Time-intensive behavioural activation for depression: A multiple baseline study.

BACKGROUND AND OBJECTIVES: Depression is the second leading cause of disability, worldwide, and increasing access to its effective/preferred treatment requires more attention. Behavioural activation and time-intensive treatment delivery both show promise in this regard, yet research into their combination is limited. This study aimed to investigate the feasibility, effectiveness, and acceptability of time-intensive behavioural activation (BA) for depression METHODS: Eight adults with major depressive disorder were recruited from three outpatient IAPT services in London. The study employed a single case experimental design with multiple baselines. All participants completed time-intensive BA, consisting of up to seven twice weekly sessions with daily prompting in-between and three optional booster sessions. Idiographic, standardised and process measures of depression symptomatology were collected. RESULTS: Treatment recruitment and retention indicated that the intervention was feasible. Visual and statistical analyses showed that relative to baseline, 6 out of 8 participants made significant improvements in all idiographic symptoms of depression following the intervention. According to standardised measures of depression, four out of eight participants were considered treatment responders. Five participants completed follow-up measures and the majority of progress was maintained after the withdrawal of the intervention. The intervention was also considered highly acceptable by participants and therapists. LIMITATIONS: Conclusions cannot be drawn about the generalizability or the long-term durability of the findings CONCLUSIONS: Overall this study provides new, but tentative evidence highlighting the potential of time-intensive BA as a feasible, effective and acceptable treatment for some adult outpatients with depression. The findings now warrant further, more rigorous evaluation of the treatment.

How equitable are psychological therapy services in South East London now? A comparison of referrals to a new psychological therapy service with participants in a psychiatric morbidity survey in the same London borough.

PURPOSE: Psychological therapy services are sometimes characterised as being small and inequitable, with an over-representation of white middle class women. The 'Improving Access to Psychological Therapies (IAPT)' initiative is a programme in England that attempts to make evidence-based therapies accessible to more people more equitably. The aim of this study is to assess whether an IAPT service is delivering an equitable service a London borough. Patients using services at the Southwark IAPT service (n = 4,781) were compared with a sub-group of participants in the South East London Community Health study (SELCOH) with diagnosable mental health problems and who were also resident in Southwark (n = 196). METHODS: We compared Southwark IAPT patients and SELCOH participants on equity criteria of age, gender, ethnicity, occupational status and benefits status. To investigate if referral pathways influenced equity, patients referred by their general practitioner (GP pathway) (n = 3,738) or who self-referred (self-referral pathway) (n = 482) were compared with SELCOH participants. RESULTS: Southwark IAPT patients significantly differed from SELCOH participants on all our equity criteria and similar differences were found with GP pathway patients. However, self-referrals did not differ from the SELCOH group on age, gender, ethnicity and benefit status. CONCLUSIONS: When compared to a community sample with diagnosable mental disorders, health disparities were found with the overall Southwark IAPT service and with GP pathway patients. Although unemployed people did access IAPT, fewer disparities were found with the self-referral pathway patients, suggesting that the IAPT self-referral pathway may be important in reducing inequitable access to services.

Women with premenstrual dysphoric disorder do not recall aberrant parenting.

Premenstrual dysphoric disorder (PMDD) is related to the affective disorders and thus is expected to share similar psychological risk factors. Depressed subjects have been found to recall lack of warmth and parental overcontrol in childhood as assessed by the Parental Bonding Instrument (PBI). The present study aimed to find out if such risk factors contributed to the development of PMDD in adulthood. Thirty-four women from South London who fulfilled rigorous criteria for PMDD and 22 controls were assessed for symptom severity, and each subject completed the PBI. All the women included in the study were free from other concurrent psychiatric disorders. Subjects with PMDD and controls had similar scores for warmth and parental overcontrol on the PBI and therefore had not been subject to more affectionless control. The PBI retained expected internal characteristics such as the inverse relationship of warmth and control scores. The findings indicate that recollection of parenting problems in childhood is not a major risk factor for subsequent development of PMDD in these women. A potential explanation for this is that PMDD is more biologically than psychosocially determined.

