Delusional Symptoms Research Articles

90th Birthday Finds Pioneer Undertaking New Challenges

90th Birthday Finds Pioneer Undertaking New Challenges

Risks of Minor and Serious Violent Victimization in Prison

The authors use the Survey of Inmates in State and Federal Correctional Facilities 2004, which includes 18,185 respondents, to examine why some inmates are more likely to experience violent victimization in prison, focusing on the effects of mental disorders, physical disabilities, and physical size. The authors test four hypotheses based on patterns of minor versus serious victimization and two mediators for provocative behaviors: verbal abuse and physical assault. (1) The authors do not find much support for the hypothesis that inmates with mental disorders, physical disabilities, or small physical size are stigmatized as being vulnerable. Inmates with symptoms of delusions are the only exception. (2) The authors do not find support for the hypothesis that inmates with mental disorders are labeled as being threatening, but they do find support for inmates with larger physical size. (3) The authors find support for the hypothesis that provocation contributes to the victimization of inmates with some types of mental disorders: personality disorders and paranoid thoughts. The victimization of inmates with other mental disorders is not explained by provocation, however. (4) The authors find tentative support for the hypothesis of reversed causality between some types of physical disabilities and serious violent victimization: Paralysis and brain injuries are probably consequences of serious violent victimization while in prison. In contrast, arthritis is a risk factor for victimization.

Amisulpride Augmentation of Clozapine in Refractory Schizophrenia

Back to table of contents Previous article Next article LettersFull AccessAmisulpride Augmentation of Clozapine in Refractory SchizophreniaHsiu-Wen Chiu, M.D., Yu-Chi Ku, M.D., Tien-Chun Li, M.D., and Hsin-Te Huang, M.D.Hsiu-Wen ChiuSearch for more papers by this author, M.D., Yu-Chi KuSearch for more papers by this author, M.D., Tien-Chun LiSearch for more papers by this author, M.D., and Hsin-Te HuangSearch for more papers by this author, M.D.Published Online:1 Jul 2011AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Clozapine, an atypical antipsychotic drug, is the first-choice medication for treatment-refractory schizophrenia. However, clozapine can cause some adverse effects, such as agranulocytosis and sialorrhea, making it difficult for patients to continue with treatment. Otherwise, treatment options for patients who are resistant to clozapine are extremely limited. Herein, the authors report the case of a patient with refractory schizophrenia treated by amisulpride augmentation of clozapine who got significant improvement not only in his positive and negative symptoms but also the side effect of salivation. This case report might provide an alternative treatment for refractory schizophrenia.Case ReportA 53-year-old man with chronic, refractory schizophrenia was hospitalized because of his symptoms of hostility, aggression, insomnia, delusions, and auditory hallucinations, despite his medication with clozapine 200 mg per day. His initial laboratory studies revealed no remarkable findings. Clozapine was titrated to 350 mg per day for marked psychotic symptoms, but it seemed to be only slightly effective. Meanwhile, he complained of salivation worsening and wanted to discontinue clozapine treatment because of this adverse effect. We then added amisulpride 600 mg per day for augmentation of clozapine. Interestingly, there was a significant improvement in his auditory hallucinations, delusions, conceptual disorganization, and on the positive and negative syndrome scale (PANSS). Also, the adverse effect of sialorrhea was improved during the following days and nights.DiscussionClozapine is used to treat severe schizophrenia symptoms in people who have not responded to or only partially responded to other antipsychotics. Sialorrhea is a common side effect leading to treatment noncompliance, occurring in about 31%–54% of patients receiving clozapine therapy.1 Amisulpride, an atypical antipsychotic, possesses a higher selective binding to the D2/D3 dopamine receptor and a minimal effect on other receptors.2 Clozapine produces moderate blocking of the D2 dopamine receptors, whereas amisulpride is a potent antagonist of D2 dopamine receptors. The efficacy of the combination may be due to the complementary receptor profile of the two drugs. In this report, amisulpride might be augmentative therapy for clozapine in patients who are not responsive to or only partially responsive to clozapine. Kreinin et al.3 reported a significant reduction in hypersalivation with addition of amisulpride to ongoing clozapine therapy. In our case, both daytime as well as nocturnal sialorrhea improved after the addition of amisulpride. However, the definite underlying mechanism is still unknown. In summary, our case suggested that amisulpride improve the antipsychotic effect of clozapine while improving the major adverse event of sialorrhea. Amisulpride augmentation of clozapine might be an optional approach to treatment-refractory schizophrenia.Department of Psychiatry, Beitou Armed Forces Hospital, 60, Xinmin Rd., Beitou Dist., Taipei 112, Taiwan.e-mail address: [email protected]com (Ms. Chiu), [email protected]com (Dr. Huang)1. Davydov L , Botts SR : Clozapine-induced hypersalivation. Ann Pharmacother 2000; 34:662–665Crossref, Medline, Google Scholar2. Natesan S , Reckless GE , Barlow KB , et al.: Amisulpride: the “atypical” atypical antipsychotic: comparison to haloperidol, risperidone, and clozapine. Schizophr Res 2008; 105(1–3):224–235Crossref, Medline, Google Scholar3. Kreinin A , Novitski D , Weizman A : Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study. Int Clin Psychopharmacol 2006; 21:99–103Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 23Issue 3 Summer 2011Pages E15-E15 Metrics PDF download History Published online 1 July 2011 Published in print 1 July 2011

