The association between endogenous testosterone level and behavioral flexibility in young men - Evidence from stimulus-outcome reversal learning.

The capacity to flexibly adapt responding to unexpected changes in the environment is crucial for survival. Several neurotransmitters have been implicated in stimulus-outcome reversal learning. Yet, it remains an open question whether inter-individual differences in the neuroactive hormone testosterone may also be related to this type of behavioral flexibility. In this study we assessed the association between endogenous testosterone level and reversal learning in young healthy men. We used an observer reversal learning task, in which subjects viewed computer-based decisions between two stimuli, of which one was currently rewarded while the other one was punished. Contingencies reversed unpredictably every 5-9 trials. Subjects had to indicate the current outcome association before the actual outcome was revealed. In the trial following an unexpected reversal either the same stimulus from the reversal (experienced reversal), or its alternative, for which the reversal had not yet been shown (inferred reversal), could be chosen by the computer, and subjects had to adapt responding accordingly. We found that testosterone predicted better post-reversal performance. This correlation was strongest in the more difficult inferred reversal condition, particularly in impulsive individuals. Collectively, these data support the view that endogenous testosterone may enhance behavioral flexibility in men, particularly when working memory demand is high and subjects have to update several stimulus-outcome contingencies at the same time. It remains to be further elucidated whether this testosterone effect was achieved through an interaction with dopaminergic transmission or through direct interplay with androgen receptors in the brain regions implicated in reversal learning.

CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia.

Affective deficits are one common denominator of schizophrenia (SZ), bipolar disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated as one of the major structures involved in emotion regulation. Previous findings of differences in amygdala volume between healthy controls and patients with SZ, BD or OCD diverge with respect to the affected hemisphere, size and direction of the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as structural and functional variation in the amygdala in healthy people and patients with BD. We were interested to investigate whether amygdala volumes differ between hemispheres, diagnostic or genotype groups, and whether any interactive effects exist. We combined genotyping of SNP rs1006737 in CACNA1C with structural MRI measurements of relative gray matter (GM) amygdala volume in patients with SZ, BD or OCD as well as healthy controls (N Total = 72). The CACNA1C genotype showed a significant effect on relative GM amygdala volume in patients with SZ. There was a significant left versus right relative GM amygdala volume decrease in patients with SZ or BD. The effects of hemisphere and diagnosis (controls vs. patients with SZ) on relative GM amygdala volume were genotype specific. Our data suggest that the CACNA1C genotype may account for some heterogeneity in the effects of hemisphere and diagnosis on amygdala volume when comparing patients with SZ and controls and point to disturbed Ca(2+)-signaling as a plausible mechanism contributing to the pathology in patients with SZ.

Reduced prefrontal gyrification in obsessive-compulsive disorder.

Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive-compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease.

Early onset of obsessive-compulsive disorder and associated comorbidity.

BACKGROUND: Previous studies have aimed to identify subtypes of obsessive-compulsive disorder (OCD) based on their age of onset (AOO). Obsessive-compulsive spectrum disorders (OCS disorders) such as tic disorders have been particularly associated with an early onset in some studies. However, subtypes of early- and late-onset OCD are unevenly determined, and the biological and the clinical validity of these subtypes are unknown. This study was undertaken to discriminate the subtypes of OCD in different AOO levels and to test the hypothesis that different AOO bands are associated with a differential pattern of comorbidity. METHODS: Two hundred fifty-two patients with OCD were interviewed directly with the German version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety Version, which provides DSM-IV diagnosis. Subgroups with different ages of onset were investigated (cut-off levels of 10, 15, and 18 years). RESULTS: Subjects with an early AOO (onset < or =10 years) were significantly more likely to have OCS disorders (odds ratio [OR]=3.46; P=.001; 95% confidence interval [CI]: 1.72-6.96), in particular tic/Tourette's disorders (OR=4.63; P=.002; 95% CI: 1.78-12.05), than were late-onset subjects. CONCLUSIONS: For most mental disorders (e.g., anxiety and mood disorders), no associations with AOO of OCD were identified. However, subjects in the early-onset group (< or =10 years) had a significant increase in comorbid tic and Tourette's disorders. Future research should examine potential neurobiological features associated with early-onset presentations of OCD. Early detection and management of comorbidities may offset impairments later in life.

