Biology of depression: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
→‎top: Wikilink.
m Added 12 dois to journal cites using AWB (10094)
Line 54: Line 54:


===Subgenual cingulate===
===Subgenual cingulate===
Recent studies have shown that [[Subgenual cingulate|Brodmann area 25]], also known as [[Subgenual cingulate]] is metabolically overactive in [[treatment-resistant depression]].<ref>{{cite journal | author = Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA |date=Oct 2000 | title = Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response | url = | journal = Biol Psychiatry | volume = 48 | issue = 8| pages = 830–43 }}</ref> This region is extremely rich in [[serotonin transporter]]s and is considered as a governor for a vast network involving areas like [[hypothalamus]] and [[brain stem]], which influences changes in appetite and sleep; the [[amygdala]] and [[Insular cortex|insula]], which affect the mood and anxiety; the [[hippocampus]], which plays an important role in memory formation; and some parts of the [[frontal cortex]] responsible for self-esteem.<ref>Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 576-578). United States of America: Pearson.</ref><ref name="sciam1">"[http://www.scientificamerican.com/article.cfm?id=faulty-circuits Faulty Circuits]", ''Scientific American'', April 2010</ref> Thus disturbances in this area or a smaller than normal size of this area contributes to depression. Deep Brain Stimulations of this area have been successful in reducing its elevated activity and thus curing depression in patients that could not be cured by anti-depressants.<ref>{{cite journal | author = Mayberg Helen S., Lozano Andres M., Voon Valerie, McNeely Heather E., Seminowicz David, Hamani Clement, Schwalb Jason M., Kennedy Sidney H. | year = 2005 | title = Deep Brain Stimulation for Treatment-Resistant Depression . | url = http://www.cell.com/neuron/abstract/S0896-6273(05)00156-X | journal = Neuron | volume = 45 | issue = | pages = 651–660 }}</ref>
Recent studies have shown that [[Subgenual cingulate|Brodmann area 25]], also known as [[Subgenual cingulate]] is metabolically overactive in [[treatment-resistant depression]].<ref>{{cite journal | author = Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA |date=Oct 2000 | title = Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response | url = | journal = Biol Psychiatry | volume = 48 | issue = 8| pages = 830–43 | doi=10.1016/s0006-3223(00)01036-2}}</ref> This region is extremely rich in [[serotonin transporter]]s and is considered as a governor for a vast network involving areas like [[hypothalamus]] and [[brain stem]], which influences changes in appetite and sleep; the [[amygdala]] and [[Insular cortex|insula]], which affect the mood and anxiety; the [[hippocampus]], which plays an important role in memory formation; and some parts of the [[frontal cortex]] responsible for self-esteem.<ref>Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 576-578). United States of America: Pearson.</ref><ref name="sciam1">"[http://www.scientificamerican.com/article.cfm?id=faulty-circuits Faulty Circuits]", ''Scientific American'', April 2010</ref> Thus disturbances in this area or a smaller than normal size of this area contributes to depression. Deep Brain Stimulations of this area have been successful in reducing its elevated activity and thus curing depression in patients that could not be cured by anti-depressants.<ref>{{cite journal | author = Mayberg Helen S., Lozano Andres M., Voon Valerie, McNeely Heather E., Seminowicz David, Hamani Clement, Schwalb Jason M., Kennedy Sidney H. | year = 2005 | title = Deep Brain Stimulation for Treatment-Resistant Depression . | url = http://www.cell.com/neuron/abstract/S0896-6273(05)00156-X | journal = Neuron | volume = 45 | issue = | pages = 651–660 | doi=10.1016/j.neuron.2005.02.014}}</ref>


===Hypothalamic-pituitary-adrenal (HPA) axis===
===Hypothalamic-pituitary-adrenal (HPA) axis===
Line 60: Line 60:


===Ventricles===
===Ventricles===
Multiple studies have found evidence of ventricular enlargement in people who have depression, particularly enlargement of the [[third ventricle]].<ref>{{Cite journal|first1=C.A.|last1=Hendrie|first2=A.R.|last2=Pickles|title=Depression as an evolutionary adaptation: Implications for the development of preclinical models|url=http://www.academia.edu/1145742/Depression_as_an_evolutionary_adaptation_Implications_for_the_development_of_preclinical_models|journal=Medical Hypotheses|year=2009|volume=72|pages=342–347|accessdate=September 25, 2013}}</ref><ref>{{Cite journal|first1=C.A.|last1=Hendrie|first2=A.R.|last2=Pickles|title=Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle|url=http://www.academia.edu/1145735/Depression_An_Evolutionary_Adaptation_Organised_Around_the_Third_Ventricle|journal=Medical Hypotheses|year=2010|volume=74|pages=735–740|accessdate=September 25, 2013}}</ref><ref>{{Cite journal|first=Yvette|last=Sheline|title=Neuroimaging studies of mood disorder effects on the brain|url=http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2803%2900347-0/abstract|journal=Biological Psychiatry|volume=54|pages=338–352|date=August 2003|accessdate=September 25, 2013}}</ref> These observations are interpreted as indicating loss of neural tissue in brain regions adjacent to the enlarged ventricle, leading to suggestions that [[cytokine]]s and related mediators of [[neurodegeneration]] may play a role in giving rise to the disease.<ref>{{Cite journal|first1=Husseini K.|last1=Manji|first2=Jorge A.|last2=Quiroz|first3=Jonathan|last3=Sporn|first4=Jennifer L.|last4=Payne|first5=Kirk|last5=Denicoff|first6=Neil A.|last6=Gray|first7=Carlos A.|last7=Zarate Jr.|first8=Dennis S.|last8=Charney|title=Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression|url=http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2803%2900117-3/abstract|volume=53|pages=707–742|date=April 2003|accessdate=September 25, 2013}}</ref><ref>Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. ''Biological Psychiatry'', 65(9), 732–741.</ref><ref>Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. ''Trends in Immunology'', 27(1), 24–31.</ref>
Multiple studies have found evidence of ventricular enlargement in people who have depression, particularly enlargement of the [[third ventricle]].<ref>{{Cite journal|first1=C.A.|last1=Hendrie|first2=A.R.|last2=Pickles|title=Depression as an evolutionary adaptation: Implications for the development of preclinical models|url=http://www.academia.edu/1145742/Depression_as_an_evolutionary_adaptation_Implications_for_the_development_of_preclinical_models|journal=Medical Hypotheses|year=2009|volume=72|pages=342–347|accessdate=September 25, 2013|doi=10.1016/j.mehy.2008.09.053}}</ref><ref>{{Cite journal|first1=C.A.|last1=Hendrie|first2=A.R.|last2=Pickles|title=Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle|url=http://www.academia.edu/1145735/Depression_An_Evolutionary_Adaptation_Organised_Around_the_Third_Ventricle|journal=Medical Hypotheses|year=2010|volume=74|pages=735–740|accessdate=September 25, 2013|doi=10.1016/j.mehy.2009.10.026}}</ref><ref>{{Cite journal|first=Yvette|last=Sheline|title=Neuroimaging studies of mood disorder effects on the brain|url=http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2803%2900347-0/abstract|journal=Biological Psychiatry|volume=54|pages=338–352|date=August 2003|accessdate=September 25, 2013|doi=10.1016/s0006-3223(03)00347-0}}</ref> These observations are interpreted as indicating loss of neural tissue in brain regions adjacent to the enlarged ventricle, leading to suggestions that [[cytokine]]s and related mediators of [[neurodegeneration]] may play a role in giving rise to the disease.<ref>{{Cite journal|first1=Husseini K.|last1=Manji|first2=Jorge A.|last2=Quiroz|first3=Jonathan|last3=Sporn|first4=Jennifer L.|last4=Payne|first5=Kirk|last5=Denicoff|first6=Neil A.|last6=Gray|first7=Carlos A.|last7=Zarate Jr.|first8=Dennis S.|last8=Charney|title=Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression|url=http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2803%2900117-3/abstract|volume=53|pages=707–742|date=April 2003|accessdate=September 25, 2013}}</ref><ref>Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. ''Biological Psychiatry'', 65(9), 732–741.</ref><ref>Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. ''Trends in Immunology'', 27(1), 24–31.</ref>