Mood disorder history and personality assessment in premenstrual dysphoric disorder.

BACKGROUND: Menstrually related dysphoria is known to be associated with other affective disorders, notably major depressive disorder and puerperal depression. The relationship between premenstrual dysphoric disorder (PMDD) and maladaptive personality disorders and traits, however, is less established, at least in part because of the methodological and nosologic difficulties in the diagnosis of both PMDD and personality disorders. This study seeks to address this problem to elucidate the relationship between PMDD, other affective disturbances commonly experienced by women, and maladaptive personality. METHOD: Axis I and II disorders were examined using standardized instruments and stringent diagnostic criteria (DSM-IV and the International Personality Disorders Examination) in 34 women with DSM-IV PMDD and 22 healthy women without severe premenstrual mood changes. RESULTS: Seventy-seven percent of the PMDD group had suffered from a past Axis I disorder in comparison with 17% of the control group. Two thirds of the parous women with PMDD had suffered from major depressive disorder in the puerperium. Personality disorder diagnoses were not highly represented in either group of women. The women with PMDD had significantly more obsessional personality traits (p < .001 ) but not absolute personality disorder diagnoses. CONCLUSION: Obsessional symptoms are known to cluster with the affective disorders and may reflect underlying temperamental and biological vulnerability. This study provides further evidence of the link between serotonergic dysregulation, personality vulnerability, and mood changes related to the female reproductive cycle.

Tryptophan depletion increases aggression in women during the premenstrual phase.

RATIONALE: Reducing serotonin by the method of tryptophan depletion (TD) has led to increased aggression but experimental studies have not used female subjects. OBJECTIVE: To evaluate the effects of TD on aggression in women in the late luteal phase of their menstrual cycle. METHODS: Healthy women were recruited and randomly assigned to an amino acid drink either depleted or with a balanced amount of tryptophan. At 4.5 h later, they competed on the competitive reaction time task. RESULTS: Women who had received the TD drink showed more behavioural aggression in response to provocation. CONCLUSION: Decreased serotonergic neurotransmission increases aggression in women as well as men.

Trait hostility and prolactin response to tryptophan enhancement/depletion.

This study investigated the relationship between trait hostility and aspects of serotonergic function by assessing the prolactin (PRL) response to acute tryptophan depletion and enhancement in 28 healthy male volunteers. Serum PRL was assessed immediately before, and 4.5 h after, administration of an amino acid drink enhanced with, or depleted of, the 5-HT precursor tryptophan. Trait hostility and DeltaPRL (value at 4.5 h minus baseline) correlated negatively following enhancement and positively following depletion, indicating that the higher the hostility the smaller the change in PRL in either direction. This is consistent with previous research reporting an association between aggression and blunted neuroendocrine responses to serotonergic agents. The results indicate the possibility that, in people high on hostility, part of the serotonergic pathway that leads to modulation of PRL release is characterised by a stage with either low capacity relative to input availability or a strong negative feedback component.

Plasma tryptophan and trait aggression.

Many studies have reported correlations between measures of aggression and indices of serotonergic function, but most have studied patient or offender populations and relatively few have investigated plasma concentrations of the serotonin precursor tryptophan. This study investigates the relationship between plasma concentrations of tryptophan and trait hostility, depression and anxiety in male healthy volunteers. Sixty-seven healthy male volunteers gave blood samples and completed trait questionnaires. Plasma tryptophan was positively correlated with the Buss-Durkee Hostility Inventory Total score and Motor Aggression subscale, but not with the Attitudinal Hostility subscale or with trait anxiety or depression. In conclusion, there is evidence for an association between high concentrations of plasma tryptophan and aggressive behaviour in men, presumably mediated by some aspect of central serotonergic function, which seems unlikely to be explained by high trait anxiety or depression.

Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila.

