Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle?

Previous studies have suggested an association between depressed mood and the dietary intake of fish. In all cases, however, dietary fish intake has been considered at the exclusion of all other aspects of the diet. This analysis investigates associations between depressed mood and dietary fish intake, while also concurrently investigating intake of a number of other dietary components. The analysis is conducted on data from 10,602 men from Northern Ireland and France screened for inclusion into the PRIME cohort study. Depressed mood was assessed using a self-report questionnaire based on the Welsh Pure Depression sub-scale of the Minnesota Multiphasic Personality Inventory, diet was assessed using a Food Frequency Questionnaire, and limited demographics were also measured. Using regression, depressed mood is initially inversely associated with dietary fish intake. On inclusion of all other dietary variables, the strength of this relationship reduces but remains, and significant associations with a number of other foods are also found. On additional inclusion of all demographic variables, the strength of the above relationships again reduces, and associations with various measures of socio-economic status and education are also significant. These findings suggest that depressed mood is associated with fish intake both directly, and indirectly as part of a diet that is associated with depression and as part of a lifestyle that is associated with depression. Additional support for these conclusions is also provided in the pattern of associations between depressed mood and diet in the two countries. The relative contributions of fish intake to depressed mood both directly and indirectly are yet to be determined. However, while diet is not measured and until lifestyle can be adequately measured, the potential roles of diet and lifestyle in the association between depressed mood and dietary fish intake should not be ignored.

Complex PTSD, interpersonal trauma and relational consequences: Findings from a treatment-receiving Northern Irish sample

Background:
The relationship between PTSD and complex PTSD remains unclear. As well as further addressing this issue, the current study aimed to assess the degree to which DESNOS (complex PTSD) was related to interpersonal trauma and had relational consequences.

Methods:
Eighty one treatment-receiving participants with a history of exposure to the ‘Troubles’ in Northern Ireland, were assessed on various forms of interpersonal trauma, including exposure to the Troubles, and measures of interpersonal and community connectedness.

Results:
DESNOS symptom severity was related to childhood sexual abuse and perceived psychological impact of Troubles-related exposure. A lifetime diagnosis of DESNOS was related to childhood Troubles-related experiences, while a current diagnosis of DESNOS was associated with childhood emotional neglect. PTSD avoidance predicted current DESNOS diagnosis and severity. Feeling emotionally disconnected from family and friends (i.e., interpersonal disconnectedness) was related to all three indices of DESNOS (i.e., lifetime diagnosis, current diagnosis and current symptom severity).

Limitations:
Sample characteristics (i.e., treatment-receiving) and size may limit the generalizability of findings.

Conclusions:
Complex PTSD is associated with PTSD but when present should be considered a superordinate diagnosis.

The Northern Ireland early onset psychosis study:Phenomenology and co-morbidity in the first 25 cases

Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study to investigate psychotic disorders in children and adolescents in this region. Young people presenting with psychotic symptoms with onset before their 18th birthday were prospectively ascertained over a three-year period (2001-2004). Those who provided informed consent were subject to a diagnostic interview using the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version. Twenty-five young people have completed the full assessment process to date. Ten young people met criteria for schizophrenia, 11 for affective psychosis, two for schizoaffective disorder and two for schizophreniform disorder. Twenty-one (80%) subjects also fulfilled criteria for at least one other DSM-IV diagnosis. In conclusion, whilst all subjects met criteria for one or other psychotic disorder, co-morbidity was common in this clinical sample. Greater awareness of the difficulties encountered when trying to reach a diagnosis in this age group may help to improve treatment outcomes.

Complex trauma and intimate relationships: The impact of shame, guilt and dissociation

Background: This study examined dissociation, shame, guilt and intimate relationship difficulties in those with chronic and complex PTSD. Little is known about how these symptom clusters interplay within the complex PTSD constellation. Dissociation was examined as a principle organizing construct
within complex PTSD. In addition, the impact of shame, guilt and dissociation on relationship difficulties was explored.
Methods: Sixty five treatment-receiving adults attending a Northern Irish service for conflict-related trauma were assessed on measures of dissociation, state and trait shame, behavioral responses to shame, state and trait guilt, complex PTSD symptom severity and relationship difficulties.
Results: Ninety five percent (n=62) of participants scored above cut-off for complex PTSD. Those with clinical levels of dissociation (n=27) were significantly higher on complex PTSD symptom severity, state and trait shame, state guilt, withdrawal in response to shame and relationship preoccupation than subclinical dissociators (n=38). Dissociation and state and trait shame predicted complex PTSD. Fear of relationships was predicted by dissociation, complex PTSD and avoidance in response to shame, while complex PTSD predicted relationship anxiety and relationship depression.
Limitations: The study was limited to a relatively homogeneous sample of individuals with chronic and complex PTSD drawn from a single service.
Conclusions: Complex PTSD has significant consequences for intimate relationships, and dissociation makes an independent contribution to these difficulties. Dissociation also has an organizing effect on
complex PTSD symptoms.

Enquiring about traumatic experiences in bipolar disorder: A case note and self- report comparison

Objectives: This study examined: (i) the prevalence of lifetime trauma, childhood trauma and trauma related to civil unrest in a Bipolar Disorder sample, and (ii) the agreement between rates of disclosure of trauma in case notes and self-report questionnaires.

Methods: The case notes of sixty participants, recruited from a geographically well-defined mental health service in Northern Ireland, were examined for reports of experiences of lifetime, childhood and traumatic events related to civil conflict. The participants also completed self-report measures of trauma.

