients were treated with olanzapine in combination with mood-stabilizers. All patients improved in manic symptoms but patients treated with olanzapine improved significantly more than those treated with other antipsychotics in depressive symptoms. LIMITATIONS The lack of randomization is a methodological limitation of this study, so these findings should be considered as preliminary. CONCLUSIONS Dysphoric symptoms are common in this population of manic patients. Olanzapine in combination with mood-stabilizers may be effective in these patients. Additional controlled studies are needed to replicate these results.

Validity and reliability of the Hamilton depression rating scale (5 items) for manic and mixed bipolar disorders.

Depressive symptoms during mania have prognostic value in bipolar disorder. For depressive symptoms, it has been proposed that shorter scales should be cost-effective and practical. To determine the usefulness of 5-item Hamilton Depression Rating Scale (HAMD-5) in manic and mixed bipolar disorder, we used a four-week follow-up prospective, observational study. Convergent and discriminant validity, internal consistency, and reliability were analyzed and compared with HAMD-21, HAMD-5, and HAMD-21 cut-off points were calculated versus CGI-BP. A total of 173 manic and mixed patients were evaluated. HAMD-5 showed appropriate convergent validity, discriminant validity, internal consistency, and test-retest reliability. Discriminant validity was higher for HAMD-5 than HAMD-21. Best cut-off point of remission was: HAMD-21 ≤5 and HAMD-5 ≤1. HAMD-5 presents appropriate validity and reliability estimates. It is comparable to HAMD-21 and focuses more specifically on depressive symptoms.

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).