| 1. |
- Brundin, Lena, et al.
(author)
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Cocaine and amphetamine regulated transcript (CART) in suicide attempters.
- 2008
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In: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 158:2, s. 117-122
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Journal article (peer-reviewed)abstract
- Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed in brain regions thought to regulate anxiety levels, depression, addiction and energy homeostasis. Individuals with a CART mutation display increased anxiety and depression. Severe anxiety is a core phenomenon of suicidality. We therefore studied levels of CART in the cerebrospinal fluid (CSF) of 98 patients with different psychiatric diagnoses, shortly after a suicide attempt. We also investigated the relationship between CSF-CART and relevant psychiatric symptoms. CART levels were determined using a radioimmunoassay and the psychiatric symptoms rated in structured interviews using the Comprehensive Psychopathological Rating Scale (CPRS) and the Karolinska Scales of Personality (KSP). No differences in CSF-CART were found between the diagnostic groups or controls. However, lower CART levels were associated with a higher degree of concentration difficulties. No significant association was found between CART levels and other psychiatric symptoms. CSF-CART correlated significantly with CSF-levels of orexin, but not with corticotrophin releasing factor (CRF). Further studies on the role of CART in psychiatric diseases where concentration difficulties are prominent, such as attention deficit disorder, are warranted.
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| 2. |
- Brundin, Lena, et al.
(author)
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Increased orexin levels in the cerebrospinal fluid the first year after a suicide attempt.
- 2009
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; Jun 2, s. 179-182
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Journal article (peer-reviewed)abstract
- BACKGROUND: The orexins (hypocretins) and cocaine and amphetamine regulated transcript (CART) are hypothalamic peptides involved in the regulation of sleep and appetite. We have previously shown that levels of both orexin-A and CART in the cerebrospinal fluid (CSF) are related to specific psychiatric symptoms. METHODS: Ten patients took part in lumbar punctures and psychiatric evaluations in conjunction to a suicide attempt and after 6 and 12 months. We measured CSF-orexin and CART using radioimmunoassays. RESULTS: Mean CSF-orexin was significantly higher at the first and second follow-up than at the suicide attempt. In contrast, mean CSF-CART did not differ over time. Total SUAS scores, as well as ratings of CPRS item 66 (global illness) were significantly lower at follow-up. At one year, there was a significant negative correlation between the change in CSF-orexin and the change in total SUAS score. LIMITATIONS: The number of patients who participated was relatively small. CONCLUSIONS: Our results support the hypothesis that orexin is involved in psychiatric symptomatology.
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| 3. |
- Brundin, Lena, et al.
(author)
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Orexin and psychiatric symptoms in suicide attempters.
- 2007
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 100:1-3, s. 259-263
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Journal article (peer-reviewed)abstract
- BACKGROUND: The orexins (hypocretins) are recently discovered hypothalamic peptides that are involved in the regulation of sleep, appetite and state of arousal. In the present study, we investigated the relationship between cerebrospinal fluid (CSF) orexin and specific psychiatric symptoms in suicidal patients. METHODS: A total of 101 patients were enrolled in the study shortly after a suicide attempt. All patients underwent a lumbar puncture after a wash-out period during which they did not receive any antipsychotic or antidepressive medication. Structured interviews were performed using the Comprehensive Psychopathological Rating Scale (CPRS). CSF-orexin-A was measured and correlated with ratings of psychiatric symptoms. RESULTS: There were significant and negative correlations between CSF-orexin and the symptoms lassitude (difficulty to initiate activities) and slowness of movement, as well as the ratings of global illness (p<0.005 for all three items, Spearman's rho). LIMITATIONS: Correlation analysis is an indirect method of investigation and does not demonstrate causal relationships. CONCLUSION: Low CSF-orexin levels are related to pronounced symptoms of inertia and reduced motor activity in suicidal patients. Interestingly, the lower the orexin levels, the higher were ratings of overall illness, as observed by a specialist in psychiatry. Our results suggest that reduced orexin levels are involved in the etiology of specific psychiatric symptoms.
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| 4. |
- Brundin, Lena, et al.
(author)
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Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder.
- 2007
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In: European Neuropsychopharmacology. - : Elsevier BV. - 1873-7862 .- 0924-977X. ; 17:Mar 6, s. 573-579
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Journal article (peer-reviewed)abstract
- Orexins are neuropeptides selectively expressed in a small number of neurons in the lateral–posterior hypothalamus. We measured orexin-A in the cerebrospinal fluid (CSF) of 66 patients with major depressive disorder (MDD), dysthymia and adjustment disorder after a suicide attempt. Blood samples confirmed that the patients were free from antidepressive and neuroleptic medication at the time of the lumbar punctures. CSF levels of orexin-A were significantly lower in patients with MDD than in patients with adjustment disorder and dysthymia. Orexin correlated significantly with CSF levels of somatostatin, delta sleep inducing peptide-like immunoreactivity (DSIP-LI) and corticotrophin releasing factor (CRF), but not with leptin or vasopressin. Plasma levels of thyroid-stimulating hormone (TSH) were not reduced in MDD patients, and did not correlate with CSF-orexin. Our results suggest that suicidal patients with MDD have distinct neurobiological features, involving compromised levels of hypothalamic peptides regulating the state of arousal.
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| 5. |
- Schultz, Kristofer, et al.
(author)
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Transthyretin in cerebrospinal fluid from suicide attempters.
- 2008
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 109:1-2, s. 205-208
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Journal article (peer-reviewed)abstract
- BACKGROUND: Earlier studies have found that transthyretin (TTR) is reduced in cerebrospinal fluid (CSF) from patients with major depressive disorder and that levels correlate negatively with suicidal ideation. The purpose of this study was to examine CSF-TTR in a cohort of suicide attempters with different psychiatric diagnoses and to further assess the relationship between CSF-TTR and suicidal behaviour as well as psychiatric symptoms. METHODS: TTR was measured using enzyme-enhanced Mancini. Diagnostics were performed with the Diagnostic and Statistical Manual of Mental Disorders. Psychiatric symptoms and suicidal behaviour were rated using the Comprehensive Psychopathological Rating Scale (CPRS), the Suicide Assessment Scale and the Suicidal Intent Scale. RESULTS: We found no significant difference in CSF-TTR levels between groups of different psychiatric diagnoses and controls. CSF-TTR correlated negatively to the CPRS item 17, "failing memory". No significant correlations between CSF-TTR and suicidal behaviour or suicide intent were found. LIMITATIONS: Correlation analysis is an indirect method of investigation and does not demonstrate causal relationships. CONCLUSIONS: We conclude that CSF-TTR is unlikely to be relevant for suicidal behaviour and that further studies in non-suicidal psychiatric patients are needed before a role of CSF-TTR in depression can be established.
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