==Altered neuroplasticity==
==Altered neuroplasticity==
Line 75: Line 75:


===Central executive network ===
===Central executive network ===
The [[central executive network]] is made up of fronto-parietal regions, including dorsolateral prefrontal cortex and lateral posterior parietal cortex.<ref name="seeley2007">{{cite journal|last=Seeley|first=W.W|author2=et al.|title=Dissociable intrinsic connectivity networks for salience processing and executive control|journal=The Journal of Neuroscience|date=February 2007|volume=27}}</ref><ref>{{cite journal|last=Habas|first=C|author2=et al.|title=Distinct cerebellar contributions to intrinsic connectivity networks|journal=The Journal of Neuroscience|date=1 July 2009|volume=29}}</ref> This network is crucially involved in high level [[cognitive functions]] such as maintaining and using information in [[working memory]], problem solving, and decision making.<ref name="menon2011"/><ref>{{cite journal|last=Petrides|first=M|title=Lateral prefrontal cortex: architecture and functional organization|journal=Philosophical Transactions of the Royal Society B|year=2005|pages=781–795}}</ref><ref>{{cite journal|last=Koechlin|first=E|author2=Summerfield, C|title=An information theoretical approach to prefrontal executive function|journal=Trends in Cognitive Sciences|year=2007|pages=229–235}}</ref><ref>{{cite journal|last=Miller|first=E.K.|author2=Cohen, J.D.|title=An intergrative theory of prefrontal cortex function|journal=Annual Review of Neuroscience|year=2001|pages=167–202}}</ref><ref>{{cite journal|last=Muller|first=N.G.|author2=Knight, R.T.|title=The functional neuroanatomy of working memory: contributions of human brain lesion studies|journal=Neuroscience|year=2006|pages=51–58}}</ref> Deficiencies in this network are common in most major psychiatric and neurological disorders, including depression.<ref>{{cite journal|last=Woodward|first=N.D.|author2=et al.|title=Functional resting-state networks are differentially affected in schizophrenia|journal=Schizophrenia Research|year=2011}}</ref><ref>{{cite journal|last=Menon|first=Vinod|author2=et al.|title=Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms|journal=Neuroimage|year=2001|volume=13|pages=433–446}}</ref> Because this network is crucial for everyday life activities, those who are depressed can show impairment in basic activities like test taking and being decisive.<ref>{{cite journal|last=Levin|first=R.L.|author2=et al.|title=Cognitive deficits in depression and functional specificity of regional brain activity.|journal=Cognitive Therapy and Research|year=2007|volume=31|page=211|page=233}}</ref>
The [[central executive network]] is made up of fronto-parietal regions, including dorsolateral prefrontal cortex and lateral posterior parietal cortex.<ref name="seeley2007">{{cite journal|last=Seeley|first=W.W|author2=et al.|title=Dissociable intrinsic connectivity networks for salience processing and executive control|journal=The Journal of Neuroscience|date=February 2007|volume=27}}</ref><ref>{{cite journal|last=Habas|first=C|author2=et al.|title=Distinct cerebellar contributions to intrinsic connectivity networks|journal=The Journal of Neuroscience|date=1 July 2009|volume=29}}</ref> This network is crucially involved in high level [[cognitive functions]] such as maintaining and using information in [[working memory]], problem solving, and decision making.<ref name="menon2011"/><ref>{{cite journal|last=Petrides|first=M|title=Lateral prefrontal cortex: architecture and functional organization|journal=Philosophical Transactions of the Royal Society B|year=2005|pages=781–795}}</ref><ref>{{cite journal|last=Koechlin|first=E|author2=Summerfield, C|title=An information theoretical approach to prefrontal executive function|journal=Trends in Cognitive Sciences|year=2007|pages=229–235}}</ref><ref>{{cite journal|last=Miller|first=E.K.|author2=Cohen, J.D.|title=An intergrative theory of prefrontal cortex function|journal=Annual Review of Neuroscience|year=2001|pages=167–202}}</ref><ref>{{cite journal|last=Muller|first=N.G.|author2=Knight, R.T.|title=The functional neuroanatomy of working memory: contributions of human brain lesion studies|journal=Neuroscience|year=2006|pages=51–58}}</ref> Deficiencies in this network are common in most major psychiatric and neurological disorders, including depression.<ref>{{cite journal|last=Woodward|first=N.D.|author2=et al.|title=Functional resting-state networks are differentially affected in schizophrenia|journal=Schizophrenia Research|year=2011}}</ref><ref>{{cite journal|last=Menon|first=Vinod|author2=et al.|title=Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms|journal=Neuroimage|year=2001|volume=13|pages=433–446|doi=10.1006/nimg.2000.0699}}</ref> Because this network is crucial for everyday life activities, those who are depressed can show impairment in basic activities like test taking and being decisive.<ref>{{cite journal|last=Levin|first=R.L.|author2=et al.|title=Cognitive deficits in depression and functional specificity of regional brain activity.|journal=Cognitive Therapy and Research|year=2007|volume=31|page=211|page=233|doi=10.1007/s10608-007-9128-z}}</ref>


