Sperry and Hebb: oil and vinegar?

The interface between so-called activity-dependent and activity-independent mechanisms of circuit development is discussed here in light of recent findings that question the role of activity in brain development. This debate is presented simplistically here in terms of Sperry's chemoaffinity hypothesis versus Hebb's rules of correlation-based synaptic change, which are often presented as being mutually exclusive – much like oil and vinegar.     

Are the SSRIs and atypical antidepressants safe and effective for children and adolescents?

PURPOSE OF REVIEW: This article summarizes recent developments in the use of selective serotonin reuptake inhibitors and atypical antidepressants to treat children and adolescents with depression at a time when their use in this context has generated considerable controversy and confusion for clinicians, patients and their families. Recent reports and recommendations from drug regulators in the UK and the US are discussed, alongside other reviews and recently published randomized controlled trials. RECENT FINDINGS: It is now widely accepted that these drugs increase the risk of suicide-related behaviours and although recently published trials have been more positive, a meta-analysis of published and unpublished trials has cast doubt about efficacy. The evidence for publication bias in the studies considered is also raised and the implications discussed. There is some evidence, however, that the combination of psychological treatment with fluoxetine may be both effective and protective against the increased risk of suicide-related behaviours, although problems over blinding suggest further research is needed to clarify this potentially positive combination treatment. SUMMARY: Current evidence supports the conclusions of the UK drug regulator in warning against the use of all the newer antidepressants except fluoxetine in this age group, and alternative therapies should be sought in the first instance. Caution is needed in interpreting drug company sponsored trials given the evidence of selective reporting and publication bias. Combining fluoxetine with a psychological treatment such as cognitive-behavioural therapy is also worth considering.     

Do pregnancy and childbirth adversities predict infant crying and colic? Findings and recommendations

Bouts of unexplained crying in 1- to 3-month-old infants are a common problem for parents and health services. One proposed explanation has linked the crying to preceding adversities, such as maternal stress and cigarette smoking during pregnancy and complications during childbirth. In the first part of this review, we argue that studies of these links have methodological shortcomings, and make recommendations about the safeguards needed to overcome these shortcomings. In part two, we present a study that assesses the relations between adversity indices and validated measures of crying in two separate cohorts of infants. Four indices of childbirth adversity predicted infant crying separately and cumulatively in cohort 1, but not in cohort 2. We conclude that there is a need for further research that includes replication and other safeguards. Infant crying is a highly emotional issue for many parents. Before researchers add to their burden by claiming that maternal prenatal anxiety, cigarette smoking, or labour medication, contribute to their baby's crying, we need to be sure of our grounds.     

α-Synuclein and Parkinsonism: Updates and Future Perspectives

Mutations in the SNCA gene, which encodes the α-synuclein protein, were the first discovered genetic causes of familial parkinsonism with Lewy pathology. To date, six different SNCA missense mutations as well as multiplications are known to cause parkinsonism. For this review, we performed a literature search to identify all published cases of SNCA-related parkinsonism to provide an updated summary of the clinical and neuropathological features of parkinsonism due to SNCA mutations. Familial parkinsonism associated with SNCA is rare, but α-synuclein aggregation is a core feature of sporadic parkinsonism, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Research into α-synuclein and parkinsonism has impacted how we define the pathology and understand the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We briefly discuss some of the lessons we have learned from research into the physiological role of α-synuclein and its pathological links to neurodegeneration and parkinsonism.     

Ethics and pain: why and for whom?

This paper gives a historical overview to the development of this special issue of Pain Medicine. A brief synopsis of the articles of this issue is offered followed by a review of characteristics of pain, pain patients, and the system we practice in, that can lead to ethical dilemmas. These issues include the inherent difficulty of "curing" chronic pain, the psychopathology of chronic pain patients, end-of-life issues, the patient-physician relationship, the use of unproven methods, the vulnerability of pain patients, the increasing economic pressures of pain clinics, litigation, and the workers' compensation system.     