Parental Burden Associated with Borderline Personality Disorder in Female Offspring

To identify aspects of parental burden associated with borderline personality disorder (BPD), an anonymous internet survey linked to BPD support websites was developed for parents to complete on their BPD offspring and unaffected siblings. The questions cover aspects of the child's life from pregnancy through young adulthood, and query about the impact of the child's BPD on six domains of the parent's life, including physical and emotional health, marriage, job, standard of living, social life, and career trajectory. Additionally, financial burden was assessed with questions pertaining to insurance and out-of pocket costs associated with the BPD disorder. BPD offspring were identified by meeting diagnostic criteria embedded within the survey and having been given a diagnosis of BPD by a professional at some point in their life. We report on 233 female offspring meeting strict criteria for BPD. Parents of daughters with BPD endorsed varying levels of impact on the six domains comprising burden with the largest impact on emotional health which was impacted in over 88% of the respondents. Over 50% of parents endorsed four or greater of the six burden items. Particular aspects of the offspring's BPD symptom profile correlated with intensity of parental burden included including problems in adolescence with acting out behavior (p < .000), property destruction (.003), delusional symptoms (.007), and hallucinatory symptoms (.008). A subgroup of respondents provided data on specific financial expenses. The average and median out-of-pocket expense was $60,087, and $10,000. Insurance costs totaled an average of $108,251 with a mean of $20,000. The average cost per year after diagnosis was $14,606 out-of-pocket and $45,573 billed to insurance. The median cost per year after diagnosis was $3,667 out-of-pocket, and $12,500 billed to insurance. After adjusting for household income, a female proband who had been raped incurred roughly $40,000 more in BPD-related costs, while a diagnosis of conduct disorder led to about $50,000 in additional costs. Parents of female offspring with BPD experience burden in multiple domains of their life and many have incurred substantial financial expense. Increasing awareness of co-morbid conditions in the BPD proband that significantly increase parental burden may be indicators for the provision of increased family support.

Schizophrénie à début précoce et agénésie partielle du corps calleux

We report a case of schizophrenia with partial agenesis of the corpus callosum in a 14-year-old girl. Diagnosis of schizophrenia was confirmed in the longitudinal follow-up and partial agenesis of the corpus callosum was found on brain MRI at the prodromal stage of disease. The prodromal symptom was progressive deterioration of social and academic adjustment in a context of non-specified psychotic disorder in the father. We found no abnormality in the development but a history of seizures that did not require specific treatment. Follow-up at 8 months showed an increase in negative symptoms and the onset of delusional symptoms and disorganization leading to the prescription of antipsychotic treatment. A review of the literature shows that agenesis of corpus callosum is the most reliable brain morphology abnormality in schizophrenia and is related to the neurodevelopmental and abnormal brain connectivity hypothesis in schizophrenia. Although this abnormality may be a marker of disease severity, our case report highlights the lack of longitudinal follow-up to allow the characterization of a specific outcome pattern of schizophrenic adolescents with partial agenesis of the corpus callosum.