A nitric oxide (NO)/cyclic GMP (cGMP) signaling pathway is thought to play an important role in mammalian vasodilation during hypoxia. We show that Drosophila utilizes components of this pathway to respond to hypoxia. Hypoxic exposure rapidly induced exploratory behavior in larvae and arrested the cell cycle. These behavioral and cellular responses were diminished by an inhibitor of NO synthase and by a polymorphism affecting a form of cGMP-dependent protein kinase. Conversely, these responses were induced by ectopic expression of NO synthase. Perturbing components of the NO/cGMP pathway altered both tracheal development and survival during prolonged hypoxia. These results indicate that NO and protein kinase G contribute to Drosophila's ability to respond to oxygen deprivation.

Tryptophan enhancement/depletion and reactions to failure on a cooperative computer game.

Twenty-eight high trait hostility male volunteers played a "cooperative" computer game 4.5 hours after an amino acid drink enhanced with, or depleted of, tryptophan. Each trial involved steering a tank through minefields following directions from an unknown "partner." Failure was experienced when the tank hit a mine or when time ran out. Subjects' moods, verbal aggression, attributions of blame, vocal acoustics, and blood pressure were assessed. Differences between tryptophan groups were not significant for primary measures of anger and verbal aggression. However, depleted subjects reported greater increases in feelings of restlessness and incompetence, were less successful in avoiding mines and showed greater increases in blood pressure during the game. Subjects in both groups sent more negative ratings when they lost the game by virtue of hitting a mine rather than losing by running out of time. However, ratings of the depleted group were less influenced by the reason for losing the game. Also, vocal acoustics showed a group X reason-for-losing interaction in the high-frequency band. Tryptophan-depleted subjects with high scores on Behavioral-Activation-System-Drive were most likely to send negative ratings and those scoring high on Buss-Durkee Hostility Inventory Assault and Guilt to report increased anger after the game.

Identification of an asymmetrically localized sensor histidine kinase responsible for temporally and spatially regulated transcription.

Caulobacter crescentus undergoes asymmetric cell division, resulting in a stalked cell and a motile swarmer cell. The genes encoding external components of the flagellum are expressed in the swarmer compartment of the predivisional cell through the localized activation of the transcription factor FlbD. The mechanisms responsible for the temporal and spatial activation of FlbD were determined through identification of FlbE, a histidine kinase required for FlbD activity. FlbE is asymmetrically distributed in the predivisional cell. It is located at the pole of the stalked compartment and at the site of cell division in the swarmer compartment. These findings suggest that FlbE and FlbD are activated in response to a morphological change in the cell resulting from cell division events.

Temporal and spatial regulation of fliP, an early flagellar gene of Caulobacter crescentus that is required for motility and normal cell division.

In Caulobacter crescentus, the genes encoding a single polar flagellum are expressed under cell cycle control. In this report, we describe the characterization of two early class II flagellar genes contained in the orfX-fliP locus. Strains containing mutations in this locus exhibit a filamentous growth phenotype and fail to express class III and IV flagellar genes. A complementing DNA fragment was sequenced and found to contain two potential open reading frames. The first, orfX, is predicted to encode a 105-amino-acid polypeptide that is similar to MopB, a protein which is required for both motility and virulence in Erwinia carotovora. The deduced amino acid sequence of the second open reading frame, fliP, is 264 amino acids in length and shows significant sequence identity with the FliP protein of Escherichia coli as well as virulence proteins of several plant and mammalian pathogens. The FliP homolog in pathogenic organisms has been implicated in the secretion of virulence factors, suggesting that the export of virulence proteins and some flagellar proteins share a common mechanism. The 5' end of orfX-fliP mRNA was determined and revealed an upstream promoter sequence that shares few conserved features with that of other early Caulobacter flagellar genes, suggesting that transcription of orfX-fliP may require a different complement of trans-acting factors. In C. crescentus, orfX-fliP is transcribed under cell cycle control, with a peak of transcriptional activity in the middle portion of the cell cycle. Later in the cell cycle, orfX-fliP expression occurs in both poles of the predivisional cell. Protein fusions to a lacZ reporter gene indicate that FliP is specifically targeted to the swarmer compartment of the predivisional cell.

