Patrick Domen

Bone mineral density as a marker of cumulative endogenous estrogen exposure: Relationship to background genetic risk of psychotic disorder

BACKGROUND Alterations in bone mineral density (BMD) in patients with psychotic disorder may reflect the effect of treatment (disease effect observed in patients but not their siblings) or, as an intermediate marker of cumulative endogenous estrogen exposure, alterations in the neuroprotective effect of estrogen in the brain (vulnerability effect observed in patients and siblings). METHODS Dual X-ray absorptiometry (DEXA) scans were acquired in 62 patients with a psychotic disorder, 67 non-psychotic siblings of patients with a psychotic disorder, and 48 controls. BMD (g/cm(2)), Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and BMD were investigated with multilevel random regression analyses. Group×sex interactions and effects of antipsychotic medication (AP) on BMD were examined. RESULTS Group was not associated with BMD outcome measures, although patients had consistently lower BMD measures compared to both siblings and controls. There were no significant group×sex interactions, but stratified analyses showed that BMD measures in female patients were significantly lower in comparison to female controls and siblings (e.g. total femoral BMD, P vs. C: B=-0.100, p=0.010; P vs. S: B=-0.104, p=0.008). After excluding female patients who used prolactin-raising AP, the effect was attenuated (e.g. total femoral BMD, P vs. C: B=-0.073, p=0.072; P vs. S: B=-0.085, p=0.051). In men, there were no significant BMD differences between patients and controls. CONCLUSION Familial risk of psychotic disorder was not associated with BMD. Instead, decreased BMD in the femur may reflect treatment effects or non-familial risk associated with low cumulative endogenous estrogen levels in women.

Microstructural white matter alterations in psychotic disorder: A family-based diffusion tensor imaging study

BACKGROUND There is evidence for microstructural white matter alterations in patients with psychotic disorder, suggesting altered interregional connectivity. Less is known about the presence and role of white matter alterations in well individuals at higher than average genetic risk for psychotic disorder. METHODS 85 patients with psychotic disorder, 93 non-psychotic siblings of patients with psychotic disorder and 80 healthy controls underwent a diffusion tensor imaging (DTI) scanning protocol. In a whole brain voxel-based analysis using Tract Based Spatial Statistics (TBSS), fractional anisotropy (FA) values were compared between the three groups. Effects of antipsychotic medication and drug use were examined. RESULTS The patients displayed significantly lower mean FA than the controls in the following regions: corpus callosum (genu, body, splenium), forceps major and minor, external capsule bilaterally, corona radiata (anterior, posterior) bilaterally, left superior corona radiata and posterior thalamic radiation bilaterally. Similar FA differences existed between the patients and siblings; the siblings did not differ from the controls. CONCLUSION Profound microstructural white matter alterations were found in the corpus callosum and other tracti and fasciculi in the patients with psychotic disorder, but not in siblings and the controls. These alterations may reflect brain pathology associated with the illness, illness-related environmental risk factors, or its treatment, rather than genetic risk.

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study

Background: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. Methods: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models. Results: Siblings revealed a significant mean FA decrease over time compared to controls (B = −0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = −0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (&khgr;2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata. Conclusion: Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.

Testing the estrogen hypothesis of schizophrenia: Associations between cumulative estrogen exposure and cerebral structural measures

BACKGROUND Bone mineral density (BMD), as an indicator of cumulative estrogen exposure, may be reduced in female patients with psychotic disorder (van der Leeuw et al., 2013), possibly reflecting reduced cerebral exposure to estrogen and alterations in neuroprotective effects. To the degree that BMD is a marker of cumulative (endogenous) estrogen exposure, we hypothesized that BMD would be positively associated with cerebral gray and white matter indices. METHODS Dual X-ray absorptiometry (DEXA) and magnetic resonance (MRI) scans were acquired in fourteen female patients diagnosed with a psychotic disorder. BMD was expressed in total BMD (g/cm(2)), Z- and T-scores. Cerebral cortical thickness (CT) (as indicator of gray matter status) and fractional anisotropy (FA) (as indicator of white matter integrity) were measured and served as the dependent variables in multilevel random regression models. BMD measures were the independent variables. RESULTS Femoral BMD measures were positively associated with CT at trend significance (total BMD: B=0.266, 95% CI: -0.019-0.552, p=0.067; Z-score: B=0.034, 95% CI: 0.001-0.067, p=0.046; T-score: B=0.034, 95% CI: 0.000-0.068, p=0.052). There were no significant associations between femoral BMD measures and FA. CONCLUSIONS The data suggest that in women with psychotic disorder, alterations in the neuroprotective effect of estrogen (as measured by BMD) impact cortical gray matter, but not white matter integrity. These findings merit further investigation and, if replicated, would lend support to the estrogen hypothesis of schizophrenia.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.