Midbrain Activation During Pavlovian Conditioning and Delusional Symptoms in Schizophrenia

Recent theories have suggested that the inappropriate activation of limbic motivational systems in response to neutral stimuli may underlie the development of delusions in schizophrenia. To investigate the activation of the amygdala, midbrain, and ventral striatum during an aversive pavlovian conditioning task in patients with schizophrenia and healthy control participants using functional magnetic resonance imaging. Cross-sectional case-control functional neuroimaging study. Academic medical center. Twenty patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and 20 healthy control participants. Regional brain activation as assessed by functional magnetic resonance imaging blood oxygen level-dependent responses, and delusional symptom severity on the Positive and Negative Syndrome Scale. Patients with schizophrenia showed abnormal activation of the amygdala, midbrain, and ventral striatum during conditioning. Activation of the midbrain in response to neutral rather than aversive cues during conditioning was correlated with the severity of delusional symptoms in the patient group (corrected P = .04). Inappropriate activation of the midbrain in response to neutral stimuli during conditioning is associated with the severity of delusional symptoms in patients with schizophrenia.

The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition

The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition

Delusion of Cotard's Syndrome Successfully Treated with a Dopamine Agonist

Back to table of contents Previous article Next article LETTERFull AccessDelusion of Cotard’s Syndrome Successfully Treated with a Dopamine AgonistTomohisa Takahashi M.D.Masashi Nibuya M.D., Ph.D.Soichiro Nomura M.D., Ph.D.,Tomohisa Takahashi M.D.Search for more papers by this authorMasashi Nibuya M.D., Ph.D.Search for more papers by this authorSoichiro Nomura M.D., Ph.D.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e27AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Cotard’s syndrome, which is characterized by delusions of negation and increased anxiety accompanied by severe depressive symptoms, is reported to be resistant to antidepressants. Although delusions are treated with neuroleptics, Cotard’s syndrome responds poorly to dopamine antagonists. Several case studies have recommended that ECT most effectively ameliorates Cotard’s syndrome. 1 In this article, we describe the case of a patient with Cotard’s syndrome that was successfully treated with dopamine augmentation therapy for treatment-resistant depression. 2Case ReportA 58-year-old woman had been diagnosed with recurrent major depression and treated with antidepressants for about 25 years. No hypomanic-to-manic episode or depressive episode with psychotic features had been observed. Because of irregular oral administration of psychotropic drugs during the remission period, she experienced a relapse of depression twice in 5 years. The present episode was that of severe depression with psychotic features. Her delusional complaints were “I cannot eat any food, because my mouth does not salivate. I would never be able to get out of the hospital. I have no money to pay for my hospital stay. My mother is dead. My mind is completely blank with no thoughts, and there seems to be no brain in my head. I would have to stay bare all my life, because I have no clothes. I cannot sleep for a moment. I cannot talk because I have lost all my words.” Suicidal ideation, anxiety, loss of interest and pleasure, agitation, weight loss of 6 kg in 2 months, and depressive mood were observed. Paroxetine (up to 40 mg/day) was administered for 36 days from the time of admission, but no improvement was observed. For augmentation for treatment-resistant depression, pramipexole (up to 0.75 mg/day) was administered as a dopamine agonist in addition to paroxetine. The depressive symptoms, including appetite loss and agitation, improved 6–9 days after the augmentation, and no worsening of delusional symptoms was observed. The delusions disappeared at 14 days after the initiation of the augmentation. No relapse of delusion and depression was observed during the 8-week follow-up period. Paroxetine, 20 mg/day, and pramipexole, 0.75 mg/day, were administered at the time of discharge.Discussion This is the second case report indicating the effectiveness of dopamine agonist augmentation therapy for treating delusions of Cotard’s syndrome. Although bromocriptine was added to clomipramine in the previous study, 3 pramipexole was chosen as the dopamine agonist 4 to avoid fibrotic cardiac valvulopathy by ergot alkaloids. The effectiveness of additional neuroleptics for the treatment of psychotic depression has also been reported. 5 Few studies, however, have addressed the effectiveness of neuroleptics in the treatment of Cotard’s syndrome. For over a hundred years, Cotard’s syndrome has survived as a distinct psychopathological diagnostic entity. The present case indicated the existence of a group of patients with psychotic depression whose depression needs to be treated first, even by enhancing dopamine activities. Considering the fact that ECT is generally ineffective in treating delusions, this case indicated the importance of treating severe depression first in Cotard’s syndrome. Department of Psychiatry, National Defense Medical College, Tokorozawa, Japan