===Default mode network===
===Default mode network===
The [[default mode network]] includes hubs in the prefrontal cortex and posterior cingulate, with other prominent regions of the network in the medial temporal lobe and angular gyrus.<ref name="menon2011"/> The default mode network is usually active during mind-wandering and thinking about social situations. In contrast, during specific tasks probed in cognitive science (for example, simple attention tasks), the default network is often deactivated.<ref>{{cite journal|last=Qin|first=P|author2=Northoff, G|title=How is our self related to midline regions and the default mode network?|journal=Neuroimage|year=2011|volume=57|pages=1221–1233}}</ref><ref>{{cite journal|last=Raichle|first=M.E.|author2=et al.|title=A default mode of brain function|journal=Proceedings of the National Academy of Sciences of the United States of America |year=2001|volume=98|pages=676–682}}</ref> Research has shown that regions in the default mode network (including medial prefrontal cortex and posterior cingulate) show greater activity when depressed participants ruminate (that is, when they engage in repetitive self-focused thinking) than when typical, healthy participants ruminate.<ref>{{cite journal|last=Cooney|first=R.E.|author2=et al.|title=Neural correlates of rumination in depression|journal=Cognitive Affective and Behavioral Neuroscience|year=2010|volume=10|issue=4|pages=470–478}}</ref> Individuals suffering from major depression also show increased connectivity between the default mode network and the subgenual cingulate and the adjoining ventromedial prefrontal cortex in comparison to healthy individuals, individuals with dementia or with autism. Numerous studies suggest that the subgenual cingulate plays an important role in the dysfunction that characterizes major depression.<ref>{{cite journal|last=Broyd|first=S.J.|author2=et al.|title=Default mode brain dysfunction in mental disorders: a systematic review|journal=Neuroscience & Biobehavioral Reviews|year=2009|volume=33|pages=279–296|doi=10.1016/j.neubiorev.2008.09.002|pmid=18824195}}</ref> The increased activation in the default mode network during rumination and the atypical connectivity between core default mode regions and the subgenual cingulate may underlie the tendency for depressed individual to get “stuck” in the negative, self-focused thoughts that often characterize depression.<ref>{{cite journal|last=Hamani|first=C|author2=et al.|title=The subcallosal cingulate gyrus in the context of major depression|journal=Biological Psychiatry|date=15 February 2011|volume=69|page=301|page=309|doi=10.1016/j.biopsych.2010.09.034}}</ref> However, further research is needed to gain a precise understanding of how these network interactions map to specific symptoms of depression.
The [[default mode network]] includes hubs in the prefrontal cortex and posterior cingulate, with other prominent regions of the network in the medial temporal lobe and angular gyrus.<ref name="menon2011"/> The default mode network is usually active during mind-wandering and thinking about social situations. In contrast, during specific tasks probed in cognitive science (for example, simple attention tasks), the default network is often deactivated.<ref>{{cite journal|last=Qin|first=P|author2=Northoff, G|title=How is our self related to midline regions and the default mode network?|journal=Neuroimage|year=2011|volume=57|pages=1221–1233|doi=10.1016/j.neuroimage.2011.05.028}}</ref><ref>{{cite journal|last=Raichle|first=M.E.|author2=et al.|title=A default mode of brain function|journal=Proceedings of the National Academy of Sciences of the United States of America |year=2001|volume=98|pages=676–682|doi=10.1073/pnas.98.2.676}}</ref> Research has shown that regions in the default mode network (including medial prefrontal cortex and posterior cingulate) show greater activity when depressed participants ruminate (that is, when they engage in repetitive self-focused thinking) than when typical, healthy participants ruminate.<ref>{{cite journal|last=Cooney|first=R.E.|author2=et al.|title=Neural correlates of rumination in depression|journal=Cognitive Affective and Behavioral Neuroscience|year=2010|volume=10|issue=4|pages=470–478|doi=10.3758/cabn.10.4.470}}</ref> Individuals suffering from major depression also show increased connectivity between the default mode network and the subgenual cingulate and the adjoining ventromedial prefrontal cortex in comparison to healthy individuals, individuals with dementia or with autism. Numerous studies suggest that the subgenual cingulate plays an important role in the dysfunction that characterizes major depression.<ref>{{cite journal|last=Broyd|first=S.J.|author2=et al.|title=Default mode brain dysfunction in mental disorders: a systematic review|journal=Neuroscience & Biobehavioral Reviews|year=2009|volume=33|pages=279–296|doi=10.1016/j.neubiorev.2008.09.002|pmid=18824195}}</ref> The increased activation in the default mode network during rumination and the atypical connectivity between core default mode regions and the subgenual cingulate may underlie the tendency for depressed individual to get “stuck” in the negative, self-focused thoughts that often characterize depression.<ref>{{cite journal|last=Hamani|first=C|author2=et al.|title=The subcallosal cingulate gyrus in the context of major depression|journal=Biological Psychiatry|date=15 February 2011|volume=69|page=301|page=309|doi=10.1016/j.biopsych.2010.09.034}}</ref> However, further research is needed to gain a precise understanding of how these network interactions map to specific symptoms of depression.


