A First Exploration: Can Eye Movement Desensitization and Reprocessing Improve Cognition in Older Adults With Posttraumatic Stress Disorder?

OBJECTIVES: In older adults, PTSD is associated with decreased verbal learning and executive dysfunction. Therefore, feasibility of EMDR-treatment to improve cognitive performance in older adults with PTSD was examined. Additionally, we investigated pre-treatment correlation with often co-occurring risk factors for cognitive decline (sleep problems, depressive disorder, physical inactivity, childhood traumatic events). DESIGN: Multicenter design with pre-post measurements. SETTING: Psychiatric Dutch hospitals Mondriaan Mental Health Center and Altrecht. PARTICIPANTS: 22 treatment-seeking PTSD-outpatients (60-84 years). INTERVENTION: Weekly one-hour EMDR session during 3, 6, or 9 months. MEASUREMENTS: PTSD was assessed with Clinician-Administered PTSD-scale for DSM-5 (CAPS-5). Verbal learning memory was measured with Auditory Verbal Learning Test (RAVLT), interference with Stroop Colour-Word Test (SCWT) and working memory with Wechsler Adult Intelligence Scale-Digit Span (WAIS-IV-DS). RESULTS: A Linear mixed-model showed significant improvement on RAVLT immediate-recall (F (1, 21) = 15.928, P = .001, 95% CI -6.98-2.20), delayed-recall (F (1, 21) = 7.095, P = .015, 95% CI -2.43-.30), recognition (F (21) = 8.885, P = .007, 95% CI -1.70- -.30), and SCWT (F (1 ,21) = 5.504, P = .029, 95% CI 4.38-72.78) but not on WAIS-IV-DS (F (20) = -1.237, P = .230, 95% CI -3.07-.78). There was no significant influence of therapy duration and CAPS-5 pre-treatment scores. There were small-medium nonsignificant correlations between CAPS-5 and cognitive performance pre-post differences, and between most cognitive measures and sleep problems, depressive disorder, and physical inactivity. CONCLUSIONS: Cognitive functioning on memory and attention possible increased in older adults with PTSD after EMDR treatment. Further research is needed with a larger sample and a control condition to corroborate these findings and to identify the possible mediating role of modifiable risk factors.

Feasibility of EMDR toward Personality Functioning in Older Adults with PTSD.

OBJECTIVES: Severe posttraumatic stress disorder (PTSD) in older adults (≥60 years) has been found to be associated with maladaptive personality functioning and personality disorders (PD). Emerging evidence in adults supports that reprocessing adverse events with Eye Movement Desensitization and Reprocessing (EMDR) could improve personality functioning and reduce full PDdiagnosis. METHODS: A multicenterfeasibilitystudy in 24 older PTSD-patients receiving weekly EMDR-sessions for either 3, 6 or 9 months. A linear-mixed-model was used with personality functioning (SIPP-SF) as dependent variable and time, PTSD-severity (CAPS-5), and "othertreatment" as predictor variables. Secondary, pre- and posttreatment percentages were calculated for the PDspresence. RESULTS: Symptom changes over time showed a significant influence of CAPS-5 on SIPP-SF (b = -1.40, 95% CI=[-2.48 to -0.33], p = .012), no significant effect of time for total SIPP-SF, and a significant improvement of SIPP-SF "identityintegration"-scale over time (b = 9.20, 95% CI=[0.97-17.42], p = .029). There was a marginal significant effect of "othertreatment" (b = 8.42, 95% CI=[-0.30-17.13], p = .058). There was 31% full PDs-decrease. CONCLUSIONS: Observed improvements in personality functioning from pre to post EMDRtreatment were explained by PTSD-severity. Identityintegration improved significantly over time. Results suggest that participants with "othertreatment" showed more severe baseline-pathology and thus lower personality functioning. CLINICAL IMPLICATIONS: EMDR, in addition to being a feasible treatment option for older adults with PTSD, improves personality functioning and reduces the presence of PDs over time.'

The Need for a Diagnostic Instrument to Assess Post-Traumatic Stress Disorder in People with Dementia: Findings from a Delphi Study.