Compensatory hyperactivations as markers of latent working memory dysfunctions in patients with obsessive-compulsive disorder: an fMRI study.

OBJECTIVE: Behavioural studies have implicated working memory (WM) deficits in obsessive-compulsive disorder (OCD). However, findings are inconsistent, which could be explained by compensation strategies used by a subgroup of OCD patients. To test this hypothesis, we examined patients without a behavioural deficit in WM during performance of different WM tasks using functional magnetic resonance imaging (fMRI). METHODS: We scaned 11 patients and 11 matched control subjects while they performed 3 verbal and spatial item-recognition tasks. RESULTS: Patients and healthy subjects engaged the same set of brain regions. However, in direct comparison, the patients exhibited significantly greater task-related activation in several frontal and parietal brain areas known to underlie WM. CONCLUSION: Patients without manifest WM deficits exhibit increased activation in frontal and parietal brain areas relative to healthy subjects during WM task performance. These hyperactivations may permit them to compensate for reduced efficiency of their WM systems and may thus serve as markers of latent WM dysfunctions.

Harm avoidance in subjects with obsessive-compulsive disorder and their families.

INTRODUCTION: This study investigates the role of harm avoidance (HA) as a possible risk factor in the familiality of obsessive-compulsive disorder (OCD). HA is considered to be a genetically influenced personality trait with an increasingly understood neuroanatomical basis. METHOD: 75 subjects with OCD from hospital sites and a community sample and their 152 first degree relatives and 75 age and sex matched controls with their 143 first degree relatives were evaluated with structured clinical interviews (DSM-IV). HA was assessed with Cloninger's Tridimensional Personality Questionnaire (TPQ). RESULTS: Subjects with OCD had higher scores of HA than controls (p

Obsessive-compulsive disorder and posttraumatic stress disorder.

BACKGROUND: Previous studies suggested an association between exposure to trauma or stressful life events and obsessive-compulsive disorder (OCD). This study investigates the hypothesis that traumatic events and posttraumatic stress disorders (PTSD) precede the onset of OCD. SAMPLING AND METHODS: 210 cases with OCD from university treatment facilities were compared with 133 sex- and age-matched controls from the adult general population. The data were derived from a German family study on OCD (GENOS). Direct interviews were carried out with the German version of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version for Anxiety Disorders (DSM-IV). RESULTS: Severe traumatization occurred in 6.2% of the OCD cases and in 8.3% of the controls. The lifetime prevalence rates of traumatization, PTSD and acute stress disorder were not different between the subjects with OCD and controls (p > 0.05). In 6 cases, acute stress disorder, subclinical or full PTSD preceded the onset of OCD, in 3 cases the trauma-related disorders and OCD occurred within the same year, in 5 other cases, the trauma-related disorders started after the onset of OCD. CONCLUSION: There is no significant association of traumatization or PTSD with OCD compared with controls. Given the low rate of trauma-related disorders occurring before (2.9%) or within (1.5%) the same year as the onset of OCD other factors than severe traumatic events determine the onset of OCD in most of the cases.

Helping alliance and outcome in psychotherapy: what predicts what in routine outpatient treatment?

This naturalistic longitudinal study analyzed the reciprocal dependency of the helping alliance and symptom outcome over the course of mid- and long-term outpatient psychotherapy as practiced in routine care in Germany. Patient-rated helping alliance and symptom distress were assessed repeatedly over a 2-year period in a sample of 259 outpatients in psychodynamic, cognitive-behavioral, and psychoanalytic psychotherapy. Hierarchical linear models showed that initial symptom distress negatively predicted subsequent quality of the helping alliance but not vice versa. Only initial symptom distress affected symptom status at the last treatment session. These results raise doubts about the helping alliance being a strong predictor of outcome and indicate that other patient and therapist variables might be more important for treatment success.