Delusion of Cotard’s Syndrome Successfully Treated with a Dopamine Agonist

Back to table of contents Previous article Next article LETTERFull AccessDelusion of Cotard’s Syndrome Successfully Treated with a Dopamine AgonistTomohisa Takahashi M.D.Masashi Nibuya M.D., Ph.D.Soichiro Nomura M.D., Ph.D.,Tomohisa Takahashi M.D.Search for more papers by this authorMasashi Nibuya M.D., Ph.D.Search for more papers by this authorSoichiro Nomura M.D., Ph.D.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e27AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Cotard’s syndrome, which is characterized by delusions of negation and increased anxiety accompanied by severe depressive symptoms, is reported to be resistant to antidepressants. Although delusions are treated with neuroleptics, Cotard’s syndrome responds poorly to dopamine antagonists. Several case studies have recommended that ECT most effectively ameliorates Cotard’s syndrome. 1 In this article, we describe the case of a patient with Cotard’s syndrome that was successfully treated with dopamine augmentation therapy for treatment-resistant depression. 2Case ReportA 58-year-old woman had been diagnosed with recurrent major depression and treated with antidepressants for about 25 years. No hypomanic-to-manic episode or depressive episode with psychotic features had been observed. Because of irregular oral administration of psychotropic drugs during the remission period, she experienced a relapse of depression twice in 5 years. The present episode was that of severe depression with psychotic features. Her delusional complaints were “I cannot eat any food, because my mouth does not salivate. I would never be able to get out of the hospital. I have no money to pay for my hospital stay. My mother is dead. My mind is completely blank with no thoughts, and there seems to be no brain in my head. I would have to stay bare all my life, because I have no clothes. I cannot sleep for a moment. I cannot talk because I have lost all my words.” Suicidal ideation, anxiety, loss of interest and pleasure, agitation, weight loss of 6 kg in 2 months, and depressive mood were observed. Paroxetine (up to 40 mg/day) was administered for 36 days from the time of admission, but no improvement was observed. For augmentation for treatment-resistant depression, pramipexole (up to 0.75 mg/day) was administered as a dopamine agonist in addition to paroxetine. The depressive symptoms, including appetite loss and agitation, improved 6–9 days after the augmentation, and no worsening of delusional symptoms was observed. The delusions disappeared at 14 days after the initiation of the augmentation. No relapse of delusion and depression was observed during the 8-week follow-up period. Paroxetine, 20 mg/day, and pramipexole, 0.75 mg/day, were administered at the time of discharge.Discussion This is the second case report indicating the effectiveness of dopamine agonist augmentation therapy for treating delusions of Cotard’s syndrome. Although bromocriptine was added to clomipramine in the previous study, 3 pramipexole was chosen as the dopamine agonist 4 to avoid fibrotic cardiac valvulopathy by ergot alkaloids. The effectiveness of additional neuroleptics for the treatment of psychotic depression has also been reported. 5 Few studies, however, have addressed the effectiveness of neuroleptics in the treatment of Cotard’s syndrome. For over a hundred years, Cotard’s syndrome has survived as a distinct psychopathological diagnostic entity. The present case indicated the existence of a group of patients with psychotic depression whose depression needs to be treated first, even by enhancing dopamine activities. Considering the fact that ECT is generally ineffective in treating delusions, this case indicated the importance of treating severe depression first in Cotard’s syndrome. Department of Psychiatry, National Defense Medical College, Tokorozawa, Japan