===Salience network===
===Salience network===
The [[salience network]] is a cingulate-frontal operculum network that includes core nodes in the anterior cingulate and anterior insula.<ref name="seeley2007"/> A salience network is a large-scale brain network involved in detecting and orienting to [[salience (neuroscience)|salient]] external stimuli and internal events.<ref name="menon2011"/> Individuals who have a tendency to experience negative emotional states (scoring high on measures of [[neuroticism]]) show an increase in the right anterior insula during decision-making, even if the decision has already been made.<ref>{{cite journal|last=Feinstein|first=J.S.|author2=et al.|title=Anterior insula reactivity during certain decisions is associated with neuroticism|journal=Social Cognition and Affective Neuroscience|date=September 2006|volume=1|issue=2|pages=136–142}}</ref> This atypically high activity in the right anterior insula is thought to contribute to the experience of negative and worrisome feelings.<ref>{{cite journal|last=Paulus|first=M.P|author2=Stein, M.B.|title=An insular view of anxiety|journal=Biological Psychiatry|year=2006|volume=60|pages=383–387}}</ref> In major depressive disorder, anxiety is often a part of the emotional state that characterizes depression.<ref>{{cite book|last=Antony|first=M.M.|title=Oxford Handbook of Anxiety and Related Disorders|year=2009|publisher=Oxford University Press}}</ref>
The [[salience network]] is a cingulate-frontal operculum network that includes core nodes in the anterior cingulate and anterior insula.<ref name="seeley2007"/> A salience network is a large-scale brain network involved in detecting and orienting to [[salience (neuroscience)|salient]] external stimuli and internal events.<ref name="menon2011"/> Individuals who have a tendency to experience negative emotional states (scoring high on measures of [[neuroticism]]) show an increase in the right anterior insula during decision-making, even if the decision has already been made.<ref>{{cite journal|last=Feinstein|first=J.S.|author2=et al.|title=Anterior insula reactivity during certain decisions is associated with neuroticism|journal=Social Cognition and Affective Neuroscience|date=September 2006|volume=1|issue=2|pages=136–142|doi=10.1093/scan/nsl016}}</ref> This atypically high activity in the right anterior insula is thought to contribute to the experience of negative and worrisome feelings.<ref>{{cite journal|last=Paulus|first=M.P|author2=Stein, M.B.|title=An insular view of anxiety|journal=Biological Psychiatry|year=2006|volume=60|pages=383–387|doi=10.1016/j.biopsych.2006.03.042}}</ref> In major depressive disorder, anxiety is often a part of the emotional state that characterizes depression.<ref>{{cite book|last=Antony|first=M.M.|title=Oxford Handbook of Anxiety and Related Disorders|year=2009|publisher=Oxford University Press}}</ref>


==References==
==References==

Revision as of 12:45, 4 May 2014

Scientific studies have found that numerous brain areas show altered activity in patients suffering from depression, and this has encouraged advocates of various theories that seek to identify a biochemical origin of the disease, as opposed to theories that emphasize psychological or situational causes. Among the theories of a biologically based cause of depression are those involving genetics and circadian rhythms, but the most prominent and widely researched is the monoamine hypothesis.

Genetic factors

In 2003 Science published an influential[1] study of Avshalom Caspi et al. who found that a gene-environment interaction (GxE) may explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR).[2] Soon after, the results were replicated by Kenneth Kendler's group, raising hopes in the psychiatric genetics community.[3][4] By 2007 there were 11 replications, 3 partial replication and 3 non-replications of this proposed GxE. However, two of the largest studies[5][6] were negative.[7] Two 2009 meta-analyses were also negative; one included 14 studies,[8] the other just five, owing to different study selection criteria.[9] A 2010 review of studies in this area found 17 replications, 8 partial replications (interaction only in females or only with one of several types of adversity), and 9 non-replications (no interaction or an interaction in the opposite direction). It also found a systematic relationship between the method used to assess environmental adversity and the results of the studies; all studies using objective indicators or structured interviews to assess stress replicated the gene–environment interaction fully or partially, whereas all non-replications relied on brief self-report measures of adversity. This review also found that both 2009 meta-analyses were significantly biased toward negative studies.[10]

Other hypothesized genomic influences are BDNF polymorphisms, but the replications studies have been mixed and insufficient as of 2005 for a meta-analysis.[11] Studies also indicate an association of BDNF to suicidal behavior.[12] However, findings from the gene-environment interactions studies suggest that the current BDNF models of depression are too simplistic.[13] A 2008 study found interactions (biological epistasis) in the signaling pathways of the BDNF and the serotonin transporter; the BDNF Val66Met allele, which was predicted to have reduced responsitivity to serotonin, was found to exercise protective effects in individuals with the short 5-HTTLPR allele that is otherwise believed to predispose individuals to depressive episodes after stressful events.[14] Thus, the BDNF-mediated signalling involved in neuroplastic responses to stress and antidepressants is influenced by other genetic and environmental modifiers.[13]

Circadian rhythm

Depression may be related to the same brain mechanisms that control the cycles of sleep and wakefulness.

Depression may be related to abnormalities in the circadian rhythm,[15] or biological clock. For example, rapid eye movement (REM) sleep—the stage in which dreaming occurs—may be quick to arrive and intense in depressed people. REM sleep depends on decreased serotonin levels in the brain stem,[16] and is impaired by compounds, such as antidepressants, that increase serotonergic tone in brain stem structures.[16] Overall, the serotonergic system is least active during sleep and most active during wakefulness. Prolonged wakefulness due to sleep deprivation[17] activates serotonergic neurons, leading to processes similar to the therapeutic effect of antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). Depressed individuals can exhibit a significant lift in mood after a night of sleep deprivation. SSRIs may directly depend on the increase of central serotonergic neurotransmission for their therapeutic effect, the same system that impacts cycles of sleep and wakefulness.[16]

Research on the effects of light therapy on seasonal affective disorder suggests that light deprivation is related to decreased activity in the serotonergic system and to abnormalities in the sleep cycle, particularly insomnia. Exposure to light also targets the serotonergic system, providing more support for the important role this system may play in depression.[18] Sleep deprivation and light therapy both target the same brain neurotransmitter system and brain areas as antidepressant drugs, and are now used clinically to treat depression.[19] Light therapy, sleep deprivation and sleep time displacement (sleep phase advance therapy) are being used in combination quickly to interrupt a deep depression in hospitalized patients.[18]

Chemicals

Monoamine

Illustration of the major elements in a prototypical synapse. Synapses are gaps between nerve cells. These cells convert their electrical impulses into bursts of chemical relayers, called neurotransmitters, which travel across the synapses to receptors on adjacent cells, triggering electrical impulses to travel down the latter cells.