Cognitive and behavioral aspects may mask posttraumatic stress disorder (PTSD) in people with dementia. PTSD severely lowers quality of life in people with dementia. Proper recognition of PTSD is essential to ensure adequate treatment. However, a valid diagnostic tool for PTSD in dementia is lacking. A Delphi study was conducted among 20 Dutch and 6 international experts in the field of PTSD and dementia care or research. The aim was to reach consensus in 3 rounds on the added value, form, content, and application for developing such an instrument. The first round confirmed the need for a new diagnostic tool for research and clinical practice. Consensus was reached on 23 statements regarding the support base and 19 related to content of the instrument. In the third round, opinions on several conceptual problems were gathered. Based on the experts' opinions, a draft version of an instrument, the TRAuma and DEmentia-interview (TRADE-interview), was developed. Clinical and research implications of this new measure are discussed.

Psychiatric comorbidities in older adults with posttraumatic stress disorder: A systematic review.

BACKGROUND: Psychiatric comorbidity is high in adults with posttraumatic stress disorder (PTSD), with up to 90% having at least one additional condition, and two-thirds having two or more other diagnoses. With an increasing aging population in industrialized counties, knowing which psychiatric disorders frequently co-occur in older adults with PTSD can have implications to improve diagnosis and treatment. This systematic literature review explores the current empirical literature on psychiatric comorbidity in older adults with PTSD. METHOD: Literature databases PubMed, Embase, PsycINFO, and CINAHL were searched. The following inclusion criteria were applied: research done since 2013, PTSD diagnosis based on diagnostic criteria according to Diagnostic and Statistics Manual-Fifth Edition, International Classification of Diseases-10th Revision (ICD-10), or ICD-11, and studies include individuals aged 60 years or older. RESULTS: Of 2068 potentially relevant papers identified, 246 articles were examined based on titles and abstracts. Five papers met the inclusion criteria and were included. Major depressive disorder and alcohol use disorder were the most frequently studied and diagnosed psychiatric comorbidities in older adults with PTSD. CONCLUSIONS AND IMPLICATIONS: Screening for depression and substance use in older adults should include an assessment of trauma and PTSD. Additional studies in the general older adult population with PTSD and a broader range of comorbid psychiatric disorders are needed.

The mental health impact of the COVID-19 pandemic and exposure to other potentially traumatic events up to old age.

We investigated whether the impact of potentially traumatic events (PTEs) on trauma-related symptoms changes across the transitional adult lifespan (i.e., 16-100 years old) and if this association differs for self-reported COVID-19-related PTEs compared to other PTEs. A web-based cross-sectional study was conducted among 7,034 participants from 88 countries between late April and October 2020. Participants completed the Global Psychotrauma Screen (GPS), a self-report questionnaire assessing trauma-related symptoms. Data were analyzed using linear and logistic regression analyses and general linear models. We found that older age was associated with lower GPS total symptom scores, B = -0.02, p < .001; this association remained significant but was substantially weaker for self-reported COVID-19-related PTEs compared to other PTEs, B = 0.02, p = .009. The results suggest an association between older age and lower ratings of trauma-related symptoms on the GPS, indicating a blunted symptom presentation. This age-related trend was smaller for self-reported COVID-19-related PTEs compared to other PTEs, reflecting the relatively higher impact of the COVID-19 pandemic on older adults.

A first insight into the clinical manifestation of posttraumatic stress disorder in dementia: a systematic literature review.