SCHIZOPHRENIA TRAVELER TYPE

DSM-IV-TR classifies schizophrenia in several types: disorganized, paranoid, catatonic, undifferentiated and residual.1 This classification is focused on the symptoms one could identify during an interview and puts less emphasis on the insight domain and discrepancies between the perception abnormalities when compared with abnormalities in thinking with and without substrate in reality. The DSM V does not include any types of schizophrenia.2 I suggest that it is important to take a closer look at an empirical observed phenomenon: traveler schizophrenia population. There are several ways to look at this phenomenon: i) there could be differences in insight earlier in the illness, partially leading to same discrepancies described in duration of untreated psychosis studies which in turn could lead to a worse or different prognosis; ii) the illness have a different course likely as result of excess in erroneous thinking, mainly a-posteriori and also apriori constructs that lead to changes in behavior, such as extensive travel patterns. In a study,3 extensive travel history (more than two states), after the schizophrenia diagnosis, was documented in 28 of 74 patients with schizophrenia. Only nine patients from the 28 with an extensive travel history settled in this area, in the 4 year follow up, as documented in their medical records and by the repeated visits in the following years. The remaining 19 patients had an average of 1.2 visits to the hospital and for those patients that had more than one visit this occurred within 2 months of the initial contact. Six of the patients that remained in the area were offered boarding home services for an average of 11 months. In another study,4 we compared the clinical course of 17 patients with the first time diagnosis of schizophrenia to 50 patients admitted with a preexisting diagnosis of schizophrenia made an average of 8 years earlier. 53% of the control group moved from a different state before being treated at this facility. Only 14.2% of the study group came from other states. The frequent traveling was often secondary to persecutory, religious or grandiose delusions rather than in response to auditory hallucinations. Patients with an established diagnosis of schizophrenia demonstrated an increased travel pattern, often connected with their delusional symptoms, when compared with patients with a recent diagnosis of schizophrenia. This can introduce bias as the patients with schizophrenia with an increased traveling behavior are less likely to be included in longer term studies due to their travel pattern and exclusion criteria of the studies. However, when they are included, they are poled with the rest of the group to which they enrolled. Also, this lead to lack of investigations to determine if they deserve a separate classification and is suggested that they have a worse prognosis. The removal of types of schizophrenia from the DSM V should not deter physicians from considering the prognostic value of individual presentation.

The jumping to conclusions bias in delusions: Specificity and changeability.

There are indications that a jumping to conclusions bias (JTC) plays a role in the formation and maintenance of delusions and should be targeted in therapy. However, it is unclear whether (a) JTC is uniquely associated with delusions or simply an epiphenomenon of schizophrenia or impaired intellectual functioning and (b) it can be changed by varying task demands, motivational factors, or feedback. Seventy-one patients with schizophrenia spectrum disorders and either acute or remitted delusions and 68 healthy controls were included. Patients were assessed with self- and observer-rated symptom measures. All participants were assessed for intellectual ability and performed the classic beads task with a ratio of 80:20. They were then presented with task variations that involved increasing the difficulty of the ratio to 60:40, introducing a rule for which correct decisions were rewarded by monetary gains and false decisions led to financial losses, and providing feedback on the accuracy of the previous decisions. Participants with current delusional symptoms took fewer draws to decision (DTD) than did those in remission and healthy controls. DTD were associated with observer-rated delusions, but controlling for negative symptoms or intelligence rendered this association insignificant. DTD increased after the difficulty of the task increased and after feedback. The study demonstrated that JTC is linked to delusions but that this association is not unique. Patients with delusions are principally able to adapt their decisions to altered conditions but still decide relatively quickly even when decisions have negative consequences. These difficulties might stem in part from impaired intellectual functioning.