Monoamines are neurotransmitters and neuromodulators that include serotonin, dopamine, norepinephrine, and epinephrine.[20] Many antidepressant drugs increase synaptic levels of the monoamine neurotransmitter serotonin, but they may also enhance the levels of two other neurotransmitters, norepinephrine and dopamine. The observation of this efficacy led to the monoamine hypothesis of depression, which postulates that the deficit of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." The proponents of this hypothesis recommend choosing the antidepressant with the mechanism of action impacting the most prominent symptoms. Anxious or irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitors, and the ones with the loss of energy and enjoyment of life—with norepinephrine and dopamine enhancing drugs.[21]

Monoamine receptors affect phospholipase C and adenylyl cyclase inside of the cell. Green arrows means stimulation and red arrows inhibition. Serotonin receptors are blue, norepinephrine orange, and dopamine yellow. Phospholipase C and adenylyl cyclase start a signaling cascade which turn on or off genes in the cell. The 5HT-3 receptor is associated with gastrointestinal adverse effects and has no relationship to the other monoamine receptors.

Consistent with the monoamine hypothesis, a longitudinal study uncovered a moderating effect of the serotonin transporter (5-HTT) gene on stressful life events in predicting depression. Specifically, depression seems especially likely to follow stressful life events, but even more so for people with one or two short alleles of the 5-HTT gene.[22] Serotonin may help to regulate other neurotransmitter systems, and decreased serotonin activity may "permit" these systems to act in unusual and erratic ways. Facets of depression may be emergent properties of this dysregulation.[23]

An offshoot of the monoamine hypothesis suggests that monoamine oxidase A (MAO-A), an enzyme which metabolizes monoamines, may be overly active in depressed people. This would, in turn, cause the lowered levels of monoamines. This hypothesis received support from a PET study, which found significantly elevated activity of MAO-A in the brain of some depressed people.[24] In genetic studies, the alterations of MAO-A-related genes have not been consistently associated with depression.[25][26] Contrary to the assumptions of the monoamine hypothesis, lowered but not heightened activity of MAO-A was associated with the depressive symptoms in youth. This association was observed only in maltreated youth, indicating that both biological (MAO genes) and psychological (maltreatment) factors are important in the development of depressive disorders.[27] In addition, some evidence indicates that problems in information processing within neural networks, rather than changes in chemical balance, might underlie depression.[28]

Since the 1990s, research has uncovered multiple limitations of the monoamine hypothesis, and its inadequacy has been criticized within the psychiatric community.[29] For one thing, serotonin system dysfunction cannot be the sole cause of depression; antidepressants usually bring serotonin levels up to normal very quickly, but it often takes at least two to four weeks before mood improves significantly. Intensive investigation has failed to find convincing evidence of a primary dysfunction of a specific monoamine system in patients with major depressive disorders. The antidepressants that do not act through the monoamine system, such as tianeptine and opipramol, have been known for a long time. Experiments with pharmacological agents that cause depletion of monoamines have shown that this depletion does not cause depression in healthy people nor does it worsen the symptoms in depressed patients.[30][31] Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.[32]

Serotonin

Many variations of the monoamine hypothesis involve the neurotransmitter serotonin, regulated by the serotonin transporter, which assists the modulation of feelings and behavior such as anxiety, anger, appetite, sexuality, sleep, mood, etc. People with depression may have differences in serotonin transporter gene length.[33] People with both alleles that are long are less likely to become depressed, while people with one short and one long or two short alleles are more likely to develop depression.[34]

The functions of serotonin are difficult to describe in a simple way. In some circumstances serotonin seems to act as a signal of "repletion" or "satisfaction". Thus, satiation after eating, and orgasm following sex, both produce release of serotonin. In animals that have hierarchical social structures, dominant individuals show higher levels of serotonin metabolites than lower-status individuals. In the brain, serotonin exerts a suppressive effect on both the reward system and punishment system[clarification needed], and therefore is likely to reduce the intensity of motivation whether aversive or appetitive.[citation needed]

Fructose

Fructose malabsorption has been associated with depression in young women. Their mood improved when their intake of fructose was restricted. The mechanisms of these effects are not well understood, but may involve low circulating levels of tryptophan, which is the precursor of serotonin.[35]

Abnormalities by brain region

Research on the brains of depressed patients usually shows disturbed patterns of interaction between multiple parts of the brain. Several areas of the brain are implicated in studies seeking to more fully understand the biology of depression:

Raphe nuclei

The sole source of serotonin in the brain is the raphe nuclei, a group of small nerve cell nuclei in the upper brain stem, located directly at the mid-line of the brain. There is some evidence for neuropathological abnormalities in the rostral raphe nuclei in depression.[36][37][38] Despite their small size, they reach very widely through their projections, and are involved in a very diverse set of functions. Most antidepressants are serotonergic.

Suprachiasmatic nucleus (SCN)

The suprachiasmatic nucleus (SCN) is the control center for the body's "biological clock." It contains neurons whose activity waxes and wanes throughout the day. The output from the SCN controls the sleep/wake cycle as well as a number of other biological rhythms, such as fluctuations in body temperature. Disturbances of these cycles are a consistent symptom of depression, especially of the melancholic type. The "classic" pattern is for depressed people to have great difficulty falling asleep at night, and then to wake bolt upright at around 3 AM. The waking is usually preceded by a rise in body temperature, which in non-depressed people does not usually occur until several hours later. It is a common observation that antidepressants produce a return to normal sleep patterns before they produce an improvement in mood: if good sleep does not return, it is a strong sign that the treatment is not going to be effective. Conversely, disruptions to sleep are often the first indication of impending relapse.[citation needed]

There is a powerful interaction between the Raphe nuclei and the SCN. On one hand, the Raphe nuclei send a strong serotonergic projection to the SCN. In animal studies, this input has been shown to modulate the ability of light to reset the timing of the biological clock: the more serotonin, the stronger the effects of light. On the other hand, the biological clock exerts a strong influence on the Raphe nuclei: serotonin levels drop during sleep, and fall almost to nothing during REM (dreaming) sleep. It is worth noting that one of the characteristics of sleep in depressed people is that REM tends to appear very soon after sleep onset, whereas in non-depressed people it does not usually dominate sleep until the last hours, in the early morning. Antidepressants are powerful suppressors of REM. [citation needed]

Ventral tegmental area (VTA)

The ventral tegmentum (or ventral tegmental area) is a small area in the basal midbrain which is a critical part of the brain's reward system. It sends projections to the nucleus accumbens that use the neurotransmitter dopamine. Addictive drugs universally increase the effects of dopamine in this system, whereas drugs that oppose dopamine produce anhedonia of the sort seen in depressed people. Dopamine-enhancers such as cocaine often relieve the lack-of-pleasure in depression, but the effects only last as long as a drug is present in the body: that is, they temporarily alleviate one of the main symptoms, but do not help to cure the disease.