Posttraumatic stress disorder (PTSD) is a prevalent disorder worldwide and often co-occurs in dementia. Both have a major impact on disease burden and quality of life. PTSD may be difficult to recognize in dementia and a structured diagnostic method is lacking. In order to get insight into the clinical diagnostics of PTSD in dementia, this systematic literature review evaluates the clinical presentation of PTSD and other relevant symptoms in people with dementia. PubMed, PsycINFO, Embase, and CINAHL were searched for all publications through 30 December 2021. Articles were included which met the following criteria: (i) description of at least one case with a current diagnosis of dementia and co-morbid PTSD; (ii) clinical presentation of symptoms being adequately described; (iii) no difference being made between chronic PTSD, PTSD with re-activation, and delayed onset PTSD. Of the 947 identified abstracts, 13 papers met the inclusion criteria and were included (describing 30 cases). Based on our rating, only one case completely fulfilled the DSM-5 criteria of PTSD. Avoidance was only described in three cases. Most commonly described symptoms were irritability and anger (E1, 9%), persistent negative emotional state (D4, 9%), and sleep disturbances (E6, 8%). In 93% of the case reports, other symptoms were also described, i.e. memory problems (58%), screaming (33.3%), and wandering (22.2%). People with dementia who have experienced a traumatic event seem to present, based on our rating method, with insufficient symptoms to meet all criteria for a PTSD DSM-5 diagnosis. The DSM-5 core symptom of avoidance was absent in most of the cases. Clinical presentation consists mainly of symptoms of irritability, anger, persistent negative emotional state, and sleep disturbances, often accompanied by other symptoms. These findings suggest that older people with dementia may have other symptom presentations than people without dementia.

Feasibility of EMDR in Older Adults with PTSD to Reduce Frailty and Improve Quality of Life.

OBJECTIVES: Posttraumatic stress disorder (PTSD) after exposure to multiple (childhood) trauma's is strongly associated with accelerated aging and high psychiatric and somatic comorbidity, influencing frailty and Quality of Life (QoL) in older adults. Eye Movement Desensitization therapy (EMDR) addresses psychological and physiologic symptoms stemming from adverse life events and therefore could influence frailty and QoL in older adults. METHODS: We conducted a multi-center feasibility study (two psychiatric hospitals) in Dutch older outpatients (N = 24; ≥60 years) with PTSD. Participants received weekly EMDR-treatment during the course of the trial (3 months to a maximum of 9 months). Frailty (Groninger Frailty Indicator) and QoL (EuroQol 5D-3L), were assessed pre- and posttreatment. RESULTS: A linear mixed-model approach showed significant reduction of frailty (F(1,23) = 9.019, p = .006) and improvement of QoL (F(1,23) = 13.787, p = .001). For both frailty and QoL, there was no significant influence of Clinician-Administered PTSD Scale (CAPS-5) pre-treatment score, therapy duration, and neither an interaction effect of therapy duration x CAPS-5 pre-treatment score. CONCLUSIONS: EMDR with older adults with PTSD showed a significant reduction of frailty and improvement of QoL. Randomized controlled studies are needed to more precisely study the impact of trauma-focused treatment in older adults on frailty and QoL and the implications this might have for lessening disease burden. CLINICAL IMPLICATIONS: Screening for PTSD in older frail adults is important to treat PTSD as a possible way to reduce frailty and improve QoL.

[Pharmacotherapy of a 67-year old female with borderline personality disorder]. / Farmacotherapeutische behandeling van een 67-jarige vrouw met een borderline persoonlijkheids­stoornis.

Pharmacotherapy in older adults with personality disorders is very complicated. On the one hand, this is caused by interference of the personality disorder in the therapeutic relationship. On the other hand, age specific factors, such as polypharmacy and changing pharmacokinetics and -dynamics play an important complicating role. In this article the difficulties of pharmacotherapy in older adults with personality disorders are illustrated by the description of a case of a 67-year old female with a borderline personality disorder. She has an extensive history of many therapies, which have not been effective in treating a variety of symptoms. This case description emphasizes the importance of making the correct diagnosis and focusing pharmacotherapy on the personality disorder. Also, decreasing polypharmacy, often a consequence of an extensive history of many - both psychiatric and somatic - treatments, plays an important role. There is a lack of evidence on pharmacotherapy in older adults with personality disorders to rely on and therefore there is a need for more research on this subject.

A Life Span Perspective on Borderline Personality Disorder.