Results: Considerable differences were found between the prevalence of trauma as measured by self-report questionnaires and case notes reports. The prevalence of lifetime trauma as measured by the Trauma History Questionnaire was 61.7% (compared to case notes prevalence of 33.3%). The prevalence of moderate and severe levels of childhood trauma as measured by the Childhood Trauma Questionnaire was 65% (case notes 21.7%). Rates of trauma related to civil unrest were 35% (case notes 3.3%). Poor levels of agreement were found between all self-report trauma measures and case notes reports. Agreement on two categories of trauma (childhood emotional neglect and childhood physical neglect) reached statistical significance but kappa scores suggest this agreement was poor (kappa = .14. p<.05; kappa = .127, p<.05). © 2011 Elsevier B.V. All rights reserved.

Conclusions: It is probable that the increased rate of trauma disclosed in the self-report questionnaire arises because clinicians during initial assessment and subsequent treatment do not consistently enquire about trauma. The need for staff training is discussed. (C) 2011 Elsevier B.V. All rights reserved.

Age related differences in mental health scale scores and depression diagnosis: Adult responses to the CIDI-SF and MHI-5.

Inconsistencies surrounding the prevalence levels of depression in later life suggest that the measurement of depression in older people may be problematic. The current study aimed to map responses to a depressive symptom scale, the Mental Health Index-5 (MHI-5) which is part of the Short form 36 (SF-36, Ware et al., 1993) against the diagnostic screening items of the Composite International Diagnostic Instrument-Short Form (CIDI-SF, Kessler et al., 1998) to examine disagreement rates across age groups. The study examined data from a national random sample of 10,641 participants living in Ireland, 58.8% were female and 19% were over 65 (SLÁN, 2007). CIDI-SF depression screening endorsement was lower in older groups, whereas mean MHI-5 depressive symptoms showed less change across age groups. Results showed that the odds of MHI-5 endorsers aged 18–44 endorsing CIDI-SF screening questions were 5 times and 4.5 times (dysphoria and anhedonia, respectively) greater than the odds of people aged 75 or more endorsing these items. Findings suggest that although the risk of depressive disorder may decrease with age, complex diagnostic screening questions may exaggerate lower rates of depression among older people.

Depression and mortality: Artifact of measurement and analysis?

Background: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data.

Methods: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models.

Results: Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost.

Limitations: Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied.

Conclusions: These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.

Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF:a family based association study

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

Inhibitors of alpha-synuclein oligomerization and toxicity: a future therapeutic strategy for Parkinson's disease and related disorders.

An abundance of genetic, histopathological, and biochemical evidence has implicated the neuronal protein, alpha-synuclein (alpha-syn) as a key player in the development of several neurodegenerative diseases, the so-called synucleinopathies, of which Parkinson's disease (PD) is the most prevalent. Development of disease appears to be linked to events that increase the intracellular concentration of alpha-syn or cause its chemical modification, either of which can accelerate the rate at which it forms aggregates. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or altered forms of alpha-syn, such as truncations, missense mutations, or chemical modifications by oxidative reactions. Aggregated forms of the protein, especially newly formed soluble aggregates, are toxic to cells, so that one therapeutic strategy would be to reduce the rate at which such oligomerization occurs. We have therefore designed several peptides and also identified small molecules that can inhibit alpha-syn oligomerization and toxicity in vitro. These compounds could serve as lead compounds for the design of new drugs for the treatment of PD and related disorders in the future.

A strategy for designing inhibitors of alpha-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders.

Convergent biochemical and genetic evidence suggests that the formation of alpha-synuclein (alpha-syn) protein deposits is an important and, probably, seminal step in the development of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). It has been reported that transgenic animals overexpressing human alpha-syn develop lesions similar to those found in the brain in PD, together with a progressive loss of dopaminergic cells and associated abnormalities of motor function. Inhibiting and/or reversing alpha-syn self-aggregation could, therefore, provide a novel approach to treating the underlying cause of these diseases. We synthesized a library of overlapping 7-mer peptides spanning the entire alpha-syn sequence, and identified amino acid residues 64-100 of alpha-syn as the binding region responsible for its self-association. Modified short peptides containing alpha-syn amino acid sequences from part of this binding region (residues 69-72), named alpha-syn inhibitors (ASI), were found to interact with full-length alpha-syn and block its assembly into both early oligomers and mature amyloid-like fibrils. We also developed a cell-permeable inhibitor of alpha-syn aggregation (ASID), using the polyarginine peptide delivery system. This ASID peptide was able to inhibit the DNA damage induced by Fe(II) in neuronal cells transfected with alpha-syn(A53T), a familial PD-associated mutation. ASI peptides without this delivery system did not reverse levels of Fe(II)-induced DNA damage. Furthermore, the ASID peptide increased (P

Molecular dynamics studies of trinucleotide repeat DNA involved in neurodegenerative disorders.

Expansion of trinucleotide repeat DNA of the classes CAG�·CTG, CGG�·CCG and GAA�·TTC are found to be associated with several neurodegenerative disorders. Different mechanisms have been attributed to the expansion of triplets, mainly involving the formation of alternate secondary structures by such repeats. This paper reports the molecular dynamics simulation of triplet repeat DNA sequences to study the basic structural features of DNA that are responsible for the formation of structures such as hairpins and slip-strand DNA leading to expansion. All the triplet repeat sequences studied were found to be more flexible compared to the control sequence unassociated with disease. Moreover, flexibility was found to be in the order CAG�·CTG > CGG�·CCG = GAA�·TTC, the highly flexible CAG�·CTG repeat being the most common cause of neurodegenerative disorders. In another simulation, a single G�·C to T�·A mutation at the 9th position of the CAG�·CTG repeat exhibited a reduction in bending compared to the pure 15-mer CAGâ�¢CTG repeat. EPM1 dodecamer repeat associated with the pathogenesis of progressive myoclonus epilepsy was also simulated and showed flexible nature suggesting a similar expansion mechanism.