A sigma 54 transcriptional activator also functions as a pole-specific repressor in Caulobacter.

The differential localization of proteins in the Caulobacter predivisional cell leads to the formation of two distinct progeny cells: a motile swarmer cell and a sessile stalked cell. Pole-specific transcription in the predivisional cell is one mechanism responsible for protein localization. Here we show that the sigma 54 transcriptional activator FlbD, which activates swarmer pole-specific transcription of a subset of late flagellar genes, is also capable of functioning as a pole-specific repressor of the early flagellar fliF operon. DNase I footprinting and methylation interference assays indicate that FlbD binds to regions of the fliF promoter at regions that would be likely to interfere with the binding of RNA polymerase. A mutation that abolishes FlbD binding results in up to a fourfold increase in fliF promoter expression. This mutation alters both the spatial and temporal pattern of fliF expression resulting in the inappropriate expression of the fliF operon in the swarmer pole of the predivisional cell. These results demonstrate that FlbD represses early flagellar gene expression in the swarmer pole of the Caulobacter predivisional cell. This is the first instance in which a protein specifically involved in pole-specific repression has been identified in Caulobacter. The restriction of FlbD activity to the swarmer pole accomplishes two regulatory missions by simultaneously activating late flagellar gene expression and repressing early flagellar genes.

Spatial and temporal phosphorylation of a transcriptional activator regulates pole-specific gene expression in Caulobacter.

Polar localization of proteins in the Caulobacter predivisional cell results in the formation of two distinct progeny cells, a motile swarmer cell and a sessile stalked cell. The transcription of several flagellar promoters is localized to the swarmer pole of the predivisional cell. We present evidence that the product of the flbD gene is the transcriptional activator of these promoters. We show that FlbD is distributed in all cell types and in both poles of the predivisional cell. We also demonstrate that FlbD can be phosphorylated, and that a FlbD kinase activity is under cell cycle control. Cells expressing a FlbD mutant that should activate transcription in the absence of phosphorylation, exhibited an alteration in the temporal pattern of flagellin transcription. Furthermore, predivisional cells expressing the mutant FlbD failed to polarly localize flagellin synthesis. We propose that the phosphorylation of FlbD is restricted to the swarmer compartment of the predivisional cell, and serves as the control point for regulating the spatial transcription of flagellar promoters.

Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis.

Complement components C3 and C5 are susceptible to limited proteolysis by an arginine-specific cysteine proteinase isolated from Porphyromonas gingivalis. This bacterium is an anaerobe commonly associated with severe periodontal disease. Infection by P. gingivalis is accompanied by an acute inflammatory response, complete with extensive neutrophil involvement. This prompted us to investigate a possible direct role for complement in periodontitis evoked by P. gingivalis. Exposure of C3 and C5 to the cysteine proteinase at molar ratios between 1:25 and 1:100 (enzyme to substrate ratios) resulted in a time-dependent, limited degradation of each component. C3 was converted in a stepwise manner to C3a-like and C3b-like fragments with evidence of extensive further degradation of the C3a-like portion of the molecule. We were unable to demonstrate C3a activity in the C3 digestion mixtures. C3 degradation appears to involve primarily the alpha-chain. Proteolysis of C5 also progresses in a stepwise manner producing an initial internal cleavage of the alpha-chain to generate 30- and 86-kDa fragments. Further digestion of the 86-kDa amino-terminal fragment of the alpha-chain leads to the release of C5a or a C5a-like fragment that is biologically active for neutrophil activation. The fact that a potent chemotactic factor, i.e. C5a, can be generated from C5 by a proteinase derived from P. gingivalis suggests a recruiting mechanism for attracting neutrophils to the gingival lesion site in periodontal disease.