PURPOSE OF REVIEW: To provide an update of a life span perspective on borderline personality disorder (BPD). We address the life span course of BPD, and discuss possible implications for assessment, treatment, and research. RECENT FINDINGS: BPD first manifests itself in adolescence and can be distinguished reliably from normal adolescent development. The course of BPD from adolescence to late life is characterized by a symptomatic switch from affective dysregulation, impulsivity, and suicidality to maladaptive interpersonal functioning and enduring functional impairments, with subsequent remission and relapse. Dimensional models of BPD appear more age neutral and more useful across the entire life span. There is a need for age-specific interventions across the life span. BPD symptoms and impairments tend to wax and wane from adolescence up to old age, and presentation depends on contextual factors. Our understanding of the onset and early course of BPD is growing, but knowledge of BPD in late life is limited. Although the categorical criteria of DSM allow for reliable diagnosis of BPD in adolescence, dimensional models appear both more age neutral, and useful up to late life. To account for the fluctuating expression of BPD, and to guide development and selection of treatment across the life span, a clinical staging model for BPD holds promise.

[Pharmacotherapy in older adults with personality disorders: a new area of attention]. / Farmacotherapie bij ouderen met persoonlijk­heids­stoornissen: een nieuw aandachtsgebied.

BACKGROUND: Pharmacotherapy in older adults with personality disorders (PD) is a new and important area of attention. Nowadays, symptom based pharmacotherapy in older adults with PD is based on multidisciplinary guidelines, which are constructed on research performed in patients up to 50 years of age. There is no specific guideline for older adults with PD. GOAL: Providing a description of patient characteristics: number of comorbid psychiatric disorders, use of medication, including polypharmacy, in older adults (≥ 65 years) with personality disorders. METHOD: A retrospective cross-sectional patient file study (n = 50) in a clinical center of excellence for older adults with personality disorders (outpatient setting). RESULTS: . From the file study, it appears that 1) the unspecified/other specified personality disorder and the borderline personality disorder (BPD) occur most frequently, 2) there is a trend (no significant difference) that older adults with BPS use most medication (somatic medication and psychotropics) and 3) there is a trend (no significant difference) that polypharmacy is the most prevalent amongst older adults with BPD. CONCLUSION: The use of medication in certain subgroups of older adults with PD tends to be high. Further research is necessary to optimize pharmacotherapy in older adults with PD.

Biomarkers associated with cognitive impairment in post-traumatic stress disorder: A systematic review of current evidence.

OBJECTIVE: This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). METHODS: A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. RESULTS: Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aß and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. CONCLUSIONS: Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD.

The feasibility of eye movement desensitization and reprocessing (EMDR) for older adults with posttraumatic stress disorder (PTSD) and comorbid psychiatric and somatic disorders.

OBJECTIVE: The aim of this study is to investigate the feasibility of eye movement desensitization and reprocessing (EMDR) therapy in older adults with posttraumatic stress disorder (PTSD), and to explicitly include information about presence of the comorbid psychiatric and somatic disorders as well as a history of traumatic events at treatment start. METHOD: A nonrandomized feasibility study in a multicenter design was conducted with 25 older PTSD patients (60-84 years). Treatment consisted of weekly 1-hour EMDR sessions for PTSD during 3, 6, or maximum 9 months. PTSD diagnosis was assessed with Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Symptom Scale-Self Report (PSS-SR). We also operationalized PTSD symptom change on CAPS-5 and PSS-SR in loss of diagnosis according to DSM-5 and remission. Remission was defined as loss of diagnosis and no longer having any PTSD symptoms according to minimum severity scores on CAPS-5 (< 12) and PSS-SR (≤ 10). Comorbid psychiatric disorders were assessed pre- (and post-)treatment and somatic disorders and presence of traumatic (childhood) events were assessed pretreatment. RESULTS: Comorbidity rates of depressive (64%), anxiety (56%), other psychiatric (32%), personality (60%), and somatic disorders (96%) were high in our sample of older adults. A linear mixed model approach showed a significant decrease in CAPS-5 scores from pre- to posttreatment for the total sample [F(1, 24) = 150.304, p < .001; Cohen's d = 2.59]. No significant main effects of therapy duration (3, 6, or 9 months), pretreatment intensity of psychopathology (BSI), or their interaction was found (all p > .05). Eighty percent lost their PTSD diagnosis and remission rate was 52% for CAPS-5 and 37.5% for PSS-SR. Remission (not loss of PTSD-diagnosis) showed a negative correlation with the number of experienced traumatic childhood events. CONCLUSION: EMDR therapy showed large treatment effect on PTSD symptom severity in older adults and this was unrelated to therapy duration and presence of comorbid psychiatric and somatic disorders pretreatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The effects of selective serotonin reuptake inhibitors on memory functioning in older adults: A systematic literature review.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to older adults. In contrast to young subjects, it is unclear whether older adults may be vulnerable to cognitive side effects. Serotonin is involved in cognitive functions (e.g. memory). It is of great importance to examine the effects of SSRIs on memory functioning in older adults. OBJECTIVES: The objective of this systematic literature review is to summarize studies in which the effects of SSRI treatment on all aspects of memory functioning in older adults are investigated. METHODS: PubMed, PsycINFO, CINAHL, and Embase were searched for all studies published until 18th of October 2021. Articles were included if they fulfilled the inclusion criteria as follows: (1) study design is (randomized) controlled trial, cross-sectional, or prospective cohort study; (2) study population consists of older adults (mean age ⩾65 years), or results for this age-group are reported separately; (3) intervention is use of an SSRI; and (4) effects on performance of any memory domain are measured and clearly described. RESULTS: The search yielded 1888 articles, of which 136 were included for the full-text review. Eventually, 40 articles were included. Most studies reported no association between SSRI use and memory functioning. The studies that found a positive association mainly investigated older adults with mental or neurological disorders (e.g. depression or stroke). A few studies found a negative association in the following subgroups: non-responders (depression), patients with frontal brain disease, and women. CONCLUSION: Overall, no consistent negative effects of SSRIs on memory functioning in older adults were found after SSRI treatment. Most studies reported no change in memory functioning after SSRI use. Some studies even showed an improvement in memory performance. Positive effects of SSRIs on memory functioning were especially found in older adults with mental or neurological disorders, such as subjects with depression or stroke.

