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Illuminating Pathways To a Healthy Brain

Depression

Depression

Depression is a profound problem in American and worldwide. Depression is more than “having a bad day” or “feeling blue”. It is a long-lasting experience of low mood, loss of enjoyment in life, loss of interest, low energy, changes in sleep and/or appetite, and a decrease in one’s ability to think clearly (cognition).

Many people with depression experience extreme distress and anguish. They may struggle each day to get up and function. They may even struggle daily to stay alive – to resist suicidal urges. Many have virtually no quality of life and are trapped in their misery.

Often family and friends cannot appreciate the depth of pain and suffering that depression can cause. “Pull yourself up by your bootstraps” or “Get over it” are familiar phrases. If it was that simple, then depression would not be such an intractable condition. Depression is found in every country of the world and in every socioeconomic class. No matter where you look, the rate of depression is about 5-7%. Talking to friends or formal psychotherapy can help, but only 30% of depressed people recover with this approach, underscoring that its more than just “a poor me” attitude.

Indeed, depression is not just one thing, despite the efforts of mainstream psychiatry to classify it into a single illness category. Nassir Ghaemi, MD, noted expert on psychopharmacology recently wrote:

“Psychiatry…practice(s) non-scientifically; we use hundreds of made-up labels for professional purposes, without really getting at the reality of what is wrong with the patient. Sometimes those patients have diseases; we don’t know what they are. Sometimes they don’t have diseases; we don’t know when that is.  (We have little understanding of) what the causes of those diseases…might be. We have a huge amount of neurobiology research now to conclude that the 20th century neurotransmitter theories of psychopharmacology basically are false. The dopamine and monoamine hypotheses of schizophrenia and depression are wrong; thus, using our drug classes to increase or decrease neurotransmitters is wrong-headed.  Instead, we now know that drugs have major second messenger effects which (cause) neuroplastic changes in the brain, including connections between neurons. The brain is literally re-sculpted. This is a slow process, and it happens differently with different drugs and in different illnesses.”

 

 What We Now Know About the Brain in Depression

Neuroimaging studies have shown several neurophysiological substrates for depression. Functional brain scans, such as SPECT (single photon emission computed tomography) or PET (positron emission tomography) have shown that while patients may present with the same symptoms of depression, they can have very different processes occurring in their brains.

The anatomic circuits of depression and mood regulation have been revealed by converging evidence from SPECT, PET and fMRI (functional magnetic resonance imaging) studies of depression and analysis of both lesions resulting in depressive symptoms and surgical lesions used to treat severe cases of depression. These convergent findings have revealed a network of brain regions, including the dorsal prefrontal cortex, ventral prefrontal cortex, anterior cingulate gyrus, amygdala, hippocampus, striatum, and thalamus in the pathophysiology of depression. Drevets and others have emphasized that depression is the result of multiple pathophysiological processes and the dysfunction of multiple pathways.

While depression may present with the same symptoms, the neuronal pathways involved likely differ from one individual to another. Depression is not a single entity, but more likely a spectrum or an array of different disease mechanisms.

Therefore it should be no surprise that not everyone responds to the same medication and that examining the function of the brain could make a critical difference in the success or failure of a treatment plan.

SPECT neuroimaging can also predict who will respond to certain antidepressants. For example, those who are likely to respond to SSRI antidepressants show increased perfusion in the ventral frontal cortex and anterior cingulate. The response to SSRI antidepressants is often decreased perfusion in these areas, as well as in the thalamus.

Distinct subtypes of depression now can be detected. Depression is often associated with decreased activity (and therefore metabolism and perfusion) of the frontal lobes, the insular cortex, and the anterior cingulate gyrus. However, some patients with depression have increased perfusion in the precuneus, which correlates with rumination and self-criticism. Some patients with depression also have decreased temporal lobe function. Many patients with depression show increased thalamic activity (metabolism or perfusion). Portions of the thalamus have direct connections to the amygdala, the seat of fear and anxiety.

In contrast, some patients with depression have markedly decreased dorsal frontal cortex and medial frontal cortex perfusion. These patients are less likely to respond to SSRI medications, but may respond better to noradrenergic antidepressants. Treatment-resistant depression may show markedly increased perfusion in the subgenual cingulate.

Depression in the elderly may be quite different. The elderly patient may show decreased perfusion throughout the frontal and temporal lobes, but increased perfusion in the thalamus.

Bipolar depression appears to be fundamentally different from unipolar depression – genetically, physiologically, neurobiologically, and with neuroimaging. Bipolar depression may appear as increased perfusion in the dorsal anterior cingulate, striatum, nucleus accumbens, temporal lobes, and with asymmetrical thalamus perfusion, but decreased prefrontal cortex perfusion.

The treatment of bipolar depression is fundamentally different from that of unipolar depression. Using typical antidepressants in bipolar depression can be potentially disastrous.

Depression often overlaps with obsessive-compulsive disorder (OCD). Two parallel anatomical circuits are involved in OCD. Patients with OCD show increased activity, manifested by increased perfusion and metabolism, in the frontal cortex, anterior cingulate gyrus, caudate, putamen and thalamus. During effective pharmacotherapy, perfusion and metabolism decreased toward normal in these areas. These same circuits also have been implicated in the patho-physiology of major depressive disorder (MDD), another illness in which intrusive, distressing thoughts recur to an extent that the ability to switch to goal-oriented, rewarding cognitive-behavioral sets is impaired.

The subgenual portion of the anterior cingulate gyrus has recently been recognized as a key area in depression as reviewed by Dr. Wayne Drevets. The subgenual anterior cingulate shows elevated activity, as shown by PET or SPECT during the depressed state, particularly in severely depressed or treatment-resistant depression (see below). Activity is reduced with effective treatment, whether by pharmacological means, transcranial magnetic stimulation or more aggressive neurosurgical means. These functional changes in the subgenual anterior cingulate can be seen with SPECT or PET.

Neuroimaging helps to diagnose neurological disorders which may masquerade as psychiatric conditions. For example, traumatic brain injury, toxic brain injury, and dementia in the elderly can all present as depression. Ultimately, the combination of neuroimaging, clinical evaluation, psychological testing as indicated, and genetic testing (for example, 5HT transporter gene polymorphisms) are more likely to reveal the most complete diagnosis and guide the clinician to the best treatment.

DepressionThe symptoms of depression also can occur in numerous other brain disorders. For example, over 40% of patients who experience a concussion (also known as mild TBI) will develop depression over the subsequent year. There is no reason to expect patients with TBI to respond the same way as those who have endogenous depression. Toxic brain injury, infectious brain disorders (chronic Lyme’s disease; Valley Fever) and Chronic Fatigue Syndrome can all present with low energy, low mood, and loss of interests – symptoms which are indistinguishable from depression. In addition, patients with severe anxiety may become depressed, but the solution for them is to fully treat their anxiety. In the elderly, depression can occur from many causes – medications, dementia, and several different forms of endogenous depression.

With so many possible neural mechanisms for depression, the value of thoroughly understanding the situation in each patient’s brain becomes clear. As discussed in Treatment, blindly throwing medications at a problem does not seem to be the answer. Rather, targeted therapy is more likely to be successful.

If you or someone you know is suffering from depression please get in touch with us today. Visit our contact us page to find out how.

 

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