Apport d’une démarche électroclinique dans le diagnostic de l’épilepsie chez une population de sujets âgés confus

Delusion symptoms often occur in old people; epilepsy is one of the main reasons behind these acute episodes. Current guidelines and recommendations from the Academy of Medicine have proposed a double clinical and electroencephalographic approach. Recently, a working group of French experts has issued an electro-clinical scale. The aim of our study was to compare the usual approach with the new one based on the electro-clinical score. All EEG requests performed since December 2008 in Bretonneau Hospital for elderly people aged over 75 years for delusion syndromes were retained for this study. One hundred and fifteen old patients from a geriatric-hospital (age 83.5+/-6.06 years) were included in this protocol. The classical diagnostic process yielded the diagnosis of epilepsy for 50 subjects. The electro-clinical scale confirmed the diagnosis of epilepsy in 30 patients and ruled it out in 29 patients. This study underscores the importance of evidence-based medicine for the diagnosis of epilepsy in old people and points out the underuse of the new technical tool, EEG-monitoring, for the management of these patients.

P03-146 - The subjective dysexecutive syndrome in schizophrenia

ObjectivesThe dysexecutive syndrome is present in half of the schizophrenia patients and is highly dependent on the dopamine functioning. We hypothesize that early and mild dysexecutive syndrome in schizophrenia is mainly subjective. The objective is to study the subjective manifestation of the dysexecutive syndrome and its relationship with other symptoms of schizophrenia.MethodsOne cross-sectional study was conducted on 60 schizophrenia out-patients (43 male; average age: 38.9 years, SD 9.4). The diagnosis were: paranoid schizophrenia 26.7%, schizoaffective disorder 25.0%, residual schizophrenia 21.7%, other schizophrenia subtypes 26.6%. The dysexecutive syndrome was assessed by DEX Scale (self-applied and applied by one external observer). Using PANSS and one addiction composite score (ACS) it was defined five symptom dimensions: negative (N1, N2, N3, N4, N6), disorganized (P2, P4, N5, N7), positive and depressive (P1, P3, G6), hostility (P5, P6, P7) and addictive (ACS). Basic symptoms were studied with FCQ-III. All the scores were transformed in to Z values. Correlations between DEX and the clinical dimensions were studied using Spearman's Rho coefficient.ResultsDysexecutive syndrome is associated with basic symptoms (self-applied: r = 0.83, p&lt; 0.001; external observer: r = 0.54, p &lt; 0.001), disorganization (external observer: r = 0.46, p = 0.001), positive and depressive symptoms (self-applied: r = 0.54, p&lt; 0.001; external observer: r = 0.44, p = 0.001) and addiction (self-applied: r = 0.35, p&lt; 0.01).ConclusionsBasic, hallucinatory, delusional and depressive symptoms in schizophrenia, as well as the disorganized dimension, could reflect the subjective experience of one dysexecutive dysfunction.

Consequences of chronic ketamine self‐administration upon neurocognitive function and psychological wellbeing: a 1‐year longitudinal study

'Recreational' use of ketamine is spreading rapidly among young people. In healthy individuals an acute dose of the N-methyl D-aspartate (NMDA) receptor antagonist ketamine induces marked psychosis-like effects and cognitive impairments, but little is known about the long-term effects of the drug. To evaluate the long-term neuropsychiatric or cognitive consequences. A total of 150 individuals were assessed, 30 in each of five groups: frequent ketamine users, infrequent ketamine users, abstinent users, polydrug controls and non-users of illicit drugs. Twelve months later, 80% of these individuals were re-tested. Cognitive deficits were mainly observed only in frequent users. In this group, increasing ketamine use over the year was correlated with decreasing performance on spatial working memory and pattern recognition memory tasks. Assessments of psychological wellbeing showed greater dissociative symptoms in frequent users and a dose-response effect on delusional symptoms, with frequent users scoring higher than infrequent, abstinent users and non-users, respectively. Both frequent and abstinent using groups showed increased depression scores over the 12 months. These findings imply that heavy use of ketamine is harmful to aspects of both cognitive function and psychological wellbeing. Health education campaigns need to raise awareness among young people and clinicians about these negative consequences of ketamine use.