Comorbidity rates of Posttraumatic Stress Disorder in dementia: a systematic literature review.

Background: Post Traumatic Stress Disorder (PTSD) has been described as an independent risk factor for cognitive decline and dementia. At the same time, cognitive deterioration and increased loss experiences in dementia may increase liability for the reactivation of traumatic memories and thereby PTSD symptoms. Objective: In order to investigate co-occurrence of PTSD in dementia this systematic literature review summarizes all the available evidence on reported comorbidity rates of PTSD in patients with dementia. Method: PubMed, Embase, PsycINFO and CINAHL were searched for potential publications investigating the co-occurrence of PTSD in dementia until 25 November 2019. Cohort and cross-sectional studies were included. To assure current comorbidity of PTSD in dementia, only publications with a recent PTSD diagnosis (<2 years before onset of dementia) were selected. Results: Of the 860 identified abstracts, three studies (0.35%) met the eligibility criteria and were included. These three studies concerned only military veteran populations, and they comprised two cross-sectional cohort studies and one prospective cohort study. The estimated comorbidity rate of PTSD in veterans with dementia varied between 4.7% and 7.8%. Conclusions: The limited research available shows comorbidity rates only in military veterans, which were possibly dependent on investigated population with respect to dementia severity and possibly associated behavioural and psychiatric symptoms of dementia (BPSD). In dementia patients the comorbidity with PTSD may be high and we suggest that worldwide the impact of PTSD in dementia is high and probably underestimated. Research and care on this topic should improve urgently with the current expanding prevalence of dementia. A first step to improve quality of dementia research and care would be to develop a structured tool to diagnose PTSD in these patients.