Nucleus accumbens (NAc)

Long-term exposure to various unavoidable stress factors decreases dopamine release in the NAc shell,[39][40] as it was shown in the forced swimming test, an animal model of depression.[41]

Anterior cingulate cortex (ACC)

The anterior cingulate cortex is activated by negative experiences of many types, and consistently shows higher levels of activity in depressed people than in non-depressed people. The functions of the ACC are controversial, but one proposal is that it mediates the conscious experience of suffering. Several decades ago, trials were made of ablating parts of the ACC in an attempt to relieve intolerable pain in patients who were terminally ill. These patients reported that after the surgery, they could still perceive the physical sensations of pain, but they no longer found them distressing. (The effects of heroin and morphine are sometimes described in the same way.) Very recently, clinical experiments were made in using deep brain stimulation to temporarily inactivate the ACC in severely depressed patients. This was not effective in all cases, but in some patients very striking results were achieved, with a perceptible lifting of mood immediately apparent to the patient as soon as the stimulus was applied.

Subgenual cingulate

Recent studies have shown that Brodmann area 25, also known as Subgenual cingulate is metabolically overactive in treatment-resistant depression.[42] This region is extremely rich in serotonin transporters and is considered as a governor for a vast network involving areas like hypothalamus and brain stem, which influences changes in appetite and sleep; the amygdala and insula, which affect the mood and anxiety; the hippocampus, which plays an important role in memory formation; and some parts of the frontal cortex responsible for self-esteem.[43][44] Thus disturbances in this area or a smaller than normal size of this area contributes to depression. Deep Brain Stimulations of this area have been successful in reducing its elevated activity and thus curing depression in patients that could not be cured by anti-depressants.[45]

Hypothalamic-pituitary-adrenal (HPA) axis

The hypothalamic-pituitary-adrenal axis is a chain of endocrine structures that are activated during the body's response to stressors of various sorts. It often shows increased activation in depressed people, but the mechanism behind this is not yet known.[46]

Ventricles

Multiple studies have found evidence of ventricular enlargement in people who have depression, particularly enlargement of the third ventricle.[47][48][49] These observations are interpreted as indicating loss of neural tissue in brain regions adjacent to the enlarged ventricle, leading to suggestions that cytokines and related mediators of neurodegeneration may play a role in giving rise to the disease.[50][51][52]

Altered neuroplasticity

Recent studies have called attention to the role of altered neuroplasticity in depression. A review found convergence of three phenomena:

  1. Chronic stress reduces synaptic and dendritic plasticity
  2. Depressed subjects show evidence of impaired neuroplasticity (e.g. shortening and reduced complexity of dendritic trees)
  3. Anti-depressant medications enhance neuroplasticity at both a molecular and dendritic level.

The conclusion is that disrupted neuroplasticity is an underlying feature of depression, and is reversed by antidepressants.[53]

Large-scale brain network theory

Instead of studying one brain region, studying large-scale brain networks is another approach to understanding psychiatric and neurological disorders,[54] supported by recent research that has shown that multiple brain regions are involved in these disorders. Understanding the disruptions in these networks may provide important insights into interventions for treating these disorders. Recent work suggests that at least three large-scale brain networks are important in psychopathology:[54]

Central executive network

The central executive network is made up of fronto-parietal regions, including dorsolateral prefrontal cortex and lateral posterior parietal cortex.[55][56] This network is crucially involved in high level cognitive functions such as maintaining and using information in working memory, problem solving, and decision making.[54][57][58][59][60] Deficiencies in this network are common in most major psychiatric and neurological disorders, including depression.[61][62] Because this network is crucial for everyday life activities, those who are depressed can show impairment in basic activities like test taking and being decisive.[63]

Default mode network

The default mode network includes hubs in the prefrontal cortex and posterior cingulate, with other prominent regions of the network in the medial temporal lobe and angular gyrus.[54] The default mode network is usually active during mind-wandering and thinking about social situations. In contrast, during specific tasks probed in cognitive science (for example, simple attention tasks), the default network is often deactivated.[64][65] Research has shown that regions in the default mode network (including medial prefrontal cortex and posterior cingulate) show greater activity when depressed participants ruminate (that is, when they engage in repetitive self-focused thinking) than when typical, healthy participants ruminate.[66] Individuals suffering from major depression also show increased connectivity between the default mode network and the subgenual cingulate and the adjoining ventromedial prefrontal cortex in comparison to healthy individuals, individuals with dementia or with autism. Numerous studies suggest that the subgenual cingulate plays an important role in the dysfunction that characterizes major depression.[67] The increased activation in the default mode network during rumination and the atypical connectivity between core default mode regions and the subgenual cingulate may underlie the tendency for depressed individual to get “stuck” in the negative, self-focused thoughts that often characterize depression.[68] However, further research is needed to gain a precise understanding of how these network interactions map to specific symptoms of depression.

Salience network

The salience network is a cingulate-frontal operculum network that includes core nodes in the anterior cingulate and anterior insula.[55] A salience network is a large-scale brain network involved in detecting and orienting to salient external stimuli and internal events.[54] Individuals who have a tendency to experience negative emotional states (scoring high on measures of neuroticism) show an increase in the right anterior insula during decision-making, even if the decision has already been made.[69] This atypically high activity in the right anterior insula is thought to contribute to the experience of negative and worrisome feelings.[70] In major depressive disorder, anxiety is often a part of the emotional state that characterizes depression.[71]

