Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the µ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Resilience in mental health: linking psychological and neurobiological perspectives.

OBJECTIVE: To review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies. METHOD: Electronic and manual literature search of MEDLINE, EMBASE and PSYCHINFO, using a range of search terms around biological and psychological factors influencing resilience as observed in human and experimental animal studies, complemented by review articles and cross-references. RESULTS: The term resilience is used in the literature for different phenomena ranging from prevention of mental health disturbance to successful adaptation and swift recovery after experiencing life adversities, and may also include post-traumatic psychological growth. Secure attachment, experiencing positive emotions and having a purpose in life are three important psychological building blocks of resilience. Overlap between psychological and biological findings on resilience in the literature is most apparent for the topic of stress sensitivity, although recent results suggest a crucial role for reward experience in resilience. CONCLUSION: Improving the understanding of the links between genetic endowment, environmental impact and gene-environment interactions with developmental psychology and biology is crucial for elucidating the neurobiological and psychological underpinnings of resilience.

Scars in depression: is a conceptual shift necessary to solve the puzzle?

Although clinical findings suggest that in the aftermath of depression a process of 'scarring' may ensue, research examining the issue of 'scars' (including biological, psychological and cognitive changes) has remained largely inconclusive. This paper proposes a new approach to the concept of 'scars' that is (i) based on a dimensional view of depression, (ii) uses methods that take into account the dynamic interplay between the person and his context, (iii) differentiates between scars following depression and scars following the factor that actually caused the depression such as stress and (iv) introduces a dynamic view of the concept of 'scars' in that it hypothesizes that scars can wax and wane. This approach may stimulate the discovery of new entries in the puzzle underlying the ontogenesis of vulnerability and resilience. Furthermore, it may provide insights that help to develop new therapies for depression.

Meeting risk with resilience: high daily life reward experience preserves mental health.

OBJECTIVE: To examine prospectively whether high reward experience (the ability to generate positive affect boosts from pleasurable daily events) protects against affective symptoms and whether environmental or genetic risk factors moderate protective effects. METHOD: At baseline, 498 female twins participated in an experience sampling study measuring reward experience in daily life. They also completed questionnaires on childhood adversity and recent stressful life events (SLE). Affective symptoms were measured at baseline and at four follow-ups using SCL-90 anxiety and depression subscales. Co-twin affective symptoms were used as indicators of genetic risk. RESULTS: Baseline reward experience did not predict follow-up affective symptoms, regardless of level of genetic risk. However, high reward experience was associated with reduced future affective symptoms after previous exposure to childhood adversity or recent SLE. CONCLUSION: High daily life reward experience increases resilience after environmental adversity; modification of reward experience may constitute a novel area of therapeutic intervention.

Unveiling patterns of affective responses in daily life may improve outcome prediction in depression: a momentary assessment study.

OBJECTIVE: Daily life affective responses are closely linked to vulnerability and resilience in depression. Prediction of future clinical course may be improved if information on daily life emotional response patterns is taken into account. METHOD: Female subjects with a history of major depression (n=83), recruited from a population twin register, participated in a longitudinal study using momentary assessment technology with 4 follow-up measurements. The effect of baseline daily life emotional response patterns (affect variability, stress-sensitivity and reward experience) on follow-up depressive symptomatology was examined. RESULTS: Both reward experience (B=-0.30, p=0.001) and negative affect variability (B=0.46, p=0.001) predicted future negative affective symptoms independent of all other dynamic emotional patterns and conventional predictors. CONCLUSION: Daily life information on dynamic emotional patterns adds to the prediction of future clinical course, independent of severity of symptoms and neuroticism score. Better prediction of course may improve decision-making regarding quantitative and qualitative aspects of treatment.

Mechanisms of gene-environment interactions in depression: evidence that genes potentiate multiple sources of adversity.

BACKGROUND: Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity. METHOD: Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA. RESULTS: All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity. CONCLUSIONS: The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.

Chronic confusional state.

An acute confusional state after infarction in the distribution of the right middle cerebral artery has been described. Patient recovery usually is excellent. Some patients, however, do not improve, resulting in a chronic confusional state.

Associations of handedness with hair color and learning disabilities.