Antecedentes: El trastorno de estrés postraumático (TEPT) ha sido descrito como un factor de riesgo independiente para el deterioro cognitivo y la demencia. De manera concurrente, el deterioro cognitivo y el incremento en la pérdida de experiencias en la demencia pueden incrementar la vulnerabilidad para la reactivación de recuerdos traumáticos y, por tanto, de síntomas del TEPT.Objetivo: Para investigar la comorbilidad del TEPT en la demencia, esta revisión sistemática resume toda la evidencia disponible de los índices de comorbilidad del TEPT en pacientes con demencia.Métodos: Se realizó una búsqueda de potenciales publicaciones investigando la comorbilidad del TEPT en demencia en PubMed, Embase, PsycINFO y CINAHL hasta el 25 de noviembre del 2019. Se incluyeron estudios de cohorte y estudios transversales. Para asegurar que la comorbilidad del TEPT en demencia sea actual, solo se seleccionaron publicaciones que incluyeran un diagnóstico reciente del TEPT (de menos de dos años desde el inicio de la demencia).Resultados: De los 860 resúmenes identificados, tres estudios (0,35%) cumplieron los criterios de inclusión y fueron seleccionados. Estos tres estudios incluyeron únicamente a poblaciones de militares veteranos. Dos de estos estudios eran de cohortes transversales y uno era un estudio de cohorte prospectiva. La comorbilidad estimada del TEPT en veteranos con demencia osciló entre un 4,7% y un 7,8%.Conclusiones: La escasa investigación disponible muestra índices de comorbilidad solo en militares veteranos, los cuales fueron posiblemente dependientes de la población investigada en relación con la severidad de la demencia y posiblemente asociados con síntomas conductuales y psiquiátricos de la demencia (BPSD por sus siglas en ingles). En los pacientes con demencia, la comorbilidad con el TEPT puede ser alta y sugerimos que, universalmente, el impacto del TEPT sobre la demencia es alto y probablemente subestimado. La investigación y la atención a este tema deberían mejorar urgentemente dado el incremento en la prevalencia de la demencia. Un primer paso para mejorar la calidad de la investigación y la atención del tema sería el desarrollar un instrumento estructurado para diagnosticar el TEPT en estos pacientes.

Selective Serotonin Reuptake-Inhibitors for Symptom-Based Treatment of Borderline Personality Disorders in Older Adults: An International Delphi Study.

OBJECTIVE: International guidelines on symptom-based treatment of borderline personality disorders (BPD) in older adults are lacking. The number of older adults (≥ 65 years) with borderline personality disorder is rising. Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) on symptoms of BPD has only been investigated in younger adults and results are ambiguous. During life, serotonergic function changes, which can influence the indication and effectiveness of SSRIs in older adults with BPD. Aim of this study is to reach consensus on the suitability of SSRIs for the treatment of older adults with BPD. METHODS: A Delphi study was conducted among eighteen international experts. In three successive rounds, a total of 16 statements addressing the treatment with SSRI's in older adults with BPD were assessed. Consensus on specific statements was reached if at least two-third of these experts agreed. RESULTS: Consensus was reached on 11 statements related to the indication and effectiveness of SSRIs in the treatment of older adults with BPD. CONCLUSION: The results of this study suggest a valuable role for SSRIs in the treatment of affective instability, and to a lesser extent impulsive behavior, in older adults with BPD. Sertraline or citalopram are suggested to be the first-choice medication but should be prescribed with some caution. Treatment recommendations have been suggested (presented in a flowchart), but still have to be investigated in clinical practice.

Comparing Intensive Trauma-Focused Treatment Outcome on PTSD Symptom Severity in Older and Younger Adults.

OBJECTIVE: To examine the treatment outcome of an intensive trauma-focused treatment program for post-traumatic stress disorder (PTSD) in older and younger adults. METHODS: A non-randomized outcome study was conducted with 62 consecutively admitted older PTSD patients (60-78 years) and 62 younger PTSD patients (19-58 years), matched on gender and availability of follow-up data. Patients participated in an intensive eight-day trauma-focused treatment program consisting of eye movement desensitization and reprocessing (EMDR), prolonged exposure (PE), physical activity, and group psycho-education. PTSD symptom severity (Clinician-Administered PTSD Scale-5 (CAPS-5)) was assessed, at pre- and post-treatment, and for a subsample (n = 31 older; n = 31 younger patients) at six-month follow-up. RESULTS: A repeated-measures ANCOVA (centered CAPS pre-treatment score as covariate) indicated a significant decrease in CAPS-5-scores from pre- to post-treatment for the total sample (partial η2 = 0.808). The treatment outcome was not significantly different across age groups (partial η2 = 0.002). There were no significant differences in treatment response across age groups for the follow-up subsample (pre- to post-treatment partial η2 < 0.001; post-treatment to follow-up partial η2 = 0.006), and the large decrease in CAPS-5 scores from pre- to post-treatment (partial η2 = 0.76) was maintained at follow-up (partial η2 = 0.003). CONCLUSION: The results suggest that intensive trauma-focused treatment is applicable for older adults with PTSD with a large within-effect size comparable to younger participants. Further research on age-related features is needed to examine whether these results can be replicated in the oldest-old (>80).