[Neuropsychiatric symptoms in Sotos syndrome. Case report and review of the literature]. / Neuropsychiatrische Symptome bei Sotos-Syndrom Kasuistik und Literaturübersicht.

Sotos syndrome, or cerebral gigantism, is a rare genetic syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial gestalt and learning difficulties. It is caused by mutations or deletions of the NSD-1 gene. Most cases are sporadic. Apart from a number of physical abnormalities that are commonly present, a high prevalence of cognitive, emotional and behavioural problems in children with Sotos syndrome can be assumed. However, there has been almost no literature about psychiatric symptoms in adults with Sotos syndrome so far; one case of psychosis was reported. In the present case, the authors present psychopathological features of an adult patient with Sotos syndrom who developed - among other things - psychotic symptoms.

Course of improvement over 2 years in psychoanalytic and psychodynamic outpatient psychotherapy.

OBJECTIVE: To assess and predict the level and course of symptomatic improvement in psychoanalytic (PAP) and psychodynamic psychotherapy (PD). METHODS: In a comprehensive longitudinal study, the course of improvement of 116 patients in PAP and of 357 patients in PD was tracked over a period of 2 years and analysed via hierarchical linear models. RESULTS: At baseline, over 90% of the patients reported substantial psychological, physical or interpersonal distress. In both forms of treatment, the course of improvement could be adequately fitted by a linear model. Symptom distress decreased notably within 2 years, with an especially sharp decline before the first formally scheduled therapy session. No significant differences between forms of treatment as to level or pace of symptom improvement could be observed. Prediction of speed of improvement was poor, with initial symptom distress showing the strongest influence while initial helping alliance had no predictive value. When comparing patients who finished their treatment within the 2-year observation period with those with still ongoing treatments, the former showed quicker symptom improvement. DISCUSSION: Strategies for the optimal allocation of valuable therapeutic resources should be reconsidered. An adaptive, outcome-oriented allocation strategy of therapeutic resources is proposed.

miR-12 and miR-124 contribute to defined early phases of long-lasting and transient memory.

MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors. Blocking miR-12, miR-124, or miR125 neither affects gustatory sensitivity nor habituation nor sensitization. Blocking the function of miR-12 and miR-124 during and shortly after 3-trial conditioning impairs different early memory phases. Although different, the function of miR-12 and miR-124 is also required for early phases of transient memory that is induced by 1-trial conditioning. Blocking miR-125 has no effect on early memory independent of the conditioning strength. These findings demonstrate that distinct miRNAs contribute to early phases of both, transient memories as well as long-lasting memories.

Text Message Feedback to Support Mindfulness Practice in People With Depressive Symptoms: A Pilot Randomized Controlled Trial.

BACKGROUND: It has been shown that mindfulness practice can be helpful in preventing relapse from depression. However, practicing mindfulness regularly at home is often a challenge for people with depression. Mobile phone text messaging (short message service, SMS) may be a feasible approach to assist regular mindfulness home practice. OBJECTIVE: The aim of this study was to evaluate the feasibility of text message-based feedback to support mindfulness practice in people with depressive symptoms after inpatient psychiatric treatment. METHODS: Participants received a manualized group introduction to three mindfulness exercises during inpatient treatment and were randomized at hospital discharge. All participants were asked to practice the exercises daily during the 4-month follow-up period. Only participants allocated to the intervention group received reinforcing feedback via mobile phone text messages after reporting their mindfulness practice via text message. Participation rates and satisfaction with the interventions were evaluated, and effects on relevant outcomes were explored. RESULTS: Of the 176 eligible inpatients invited to participate, 65.9% (116/176) attended the introductory mindfulness group at least once, 33.0% (58/176) were willing to participate in the study, and 41 were randomized. The majority 85% (35/41) of these participants completed the study. Among the participants allocated to the intervention group (n=21), 81% (17/21) used the text message support at least once. The average number of text messages sent during the intervention period was 14 (SD 21, range 0-91). Satisfaction rates were high. Preliminary analyses of the effects of the intervention yielded mixed results. CONCLUSIONS: Findings indicate that text messaging following inpatient treatment is feasible for some, but not for all people with depressive symptoms. Modest use of the text messaging intervention and its mixed effects imply that dose and ingredients of the intervention should be increased for this group of patients in a future full-size RCT. Such a larger study should also include a process evaluation to investigate moderators of the effect of mindfulness practice and text message feedback on clinical outcome. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 58808893; http://www.controlled-trials.com/ISRCTN58808893 (Archived by Webcite at http://www.webcitation.org/6pmrDRnGt).

Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects.

OBJECTIVE: Studies of the familiality of obsessive-compulsive disorder (OCD) have yielded inconsistent results. This study compared the familial aggregation of OCD in first-degree relatives of community subjects with never-treated OCD, outpatients with OCD, and comparison subjects. METHOD: Fifteen persons from the community with untreated OCD were matched on age and interview type (direct or through family informants) with 90 OCD patients from four treatment facilities and 70 comparison subjects. Direct or indirect interviews using the German-language version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version for Anxiety Disorders (DSM-IV) were obtained from 58, 285, and 247 first-degree relatives, respectively, of the three groups. The rate of OCD in case versus comparison relatives was assessed with chi-square tests, and odds ratios were calculated for risk estimation. Cox proportional hazards analysis was used to estimate the age-related risk of relatives of being affected by OCD. RESULTS: Cox proportional hazards analyses revealed a 6.2-fold higher risk (hazard ratio) for relatives of all OCD cases for definite OCD and a 2.2-fold higher risk for subclinical OCD compared with relatives of comparison subjects. For relatives of community subjects with OCD, the risk for definite OCD (10.3% versus 5.6%) was 1.6, and the risk for subclinical OCD (15.4% versus 4.1%) was 3.4 compared with relatives of OCD patients from treatment sites. CONCLUSIONS: These results from the first controlled European family study of OCD confirm earlier U.S. data on the familiality of OCD in patients recruited from treatment facilities. The finding of a comparable familial aggregation of definite OCD and a higher familial aggregation of subclinical OCD in relatives of never-treated persons with OCD from the community strongly supports the impact of familial-genetic factors in OCD.

Dopamine transporter genotype influences N-acetyl-aspartate in the left putamen.

INTRODUCTION: Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis. MATERIAL AND METHODS: Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3'-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. (1)H-MRS was performed in the above-mentioned brain regions. RESULTS: The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype. CONCLUSION: The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.

Alexithymia in obsessive-compulsive disorder - results from a family study.

BACKGROUND: Previous studies have suggested an association between alexithymia and obsessive-compulsive disorder (OCD). However, it is unclear to which extent alexithymic traits in OCD patients reflect familial deficits in cognitively processing and communicating feelings that are also present in their first-degree relatives. This study investigates the hypotheses of an elevated level of alexithymia in subjects with OCD and their first-degree relatives compared to controls and their first-degree relatives. METHODS: 82 cases with OCD and 169 first-degree relatives were compared to 76 controls and 144 first-degree relatives from a German family study on OCD (GENOS). All subjects completed the 20-item Toronto Alexithymia Scale (TAS-20). Direct or family informant interviews were carried out with the German version of the Schedule for Affective Disorders and Schizophrenia - lifetime version for anxiety disorders (DSM-IV). RESULTS: OCD was associated with significantly higher scores of alexithymia. However, first-degree relatives of OCD cases and of controls did not differ in TAS-20 scores. In linear regression analyses, the TAS-20 total score showed significant intrafamilial associations within the families of control subjects but not within families of OCD cases. CONCLUSION: OCD is a severe mental disorder that is associated independently from other current comorbid axis I disorders with deficits in identifying and expressing feelings. However, alexithymia does not represent a familial risk factor for OCD.

