Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.

BACKGROUND: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. METHODS: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. RESULTS: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). CONCLUSIONS: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.

Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder.

It has been hypothesized that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), although experimental data regarding the contribution of BDNF gene polymorphisms to this psychiatric disorder are controversial. Recently, changes in BDNF serum levels have been reported in children with ADHD, but there are no studies about the possible role of this neurotrophin in adults. A total of 54 Caucasoid ADHD adults, including the predominantly inattentive and combined types (aged 33.43 ± 8.99 yr) and 59 Caucasoid unrelated healthy controls (aged 35.52 ± 9.37 yr) were included in a study to evaluate BDNF levels in serum. Medical, neurological and psychiatric co-morbidities were excluded. Clinical data concerning ADHD diagnosis and blood samples for patients and controls were collected. BDNF serum levels were significantly lower in adults with ADHD compared to healthy controls (p < 0.0001). Although the combined type of ADHD subgroup displayed lower BDNF serum levels than the inattentive type, the differences did not reach statistical significance. No significant correlations were found between serum BDNF levels and scores on the Conners' Adult ADHD Rating Subscales. These results suggest a role for BDNF in ADHD, at least in those patients whose disorder persists throughout life. Low BDNF levels may contribute to the neurodevelopmental deficits of ADHD and to the persistence of the disorder into adulthood. BDNF differences between ADHD subtypes should be further studied.

Serum brain-derived neurotrophic factor levels and cocaine-induced transient psychotic symptoms.

BACKGROUND: Cocaine-induced psychosis (CIP) is among the most serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the involvement of BDNF in CIP are lacking. METHODS: A total of 22 cocaine-dependent patients (aged 33.65 ± 6.85) who had never experienced psychotic symptoms under the influence of cocaine (non-CIP) and 18 patients (aged 34.18 ± 8.54) with a history of CIP completed a 2-week detoxification program in an inpatient facility. Two serum samples were collected from each patient at baseline and at the end of the protocol. Demographic, consumption and clinical data were recorded for all patients. A paired group of healthy controls was also included. RESULTS: At the beginning of the detoxification treatment, serum BDNF levels were similar in both the non-CIP and the CIP groups. During early abstinence, the non-CIP group exhibited a significant increase in serum BDNF levels (p = 0.030), whereas the CIP group exhibited a decrease. Improvements in depression (Beck Depression Inventory, BDI, p = 0.003) and withdrawal symptoms (Cocaine Selective Severity Assessment, CSSA, p = 0.013) show a significant positive correlation with serum BDNF levels in the non-CIP group, whereas no correlation between the same variables was found in the CIP group. CONCLUSIONS: This study suggests that BDNF plays a role in the transient psychotic symptoms associated with cocaine consumption. In the non-CIP group, the increase in serum BDNF appears to be driven by the effects of chronic cocaine consumption and withdrawal. In contrast, patients with CIP share some of the neurotrophic deficiencies that characterize schizophrenia and psychosis.

Peripheral levels of BDNF and opiate-use disorder: literature review and update.

Several neurobiological factors are related to opiate-use disorder (OUD), and among them, neurotrophins have a relevant role. Brain-derived neurotrophic factor (BDNF) is a central neurotrophin involved in many neuronal processes, and it has been related to several psychiatric diseases and addictive disorders. BDNF can be measured in plasma and serum; its levels may reflect BDNF concentrations in the central nervous system (CNS) and, indirectly, CNS processes. Hence, peripheral BDNF could be a biomarker in clinical practice. This manuscript explores the findings about peripheral BDNF and OUD in humans. Opiates induce neurotoxicity in the CNS, which may be correlated with modifications in BDNF expression. Thus, basal levels of peripheral BDNF in OUD patients may be altered, which could be modified with abstinence. Also, opiates may modify epigenetic processes that may be associated with peripheral concentrations of BDNF, and in this line, withdrawal could reflect recovering processes in the CNS. Additionally, treatment modifies the peripheral concentrations of BDNF, but the clinical implications of those changes are yet not elucidated. No specific conclusion can be performed and more investigation in this area is necessary to elucidate the real potential of peripheral BDNF as a biomarker.

Cocaine-induced Psychosis and Brain-derived Neurothrophic Factor in Patients with Cocaine Dependence: Report of Two Cases.

Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further.

Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be associated with relapse in cocaine-dependent patients.

Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans and drug seeking in rodents. Based on this, the aim of this study was to explore the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2 weeks abstinence program. Organic and psychiatric co-morbidities were excluded. Two serum samples were collected for each subject at baseline and at after 14 abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow-up, after which they were classified into early relapsers (ER) (resumed during the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14 days after discharge). The only clinical differences between groups were the number of consumption days during the last month before detoxification. Serum BDNF levels increased significantly across the 12 days of abstinence in the LR group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group, the change of serum BDNF during abstinence negatively correlated with the improvement in depressive symptoms (p=0.02). These results suggest that BDNF has a role in relapse to cocaine consumption in abstinent addicts, although the underlying neurobiological mechanisms remain to be clarified.

Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine.

RATIONALE: Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD). Although animal models have provided evidence that brain-derived neurotrophic factor (BDNF) is involved in the effects of ATX in the brain, there are no studies of BDNF in ADHD patients undergoing treatment with ATX. OBJECTIVES: The aim of this study was to evaluate the possible changes in serum levels of BDNF in adults treated with ATX and its relationship with clinical improvement. METHODS: A total of 54 adults with ADHD (age 33.43 ± 8.99 years) without any medical or psychiatric comorbidities were treated with ATX for 3 months; 35 of them completed the protocol. The clinical data for ADHD diagnosis, including Conners' ADHD Rating Scale and blood samples, were collected at baseline (V1) and at the end of the treatment (V2). RESULTS: Adults with ADHD who completed ATX treatment for 3 months showed a significant improvement in their clinical symptoms. No significant differences were found in BDNF levels before and after treatment with ATX in the whole group of patients (p = 0.15). The inattentive subgroup of ATX responders showed a decrease of serum BDNF after 3 months of ATX treatment (p = 0.05) not present in the combined subtype (p = 0.82). CONCLUSIONS: These results suggest that BDNF is not directly involved in the neurobiological mechanisms of ATX-induced improvement of clinical symptoms of ADHD. The differences between the combined and inattentive subtypes in serum BDNF changes suggest selective ATX-induced effects in the function of brain circuitry.

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence.

Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65 ± 6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52 ± 9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.