Brain MRI May Pinpoint Those at High Psychosis Risk

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessBrain MRI May Pinpoint Those at High Psychosis RiskMark MoranMark MoranSearch for more papers by this authorPublished Online:2 Oct 2009https://doi.org/10.1176/pn.44.19.0027A region of the hippocampus appears to be uniquely activated during functional magnetic resonance imaging (MRI) among individuals who later go on to develop psychosis. Using cerebral blood volume mapping, the region—known as the CA1 subfield of the hippocampus—was found to be hyperactive among those individuals who were at high risk of psychosis and who later developed a first-episode psychotic disorder. Moreover, hyperactivity in the CA1 subfield also tracked positively with increasing severity of delusional symptoms and with avolition and social withdrawal—two “negative” symptoms associated with worsening outcome.The report appeared in the September Archives of General Psychiatry. The lead author is Scott Small, M.D., the Herbert Irving Associate Professor of Neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center.“Functional imaging can tell you where in the brain something is happening, not what is happening,” said first author Scott Schobel, M.D., an assistant professor of clinical psychiatry at Columbia University College of Physicians and Surgeons, in an interview with Psychiatric News. “But what this hyperactive state strongly suggests is an increase in metabolism that is plausibly linked to dysfunction in the glutamate system.”Though far from conclusive, the finding points to the possibility in the future of a screen for determining which high-risk (or“ prodromal”) patients are likely to go on to develop a first-episode psychosis. Using clinical criteria today, clinicians can reliably predict approximately 50 percent to 60 percent of high-risk individuals who will go on to develop a psychotic disorder.“The idea would be that one could use brain imaging as a snapshot of illness severity within the CA1 subfield,” Schobel said. “It could potentially be used to identify those within the high-risk population who have abnormal activity above a certain threshold to selectively target this group with clinical treatments aimed at preventing illness progression, including potentially a glutamate-modulating therapy and/or cognitive therapy.”Schobel said the study relied on a new high-resolution MRI technique developed by Small. In the study, cerebral blood volume mapping with the new technique was used on 18 patients with schizophrenia, 18 age-matched, healthy control subjects, and 18 individuals with prodromal psychosis.In a first between-group analysis comparing patients with schizophrenia and controls, abnormal cerebral blood volume (CBV) was found in the CA1 subfield and in the orbitofrontal cortex; abnormal decreases in CBV were found in the dorsolateral prefrontal cortex. In a second longitudinal analysis, abnormal CBV increases in the CA1 subfield predicted clinical progression to psychosis among the 18 prodromal individuals.Finally, a third analysis showed that CBV levels in the CA1 subfield correlated with severity of symptoms of psychosis.“Progressive hyperfunctionality of the CA1 subfield was positively associated with worsening delusional severity,” Schobel told Psychiatric News. “That was also found in the groups when you looked at them separately—in both [the prodromal and schizophrenia] groups, worsening delusions were associated with greater hyperactivity.“Moreover, in the prodromal group, hyperactivity also tracked positively with avolition and social withdrawal,” Schobel said. The latter are negative symptoms associated with worsening outcome.The findings are an important first step in the effort to prevent schizophrenia or to more rapidly treat those who do experience a first-episode of psychosis.In a statement released by Columbia University announcing the study, Jeffrey Lieberman, M.D., who is leading a new effort at the National Institute of Mental Health to develop optimal treatments for first-episode psychosis, cited the benefits of early intervention.“Research has shown that early intervention and treatment can prevent the debilitating effects of schizophrenia by dramatically slowing progression, reducing mortality and disability, and increasing recovery of one of mankind's most costly mental disorders,” said Lieberman, who is Lawrence E. Kolb Professor and chair of the Department of Psychiatry at Columbia University and director of the New York State Psychiatric Institute.An abstract of “Differential Targeting of the CA1 Subfield of the Hippocampal Formation by Schizophrenia and Related Disorders” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/66/9/938>.▪ ISSUES NewArchived

Symptoms of delusion: the effects of discontinuation of low‐dose venlafaxine

Objective:We report a patient who experienced delusional symptoms during gradual discontinuation of low-dose venlafaxine and required antipsychotic treatment.Method:Case report.Results:A 31-year-old woman with major depression had been treated abroad with venlafaxine before returning to Japan. Since venlafaxine is unavailable here, we supplemented her regular venlafaxine dosage of 37.5 mg/day with clomipramine 20 mg/day. After 5 weeks we reduced venlafaxine to 18.75 mg/day and uptitrated clomipramine to 40 mg/day. Four days later she developed delusions of reference, palpitations and nausea. Clomipramine was increased to 60 mg/day, and her symptoms subsided. Eight weeks later her supply of venlafaxine ran out, and within 4 days her condition deteriorated into more severe symptoms that required 4 months’ antipsychotic treatment.Conclusion:We speculate that her symptoms were discontinuation syndrome, including psychotic symptoms and physical symptoms, caused by (i) venlafaxine-clomipramine interaction and/or (ii) the serotonin reuptake inhibitor-like effects of low-dose venlafaxine.