References

  1. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19890228, please use {{cite journal}} with |pmid=19890228 instead.
  2. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1126/science.1083968, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1126/science.1083968 instead.
  3. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15867106, please use {{cite journal}} with |pmid=15867106 instead.
  4. ^ http://www.esi-topics.com/nhp/2006/september-06-KennethSKendler.html
  5. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1017/S0033291704002727, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1017/S0033291704002727 instead.
  6. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.biopsych.2005.07.014, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/j.biopsych.2005.07.014 instead.
  7. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/sj.mp.4002067, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/sj.mp.4002067 instead.
  8. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1001/jama.2009.878, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1001/jama.2009.878 instead.
  9. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.biopsych.2008.06.009, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/j.biopsych.2008.06.009 instead.
  10. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/mp.2009.123, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/mp.2009.123 instead.
  11. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.biopsych.2005.08.024, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/j.biopsych.2005.08.024 instead.
  12. ^ Dwivedi Y (2009). "Brain-derived neurotrophic factor: role in depression and suicide". Neuropsychiatr Dis Treat. 5: 433–49. doi:10.2147/NDT.S5700. PMC 2732010. PMID 19721723.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ a b Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/nature07455, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/nature07455 instead.
  14. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/mp.2008.32, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/mp.2008.32 instead.
  15. ^ Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 578-582). United States of America: Pearson.
  16. ^ a b c Adrien J.. Neurobiological bases for the relation between sleep and depression. Sleep Medicine Review. 2003;6(5):341–51. PMID 12531125.
  17. ^ Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 578-580). United States of America: Pearson.
  18. ^ a b Terman M. Evolving applications of light therapy. Sleep Medicine Review. 2007;11(6):497–507. doi:10.1016/j.smrv.2007.06.003. PMID 17964200.
  19. ^ Benedetti F, Barbini B, Colombo C, Smeraldi E. Chronotherapeutics in a psychiatric ward. Sleep Medicine Review. 2007;11(6):509–22. doi:10.1016/j.smrv.2007.06.004. PMID 17689120.
  20. ^ Neil Carlson: Foundations of Physiological Psychology, 6th ed. 2005. ISBN 0-205-42723-5 Page: 108
  21. ^ Nutt DJ (2008). "Relationship of neurotransmitters to the symptoms of major depressive disorder". Journal of Clinical Psychiatry. 69 Suppl E1: 4–7. PMID 18494537.
  22. ^ Caspi A; et al. (2003). "Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene". Science. 301 (5631): 386–89. Bibcode:2003Sci...301..386C. doi:10.1126/science.1083968. PMID 12869766. {{cite journal}}: Explicit use of et al. in: |author= (help)
  23. ^ Mandell AJ, Knapp S (1979). "Asymmetry and mood, emergent properties of serotonin regulation: A proposed mechanism of action of lithium". Archives of General Psychiatry. 36 (8): 909–16. doi:10.1001/archpsyc.1979.01780080083019. PMID 454111.
  24. ^ Meyer JH, Ginovart N, Boovariwala A; et al. (November 2006). "Elevated monoamine oxidase a levels in the brain: An explanation for the monoamine imbalance of major depression". Archives of General Psychiatry. 63 (11): 1209–16. doi:10.1001/archpsyc.63.11.1209. PMID 17088501. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  25. ^ Huang SY, Lin MT, Lin WW; Huang CC; Shy MJ; Lu RB (19 December 2007). "Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population". World Journal of Biological Psychiatry. 10 (4 Pt 2). Informa Healthcare: 544–51. doi:10.1080/15622970701816506. PMID 19224413. Retrieved 20 September 2008.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW (September 2005). "Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response". Neuropsychopharmacology. 30 (9): 1719–23. doi:10.1038/sj.npp.1300785. PMID 15956990.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Cicchetti D, Rogosch FA, Sturge-Apple ML (2007). "Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: depressive symptomatology among adolescents from low socioeconomic status backgrounds". Dev. Psychopathol. 19 (4): 1161–80. doi:10.1017/S0954579407000600. PMID 17931441.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Castrén, E (2005). "Is mood chemistry?". Nature Reviews Neuroscience. 6 (3): 241–46. doi:10.1038/nrn1629. PMID 15738959.
  29. ^ Hirschfeld RM (2000). "History and evolution of the monoamine hypothesis of depression". Journal of Clinical Psychiatry. 61 Suppl 6: 4–6. PMID 10775017.
  30. ^ Delgado PL, Moreno FA (2000). "Role of norepinephrine in depression". J Clin Psychiatry. 61 Suppl 1: 5–12. PMID 10703757.
  31. ^ Delgado PL (2000). "Depression: the case for a monoamine deficiency". Journal of Clinical Psychiatry. 61 Suppl 6: 7–11. PMID 10775018.
  32. ^ Lacasse J, Leo J (2005). "Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature". PLoS Med. 2 (12): e392. doi:10.1371/journal.pmed.0020392. PMC 1277931. PMID 16268734.{{cite journal}}: CS1 maint: unflagged free DOI (link) Free full text, open-access source
  33. ^ Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 575-576). United States of America: Pearson.
  34. ^ Avshalom Caspi, Karen Sugden, Terrie E. Moffitt, Alan Taylor, Ian W. Craig, HonaLee Harrington, Joseph McClay, Jonathan Mill, Judy Martin, Antony Braithwaite, and Richie Poulton (July 2003). "Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene". Science. 301 (5631): 386–389. doi:10.1126/science.1083968. PMID 12869766.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ P. R. GIBSON, E. NEWNHAM, J. S. BARRETT, S. J. SHEPHERD, J. G. MUIR (February 2007). "Review article: fructose malabsorption and the bigger picture". Alimentary Pharmacology & Therapeutics. 25 (4): 349–363. doi:10.1111/j.1365-2036.2006.03186.x. PMID 17217453.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ Underwood MD, Khaibulina AA, Ellis SP, Moran A, Rice PM, Mann JJ, Arango V (August 1999). "Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims". Biol Psychiatry. 46 (4): 473–83. doi:10.1016/S0006-3223(99)00043-8. PMID 10459396.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ (December 2001). "Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims". Neuropsychopharmacology. 25 (6): 892–903. doi:10.1016/S0893-133X(01)00310-4. PMID 11750182.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Matthews PR, Harrison PJ (March 2012). "A morphometric, immunohistochemical, and in situ hybridization study of the dorsal raphe nucleus in major depression, bipolar disorder, schizophrenia, and suicide". J Affect Disord. 137 (1–3): 125–134. doi:10.1016/j.jad.2011.10.043. PMC 3314923. PMID 22129767.