Innovatief leerboek persoonlijke psychiatrie

Psychiatrie is een prachtvak. In 150 jaar is ook eindeloos veel kennis vergaard. En we hebben slimme structuren bedacht voor het optimaliseren van hulpverlening. Maar zijn we inmiddels niet verdwaald in onze goede bedoelingen? Zien we elk afzonderlijk individu met psychische problemen nog wel staan? Dit leerboek heeft een focus. De patient. De zestig auteurs die hebben meegewerkt staan natuurlijk op de schouders van de groten uit het psychiatrische vak. Ze hoeven het wiel niet uit te vinden. Maar ze hebben wel even adem gehaald voordat ze hun kennis en ervaring in een didactisch verantwoorde vorm goten. Om de mens met psychische problemen echt centraal te kunnen stellen bleek het noodzakelijk om in eerste instantie veel te schiften. Er is teveel classificatie. Een overmaat aan diagnostische varianten helpt de patient meestal niet verder. Het volgen van protocollen vergt veel tijd die ten koste gaat van effectieve therapie. Na bestudering van dit boek zal het vak misschien wat afgeslankt lijken: minder verfijnde diagnostiek, een overzichtelijk aantal syndromen in de plaats van eindeloos veel symptomen. Minder bewegwijzerde zorgpaden. Maar het vak wordt ook verrijkt: met ‘persoonlijke psychiatrie’. Hoe organiseer je persoonlijke aandacht voor elke individuele patient? Hoe profiteert de client van het inzicht dat psychische problemen gewoon kleinere of grotere verschuivingen zijn in de verhouding van stressoren en kwetsbaarheden? En vooral: hoe wordt een client praktisch en steeds opnieuw geholpen op de weg naar herstel? Noem het een nieuw paradigma. Noem het ‘nieuwe ggz’. Maar het gaat beslist niet om oude wijn in nieuwe zakken. Deze publicatie maakt bestaande literatuur niet obsoleet. Wel beoogt dit leerboek uitdrukkelijk het, opnieuw, scherp stellen van de (persoonsgerichte) psychiatrische missie.

11 Een bescheiden begin: wat we nog niet weten en nog niet kunnen

‘In een wereld zonder spinnen is er geen spinnenfobie’. De sensorische (zintuiglijke) prikkel is essentieel: het zien of voelen van spinnen is voorwaardelijk voor een angstreactie. Hetzelfde geldt voor de paranoide waan: zonder de waarneming van de ‘achtervolger’ of mogelijke camera is er geen gevoel van bedreiging. Ook het verlangen naar een borrel ontstaat pas bij het passeren van een kroeg. De context is een bepalende factor voor dergelijke ervaringen.

1 Psychiatrie ontward

Voor veel mensen is de psychiatrie een lastig te doorgronden medisch vakgebied. Dit geldt zelfs voor insiders maar eens temeer voor mensen die werkzaam zijn buiten de ggz. Waarom is de psychiatrie zo moeilijk? Vaak wordt het vak door studenten en anderen die niet zo bekend zijn met het vakgebied gepercipieerd als vaag of zweverig. Het lijkt moeilijk om te doorgronden wat het vakgebied precies inhoudt. Iedereen heeft weleens psychische klachten, voelt zich bijvoorbeeld een periode somber. Maar wanneer noem je dat een ‘ziekte’?