Forms containing the Edinburgh handedness inventory and questions about learning disabilities, hair color, self-described handedness, age, gender, parental handedness and twinning were received from 1117 randomly selected professionals. Laterality scores (LS, range -100 to +100) were calculated for each respondent based on the handedness inventory and were correlated with the above variables. Among blonds, the frequency of non right-handedness (NRH, LS less than or equal to 70) was 44% compared to 24% of non-blonds (chi 2 = 23.5, P less than 0.0001). Learning disabilities (LD) were present in 9% of NRH (LS less than or equal to 70) as against 3% of those with LS greater than 70 (chi 2 = 22.1, P less than 0.0001). Associations between LS and self-described handedness, parental handedness, gender, and age are also presented. Possible explanations for the association of hair color and handedness are discussed in light of recent data on altered visual system pathways in albinos. Problems in the measurement of handedness are discussed.

Stuttering: disappearance and reappearance with acquired brain lesions.

Despite 60 years of study, the brain mechanisms for stuttering are unknown. In an effort to shed light on these mechanisms, we studied two cases in which the fluency of speech changed after brain damage in adulthood. The first, an ambidextrous man, ceased to stutter after a head injury. The second, a converted left-handed man, experienced recurrence of childhood stuttering after a stroke.

Reproductive endocrine disorders in men with partial seizures of temporal lobe origin.

Twenty consecutive men with partial seizures of temporal lobe origin were evaluated for sexual or reproductive dysfunction. Eleven (55%) had diminished sexual interest or reduced potency. Nine of them had reproductive endocrine disorders, with features of hypogonadotropic hypogonadism in five, hyperprolactinemia in two, and hypergonadotropic hypogonadism in two. Among these nine were cases in which the reproductive endocrine abnormalities could not readily be attributed to antiseizure medication use. Other possible interpretations are as follows: epileptic discharges in medial temporal lobe structures may disrupt hypothalamic regulation of pituitary secretion, hypogonadism may promote the development of epileptic discharges, and temporal lobe epilepsy and associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of both the brain and the reproductive system.

Reproductive endocrine disorders in women with partial seizures of temporal lobe origin.

Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.

Handedness is not a unidimensional trait.

Most theories about the inheritance of hand preference assume that handedness is a unidimensional trait which forms a continuous distribution. This paper demonstrates that sampling a wide range of manual activities reveals dimensions of hand preference that are independent. 180 right handed and 110 left handed adults indicated their hand preference for 55 activities according to a five point scale. A Varimax Factor Analysis revealed four factors which accounted for 80 percent of the variance. Factor 3 was of special interest because it represented behaviors which rely upon the axial musculature and involve strength more than dexterity. Hand preference for items on this factor were less laterally biased than on factors which included such fine motor behaviors as writing or drawing. These results suggest that manual preference is governed by more than one neural system and that these systems may be independently lateralized.

Cortical anomalies in brains of New Zealand mice: a neuropathologic model of dyslexia?

Cortical anomalies have been reported in the brains of dyslexic individuals. In addition, dyslexic and left-handed individuals have a higher than expected rate of some immune-related diseases. The possible association between immune and cerebrocortical pathology was investigated in the immune-defective New Zealand Black mouse and its hybrid with the New Zealand White mouse. Structural anomalies similar to those present in the dyslexic brain were seen in the brains of these mice.

Developmental dyslexia: four consecutive patients with cortical anomalies.

We report the neuroanatomical findings in 4 consecutively studied brains of men with developmental dyslexia. The patients, who ranged in age between 14 and 32 years, were diagnosed as dyslexic during life. Nonrighthandedness and several autoimmune and atopic illnesses were present in the personal and family histories. All brains showed developmental anomalies of the cerebral cortex. These consisted of neuronal ectopias and architectonic dysplasias located mainly in perisylvian regions and affecting predominantly the left hemisphere. Furthermore, all brains showed a deviation from the standard pattern of cerebral asymmetry characterized by symmetry of the planum temporale. The neuroanatomical findings in these 4 patients are discussed with reference to developmental cortical anomalies, cerebral asymmetries, reorganization of the brain after early lesions, and the association between learning disorders, left handedness, and diseases of the immune system.