  39. ^ Di Chiara G, Loddo P, Tanda G (1999). "Reciprocal changes in prefrontal and limbic dopamine responsiveness to aversive and rewarding stimuli after chronic mild stress: implications for the psychobiology of depression". Biol. Psychiatry. 46 (12): 1624–33. doi:10.1016/S0006-3223(99)00236-X. PMID 10624543.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  40. ^ Scheggi S, Leggio B, Masi F; et al. (2002). "Selective modifications in the nucleus accumbens of dopamine synaptic transmission in rats exposed to chronic stress". J. Neurochem. 83 (4): 895–903. doi:10.1046/j.1471-4159.2002.01193.x. PMID 12421362. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  41. ^ Rossetti ZL, Lai M, Hmaidan Y, Gessa GL (1993). "Depletion of mesolimbic dopamine during behavioral despair: partial reversal by chronic imipramine". Eur. J. Pharmacol. 242 (3): 313–5. doi:10.1016/0014-2999(93)90257-I. PMID 8281997.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA (October 2000). "Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response". Biol Psychiatry. 48 (8): 830–43. doi:10.1016/s0006-3223(00)01036-2.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  43. ^ Carlson, N. (2013). Physiology of behavior. (11 ed., pp. 576-578). United States of America: Pearson.
  44. ^ "Faulty Circuits", Scientific American, April 2010
  45. ^ Mayberg Helen S., Lozano Andres M., Voon Valerie, McNeely Heather E., Seminowicz David, Hamani Clement, Schwalb Jason M., Kennedy Sidney H. (2005). "Deep Brain Stimulation for Treatment-Resistant Depression ". Neuron. 45: 651–660. doi:10.1016/j.neuron.2005.02.014.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  46. ^ Pariante CM, Lightman SL. (September 2008). "The HPA axis in major depression: classical theories and new developments". Trends Neurosci. 31 (9): :464–468. doi:10.1016/j.tins.2008.06.006. PMID 18675469.
  47. ^ Hendrie, C.A.; Pickles, A.R. (2009). "Depression as an evolutionary adaptation: Implications for the development of preclinical models". Medical Hypotheses. 72: 342–347. doi:10.1016/j.mehy.2008.09.053. Retrieved 25 September 2013.
  48. ^ Hendrie, C.A.; Pickles, A.R. (2010). "Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle". Medical Hypotheses. 74: 735–740. doi:10.1016/j.mehy.2009.10.026. Retrieved 25 September 2013.
  49. ^ Sheline, Yvette (August 2003). "Neuroimaging studies of mood disorder effects on the brain". Biological Psychiatry. 54: 338–352. doi:10.1016/s0006-3223(03)00347-0. Retrieved 25 September 2013.
  50. ^ Manji, Husseini K.; Quiroz, Jorge A.; Sporn, Jonathan; Payne, Jennifer L.; Denicoff, Kirk; Gray, Neil A.; Zarate Jr., Carlos A.; Charney, Dennis S. (April 2003). "Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression". 53: 707–742. Retrieved 25 September 2013. {{cite journal}}: Cite journal requires |journal= (help)
  51. ^ Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65(9), 732–741.
  52. ^ Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology, 27(1), 24–31.
  53. ^ Christopher Pittenger and Ronald S Duman (2008). "Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms". Neuropsychopharmacology. 33 (1): 88–109. doi:10.1038/sj.npp.1301574. PMID 17851537Template:Inconsistent citations{{cite journal}}: CS1 maint: postscript (link)
  54. ^ a b c d e Menon, Vinod (October 2011). "Large-scale brain networks and psychopathology: a unifying triple network model". Trends in Cognitive Sciences. 15 (10).
  55. ^ a b Seeley, W.W; et al. (February 2007). "Dissociable intrinsic connectivity networks for salience processing and executive control". The Journal of Neuroscience. 27. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  56. ^ Habas, C; et al. (1 July 2009). "Distinct cerebellar contributions to intrinsic connectivity networks". The Journal of Neuroscience. 29. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  57. ^ Petrides, M (2005). "Lateral prefrontal cortex: architecture and functional organization". Philosophical Transactions of the Royal Society B: 781–795.
  58. ^ Koechlin, E; Summerfield, C (2007). "An information theoretical approach to prefrontal executive function". Trends in Cognitive Sciences: 229–235.
  59. ^ Miller, E.K.; Cohen, J.D. (2001). "An intergrative theory of prefrontal cortex function". Annual Review of Neuroscience: 167–202.
  60. ^ Muller, N.G.; Knight, R.T. (2006). "The functional neuroanatomy of working memory: contributions of human brain lesion studies". Neuroscience: 51–58.
  61. ^ Woodward, N.D.; et al. (2011). "Functional resting-state networks are differentially affected in schizophrenia". Schizophrenia Research. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  62. ^ Menon, Vinod; et al. (2001). "Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms". Neuroimage. 13: 433–446. doi:10.1006/nimg.2000.0699. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  63. ^ Levin, R.L.; et al. (2007). "Cognitive deficits in depression and functional specificity of regional brain activity". Cognitive Therapy and Research. 31: 233. doi:10.1007/s10608-007-9128-z. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  64. ^ Qin, P; Northoff, G (2011). "How is our self related to midline regions and the default mode network?". Neuroimage. 57: 1221–1233. doi:10.1016/j.neuroimage.2011.05.028.
  65. ^ Raichle, M.E.; et al. (2001). "A default mode of brain function". Proceedings of the National Academy of Sciences of the United States of America. 98: 676–682. doi:10.1073/pnas.98.2.676. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  66. ^ Cooney, R.E.; et al. (2010). "Neural correlates of rumination in depression". Cognitive Affective and Behavioral Neuroscience. 10 (4): 470–478. doi:10.3758/cabn.10.4.470. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  67. ^ Broyd, S.J.; et al. (2009). "Default mode brain dysfunction in mental disorders: a systematic review". Neuroscience & Biobehavioral Reviews. 33: 279–296. doi:10.1016/j.neubiorev.2008.09.002. PMID 18824195. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  68. ^ Hamani, C; et al. (15 February 2011). "The subcallosal cingulate gyrus in the context of major depression". Biological Psychiatry. 69: 309. doi:10.1016/j.biopsych.2010.09.034. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  69. ^ Feinstein, J.S.; et al. (September 2006). "Anterior insula reactivity during certain decisions is associated with neuroticism". Social Cognition and Affective Neuroscience. 1 (2): 136–142. doi:10.1093/scan/nsl016. {{cite journal}}: Explicit use of et al. in: |author2= (help)
  70. ^ Paulus, M.P; Stein, M.B. (2006). "An insular view of anxiety". Biological Psychiatry. 60: 383–387. doi:10.1016/j.biopsych.2006.03.042.
  71. ^ Antony, M.M. (2009). Oxford Handbook of Anxiety and Related Disorders. Oxford University Press.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Biology_of_depression&oldid=607020085"