[Patient and therapist satisfaction in outpatient psychotherapy]. / Zufriedenheit von Patienten und Therapeuten mit ambulanter Psychotherapie.

Increasing attention is devoted to the patient perspective in mental health services research. Consequently, patient satisfaction has taken a prominent role and is frequently applied as an indicator of treatment quality and even outcome. However, the suitability of patient satisfaction for assessing quality of mental health services is doubtful, and there is a lack of longitudinal data especially for outpatient psychotherapy. By using data of the TRANS-OP study, we examine the course of patient satisfaction in outpatient psychotherapy over time and its predictors such as symptom change and duration of treatment. Furthermore, the relation between treatment satisfaction ratings of patients and therapists will be scrutinized. This study was conducted by the Center for Psychotherapy Research in Stuttgart (now Heidelberg) in cooperation with the Deutsche Krankenversicherung. N = 714 participants who applied for reimbursement of outpatient psychotherapy were consecutively recruited and asked to provide data at five (therapists two) measurement points during a two-year period. In line with previous evidence, high rates of patient satisfaction have been found, and also therapists appraised favorably the quality of their treatments. Course of patient satisfaction was found to be markedly stable over time. While some variables related to initial patient satisfaction, its course could hardly be predicted. Treatment outcome and session number moderately affected satisfaction at treatment termination. Concordance between patients' and therapists' satisfaction ratings was poor. Implications of these findings for research and practice are discussed.

Titanium-based molecular squares and rectangles: syntheses by self-assembly reactions of titanocene fragments and aromatic N-heterocycles.

This paper reports on the potential of titanium compounds as building blocks for supramolecular polygons. Self-assembly reactions of low-valent titanocene units and N-heterocyclic bridging ligands lead to novel titanium-based supramolecular squares. Pyrazine (3), 4,4'-bipyridine (4), and tetrazine (5) were used as bridging ligands, and the acetylene complexes [Cp2Ti{eta2-C2(SiMe3)2}] (1) and [(tBuCp)2Ti{eta2-C2(SiMe3)2}] (2) as sources of titanocene fragments. Molecular rectangles can be synthesized by stepwise reduction of the titanocene dichlorides [Cp(2)TiCl2] and [(tBuCp)2TiCl2] and consecutive coordination of two different bridging ligands. The resulting complexes are the first examples of molecular rectangles containing bent metallocene corner units. Single-crystal X-ray analyses of the tetranuclear compounds revealed the geometric properties of the molecular polygons in the solid state. Comparison of bond lengths and angles in coordinated and free ligands reveals the reduced state of the bridging ligand in the low-valent titanium compounds. The syntheses and properties of these novel, highly air- and moisture-sensitive compounds are discussed.

Interpersonal problems and outcome in outpatient psychotherapy: findings from a long-term longitudinal study in Germany.

We used a comprehensive longitudinal data set from Germany to examine trajectories of symptom distress depending on interpersonal problems at study intake measured via the Inventory of Interpersonal Problems-64 (IIP-64; Horowitz, Strau, & Kordy, 1994). Participants (N=622) underwent mid- or long-term outpatient psychotherapy (either psychodynamically oriented psychotherapy, cognitive behavioral therapy, or analytic psychotherapy). Data comprises up to 5 assessments during a 2-year period and was analyzed via hierarchical linear modeling. In the analytic psychotherapy subgroup, initial symptom level was higher in submissive patients. Initial interpersonal problems were not predictive of the rate of symptom change during therapy. Only in psychodynamic treatments, low affiliation positively affected treatment outcome. Interpersonal problems at intake were not related to the number of utilized sessions and utilization rate across treatment subgroups. We discuss the findings and outline future research topics.