Sex differences in the effect of acute tryptophan depletion on declarative episodic memory: a pooled analysis of nine studies.

Acute tryptophan depletion (ATD) studies have shown that serotonin plays a role in learning and memory processes. In this study, we performed a pooled analysis of nine ATD studies in order to examine the nature of the memory-impairing effects of ATD and mediating factors, such as gender, age and vulnerability for disease in which disturbed serotonin was hypothesized to play a role. All studies that were used in this pooled analysis assessed declarative episodic memory using a verbal learning task paradigm. Immediate recall, delayed recall, and delayed recognition scores were examined. A total of 211 participants were included in the analysis. The analysis revealed that ATD impaired not only delayed recall, but also immediate recall. The ATD-induced impairments were larger in females than in males. Furthermore, ATD did not interact with any other serotonergic vulnerability and age. This suggests that the only factor that actually has the properties of a serotonergic vulnerability factor for declarative memory performance is female gender. The findings provide further support for a critical role of serotonin in declarative episodic memory.

Tryptophan modulation and cognition.

The interest in the function of the serotonergic system in relation to cognition stems from three sources: (1) the association of depression, cognitive dysfunction and 5-HT dysregulation; (2) the association of drug-induced 5-HT dysregulation and cognitive dysfunction; and (3) the association of cognitive performance and serotonergic function per se. We performed several experiments in subjects at risk for cognitive impairment and in healthy volunteers, in which 5-HT was manipulated by means of either tryptophan depletion or tryptophan loading. The results show that tryptophan and cognitive performance are associated in a complex non-linear fashion. Dissociations are observed between cognitive functions: tryptophan depletion impairs memory consolidation but improves focussed attention; as well as between subject groups: tryptophan depletion impairs problem solving in healthy 1st degree relatives of bipolar depressed patients but improves it in healthy volunteers without such a family history. It was demonstrated that the mood- and memory effects of tryptophan-depletion were specifically mediated by the depletion of tryptophan and also that the observed memory and cognitive deficits were emotionally biased in a manner consistent with depressive symptoms. We conclude that experimental manipulations of tryptophan mediate temporal and frontal cognitive functions such as memory consolidation and working memory respectively, in an opposite manner.

Can formulation affect tryptophan depletion results? Hints from studies in experimental panic.

RATIONALE: Acute Tryptophan Depletion (ATD) is a specific serotonergic challenge tool. Central serotonergic effects of different ATD procedures are possibly not those that are usually assumed. OBJECTIVES: In this paper we review data of ATD in an experimental fear model to investigate whether and how methodological differences may affect fear outcomes. Next we point to discrepancies of studies in our laboratory in order to test the hypotheses formulated in the review. METHODS: Literature was searched in PubMed and MEDLINE and studies of our laboratory were compared. RESULTS: Eight studies were included in the review: five in patients with panic disorder, three in healthy individuals. Methodologically the studies in our laboratory were quite similar except for the applied ATD mixtures. CONCLUSIONS: ATD exerts fear-enhancing effects in patients with panic disorders, more than in healthy individuals. However, our findings are inconclusive. The discrepant findings of studies in our laboratory can possibly be explained by differences in the ATD mixtures used. We suggest mechanisms as to how these might have affected the central availability of tryptophan and hence serotonin.

Stress, cortisol and memory as markers of serotonergic vulnerability.

OBJECTIVES: In the present paper the association of stress-induced cortisol with memory impairment is discussed Methods: An experiment is described in which an attempt is made to block stress-induced cortisol by lowering 5-HT neurotransmission by means of acute tryptophan depletion (ATD). Forty-five healthy control subjects participated in the experiment. RESULTS: Stress-induced peak cortisol and immediate memory performance were negatively associated. ATD tended to block stress-induced cortisol response. ATD also blocked the association between peak cortisol response and memory impairment. CONCLUSIONS: Stress-induced cortisol and its association with memory impairment is mediated at least partially by serotonin.