„A chemical love story“: Treatment of a gamma-butyrolacton (GBL)-dependent chemistry student with diazepam – a case report

We describe the case of a 25 year old chemistry student and highly experienced drug user with a GBL dependency. He developed his addiction in a group of chemistry students indulging in an experimental and recreational use of various substances at the local chemistry department. The patient was admitted to our in-patient detoxification unit after a 3-year history of increasing dependence on GBL. Before admission he predominately used GBL. His use had escalated to the point where he was taking 2ml GBL every hour, waking up at night to take it. The daily use reached up to 50ml without being sufficient to suppress withdrawal symptoms consisting of agitation, severe tremor, sweating and massive insomnia. To cope with these symptoms, repeated application of diazepam was necessary. In the first 24h after admission he received several hundreds mg diazepam with persisting insomnia. In the course of treatment he also needed haloperidol because of delusional symptoms. Under high dose diazepam treatment his symptoms gradually improved and by the third day of hospitalization delusions, tremor and sweating slowly resolved, while the insomnia persisted. The patient was commenced on a diazepam reducing regime 1 week after admission from 30mg over 10 days. Further detoxification was uneventful and after suspension of the diazepam the symptoms did not recur. He was also treated for depression and was subsequently discharged in a stable condition 11 weeks after admission.

Delusion Symptoms and Response to Antipsychotic Treatment are Associated with the 5-HT2A Receptor Polymorphism (102T/C) in Alzheimer's Disease: A 3-Year Follow-up Longitudinal Study

Although the etiology of psychotic symptoms (hallucinations and delusions) in Alzheimer's disease is still not known, alterations in serotonergic neurotransmission have been proposed. In a 3-year follow-up study, we evaluated the association of serotonin (5-HT) receptor 5-HT2a 102T/C polymorphism (allelic variants CC, CT and TT) with psychotic symptom severity and response to treatment with atypical antipsychotics (risperidone, olanzapine and quietapine) in 80 patients with a diagnosis of probable Alzheimer's disease. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity (FxS) of psychotic and other behavioral symptoms. There was a significant difference in the NPI FxS delusion score among the three variants of the 5-HT2a 102T/C polymorphism, with patients carrying the TT genotype the most delusional during the follow-up period. In particular, NPI FxS delusion score was higher in TT than in CC genotype at year 2. Moreover, patients with delusion symptoms carrying the CT and TT genotypes were resistant to the treatment with antipsychotic drugs. Thus our study, although at preliminary level, suggests that the presence of T allele of the 102T/C polymorphism in patients with Alzheimer's disease is associated with both increased presence of delusion symptoms and treatment-resistance to second generation antipsychotic drugs.

Mental illness, nativity, gender and labor supply.

We analyzed the impacts of nativity and mental health (MH) on work by gender for non-elderly adults using the 2002 National Survey on Drug Use and Health. We employed two indicators of MH - the K6 scale of Mental Illness (MI) and an indicator for symptoms of Mania or Delusions (M/D). Instrumental variable (IV) models used measures of social support as instruments for MI. Unadjusted work rates were higher for immigrants (vs US-born adults). Regressions show that MI is associated with lower rates of work among US-born males but not immigrant males and females; M/D is associated lower rates of work among US-born males and females, and among immigrant males. Results did not change using IV models for MI. Most persons with MI work, yet symptom severity reduces labor supply among natives especially. Immigrants' labor supply is less affected by MI.

5-HT2A gene variants influence specific and different aspects of antidepressant response in Japanese and Italian mood disorder patients

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants.