Samet Kose

Cloninger's temperament and character dimensions of personality in patients with major depressive disorder.

In this present study, we examined the relationship between the Cloningers dimensional psychobiologic model of personality and depression in an outpatient population with major depressive disorder. Eighty-one depressed outpatients (67 women, 14 men) and 51 healthy controls (35 women, 16 men) filled out the Turkish version of the Temperament and Character Inventory (TCI). Depression severity was evaluated by using the 17-item Hamilton Depression Rating Scale and the 21-item Beck Depression Inventory. Depressed patients exhibited statistically significant higher scores for harm avoidance and lower scores for self-directedness compared to healthy controls. Sentimentality (RD1) and dependence (RD4) subscale scores of reward dependence and spiritual acceptance (ST3) subscale of self-transcendence were significantly higher; attachment (RD3) subscale of reward dependence, responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), and congruent second nature (SD5) subscales of self-directedness were significantly lower in the depressed group. In the depressed patient group, main effects of sex were significant for reward dependence and cooperativeness; the scores of both dimensions were higher for women. The Beck Inventory was positively correlated with harm avoidance and negatively correlated with novelty seeking and self-directedness dimensions (P < .05). The duration of depression (16.33 +/- 20.18 months) or the mean onset age of depression (28.68 +/- 8.11 years) did not show significant correlations with TCI scales. This study confirms the relationship between harm avoidance and depression and suggests a relationship between self-directedness and depression.

Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression

Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Regional Brain Activation during Meditation Shows Time and Practice Effects: An Exploratory FMRI Study

Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8) and long-term (n = 5) practitioners (>10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders

BACKGROUND Vagus nerve stimulation (VNS) is an effective anticonvulsant device and has shown antidepressant effects in chronic treatment resistant depression. Because the vagus nerve sends information to brain regions important in anxiety regulation (locus coeruleus, orbitofrontal cortex, insula, hippocampus and amygdala), this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize anxiety disorders. On the basis of this reasoning and reports of anxiolytic effects of VNS in patients treated for epilepsy and depression, we organized an open-label pilot acute trial of adjunctive VNS on top of stable medications, followed by long-term follow-up, to assess the safety and potential efficacy of VNS for patients with treatment resistant anxiety disorders. METHODS Eleven adult outpatients with treatment resistant obsessive-compulsive disorder (OCD), panic disorder (PD), or posttraumatic stress disorder (PTSD) were recruited. Patients had failed several medication trials as well as cognitive behavioral therapy (CBT). All patients were rated with the Hamilton Anxiety Scale (HAM-A) and the clinical global impressions improvement scale (CGI-I). Patients with OCD were also rated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Patients were maintained on their current psychotropic medications at fixed doses during the acute 12-week phase. Changes in medications and VNS stimulus parameters were allowed during the long-term follow-up. Response was defined as a 50% or greater improvement on the HAM-A for all patients and a 25% or greater improvement on the Y-BOCS for patients with OCD. RESULTS Eleven patients were recruited. Seven patients had a primary diagnosis of OCD, two had PTSD, and one had PD. One OCD patient changed their mind and was never implanted. One patient with OCD withdrew consent before the end of the acute phase, so long-term results were available for nine patients. Three patients were acute responders, based on the HAM-A, and there was some improvement in anxiety ratings over time (with statistically significant improvements at 14 of 18 quarters during long-term follow-up). Of the seven patients with OCD who received stimulation, three were acute responders, based on the Y-BOCS, and there was some improvement in Y-BOCS scores over time (with statistically significant improvements at 7 of 18 quarters during long-term follow-up). VNS was relatively well tolerated. Four years after implantation, four patients (diagnoses two OCD, one PD, one PTSD) were still receiving VNS with continued and sustained improvement in anxiety scores compared with their baseline scores. CONCLUSIONS These patients with treatment-resistant anxiety disorders generally tolerated VNS treatment, and there was evidence of acute and long-term improvement in some patients. These open data suggest that further double-blind studies assessing the VNS role in treating anxiety disorders, particularly OCD, may be warranted.

A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia

Dopamine D1 receptors play an important role in memory and cognition in non-human primates. Dopamine D1 agonists have been shown to reverse performance deficits in both aged non-human primates and in primates with lesions to dopamine systems. This study explored whether a single dose of the first full D1 agonist dihydrexidine (DAR-0100) would cause changes in brain activity (perfusion) in dopamine-rich brain regions. We used a new gadolinium-contrast magnetic resonance perfusion scanning technique to measure brain activity. A within-subject cross-over double-blind randomized design was used in 20 adults with SCID-diagnosed schizophrenia. Each morning at 0800 h, they were scanned on a 3.0 T MRI scanner for perfusion. They then received either 20 mg of dihydrexidine, or placebo, subcutaneously over 15 min. Over the next 45 min, they had intermittent MRI scans. Two days later, they had a repeat of the Day 1 schedule, but received the opposite treatment from that given on the first day. Within-day, as well as between-day, comparisons were made to test for perfusion effects of dihydrexidine. Analysis revealed that dihydrexidine induced a significant increase in both prefrontal and non-prefrontal perfusion compared to placebo. The greatest increases occurred approximately 20 min after dihydrexidine infusion, consistent with the short pharmacokinetic half-life of dihydrexidine. These data are consistent with the hypothesis formulated from studies of non-human primates that dihydrexidine and other D1 agonists may be able to modulate prefrontal dopaminergic function.

Brain stimulation for the treatment of psychiatric disorders

Purpose of review There has been a resurgence of interest in brain stimulation techniques as therapies for psychiatric disorders. Various names are used for this class of treatments: neuromodulation, somatic therapies, brain stimulation techniques. The methods in this class range from non-invasive (transcranial magnetic stimulation) to invasive brain surgery (deep brain stimulation). Recent findings Within the past year, the results of several large multicenter trials have been published, clearing the way for US Food and Drug Administration approval of vagus nerve stimulation for recurrent treatment-resistant depression and a pending consideration of approving transcranial magnetic stimulation for the treatment of depression. Summary This article reviews the most important recent clinically relevant manuscripts in this rapidly expanding new field.

Inverse Effects of Oxytocin on Attributing Mental Activity to Others in Depressed and Healthy Subjects: A Double-Blind Placebo Controlled fMRI Study

Background: Oxytocin is a stress-attenuating and pro-social neuropeptide. To date, no study has looked at the effects of oxytocin in modulating brain activity in depressed individuals nor attempted to correlate this activity with attribution of mental activity in others. Method: We enrolled 10 unmedicated depressed adults and 10 matched healthy controls in a crossover, double blind placebo controlled fMRI 40 i.u. intra-nasal oxytocin study (20 i.u. per nostril). Each subject performed reading the mind in the eyes task (RMET) before and after inhalation of oxytocin or placebo control for a total of 80 scans. Results: Before oxytocin administration, RMET engaged the medial and lateral prefrontal cortex, amygdala, insula and associative areas. Depressed subjects showed increased anterior ventral activation for the RMET minus gender identification contrast whereas matched controls showed increased dorsal and frontal activity. Compared to placebo, oxytocin in depressed subjects showed increased activity in the superior middle frontal gyrus and insula, while controls exhibited more activity in ventral regions. Oxytocin also led to inverse effects in reaction times on attribution task between groups, with controls getting faster and depressed individuals slower to respond. Conclusion: Depression is associated with increased paralimbic activity during emotional mental attribution of others, appearing to be distinctly modulated by oxytocin when compared to healthy controls. Further studies are needed to explore long-term exposure to pro-social neuropeptides on mood in depressed populations and assess their clinical relevance.

Normative data and factorial structure of the Turkish version of the Temperament and Character Inventory

Cloningers dimensional psychobiological model of personality accounts for both normal and abnormal variation in 2 major personality components: temperament and character. Here, we examined the psychometric properties of the Turkish version of the Temperament and Character Inventory (TCI) in a healthy Turkish population, obtaining normative data for the Turkish TCI. The study was conducted in healthy volunteers at both Karadeniz Technical University School of Medicine and Atatürk University School of Medicine (n = 683). The Turkish sample had significantly lower mean scores on Novelty Seeking and Reward Dependence and higher mean scores on Harm Avoidance than the American sample. The Turkish sample had significantly lower scores on Self-Directedness, Cooperativeness, and Self-Transcendence. Self-Directedness and Harm Avoidance, Cooperativeness and Reward Dependence, and Cooperativeness and Self-Directedness were intercorrelated. The Cronbach coeficients were between 0.60 and 0.85 on temperament dimensions, and between 0.82 and 0.83 on character dimensions. The lowest Cronbach coefficients were found in Reward Dependence (0.60) and Persistence (0.62). A principal axis factor analysis with a 4-factor solution revealed the highest loadings on Novelty Seeking and Harm Avoidance and relatively weaker loadings on Reward Dependence and Persistence. A 3-factor solution for character subscales indicated the highest loadings on Cooperativeness and Self-Transcendence. The factorial structure was consistent with Cloningers 7-factor model of personality, and test-retest indicated a good stability of scores over time. The reliability and factorial validity of the Turkish version of the TCI are therefore supported.

Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders

Vagus nerve stimulation is an interesting new approach to treating neuropsychiatric diseases within the class of brain-stimulation devices sometimes labeled ‘neuromodulators’. With vagus nerve stimulation, a battery-powered generator implanted in the chest wall connects to a wire wrapped around the vagus nerve in the neck, and sends intermittent pulses of electricity along the nerve directly into the brain. This mechanism takes advantage of the natural role of the vagus nerve in conveying information into the brain concerning homeostatic information (e.g., hunger, chest pain and respirations). Vagus nerve stimulation therapy is US FDA approved for the adjunctive treatment of epilepsy and has recently been FDA approved for the treatment of medication-resistant depression. Owing to its novel route into the brain, it has no drug–drug interactions or systemic side effects. This treatment also appears to have high long-term tolerability in patients, with low rates of patients relapsing on vagus nerve stimulation or becoming tolerant. However, alongside the excitement and enthusiasm for this new treatment, a lack of Class I evidence of efficacy in treating depression is currently slowing down adoption by psychiatrists. Much more research is needed regarding exactly how to refine and deliver the electrical pulses and how this differentially affects brain function in health and disease.

Alexithymia and dissociative tendencies in an adolescent sample from Eastern Turkey

Abstract  Alexithymia and dissociative reactions are two strategies that have been put forward as coping mechanisms to alleviate painful emotions. Adult studies reveal an association between alexithymia and dissociation. In line with the coping hypothesis, it was predicted that the relationship between alexithymia and dissociative tendencies would be partly mediated by current levels of stress and past traumatic experiences. Dissociation may also be related to enhanced fantasizing, although alexithymia has traditionally been associated with an incapacity to fantasize. This relationship has not been studied well in adolescents. In the present study, 173 randomly selected high school students from Eastern Turkey were assessed with the Adolescent Dissociative Experiences Scale, the Beck Depression and Anxiety inventories, the Rosenberg Self‐esteem Scale and the Toronto Alexithymia Scale. Correlation analyses followed by stepwise regression analyses were performed. ‘Difficulty identifying feelings’ subscale of Toronto Alexithymia Scale, anxiety level and the history of physical abuse emerged as predictors of dissociative tendencies. It seems that in this group, dissociation is associated with anxiety and with difficulty in identifying feelings. Physical abuse also contributes to dissociation. The adolescent who is alexithymic may be more prone to dissociation when compared to their non‐alexithymic peers. Helping alexithymic adolescents describe their body experiences may decrease their tendency to dissociation by increasing their ability to verbally identify their stressors.