Dual diagnosis and psychosocial interventions—Introduction and commentary

Treatment of patients with concurrent mental illness and substance abuse represents a challenge to the traditional treatment systems. This article gives: 1) an introduction of the concept and frequency of dual diagnosis (DD), 2) a presentation and discussion of the latest guidelines on DD treatment, 3) status on the current situation in the DD field in Denmark, and 4) potentials for future research. The article is based on systematic examination of evidence-based research and popularized latest guidelines on DD treatment. Methodologically, both treatment and research is challenged by the diversity in DD combinations. Although integrated treatment with the inclusion of cognitive–behavioural therapy, motivational interviewing and family intervention in DD treatment show promising results, it remains to establish which treatment programme is the most qualified in improving mental health and reducing substance use. A future priority is the development of DD treatment that targets specific co-morbid combinations and treatment needs.     

Psychiatric and behavioral symptoms in Alzheimer’s disease and other dementias: Etiology and management

Psychiatric and behavioral symptoms are common in all types of dementia and have important consequences for patients, caregivers, and society. This paper reviews recent studies of the etiology and management of these symptoms. Genetic and neurochemical studies indicate that cholinergic, serotonergic, and dopaminergic systems may influence the risk of psychiatric symptoms in patients with dementia. There is still no consensus regarding the management of such symptoms. Controlled studies of psychosocial interventions, usually performed in the nursing home setting, report encouraging results. Atypical antipsychotics may be effective in some cases but have a high risk of adverse events. There is emerging evidence that cholinesterase inhibitors may reduce and prevent such symptoms. More studies are needed to clarify the role of cholinergic and other psychotropic agents as well as nonpharmacologic interventions for psychiatric and behavioral symptoms in patients with dementia.     

Cholinergic and Nadph-δ neurons in the pedunculopontine and laterodorsal tegmental nuclei of human and nonhuman primates

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are —two to three times more numerous in humans than in monkeys but their density is —three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.     

Physical and mental decline and yet rather happy? A study of Danes aged 45 and older

Objectives: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older.

Method: Three Danish population-based surveys including 11,307 participants aged 45+ years, of whom 2411 were in the age group of 90+, were conducted in the period 1995–2001. The participation rate in the three surveys was between 63% and 82% and the same design and the same instrument were used. Self-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups.

Results: Overall, successively older age groups performed worse than the youngest age group (45–49 years), and the estimated linear decline was greater after age 70 than before age 70. For example, when comparing the oldest age group (90+ years) with the youngest, the T-score differences were found to be the largest for the mobility score (men: 40.2, women: 41.4), followed by the cognitive function (men: 22.0, women: 24.9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0).

Conclusion: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness to a similarly notable extent, although, in this study, cohort and age effects cannot be disentangled.     

Sexuality and mental health: Issues and what next?

Abstract

Human sexuality plays a major role in an individual's existence and functioning. In addition, rightly or wrongly sexuality often defines people and also affects social attitudes. These attitudes, if negative, can contribute to stigma and prevent people from help seeking if they are suffering from mental health problems. Recent changes in policy towards same-sex relationships have been positive in many countries including the UK and the USA, whereas in others such as Russia and Uganda attitudes have become more negative and punitive. Sexual activity is seen as having both pleasurable and procreational functions which contribute to society's attitudes to homosexual behaviour. Inevitably, individual responses to their own sexuality and sexual behaviour will be influenced by social attitudes. To ensure that those with various sexual variations can access psychiatric services without discrimination, various levels of interventions are needed. Here we discuss different levels of intervention and organizational change that may make it possible. Social organization and institutional organization of services need to be sensitive, especially as rates of many mental disorders are high in individuals who may be sexually variant. Those providing services need to understand their own negative attitudes as well as prejudices to ensure that services are emotionally accessible.     

Assessment of free and cued recall in Alzheimer’s disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test

Alzheimer’s disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients’ groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients’ groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.